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Bilateral recurrent laryngeal nerve palsy following anterior cervical surgery subsequent to contralateral apical lung radiotherapy.

Unilateral recurrent laryngeal nerve palsy is a potential complication of the anterior approach for cervical surgery. It is a rare complication of radiotherapy to the neck. Only one case has been reported following radiotherapy apical lung cancer. It can result in unilateral vocal cord paralysis. We report a patient who demonstrated bilateral vocal cord paralysis immediately following right-sided anterior cervical surgery, with significant consequences, including aphonia, respiratory distress and subsequent takotsubo cardiomyopathy. She was diagnosed with acute, (temporary) post-operative right recurrent laryngeal nerve palsy, on the background of undetected and previously asymptomatic left recurrent laryngeal nerve palsy following radiotherapy for left apical lung cancer. The possibility of recurrent laryngeal nerve palsy should be considered in patients with previous apical lung cancer and or radiotherapy. Patents undergoing subsequent anterior cervical surgery should be considered for the appropriate precautions in the form of same-side surgery or pre-operative investigation for vocal cord paralysis.

Effects of scenario-based attribution on collective emotions and stigma toward persons with COVID-19 A cross-sectional survey.

During this COVID-19 pandemic, many people experience and share emotions such as fear, anxiety, sadness, anger, and disgust, which can be regarded as collective emotions. This study investigated the effects of scenario-based attribution for serious diseases on collective emotions and social stigma. Participants were 297 healthy adults who met two conditions (1) not having tested positive for COVID-19 (including their family members or close friends) and no experience of self-quarantine and (2) not having been diagnosed with lung cancer, and not having family members or close friends diagnosed with it. Three hundred participants were recruited, through a company conducting online surveys. A total of 297 data sets were analyzed, excluding data supplied by three participants who might have responded unreliably to the filler question. Scenarios were recorded according to attribution type (internal vs. external) and disease (COVID-19 vs. lung cancer). A 2 × 2 factorial design was used, whereby participants were randomly assigned to one of four conditions. The COVID-19 condition showed higher scores on the perceived risk and fear of the disease compared to the lung cancer one. The COVID-19internal attribution condition showed the highest scores for fear and anger toward scenario characters, and the lung cancerexternal attribution condition showed higher sympathy scores than other conditions. Although attribution to COVID-19 was not directly related to social stigma, it could evoke negative emotions toward infected people. The findings suggest that attributions of serious diseases such as COVID-19 to infected persons can influence collective emotions and the level of social stigma associated with the disease. Attention to the collective emotions and stigma associated with disease is a key component for communities and countries to recover from and respond to its impacts.

Roles of Community Pharmacists in Cancer Management.

Community pharmacists are among the most easily accessible healthcare practitioners and are usually the first point of contact with the public or community. This is often due to their accessibility, credibility, and widespread within the public sector making them essential members of the healthcare team with significant contributions to the delivery of public health care. Community pharmacists, in addition to their known educational and awareness-raising roles, may play an essential role in risk assessment and screening of patients, detection of symptoms of probable malignancy, and cancer treatments. The pharmacy profession has been evolving from dispensing roles into more patient-oriented outcomes and pharmacists are now participating in more clinical interventions. This places community pharmacists in the best position to provide the necessary knowledge and healthcare to benefit populations at risk of cancer. Active involvement of community pharmacists in the care and management of cancer will significantly contribute to screening and risk assessment, early detection, treatment and eradication of breast, cervical, lung, ovarian and other forms of cancer. As a result, the community pharmacy setting must the developed to maximize its full potential in cancer care.

The role of antiangiogenic monoclonal antibodies combined to EGFR-TKIs in the treatment of advanced non-small cell lung cancer with activating EGFR mutations acquired resistance mechanisms and strategies to overcome them.

As of today, only two antiangiogenic monoclonal antibodies plus epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) combinations are FDA and EMA-approved and are recommended by American Society of Clinical Oncology, European Society for Medical Oncology, and National Comprehensive Cancer Network for the first-line treatment of EGFR advanced non-small cell lung cancer patients erlotinib plus bevacizumab and erlotinib plus ramucirumab. However, all treated patients eventually become unresponsive to such drugs, due to several different acquired resistance mechanisms, mainly represented by T790M substitutions and MET amplifications. While osimertinib treatment in T790M patients still represents the only approved treatment, MET-TKIs will likely change this status quo in the near future. In fact, existing clinical data strongly support a role for MET-TKI-based combinations in EGFR MET-amplified patients, possibly revolutionizing our current treatment algorithm. Chemotherapy plus immunotherapy plus antiangiogenic therapy combinations could also represent another useful addition.

Postoperative pain and quality of life after lung cancer surgery a prospective observational study.

We aimed to identify the factors associated with postoperative pain, quality of life, and development of chronic pain after lung cancer surgery, including pain sensation threshold, fentanyl sensitivity, and surgical procedures. We conducted a single-center prospective observational study involving lung cancer patients. Brief pain inventory, including nine items concerning pain and quality of life, was investigated at 1 week, 1 month, and 3 months postoperatively. Pain sensation threshold and fentanyl sensitivity were assessed preoperatively. Of the 146 patients who were enrolled, 100 who met our criteria were analyzed. Thoracoscopic surgery was performed in 42 patients and minimally invasive thoracotomy in 58 patients. Pain sensation threshold and fentanyl sensitivity were normally distributed among the patients and were not significantly associated with brief pain inventory scores at each postoperative time-point. The average pain score 1 week after the operation was significantly higher in the thoracotomy group than in the thoracoscopic surgery group (P<0.050). The worst pain scores did not differ between the groups at all the examination periods. Pain sensation threshold, fentanyl sensitivity, and surgical procedures were not related to the incidence of post-thoracotomy pain syndrome. Individual pain sensation threshold and fentanyl sensitivity were not associated with subjective postoperative pain score, quality of life score, or development of post-thoracotomy pain syndrome.

Diagnosis and prognosis of non-small cell lung cancer based on machine learning algorithms.

Non-small cell lung cancer (NSCLC) has been the subject of intense scholarly debate. We aimed to identify the potential biomarkers via bioinformatics analysis. Three datasets were downloaded from gene expression omnibus database (GEO). R software was applied to screen differentially expressed genes (DEGs)and analyze immune cell infiltrates. Gene set enrichment analysis (GSEA) showed significant function and pathway in two groups. The diagnostic markers were further investigated by multiple machine learning algorithms least absolute shrinkage and selection operator (LASSO) and support vector machine-recursive feature elimination (SVM-RFE). Various online analytic platforms were utilized to explore the expression and prognostic value of differential genes. Furthermore, western blotting was performed to test the effects of genes on cell proliferation in vitro. We identified 181 DEGs shared by two datasets and selected nine diagnostic markers. Those genes were also significantly overexpressed in the third dataset. Topoisomerase II alpha (TOP2A) is overexpressed in lung cancer and associated with a poor prognosis, which was confirmed using immunohistochemistry (IHC) and western blotting. Additionally, TOP2A showed a negative correlation with immune cells, such as CD8 T cells, eosinophils and natural killer (NK) cell. Collectively, for the first time, we applied multiple machine learning algorithms, online databases and experiments in vitro to show that TOP2A is a potential biomarker for lung adenocarcinoma and could facilitate the development of new treatment strategies.

Recent updates on structural aspects of ALK inhibitors as an anticancer agent.

Presently, several protein kinases have been discovered with the aim to treat various cancers. Anaplastic lymphoma kinase (ALK) is a tyrosine kinase receptor that plays a role in the pathogenesis of a wide variety of human cancers known as ALCLs, NSCLC, ovarian cancer, breast cancer, colorectal cancer, neuroblastoma, etc. The full-length ALK receptor is a classical receptor tyrosine kinase composed of an amino-terminal extracellular domain and an intracellular tyrosine kinase domain. Crizotinib is a strong oral small-molecule first tyrosine kinase inhibitor of ALK to be used in the treatment of ALK-dependent NSCLC. Due to the drug resistance of first generation ALK inhibitors, researchers are trying to design and synthesize novel ALK inhibitors with various heterocyclic rings in which 2,4-diarylaminopyrimidine derivatives with a specific N-(3-pyridinylmethyl)urea moiety, 2-amino-4-(1-piperidine) pyridine derivatives, 7-azaindole and carboxamide derivatives and some others produced potential compounds. To overcome drug resistance, to get better affinity and to reduce drug toxicity, there is an urgent need for novel ALK inhibitors. The present review describes the ALK signaling, their inhibitors and related structure activity relationships for the development of potential ALK inhibitors.

A Case of Remission of Metastatic Germ Cell Tumor in an Elderly Patient by Multimodal Treatment.

There have been few reports of multimodal treatment such as chemotherapy and surgical resection for testicular tumors over 40 years old. In this case, a 64-year-old man with nonseminoma, pT2N2M1aS1, stage IIIb, IGCCC good prognosis completed induction chemotherapy, followed by retroperitoneal lymph node dissection and resection of lung metastases. Chemotherapy (4 courses of etoposide and cisplatin therapy) was completed without serious adverse events other than grade 4 neutropenia. Resection of the residual tumor confirmed no viable tumor cells. There was no evidence of recurrence or elevation of tumor markers in the following 6 months. Similar cases could increase with the increase of testicular tumors in the elderly.

A Case of Metastatic Ureteral Cancer Treated with Pembrolizumab without Relapse of Ocular Myasthenia Gravis.

A 77-year-old man complaining of gross hematuria was referred to our hospital for further examination and treatment. The contrast-enhanced computed tomographic (CT) scan revealed a left ureteral tumor, multiple bladder tumors, para-aortic lymph node metastasis, left supraclavicular lymph node metastasis, multiple liver metastases, and multiple lung metastases. Transurethral resection was performed. One of the multiple bladder tumors, located at the bladder neck, was pathologically diagnosed as urothelial carcinoma, pT1, high grade, G2．We diagnosed the patient with metastatic ureteral cancer (T4N2M1, stage IV). We stated gemcitabine, cisplatin (GC) therapy, but stopped after the first course due to gemcitabine drug eruption. We changed the regimen to methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) therapy and the cycle was completed without complications. However, CT scan showed disease progression. After palliative irradiation of the primary lesion, we administered pembrolizumab. Although he was asymptomatic, we diagnosed him with ocular myasthenia gravis because of a high level of serum anti-acetylcholine receptor antibodies and a temporary ptosis in his past history. In spite of the possibility of relapse of myasthenia gravis, treatment with pembrolizumab was continued with his consent since there were no other treatment options. After two courses of pembrolizumab, he was hospitalized due to disease progression and died about three weeks after admission. Myasthenia gravis is a possible immune-related adverse event of pembrolizumab, However, there have been few reports on the successful treatment with this agent in patients with previously diagnosed myasthenia gravis. We report, here, a case of metastatic ureteral carcinoma safely treated with pembrolizumab without relapse of ocular myasthenia gravis.

The main e-cigarette component vegetable glycerin enhances neutrophil migration and fibrosis in endotoxin-induced lung injury via p38 MAPK activation.

We investigated the effects of vegetable glycerin (VG), a main e-cigarette constituent, on endotoxin-induced acute lung injury (ALI). Mice received intratracheal administration of 30% VG in phosphate buffered saline (PBS) vehicle or only PBS (control) for 4 days. On Day 5, mice received an intratracheal instillation of lipopolysaccharide (LPS) (LPS group and VG LPS group) or PBS (VG group and control group). Lung histopathology, expression of chemokine receptors, and regulatory signaling were analyzed 24 h after the Day 5 treatment. VG significantly increased ALI-associated histopathological and fibrotic changes in both the VG group and LPS-induced ALI mice (VG LPS group). Immunohistochemistry (IHC) and western blot analyses revealed that VG administration resulted in upregulation of neutrophil markers lymphocyte antigen 6 complex locus G6D (Ly6G) and myeloperoxidase (MPO) as well as upregulation of the expression of transforming growth factor-β (TGF-β), a central mediator of fibrogenesis, in the lungs of both VG and VG LPS groups. VG enhanced the expression of adhesion molecules very late antigen 4 (VLA-4) and vascular cell adhesion molecule 1 (VCAM-1) and increased activation of p38 mitogen-activated protein kinase (p38 MAPK) to prompt neutrophil recruitment in the lungs of mice with ALI. Intraperitoneal administration of a p38 inhibitor attenuated these histopathological changes significantly as well as VG-induced upregulation in expression of Ly6G, MPO, VLA-4, VCAM-1, TGF-β, and collagen-1 in mice with ALI. In conclusion, VG enhances neutrophil chemotaxis and fibrosis and it amplifies the inflammatory response associated with LPS-induced ALI in the lungs via enhancement of p38 MAPK activity.

Downregulation of Linc00173 increases BCL2 mRNA stability via the miR-1275PROCA1ZFP36L2 axis and induces acquired cisplatin resistance of lung adenocarcinoma.

LINC00173 had been reported as a cisplatin (cis-diamminedichloroplatinum, DDP) chemotherapy-resistant inducer in small-cell lung cancer (SCLC) and lung squamous cell carcinoma (LUSC). This study aimed to display reverse data for LINC00173 as a DDP chemosensitivity-inducing factor in lung adenocarcinoma (LUAD). LINC00173 was screened from the Gene Expression Omnibus database (GSE43493). The expression level of LINC00173 in LUAD tissues and cell lines was detected using in situ hybridization and quantitative reverse transcription-polymerase chain reaction. Colony formation, cell viability, half-maximal inhibitory concentration, flow cytometry, and xenograft mouse model were used to evaluate the role of LINC00173 in the chemosensitivity of LUAD to DDP. The mechanism of LINC00173 in DDP resistance by mediating miR-1275PROCA1ZFP36L2 axis to impair BCL2 mRNA stability was applied, and co-immunoprecipitation, chromatin immunoprecipitation, RNA antisense purification, RNA immunoprecipitation, and luciferase reporter assays were performed. LINC00173 downregulation in patients with DDP-resistant LUAD was correlated with poor prognosis. Further, LINC00173 expression was significantly reduced in DDP-resistant LUAD cells and DDP-treated human LUAD tissues. Suppressed LINC00173 expression in LUAD cells enhanced DDP chemoresistance in vivo and in vitro, while restored LINC00173 expression in DDP-resistant LUAD cells markedly regained chemosensitivity to DDP. Mechanistically, DDP-resistant LUAD cells activated PI3KAKT signal and further elevated the c-Myc expression. The c-Myc, as an oncogenic transcriptional factor, bound to the promoter of LINC00173 and suppressed its expression. The reduced LINC00173 expression attenuated the adsorption of oncogenic miR-1275, downregulating the expression of miR-1275 target gene PROCA1. PROCA1 played a potential tumor-suppressive role inducing cell apoptosis and DDP chemosensitivity via recruiting ZFP36L2 to bind to the 3 untranslated region of BCL2, reducing the stability of BCL2 mRNA and thus activating the apoptotic signal. This study demonstrated a novel and critical role of LINC00173. It was transcriptionally repressed by DDP-activated PI3KAKTc-Myc signal in LUAD, promoting DDP-acquired chemotherapeutic resistance by regulating miR-1275 to suppress PROCA1ZFP36L2-induced BCL2 degradation, which led to apoptotic signal reduction. These data were not consistent with the previously described role of LINC00173 in SCLC or LUSC, which suggested that LINC00173 could play fine-tuned DDP resistance roles in different pathological subtypes of lung cancer. This study demonstrated that the diminished expression of LINC00173 might serve as an indicator of DDP-acquired resistance in LUAD.

Ten-year trends in the treatment and intervention timing for patients with metastatic spinal tumors a retrospective observational study.

Cancer treatment has recently evolved due to the advances in comprehensive therapies, including chemotherapy and radiotherapy. The aspect of cancer-related bone metastasis has undergone a paradigm shift with the transformation of orthopedic interventions for spinal metastasis. We performed this retrospective observational study to investigate the changes in patient status and metastatic spine-tumor treatment over the past decade. We included 186 patients (122 men and 64 women mean age 67.6 years) who were referred to our hospital between 2009 and 2018 and were diagnosed and treated for metastatic spinal tumors. We classified the patients into early (81 patients from 2009 to 2013) and late (105 patients from 2014 to 2018) groups. The following components were investigated and compared between the groups primary tumor, time taken from subjective-symptom onset to hospital visit, primary tumor evaluation during the visit, walking capacity due to lower paralysis during the visit, local treatment details, and post-treatment functional prognosis. Predominant primary tumors with similar trends in both groups included lung cancer, multiple myeloma, and prostate cancer. The percentage of non-ambulatory patients during the consultation was significantly lower in the late group (28% vs. 16%, P 0.04). Among non-ambulatory patients at the time of hospital visit, the mean time from the primary doctor consultation to our hospital visit was 2.8 and 2.1 days in the early and late groups, respectively. In both groups, surgical procedures were performed promptly on the non-ambulatory patients however, postoperative lower function did not improve in approximately half of the patients. Our findings demonstrated that in recent years, patients tended to be referred promptly from their previous doctors under a favorable collaboration system. However, the effectiveness of lower paralysis treatment remains limited, and it is important to raise awareness regarding the importance of early consultation among the general public for earlier detection.

The three steps method for uniportal video-assisted thoracoscopic right upper lobectomy.

The uniportal video-assisted thoracoscopic right upper lobectomy (UVATRUL), as a common procedure for thoracic surgeons, is difficult to manipulate and has some inherent challenges. To solve both of problems, we summarized a series of techniques as the three steps method and investigated its feasibility on the patients of right upper lung cancer. Forty-eight patients with right upper lobe lung cancer who underwent the three steps method UVATRUL in our hospital from January 2020 to May 2022 were selected as the three steps method group. Forty-seven patients who underwent the traditional UVATRUL were selected as the traditional method group. The intraoperative condition and postoperative condition of the two groups were retrospectively analysed. Multiple linear regression analysis was carried out to analyze the relationship between positive results and surgical method. All patients had successfully completed their surgeries. There was no significant difference between the two groups in respect of intraoperative blood loss, rate of conversion, day one thoracic drainage volume, chest tube indwelling time, incidence of postoperative complications, number of lymph node, and postoperative hospital stay (P > 0.05). Operative time of the three steps method group was significantly shorter than the traditional method group (P < 0.001), and number of reloads used was also significantly less than the traditional method group (P 0.014). Multiple linear regression analysis showed that operative time (β - 0.470, P < 0.001), and number of reloads (β - 0.254, P 0.007) correlated with surgical method. Compared with the traditional UVATRUL, the three steps method trims the surgery procedures, shortens the operative time, and reduces the use of reloads which makes it an effective procedure for UVATRUL.

Long-term exposure to low-level arsenic in drinking water is associated with cause-specific mortality and hospitalization in the Mt. Amiata area (Tuscany, Italy).

Arsenic in drinking water is a global public health concern. This study aims to investigate the association between chronic low-level exposure to arsenic in drinking water and health outcomes in the volcanic area of Mt. Amiata in Italy, using a residential cohort study design. Chronic exposure to arsenic in drinking water was evaluated using monitoring data collected by the water supplier. A time-weighted average arsenic exposure was estimated for the period 2005-2010. The population-based cohort included people living in five municipalities in the Mt. Amiata area between 01011998 and 31122019. Residence addresses were georeferenced and each subject was matched with arsenic exposure and socio-economic status. Mortality and hospital discharge data were selected from administrative health databases. Cox proportional hazard models were used to test the associations between arsenic exposure and outcomes, with age as the temporal axis and adjusting for gender, socio-economic status and calendar period. The residential cohort was composed of 30,910 subjects for a total of 407,213 person-years. Analyses reported risk increases associated with exposure to arsenic concentrations in drinking water > 10 µgl for non-accidental mortality (HR 1.07 95%CI1.01-1.13) and malignant neoplasms in women (HR 1.14 95%CI0.97-1.35). Long-term exposure to arsenic concentrations > 10 µgl resulted positively associated with several hospitalization outcomes non-accidental causes (HR 1.06 95%CI1.03-1.09), malignant neoplasms (HR 1.10 95%CI1.02-1.19), lung cancer (HR 1.85 95%CI1.14-3.02) and breast cancer (HR 1.23 95%CI0.99-1.51), endocrine disorders (HR 1.13 95%CI1.02-1.26), cardiovascular (HR 1.12 95%CI1.06-1.18) and respiratory diseases (HR 1.10 95%CI1.03-1.18). Some risk excesses were also observed for an exposure to arsenic levels below the regulatory standard, with evidence of exposure-related trends. Our population-based cohort study in the volcanic area of Mt. Amiata showed that chronic exposure to arsenic concentrations in drinking water above the current regulatory limit was associated with a plurality of outcomes, in terms of both mortality and hospitalization. Moreover, some signs of associations emerge even at very low levels of exposure, ​​below the current regulatory limit, highlighting the need to monitor arsenic concentrations continuously and implement policies to reduce concentrations in the environment as far as possible.

Evaluation of the radiofrequency identification lung marking system a multicenter study in Japan.

The radiofrequency identification (RFID) lung marking system is a novel technique using near-field radio-communication technology. The purpose of this study was to investigate the utility and feasibility of this system in the resection of small pulmonary nodules. We retrospectively reviewed clinical records of 182 patients who underwent sublobar resection with the RFID marking system between March 2020 and November 2021 in six tertial hospitals in Japan. Target markings were bronchoscopically made within 3 days before surgery. The contribution of the procedure to the surgery and safety was evaluated. Target nodule average diameter and depth from the lung surface were 10.9 ± 5.4 mm and 14.6 ± 9.9 mm, respectively. Radiologically, one third of nodules appeared as pure ground-glass nodules (GGNs) on CT. The average distance from target nodule to RFID tag was 8.9 ± 7.1 mm. All surgical procedures were completed by video-assisted thoracoscopic surgery. Planned resection was achieved in all cases without any complications. The surgeons evaluated this system as helpful in 93% (necessary 67%, useful 26%) of cases. Nodule radiological features (p < 0.001) and type of surgery (p 0.0013) were associated with the degree of contribution. In most cases, identification of the RFID tag was required within 1 min despite adhesion (p 0.27). The RFID lung marking system was found to be safe and effective during successful sublobar resection. Patients with pure GGNs are the best candidates for the system.

Changes in the number of cancer diagnosis practices due to the COVID-19 pandemic interrupted time-series analysis using the National Database of Japan.

This study aimed to reveal the impact of coronavirus disease 2019 on the number of practices commonly used for cancer diagnosis in Japan. The sampling dataset of the National Database of Japan from January 2015 to January 2021 was used to generate 25-point time-series data for the number of practices (21 points before and 4 points during the pandemic outbreak). The decreased number was estimated by interrupted time-series analysis using a seasonal autoregressive integrated moving average model. Using the pre-pandemic data, expected counterfactual numbers during the pandemic were predicted, and decreased rate was calculated. In most practices, the number dramatically decreased in the early stage of the pandemic and recovered rapidly thereafter. As of April 2020, gastric endoscopy decreased at the top of the practices (- 42.1%, with 95% confidence intervals of - 50.5% and - 33.7%), followed by gastric biopsy (- 38.6%, with 95% confidence intervals of - 46.7% and - 30.6%). The period of declined practices for lung cancer was relatively prolonged. The number of sentinel lymph node biopsies for breast cancer and colposcopies and biopsies for cervical cancer did not decrease in April 2020, but significantly decreased later in July 2020, which is assumed to be the time lapse after the primary testing before surgical treatment or intense scrutiny. In general, the number of practices for cancer diagnosis in Japan showed only a temporary decline, which was concordant with reports from several other countries.

Cirrhotic and non-cirrhotic huge hepatocellular carcinoma (≥ 10 cm) a comparative study of surgical management and follow-up treatment in a single institution.

Liver resection (LR) of huge hepatocellular carcinoma (HCC) has increasingly been regarded as a viable option of enhanced efficacy for patients, but most studies have focused on comparing various tumor sizes and the outcomes of surgery. The study aim was to evaluate the clinicopathologic characteristics and surgical outcomes of huge HCC with and without cirrhosis that underwent LR, and to delineate the treatment for recurrence. Sixty-three patients with huge HCC who underwent hepatectomy from 2010 to 2019 were enrolled and reviewed. Clinicopathological findings, surgical outcomes of the entire cohort, and differences between the cirrhotic and non-cirrhotic groups were analyzed. Forty patients (60.3%) had huge HCC with cirrhosis. Clinicopathological findings were not different between the two groups, except tumor size ≥ 15 cm (40% in cirrhosis vs 17.4% in non-cirrhosis, p 0.024) and major portal vein tumor thrombus were detected only in the cirrhosis group (11 patients, p 0.006). Extended LR was performed in 13 cirrhotic patients (32.5%) and in 1 non-cirrhotic patient (4.4%) (p 0.010). Operative data, postoperative complications including postoperative liver failure, and pattern of recurrence were not different between the two groups. For the entire cohort, mortality rate was 1.5%. The 1-, 3-, and 5-year overall survival rates (OS) were 81%, 54%, and 39%. Multivariate analysis showed resection margin ≥ 0.1 cm was a good prognostic factor for OS (HR 0.247 (p 0.017)). For tumor recurrence, local ablative treatment for liver recurrence and resection for lung recurrence provided good long-term outcomes. Although huge HCC with cirrhosis has been a more unfavorable tumor, LR still provided long-term survival with acceptable risk morbidity and mortality.

A risk stratification and prognostic prediction model for lung adenocarcinoma based on aging-related lncRNA.

To create a risk model of aging-related long non-coding RNAs (arlncRNAs) and determine whether they might be useful as markers for risk stratification, prognosis prediction, and targeted therapy guidance for patients with lung adenocarcinoma (LUAD). Data on aging genes and lncRNAs from LUAD patients were obtained from Human Aging Genomic Resources 3 and The Cancer Genome Atlas, and differential co-expression analysis of established differentially expressed arlncRNAs (DEarlncRNAs) was performed. They were then paired with a matrix of 0 or 1 by cyclic single pairing. The risk coefficient for each sample of LUAD individuals was obtained, and a risk model was constructed by performing univariate regression, least absolute shrinkage and selection operator regression analysis, and univariate and multivariate Cox regression analysis. Areas under the curve were calculated for the 1-, 3-, and 5-year receiver operating characteristic curves to determine Akaike information criterion-based cutoffs to identify high- and low-risk groups. The survival rate, correlation of clinical characteristics, malignant-infiltrating immune-cell expression, ICI-related gene expression, and chemotherapeutic drug sensitivity were contrasted with the high- and low-risk groups. We found that 99 DEarlncRNAs were upregulated and 12 were downregulated. Twenty pairs of DEarlncRNA pairs were used to create a prognostic model. The 1-, 3-, and 5-year survival curve areas of LUAD individuals were 0.805, 0.793, and 0.855, respectively. The cutoff value to classify patients into two groups was 0.992. The mortality rate was higher in the high-risk group. We affirmed that the LUAD outcome-related independent predictor was the risk score (p < 0.001). Validation of tumor-infiltrating immune cells and ICI-related gene expression differed substantially between the groups. The high-risk group was highly sensitive to docetaxel, erlotinib, gefitinib, and paclitaxel. Risk models constructed from arlncRNAs can be used for risk stratification in patients with LUAD and serve as prognostic markers to identify patients who might benefit from targeted and chemotherapeutic agents.

Oxidative stress-triggered Wnt signaling perturbation characterizes the tipping point of lung adeno-to-squamous transdifferentiation.

Lkb1 deficiency confers the Kras-mutant lung cancer with strong plasticity and the potential for adeno-to-squamous transdifferentiation (AST). However, it remains largely unknown how Lkb1 deficiency dynamically regulates AST. Using the classical AST mouse model (Kras

Evaluation of a novel ELISA test using synthetic mycolic acid antigens for serodiagnosis of non-tuberculous mycobacterial (NTM) infections.

The diagnosis of non-tuberculous mycobacteria (NTM) is a particular challenge in people with cystic fibrosis. Current standard diagnostic approaches rely on serial sputum culture, which is resource demanding, dependent on patient expectoration and may be compromised by excessive decontamination, conventional bacterial overgrowth and masking by concomitant oral and nebulised antibiotics. An alternative rapid, reliable and inexpensive diagnostic method is therefore urgently needed. Serum of patients with

Novel role of microphthalmia-associated transcription factor in modulating the differentiation and immunosuppressive functions of myeloid-derived suppressor cells.

Microphthalmia-associated transcription factor (MITF) is a master regulator of melanogenesis and is mainly expressed in melanoma cells. MITF has also been reported to be expressed in non-pigmented cells, such as osteoclasts, mast cells, and B cells. However, the roles of MITF in immunosuppressive myeloid cells, including myeloid-derived suppressor cells (MDSCs), remain unclear. Here, we investigated the role of MITF in the differentiation process of MDSCs during tumor development. In vitro-generated murine MDSCs and primary MDSCs from breast cancer-bearing mice or lung carcinoma-bearing mice were used to determine the expression level of MITF and the activity of MDSCs. Additionally, we investigated whether in vivo tumor growth can be differentially regulated by coinjection of MDSCs in which MITF expression is modulated by small molecules. Furthermore, the number of MITF The expression of MITF was strongly increased in MO-MDSCs from tumors of breast cancer-bearing mice compared with polymorphonuclear MDSCs. We found that MITF expression in MDSCs was markedly induced in the tumor microenvironment (TME) and related to the functional activity of MDSCs. MITF overexpression in myeloid cells increased the expression of MDSC activity markers and effectively inhibited T-cell proliferation compared with those of control MDSCs, whereas shRNA-mediated knockdown of MITF in myeloid cells altered the immunosuppressive function of MDSCs. Modulation of MITF expression by small molecules affected the differentiation and immunosuppressive function of MDSCs. While increased MITF expression in MDSCs promoted breast cancer progression and CD4 Our results indicate that MITF regulates the differentiation and function of MDSCs and can be a novel therapeutic target for modulating MDSC activity in immunosuppressive s.

Use of durvalumab in stage III non-small-cell lung cancer based on eligibility for the PACIFIC study.

Durvalumab following concurrent chemoradiotherapy is standard treatment for unresectable stage III non-small-cell lung cancer based on the results of the PACIFIC trial. Based on trial criteria, not all patients are eligible for durvalumab in routine clinical practice. We evaluated eligibility for durvalumab in a real-world clinical setting and the impact of eligibility on outcomes. Consecutive patients treated with concurrent chemoradiotherapy at two tertiary centers between January 2015 and June 2022 were assessed. Clinical characteristics and outcomes were evaluated based on eligibility criteria for the PACIFIC trial. A total of 126 patients were included. Seventy patients (56%) were eligible for durvalumab. Ineligibility was associated with shorter progression-free survival of 9.7 months versus 18.4 months (hazard ratio HR 0.61, 95% confidence interval CI 0.39-0.95, p 0.029) and overall survival of 26.4 months versus 58.7 months (HR 0.47, 95% CI 0.28-0.80, p 0.005). Common reasons for ineligibility were history of previous malignancy (32%) and progressive disease or death during chemoradiotherapy (25%). Ineligible patients who received durvalumab had similar outcomes to eligible patients who received durvalumab. In a real-world cohort, adjuvant durvalumab is safe and beneficial in a substantial proportion of patients who would not have been eligible for the PACIFIC trial.

Reconstructed lung doses for the million person study cohort of 26,650 Tennessee Eastman corporation workers employed between 1942 and 1947.

Tennessee Eastman Corporation workers were exposed to uranium dust resulting in high-linear energy transfer (LET) irradiation to lung tissue. In this work, radiation lung doses were reconstructed for 26 650 men and women working at the plant between 1942 and 1947. Site air monitoring data of uranium concentrations and payroll records were used to determine the daily inhaled activities and annualized lung doses. Variations in the activity median aerodynamic diameter of the uranium dust, the solubility of particulate matter in the lungs and the sex-specific breathing rate were investigated as part of a sensitivity analysis. Male and female mean lung doses of 18.9 and 32.7 mGy, respectively, from high-LET alpha irradiation, and there was general agreement with evaluations from previously published epidemiological studies. Annual lung dose estimates and sensitivity analysis for the 26 650 workers in the TEC cohort have been archived on the United States Department of Energy Comprehensive Epidemiologic Data Resource.

Physical and biological dosimetric margin according to prescription method for stereotactic body radiation therapy.

This study aimed to expand the biological conversion factor (BCF) model, which converts the physical dosimetric margin (PDM) to the biological dosimetric margin (BDM) for point prescription with 3-dimensional conformal radiation therapy (3DCRT) and the marginal prescription method with volumetric-modulated arc radiotherapy (VMAT). The VMAT of the marginal prescription and the 3DCRT of the point prescription with lung stereotactic body radiation therapy (SBRT) by using RayStation were planned. The biological equivalent dose (BED) for a dose per fraction (DPF) of 3-20 Gy was calculated from these plans. The dose was perturbed with the calculation using a 1-mm step isocenter shift. The dose covering 95% of the target was greater than or equal to 90% of the prescribed physical dose, and the BED were defined as the PDM and BDM, respectively. The BCF was created as a function of the DPF. The PDM and BDM for all DPFs were larger with the point prescription method than with the marginal prescription method. The marginal prescription method with a 60% isodose line had a larger PDM and BDM. The BCF with the point prescription was smaller than that with the marginal prescription in the left-right (LR), anterior-posterior (AP) and cranio-caudal (CC) directions. In the marginal prescription method, the 60% isodose line had a higher BCF. In conclusion, the improved BCF method could be converted to BDM for point prescription with 3DCRT and marginal prescription method with VMAT, which is required for stereotactic radiation therapy in radiobiology-based treatment planning.

Molecular imaging of chemokine-like receptor 1 (CMKLR1) in experimental acute lung injury.

The lack of techniques for noninvasive imaging of inflammation has challenged precision medicine management of acute respiratory distress syndrome (ARDS). Here, we determined the potential of positron emission tomography (PET) of chemokine-like receptor-1 (CMKLR1) to monitor lung inflammation in a murine model of lipopolysaccharide-induced injury. Lung uptake of a CMKLR1-targeting radiotracer,

ATOH8 binds SMAD3 to induce cellular senescence and prevent Ras-driven malignant transformation.

The process of oncogene-induced senescence (OIS) and the conversion between OIS and malignant transformation during carcinogenesis is poorly understood. Here, we show that following overactivation of oncogene Ras in lung epithelial cells, high-level transforming growth factor β1 (TGF-β1)-activated SMAD3, but not SMAD2 or SMAD4, plays a determinant role in inducing cellular senescence independent of the p53p16p15 senescence pathways. Importantly, SMAD3 binds a potential tumor suppressor ATOH8 to form a transcriptional complex that directly represses a series of cell cycle-promoting genes and consequently causes senescence in lung epithelial cells. Interestingly, the prosenescent SMAD3 converts to being oncogenic and essentially facilitates oncogenic Ras-driven malignant transformation. Furthermore, depleting Atoh8 rapidly accelerates oncogenic Ras-driven lung tumorigenesis, and lung cancers driven by mutant Ras and Atoh8 loss, but not by mutant Ras only, are sensitive to treatment of a specific SMAD3 inhibitor. Moreover, hypermethylation of the

Durable response to osimertinib in an advanced lung adenocarcinoma patient with an uncommon EGFR T854A mutation A case report.

Epidermal growth factor receptor (EGFR) T854A mutation in exon 21 is an uncommon EGFR mutation in patients with non-small cell lung cancer (NSCLC). It is a secondary EGFR mutation after first- and second-generation EGFR tyrosine kinase inhibitors (TKIs). All EGFR T854A mutations were co-occurred with EGFR L858R mutation in cis. There is still no clear evidence to guide the therapeutic options for patients with both EGFR T790M and T854A mutations. A 60-year-old Chinese woman with no smoking history presented with a maximum diameter of 32.9 mm mass located in the right lower lung lobe. The patient was diagnosed with stage IVA lung adenocarcinoma with an exceptionally uncommon EGFR T854A mutation in exon 21 was detected concomitantly with EGFR T790M in blood by next-generation sequencing (NGS). The patient was initially treated with first-line afatinib. After disease progression, osimertinib was administered. Our patient exhibited a partial response (PR) to osimertinib with progression-free survival of nearly 8 months. Our study indicates that patients with NSCLC who are positive for uncommon EGFR T854A and T790M mutations might benefit from treatment with osimertinib.

A huge chest wall angiomatosis with pleural and rib invasion A case report.

Angiomatosis is a rare non-neoplastic proliferative vascular lesion that typically develops during childhood or adolescence with a female predominance. Management of angiomatosis is challenging because of the manifestation of a wide variety of lesions as well as their invasive and highly recurrent nature. We report the case of a 74-year-old man who presented with a right lower back mass that persisted for a decade. The mass progressively enlarged and had been painful in the previous month. Computed tomography (CT) revealed suspected lipomatous sarcoma with invasion of the ribs, pleurae, and lung parenchyma. The final pathological examination revealed angiomatosis. The patient underwent wide composite excision of the tumor along with excision of the pleura and lung nodules in the right lower and middle lobes via video-assisted thoracoscopic surgery (VAST). Fasciocutaneous rotational flap reconstruction was performed immediately after the wide composite excision and video-assisted thoracoscopic surgery (VAST). The patient recovered uneventfully, was discharged without complications, and tolerated the daily activities well. Angiomatosis is a rare benign vascular tumor that frequently mimics malignancy. Even if the patient profile does not match the reported epidemiology of this disease, differential diagnosis should be considered. Complete resection is the mainstay of treatment for the prevention of recurrence.

Peritoneal carcinomatosis secondary to metastatic lung cancer complicated with acute suppurative appendicitis A case report and literature review.

Lung cancer (LC) is a malignant tumor with the highest morbidity and mortality in the world. The most common metastatic sites of LC are the brain (47%), bone (36%), liver (22%), adrenal glands (15%), thoracic cavity (11%) and distant lymph nodes (10%). Peritoneal carcinomatosis (PC) is a rare clinical event in LC patients. Considering the rarity and nonspecific clinical symptoms of peritoneal metastasis among LC patients, a case of peritoneal metastasis secondary to LC incidentally observed by laparoscopic appendectomy is unusual. Here, we present a 53-year-old never-smoker woman who presented to the emergency department with a 2-day history of pain in the right abdominal quadrant. Later, laparoscopy revealed acute suppurative appendicitis accompanied by a peritoneal metastatic mass. The patient was diagnosed with PC secondary to metastatic LC complicated with acute suppurative appendicitis by immunohistochemistry. Positron emission tomography computed tomography (PET CT) findings further strengthen the evidence of PC from LC. Based on the results of genomic analysis, the patient received targeted therapy with osimertinib 80 mgd. Due to the discovery of new targets, the use of molecular therapies improved progression-free survival (PFS) and overall survival (OS), which increases the chance of identifying peritoneal metastasis of LC. For LC patients with abdominal symptoms, clinicians should be aware of the possibility of peritoneal metastasis from LC, especially for patients diagnosed with lung adenocarcinoma or with pleural effusion.

Identification and verification of microRNA signature and key genes in the development of osteosarcoma with lung metastasis.

Osteosarcoma (OS) is a heterogeneous malignant spindle cell tumor in children under the age of 20. This study aims to research the association between Solute Carrier Family 7 Member 8 (SLC7A8) as well as related genes and OS. OS and normal samples (GSE38698 and GSE85537) were downloaded from Gene Expression Omnibus dataset. The bioinformatics analysis was performed to distinguish 2 differentially expressed genes, prognostic candidate genes and functional enrichment pathway. Immunohistochemistry and quantitative real-time PCR were utilized for further study. There were 5 DEMs and 10 differentially expressed genes in cancer tissues compared to normal tissues. According to the km-plot software, ARHGEF3, BSN, PQLC3, and SLC7A8 were significantly related to the overall survival of patients with OS. Furthermore, Multivariate analysis included that SLC7A8 was independent risk factors for OS patients. Furthermore, immunohistochemistry and quantitative real-time PCR outcomes indicated that the expression level of SLC7A8 and hsa-miR-506 was differentially expressed in lung metastasis OS tissues and non-metastasis tissues. The prognostic model based on the miRNA-mRNA network could provide predictive significance for prognosis of OS patients, which would be worthy of clinical application. Our results concluded that SLC7A8 may play a key role in the development of OS.

Cytokine release syndrome induced by pembrolizumab A case report.

Cytokine release syndrome (CRS) is an immune hyperactivation phenomenon in immunotherapy and, unlike other immune-related adverse events, only a few case reports have documented CRS due to the use of immune checkpoint inhibitors. In this article, we report a case of 2 episodes of CRS and delirium caused by pembrolizumab in a short period of time. This helps clinicians to understand CRS and to improve the diagnosis and treatment of immune-related adverse events. A 67-year-old patient with lung cancer developed fever, delirium, acute renal insufficiency, and acute cardiac insufficiency after 9 cycles of pablizumab therapy, and reappeared with these symptoms 1 week after improvement with glucocorticoid therapy. The patient presented with concomitant cardiac insufficiency, hepatic and renal failure, delirium with high C-reactive protein levels and the patients response to glucocorticoids, and exclusion of cerebrovascular accident and severe infection, resulting in a final diagnosis of CRS. Glucocorticoid therapy and symptomatic support treatment. After 2 hospitalizations, the patient did not develop CRS. To our knowledge, this is the first case of delirium and CRS that occurred twice in a short period of time. This patient had no immune-related adverse reactions during the previous 9 immunotherapy sessions. This adverse reaction occurred after the inflammation of the wisdom teeth and was presumed to be related to an overstimulation of the immune response due to infection. Premature discontinuation of hormones for the patients 1st treatment of CRS may be the reason for the 2nd occurrence of CRS. Therefore, timely and full course of glucocorticosteroids is a key therapeutic measure to cause CRS after the use of immune checkpoint inhibitors.

Prognostic factors and survival prediction for patients with metastatic lung adenocarcinoma A population-based study.

The prognosis of metastatic lung adenocarcinoma (MLUAD) varies greatly. At present, no studies have constructed a satisfactory prognostic model for MLUAD. We identified 44,878 patients with MLUAD. The patients were randomized into the training and validation cohorts. Cox regression models were performed to identify independent prognostic factors. Then, R software was employed to construct a new nomogram for predicting overall survival (OS) of patients with MLUAD. Accuracy was assessed by the concordance index (C-index), receiver operating characteristic curves and calibration plots. Finally, clinical practicability was examined via decision curve analysis. The OS time range for the included populations was 0 to 107 months, and the median OS was 7.00 months. Nineteen variables were significantly associated with the prognosis, and the top 5 prognostic factors were chemotherapy, grade, age, race and surgery. The nomogram has excellent predictive accuracy and clinical applicability compared to the TNM system (C-index 0.723 vs 0.534). The C-index values were 0.723 (95% confidence interval 0.719-0.726) and 0.723 (95% confidence interval 0.718-0.729) in the training and validation cohorts, respectively. The area under the curve for 6-, 12-, and 18-month OS was 0.799, 0.764, and 0.750, respectively, in the training cohort and 0.799, 0.762, and 0.746, respectively, in the validation cohort. The calibration plots show good accuracy, and the decision curve analysis values indicate good clinical applicability and effectiveness. The nomogram model constructed with the above 19 prognostic factors is suitable for predicting the OS of MLUAD and has good predictive accuracy and clinical applicability.

Expression and prognosis analyses of the fibronectin type-III domain-containing (FNDC) protein family in human cancers A Review.

Despite advancements in early detection and treatment, cancer continues to pose a threat to human health and is the leading cause of death worldwide. According to recent research, the fibronectin type-III domain-containing (FNDC) protein family has been implicated in several different human disorders. However, little is known regarding their expression and prognostic significance in most human malignancies. We carried out a thorough cancer vs. normal expression study using the Oncomine and Tumor Immune Estimation Resource (TIMER) databases, as well as a prognostic evaluation using the Kaplan-Meier (KM) plotter and PrognoScan databases. Oncomine revealed that the mRNA expression levels of FNDC1, FNDC3A, and FNDC3B were higher in most malignancies than in normal tissues, but the mRNA expression levels of FNDC4, FNDC5, FNDC7, and FNDC8 were downregulated in most cancers when compared with normal tissues. In survival analyses based on KM Plotter and PrognoScan, all members of the FNDC family displayed significant correlations with survival outcomes in breast, gastric, and ovarian cancers. Furthermore, the whole FNDC family, except for FNDC7 and FNDC8, was found to have substantial predictive effects in lung adenocarcinoma, but not in squamous cell lung cancer. In addition, potential connections between several FNDC family members and survival results in liver and colorectal malignancies were discovered in this study. One or more members of the FNDC family demonstrated statistically significant differences in expression between cancer and normal tissues, suggesting that they could be used as prognostic biomarkers for specific cancers.

ALK-positive lung adenocarcinoma in a patient with rheumatoid arthritis with long-term treatment for organizing pneumonia A case report.

Rheumatoid arthritis (RA) causes inflammation in various organs including the lungs. Pulmonary manifestations include inflammation of the pleura, vasculature, airway, and parenchyma, including interstitial lung disease (ILD). RA-organizing pneumonia (OP) is the third most common cause of RA-ILD. Cases of OP coexistingcomplicated with lung cancer have been reported. Therefore, lung cancer can represent a diagnostic challenge, especially in patients with underlying pulmonary diseases including OP. An 81-year-old woman with a 12-year history of RA-OP underwent multiple transbronchial lung biopsies (TBLBs), all of which resulted in no malignant findings. She was treated with prednisolone (PSL) depending on the deteriorated infiltrations. At admission, chest computed tomography (CT) images showed exacerbation of left S8 consolidation on chest CT. Additionally, her RA activity was exacerbated, and PSL dose was increased to 30 mgday, which resulted in improved dyspnea and consolidation. Accordingly, PSL dose was gradually decreased. However, 6 months later, when PSL dose was 11 mgd, due to a worsening of consolidation and the joint symptoms of RA, PSL dose was increased to 20 mgd and tacrolimus 2 mgd was administered. 3 months after the increase in PSL dose, dyspnea improved and PSL dose was reduced to 15 mgd however, she was admitted to our hospital because of low back pain. Spinal magnetic resonance imaging showed bone metastases in the third and fifth lumbar vertebrae, and lung cancer was suspected as the primary tumor on CT. TBLB was performed on the left B8 infiltrate, which showed no evidence of malignancy in the previous TBLB. Pathological examination of TBLB on the left B8 revealed an adenocarcinoma that was positive for anaplastic lymphoma kinase. Physicians should be aware of the development of lung cancer in regions with OP, even after a partial response to corticosteroid therapy.

Packing with alpha-tricalcium phosphate followed by curettage and phenol-ethanol ablation for appendicular giant cell tumor of bone.

Giant cell tumor of bone (GCTB) is an intermediate and locally aggressive bone tumor. Alpha-tricalcium phosphate (alpha-TCP) is an adjustable bone substitute used to fill various sizes of bone cavities after curettage for GCTB. This study aimed to evaluate the surgical outcome of packing with alpha-TCP followed by curettage and phenol-ethanol ablation. We retrospectively reviewed data of 16 patients with GCTB who underwent primary surgery in our institute between January 2009 and April 2021. Data of Campanacci grading system number of local recurrences and distant metastases local recurrence-free survival rate using the Kaplan-Meier method oncological outcomes and complications after surgery (secondary osteoarthritis and postoperative fracture) were evaluated in this study. Regarding the Campanacci grading system, 2 patients were classified as grade I, 14 as grade II, and none as grade III. The 5-year local recurrence-free survival rate was 77.8% in all cases. Lung metastasis was not detected in this study. Oncological outcomes were continuous disease free, 13 patients alive with disease, 3 patients and no evidence of disease or death of disease, none of the patients. Secondary osteoarthritis after surgery was not detected in the present study. Packing with alpha-TCP followed by curettage and phenol-ethanol ablation for appendicular GCTB may be safe and effective in suppressing the risk of secondary osteoarthritis.

A novel prognostic signature for lung adenocarcinoma based on cuproptosis-related lncRNAs A Review.

Lung adenocarcinoma (LUAD) is a highly heterogeneous disease with complex pathogenesis, high mortality, and poor prognosis. Cuproptosis is a new type of programmed cell death triggered by copper accumulation that may play an important role in cancer. LncRNAs are becoming valuable prognostic factors in cancer patients. The effect of cuproptosis-related lncRNAs (CRlncRNAs) on LUAD has not been clarified. Based on the Cancer Genome Atlas database, CRlncRNAs were screened by co-expression analysis of cuproptosis- related genes and lncRNAs. Using CRlncRNAs, Cox and LASSO regression analyses constructed a risk prognostic model. The predictive efficacy of the model was assessed and validated using survival analysis, receiver operating characteristic curve, univariate and multifactor Cox regression analysis, and principal component analysis. A nomogram was constructed and calibration curves were applied to enhance the predictive efficacy of the model. Tumor Mutational Burden analysis and chemotherapeutic drug sensitivity prediction were performed to assess the clinical feasibility of the risk model. The novel prognostic signature consisted of 5 potentially high-risk CRlncRNAs, MAP3K20-AS1, CRIM1-DT, AC006213.3, AC008035.1, and NR2F2-AS1, and 5 potentially protective CRlncRNAs, AC090948.1, AL356481.1, AC011477.2, AL031600.2, and AC026355.2, which had accurate and robust predictive power for LUAD patients. Collectively, the novel prognostic signature constructed based on CRlncRNAs can effectively assess and predict the prognosis of patients and provide a new perspective for the diagnosis and treatment of LUAD.

COVID-19 outcomes by cancer status, site, treatment, and vaccination.

Studies have shown an increased risk of severe SARS-CoV-2 related (COVID-19) disease outcome and mortality for cancer patients, but it is not well understood if associations vary by cancer site, cancer treatment, and vaccination status. Using electronic health record data from an academic medical center, we identified a retrospective cohort of 260,757 individuals tested for or diagnosed with COVID-19 from March 10, 2020, to August 1, 2022. Of these, 52,019 tested positive for COVID-19 of whom 13,752 had a cancer diagnosis. We conducted Firth-corrected logistic regression to assess the association between cancer status, site and treatment, vaccination, and four COVID-19 outcomes hospitalization, intensive care unit admission, mortality, and a composite severe COVID outcome. Cancer diagnosis was significantly associated with higher rates of severe COVID, hospitalization, and mortality. These associations were driven by patients whose most recent initial cancer diagnosis was within the past three years. Chemotherapy receipt, colorectal cancer, hematologic malignancies, kidney cancer and lung cancer were significantly associated with higher rates of worse COVID-19 outcomes. Vaccinations were significantly associated with lower rates of worse COVID-19 outcomes regardless of cancer status. Patients with colorectal cancer, hematologic malignancies, kidney cancer or lung cancer or who receive chemotherapy for treatment should be cautious because of their increased risk of worse COVID-19 outcomes, even after vaccination. Additional COVID-19 precautions are warranted for people with certain cancer types and treatments. Significant benefit from vaccination is noted for both cancer and cancer-free patients.

Recombinant single-cycle influenza virus with exchangeable pseudotypes allows repeated immunization to augment anti-tumour immunity with immune checkpoint inhibitors.

Virus-based tumour vaccines offer many advantages compared to other antigen-delivering systems. They generate concerted innate and adaptive immune response, and robust CD8

Metabolite profiling, in vitro and in silico assessment of antibacterial and anticancer activities of Alternaria alternata endophytic in Jatropha heynei.

Fungal endophytes produce a range of structurally diverse metabolites with bioactive principles. In this study, an endophytic fungus Alternaria alternata was isolated from Jatropha heynei and cultured in potato dextrose liquid broth. Culture filtrate of A. alternata was extracted in ethyl acetate and metabolites were characterized by QTOF-HRLCMS. Among compounds detected, spectral compounds such as kigelinone, and levofuraltadone were reported with antibacterial property, while 2-hydroxychrasophanol, isoathyriol, glycophymoline, columbianetin and kaempferol 3-O-β-D- galactoside were reported with cytotoxic properties. Partially purified metabolites of A. alternata showed significant antibacterial activity against tested clinical bacterial strains by agar well diffusion method. High zone of inhibition was recorded against Enterococcus faecalis, Pseudomonas syringae and Klebsiella pneumoniae. In vitro anticancer activity of fungal extract by MTT assay displayed high cytotoxic effect on human lung carcinoma cancer cell line (A549) with IC

The effect of spiritual well-being on illness perception of lung cancer patıents.

The aim of this study is to examine the effect of spiritual well-being on the perception of people who have lung cancer. The study was conducted with 100 volunteered patients with living lung cancer who were monitored and treated at a university hospital in Turkey. Patient Identification Form, Spiritual Well-Being Scale and Illness Perception Scale were used for the data collection procedure. Using SPSS 21.0 program, independent sample t-test and one-way ANOVA test were performed in statistical analyses. The probability value was considered significant as p < 0.05. The mean score of Spiritual Well Being (SWB) was found 28.48 ± 7.20. The findings were as follows (1) the patients who stated that they comply with the drug treatment had a high score, and SWB scores were found to be lower in those who thought that the disease could not be cured. (2) there was a significant positive relationship among SWB and sub-dimensions of the illness perceptions acute-chronic duration (p .668), personal control (p .811), treatment control (p .682), emotional representation (p 0.184) 3), as the SWB mean score increases, the scores in the illness perception section increase 4 however, when the SWB score increases, the cyclic time decreases. It was concluded that the spiritual well-being of people who have lung cancer positively affects the perception of the disease. It was further suggested that spiritual well-being should be evaluated and improved within holistic care in order to ensure patients perception of disease and compliance with treatment.

Automated lung cancer assessment on 18F-PETCT using Retina U-Net and anatomical region segmentation.

To develop and test a Retina U-Net algorithm for the detection of primary lung tumors and associated metastases of all stages on FDG-PETCT. A data set consisting of 364 FDG-PETCTs of patients with histologically confirmed lung cancer was used for algorithm development and internal testing. The data set comprised tumors of all stages. All lung tumors (T), lymphatic metastases (N), and distant metastases (M) were manually segmented as 3D volumes using whole-body PETCT series. The data set was split into a training (n 216), validation (n 74), and internal test data set (n 74). Detection performance for all lesion types at multiple classifier thresholds was evaluated and false-positive-findings-per-case (FPc) calculated. Next, detected lesions were assigned to categories T, N, or M using an automated anatomical region segmentation. Furthermore, reasons for FPs were visually assessed and analyzed. Finally, performance was tested on 20 PETCTs from another institution. Sensitivity for T lesions was 86.2% (95% CI 77.2-92.7) at a FPc of 2.0 on the internal test set. The anatomical correlate to most FPs was the physiological activity of bone marrow (16.8%). TNM categorization based on the anatomical region approach was correct in 94.3% of lesions. Performance on the external test set confirmed the good performance of the algorithm (overall detection rate 88.8% (95% CI 82.5-93.5%) and FPc 2.7). Retina U-Nets are a valuable tool for tumor detection tasks on PETCT and can form the backbone of reading assistance tools in this field. FPs have anatomical correlates that can lead the way to further algorithm improvements. The code is publicly available. • Detection of malignant lesions in PETCT with Retina U-Net is feasible. • All false-positive findings had anatomical correlates, physiological bone marrow activity being the most prevalent. • Retina U-Nets can build the backbone for tools assisting imaging professionals in lung tumor staging.

Epitranscriptomic

Quality-of-life outcomes and risk prediction for patients randomized to NivolumabIpilimumab vs Nivolumab on LungMAP-S1400I.

An important issue for patients with cancer treated with novel therapeutics is how they weigh the effects of treatment on survival and quality-of-life (QOL). We compared QOL in patients enrolled to SWOG-1400I, a substudy of the LungMAP biomarker-driven master protocol. SWOG S1400I was a randomized phase III trial comparing nivolumabipilimumab vs nivolumab for treatment of immunotherapy-naïve disease in advanced squamous cell lung cancer. The primary endpoint was the MDASI-LC severity score at Week-7 and Week-13 with a target difference of 1.0 points, assessed using multivariable linear regression. A composite risk model for progression-free and overall survival was derived using best-subset selection. Among 158 evaluable patients, median age was 67.6 years and most were male (66.5%). The adjusted MDASI-LC severity score was 0.04 points (95%-CI, -0.44 to 0.51, p.89) at Week-7 and 0.12 points (95%-CI, -0.41 to 0.65, p.66) at Week-13. A composite risk model showed that patients with high levels of both appetite loss and shortness-of-breath had a 3-fold increased risk of progression or death (HR 3.06, 95%-CI, 1.88-4.98, p<.001) - and that those with high levels of both appetite loss and work limitations had a 5-fold increased risk of death (HR 5.60, 95%-CI, 3.27-9.57, p<.001) - compared to those with neither risk category. We found no evidence of a benefit of ipilimumab added to nivolumab compared to nivolumab alone for QOL in S1400I. A risk model identified patients at high risk of poor survival, demonstrating the prognostic relevance of baseline patient-reported outcomes even in those with previously-treated advanced cancer.

Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, often metastasizes to the lungs. The implications of lysine lactylation (Kla), a recently identified histone post-translational modification (PTM), in the pathology of HCC remain unclear. Here, we report the first proteomic survey of this specific modification in HCC (with no metastasis during 3 years of follow-up), normal liver tissues, and lung metastasis samples of HCC. Of the 2045 modification sites detected on 960 proteins, 1438 sites on 772 proteins contained quantitative information. Subsequently, we analyzed the differentially modified proteins among the different groups. Differentially lactylated proteins were found to be involved in several biological processes, including-but not limited to-amino acid metabolism, ribosomal protein synthesis, and fatty acid metabolism. In addition, we identified numerous highly valuable lactate-modified proteins from the literature. Among them, we verified the lactate modification levels of the following two tumor-related proteins and obtained similar results USP14 and ABCF1. These two modified proteins will be further investigated in our future studies. This paper is the first report on the lactylome of HCC and it provides a reliable foundation for further research on Kla in HCC.

Topological structure and global features enhanced graph reasoning model for non-small cell lung cancer segmentation from CT.

Construction and Validation of a Novel Immune-Related Gene Pairs-Based Prognostic Model in Lung Adenocarcinoma.

Focus on immune-related gene pairs (IRGPs) and develop a prognostic model to predict the prognosis of patients with lung adenocarcinoma (LUAD). First, the LUAD patient dataset was downloaded from The Cancer Genome Atlas database, and paired analysis of immune-related genes was subsequently conducted. Then, LASSO regression was used to screen prognostic IRGPs for building a risk prediction model. Meanwhile, the Gene Expression Omnibus database was used for external validation of the model. Next, the clinical predictive power of IRGPs features was assessed by uni-multivariate Cox regression analysis, the infiltration of key immune cells in high and low IRGPs risk groups was analyzed with CIBERSORT, quanTIseq, and Timer, and the key pathways enriched for IRGPs were assessed using the Kyoto Encyclopedia of Genes and Genomes. Finally, the expression and related functions of key immune cells and genes were verified by immunofluorescence and cell experiments of tissue samples. It was revealed that the risk score of 19 IRGPs could be used as accurate indicators to evaluate the prognosis of LUAD patients, and the risk score was mainly related to T cell infiltration based on CIBERSORT analysis. Two genes of IRGPs, IL6, and CCL2, were found to be closely associated with the expression of PD-1PD-L1 and the function of T-cells. Depending on the results of tissue immunofluorescence, IL6, CCL2, and T cells were highly expressed in the LUAD tissues of patients. Furthermore, IL6 and CCL2 were positively correlated with the expression of T cells. Besides, qRT-PCR assay in four different LUAD cells proved that IL6 and CCL2 were positively correlated with the expression of PD-L1 (P < .001). Based on 19 IRGPs, an effective prognosis model was established to predict the prognosis of LUAD patients. In addition, IL6 and CCL2 are closely related to the function of T-cells.

cRGD-targeted gold-based nanoparticles overcome EGFR-TKI resistance of NSCLC

Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is a first-line targeted drug for the treatment of advanced non-small cell lung cancer (NSCLC) in clinical practice, but EGFR-TKI-acquired resistance limits its therapeutic effect. To address this challenge, a novel multifunctional gold-based targeted nanoparticle-based drug delivery system is fabricated. The gold-based nanoparticle is loaded with the EGFR-TKI (gefitinib) and IR780, and the surface-modified gold nanoshell layer has a photothermal effect for thermally triggered drug release. Finally, the unique binding of cyclic arginine-glycine-aspartic acid (cRGD) to the α

Painful ischemic monomelic neuropathy An unusual complication in a lung cancer patient.

Ischemic monomelic neuropathy (IMN) is a rare type of acute axonal neuropathy which results from ischemia of multiple nerves in affected limb. The electroneuromyography is useful in detecting characteristic features of this neuropathy. It usually occurs after vascular interventions. Here, we present the first case who has IMN secondary to lung cancer andor chemo-therapy and aim to draw attention to this infrequently recognized entity.

Frizzled-7-targeting antibody (SHH002-hu1) potently suppresses non-small-cell lung cancer via Wntβ-catenin signaling.

Non-small-cell lung cancer (NSCLC) is one of the deadliest cancers worldwide, and metastasis is considered one of the leading causes of treatment failure in NSCLC. Wntβ-catenin signaling is crucially involved in epithelial-mesenchymal transition (EMT), a crucial factor in promoting metastasis, and also contributes to resistance developed by NSCLC to targeted agents. Frizzled-7 (Fzd7), a critical receptor of Wntβ-catenin signaling, is aberrantly expressed in NSCLC and has been confirmed to be positively correlated with poor clinical outcomes. SHH002-hu1, a humanized antibody targeting Fzd7, was previously successfully generated by our group. Here, we studied the anti-tumor effects of SHH002-hu1 against NSCLC and revealed the underlying mechanism. First, immunofluorescence (IF) and near-infrared (NIR) imaging assays showed that SHH002-hu1 specifically binds Fzd7

Inhibition of ribosome assembly factor PNO1 by CRISPRCas9 technique suppresses lung adenocarcinoma and Notch pathway Clinical application.

Growth is crucially controlled by the functional ribosomes available in cells. To meet the enhanced energy demand, cancer cells re-wire and increase their ribosome biogenesis. The RNA-binding protein PNO1, a ribosome assembly factor, plays an essential role in ribosome biogenesis. The purpose of this study was to examine whether PNO1 can be used as a biomarker for lung adenocarcinoma and also examine the molecular mechanisms by which PNO1 knockdown by CRISPRCas9 inhibited growth and epithelial-mesenchymal transition (EMT). The expression of PNO1 was significantly higher in lung adenocarcinoma compared to normal lung tissues. PNO1 expression in lung adenocarcinoma patients increased with stage, nodal metastasis, and smoking. Lung adenocarcinoma tissues from males expressed higher PNO1 than those from females. Furthermore, lung adenocarcinoma tissues with mutant Tp53 expressed higher PNO1 than those with wild-type Tp53, suggesting the influence of Tp53 status on PNO1 expression. PNO1 knockdown inhibited cell viability, colony formation, and EMT, and induced apoptosis. Since dysregulated signalling through the Notch receptors promotes lung adenocarcinoma, we measured the effects of PNO1 inhibition on the Notch pathway. PNO1 knockdown inhibited Notch signalling by suppressing the expression of Notch receptors, their ligands, and downstream targets. PNO1 knockdown also suppressed CCND1, p21, PTGS-2, IL-1α, IL-8, and CXCL-8 genes. Overall, our data suggest that PNO1 can be used as a diagnostic biomarker, and also can be an attractive therapeutic target for the treatment of lung adenocarcinoma.

Cell senescence, a new target for respiratory viral infections From influenza virus to SARS-CoV-2.

The accumulation of senescent cells in tissues is a key process of aging and age-related diseases, including lung diseases such as chronic obstructive pulmonary disease, lung fibrosis, or cancer. In recent years, the spectrum of respiratory diseases associated with cellular senescence has been broadened, in particular acute viral pulmonary infections, foremost among which is coronavirus disease 2019 (COVID19), which is particularly severe in the elderly or in subjects with comorbidities. Influenza virus infection, which strikes more severely at the extreme ages of life, is also associated with severe pulmonary senescence. Cellular senescence potentially represents an original target for attacking these diseases, although its specific mechanisms remain largely misunderstood. New anti-senescent therapeutic approaches are thus proposed during severe viral pulmonary infections, with the aim of preventing acute effects andor, in the longer term, pulmonary sequelae. L’accumulation de cellules sénescentes dans les tissus est un processus clé du vieillissement et des maladies chroniques liées à l’âge, notamment les maladies pulmonaires telles la bronchopneumopathie chronique obstructive, la fibrose pulmonaire, ou le cancer. Ces dernières années ont permis d’élargir le spectre des maladies respiratoires associées à une sénescence cellulaire, en particulier les infections pulmonaires aiguës virales, au premier rang desquelles la maladie à coronavirus 2019 (COVID19), particulièrement sévère chez le sujet âgé ou atteint de comorbidités. L’infection par le virus influenza qui frappe plus sévèrement les âges extrêmes de la vie est également associée à une forte sénescence pulmonaire. La sénescence cellulaire représente potentiellement une cible originale pour s’attaquer à ces maladies, bien que ses mécanismes spécifiques restent largement incompris. De nouvelles approches thérapeutiques à visée anti-sénescente sont ainsi proposées au cours des infections pulmonaires virales sévères, dans un but de prévention des effets aigus etou, à plus long terme, des séquelles pulmonaires.

Early Identification and Intervention in Malignant Transformation of Respiratory Papillomatosis.

BACKGROUND Human papilloma virus is a ubiquitous and preventable disease with the potential to cause recurrent respiratory papillomatosis. These papillomas affect the mucosal surface of the airways and may lead to airway obstruction. The papillomas require excision when breathing is compromised, and may be fatal if untreated. Rarely, these papillomas progress to cancer. CASE REPORT We report the case of a 21-year-old woman with a history of HPV 11- and 16-positive recurrent laryngeal and respiratory papillomatosis (RRP) since the age of 7 months, requiring multiple local resections in her respiratory tract. Chest CT demonstrated multiple cavitary lesions throughout both lungs with a rapidly growing mass that occupied most of her right lung. Imaging supported a diagnosis of malignant transformation to squamous cell carcinoma of the lung. Bilateral involvement of the lungs indicated stage IVa squamous cell lung cancer, which is not curable. CONCLUSIONS Clinicians should suspect malignant transformation in patients with HPV type 11, especially if they have required multiple excisions. Earlier age at onset and number of excisions may be predictors for severity of the disease course. These patients need continued surveillance imaging to allow early interventions if malignant transformation occurs. We present the case of a 21-year-old being diagnosed with an incurable disease that may have been avoided with adequate preventive care.

In Silico Re-Optimization of Atezolizumab Dosing Using Population Pharmacokinetic Simulation and Exposure-Response Simulation.

Atezolizumab, a humanized monoclonal antibody against programmed cell death ligand 1 (PD-L1), was initially approved in 2016, around the same time that the sponsor published the minimum serum concentration to maintain the saturation of receptor occupancy (6 μgmL). The initially approved dose regimen of 1200 mg every 3 weeks (q3w) was subsequently modified to 840 mg q2w or 1680 mg q4w through pharmacokinetic simulations. Yet, each standard regimen yields steady-state trough concentrations (C

Two Molecular Weights Holothurian Glycosaminoglycan and Hematoporphyrin Derivative-Photodynamic Therapy Inhibit Proliferation and Promote Apoptosis of Human Lung Adenocarcinoma Cells.

Holothurian glycosaminoglycan (hGAG) is extracted from the body wall of the sea cucumber, and previous studies have shown many unique bioactivities of hGAG, including antitumor, anti-angiogenesis, anti coagulation, anti thrombosis, anti-inflammation, antidiabetic effect, antivirus, and immune regulation. The effects of 3W and 5W molecular weights hGAG with hematoporphyrin derivative-photodynamic therapy (HPD-PDT) on lung cancer were investigated. Human lung adenocarcinoma A549 cells were divided into 6 groups control group, 3W molecular weight hGAG group, 5W molecular weight hGAG group, HPD-PDT group, 3W molecular weight hGAG HPD-PDT group, and 5W molecular weight hGAG HPD-PDT group. Cell morphology was observed under inverted phase contrast microscope. Cell proliferative activity was detected by CCK8 and cell apoptosis was assayed by Hoechst33258 staining and flow cytometry. The results showed that two different molecular weights hGAG could inhibit proliferation, promote apoptosis rates of A549 cells, and enhance the sensitivity of A549 cells to HPD-PDT. The combined use of hGAG and HPD-PDT has synergistic inhibitory effects on A549 cells, and the effects of 3W molecular weight hGAG are better than that of 5W molecular weight hGAG.

CT ventilation image-guided helical Tomotherapy at sparing functional lungs for locally advanced lung cancer analysis of dose-function metrics and the impact on pulmonary toxicity.

CT ventilation image (CTVI)-guided radiotherapy that selectively avoids irradiating highly-functional lung regions has potential to reduce pulmonary toxicity. Considering Helical TomoTherapy (HT) has higher modulation capabilities, we investigated the capability and characteristic of HT at sparing functional lungs for locally advanced lung cancer. Pretreatment 4DCT scans were carried out for 17 patients. Local lung volume expansion (or contraction) during inspiration is related to the volume change at a given lung voxel and is used as a surrogate for ventilation. The ventilation maps were generated from two sets of CT images (peak-exhale and peak-inhale) by deformable registration and a Jacobian-based algorithm. Each ventilation map was normalized to percentile images. Six plans were designed for each patient one anatomical plan without ventilation map and five functional plans incorporating ventilation map which designed to spare varying degrees of high-functional lungs that were defined as the top 10%, 20%, 30%, 40%, and 50% of the percentile ventilation ranges, respectively. The dosimetric and evaluation factors were recorded regarding planning target volume (PTV) and other organs at risk (OARs), with particular attention to the dose delivered to total lung and functional lungs. An established dose-function-based normal tissue complication probability (NTCP) model was used to estimate risk of radiation pneumonitis (RP) for each scenario. Patients were divided into a benefit group (8 patients) and a non-benefit group (9 patients) based on whether the RP-risk of functional plan was lower than that of anatomical plan. The distance between high-ventilated region and PTV, as well as tumor volume had significant differences between the two groups (P < 0.05). For patients in the benefit group, the mean value of fV5, fV10, fV20, and fMLD (functional V5, V10, V20, and mean lung dose, respectively) were significantly lower starting from top 30% functional plan than in anatomical plan (P < 0.05). With expand of avoidance region in functional plans, the dose coverage of PTV is not sacrificed (P > 0.05) but at the cost of increased dose received by OARs. Ventilation image-guided HT plans can reduce the dose received by highly-functional lung regions with a range up to top 50% ventilated area. The spatial distribution of ventilation and tumor size were critical factors to better select patients who could benefit from the functional plan.

Association between radiotherapy and risk of second primary malignancies in patients with resectable lung cancer a population-based study.

The most common form of treatment for non-metastatic lung cancer is surgery-based combination therapy, which may also include adjuvant radiotherapy or chemotherapy. Second primary malignancies (SPMs) are uncommon but significant radiation side effects in patients with resectable lung cancer, and SPMs have not been adequately investigated. Our study aims to assess the correlations of radiotherapy with the development of SPMs in patients with resectable lung cancer. We screened for any primary malignancy that occurred more than five years after the diagnosis of resectable lung cancer. Based on the large cohort of the Surveillance, Epidemiology and End Results database, radiotherapy-correlated risks were estimated using the Poisson regression analysis and the cumulative incidence of SPMs was calculated using Fine-Gray competing risk regression analysis. Among the 62,435 patients with non-metastatic lung cancer undergoing surgery, a total of 11,341 (18.16%) patients have received radiotherapy. Our findings indicated that radiotherapy was substantially related to a high risk of main second solid malignancies (RR 1.21 95%CI, 1.08 to 1.35) and a negligible risk of main second hematologic malignancies (RR 1.08 95%CI, 0.84 to 1.37). With the greatest number of patients, the risk of acquiring a second primary gastrointestinal cancer was the highest overall (RR 1.77 95 percent CI, 1.44 to 2.15). The cumulative incidence and standardized incidence ratios of SPMs revealed similar findings. Furthermore, the young and the elderly may be more vulnerable, and the highest risk of acquiring most SPMs was seen more than ten years after lung cancer diagnosis. Additionally, more attention should be paid to the second primary gastrointestinal cancer in young individuals with resectable lung cancer. After receiving radiotherapy, an increased risk of developing second primary solid and gastrointestinal cancers was observed for patients with resectable lung cancer. The prevention of SPMs associated with radiotherapy requires further attention.

Postoperative survival of pulmonary invasive mucinous adenocarcinoma versus non-mucinous invasive adenocarcinoma.

In 2015, the World Health Organization renamed mucinous bronchioloalveolar adenocarcinoma as pulmonary invasive mucinous adenocarcinoma (IMA). Due to its low incidence and unclear prognosis with surgical treatment, previous studies have presented opposing survival outcomes. We aimed to investigate the differences in surgical prognosis and prognosis-related risk factors by comparing IMA with non-mucinous invasive adenocarcinoma (NMA). A total of 20,914 patients diagnosed with IMA or NMA from 2000 to 2014 were screened from the Surveillance, Epidemiology, and End Results database. The screened patients were subjected to propensity score matching (PSM) in a 14 ratio to explore the survival differences between patients with IMA and NMA and the factors influencing prognosis. For all patients, IMA was prevalent in the lower lobes of the lungs (p < 0.0001), well-differentiated histologically (p < 0.0001), less likely to have lymph node metastases (94.4% vs. 72.0%, p < 0.0001) and at an earlier pathological stage (p 0.0001). After PSM, the IMA cohort consisted of 303 patients, and the NMA cohort consisted of 1212 patients. Kaplan‒Meier survival analysis showed no difference in overall survival (OS) between patients in the IMA cohort and those in the NMA cohort (p 0.7). Cox proportional hazards analysis showed that differences in tumor pathological type did not influence OS between the two cohorts (p 0.65). Age (HR 1.98, 95% CI 1.7-2.31, p < 0.0001), gender (HR 0.64, 95% CI 0.55-0.75, p < 0.0001), and radiation treatment (HR 2.49, 95% CI 1.84-3.37, p < 0.0001) were independent predictors of patient OS. There was no significant difference in OS between patients with IMA and those with NMA after surgical treatment. Age, sex, and radiation treatment can independently predict OS.

Comparison of whole-body 18F-FDG PETCT and PETMRI for distant metastases in patients with malignant tumors a meta-analysis.

As a first-line imaging modality, whole-body fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)computed tomography (CT) and 18F-FDG PETmagnetic resonance imaging (MRI) had been widely applied in clinical practice. However, 18F-FDG PETMRI may be superior to PETCT for the diagnosis of distant metastases in patients with advanced-stage. Therefore, it is timely and important to systematically determine the diagnostic accuracy of 18F-FDG PETMRI compared with that of 18F-FDG PETCT for the diagnosis of distant metastases. This study aimed to compare the diagnostic accuracy of 18F-FDG PETCT and PETMRI for the diagnosis of distant metastases in patients with malignant tumors. Relevant studies using both 18F-FDG PETCT and PETMRI for assessment of distant metastases in patients with malignant tumors were searched in PubMed, Embase, The Cochrane Library, and Scopus from January 2010 to November 2023. Two reviewers independently selected studies according to the inclusion and exclusion criteria. A reviewer extracted relevant data and assessed the quality of the eligible studies. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and area under the summary receiver operating characteristic curve (AUC) for 18F-FDG PETCT and PETMRI were analyzed. Subgroup analysis was performed. Across 14 studies (1042 patients), 18F-FDG PETMRI had a higher sensitivity (0.87 versus 0.81), AUC value (0.98 versus 0.95), and similar specificity (0.97 versus 0.97), than PETCT for detecting distant metastases. In 3 studies of breast cancer (182 patients), 18F-FDG PETMRI had a higher sensitivity (0.95 versus 0.87) and specificity (0.96 versus 0.94) than PETCT. In 5 studies of lung cancer (429 patients), 18F-FDG PETCT had a higher sensitivity (0.87 versus 0.84) and a lower specificity (0.95 versus 0.96) to PETMRI. 18F-FDG PETMRI and PETCT both performed well as detectors of distant metastases in patients with malignant tumors, and the former has higher sensitivity. The subgroup analysis highlights that 18F-FDG PETMRI and PETCT hold different advantages for distant metastases staging in different tumors, PETMRI has a higher accuracy in patients with breast cancer patients, while PETCT has a higher accuracy in patients with lung cancer.

Clinical features and lipid metabolism genes as potential biomarkers in advanced lung cancer.

Lung cancer is one of the most lethal tumors with a poor survival rate even in those patients receiving new therapies. Metabolism is considered one of the hallmarks in carcinogenesis and lipid metabolism is emerging as a significant contributor to tumor metabolic reprogramming. We previously described a profile of some lipid metabolism related genes with potential prognostic value in advanced lung cancer. To analyze clinical and pathological characteristics related to a specific metabolic lipid genomic signature from patients with advanced lung cancer and to define differential outcome. Ninety samples from NSCLC (non-small cell lung cancer) and 61 from SCLC (small cell lung cancer) patients were obtained. We performed a survival analysis based on lipid metabolic genes expression and clinical characteristics. The primary end point of the study was the correlation between gene expression, clinical characteristics and survival. Clinical variables associated with overall survival (OS) in NSCLC patients were clinical stage, adenocarcinoma histology, Eastern Cooperative Oncology Group (ECOG), number and site of metastasis, plasma albumin levels and first-line treatment with platinum. As for SCLC patients, clinical variables that impacted OS were ECOG, number of metastasis locations, second-line treatment administration and Diabetes Mellitus (DM). None of them was associated with gene expression, indicating that alterations in lipid metabolism are independent molecular variables providing complementary information of lung cancer patient outcome. Specific clinical features as well as the expression of lipid metabolism-related genes might be potential biomarkers with differential outcomes.

Costs of traditional Chinese medicine treatment for inpatients with lung cancer in China a national study.

Traditional Chinese Medicine (TCM) has long been a widely recognized medical approach and has been covered by Chinas basic medical insurance schemes to treat lung cancer. But there was a lack of nationwide research to illustrate the impact of the use of TCM on lung cancer patients economic burden in mainland China. Therefore, we conduct a nationwide study to reveal whether the use of TCM could increase or decrease the medical expenditure of lung cancer inpatients in mainland China. This is a 7-year cross-sectional study from 2010 to 2016. The data is a random sample of 5% from lung cancer claims data records of Chinese Urban Employee Basic Medical Insurance (UEBMI) and Urban Resident Basic Medical Insurance (URBMI). Mann-Whitney test was used to compare inpatient cost data with positive skewness. Ordinary least squares regression analysis was performed to compare the total TCM users hospitalization cost with TCM nonusers, to examine whether TCM use is the key factor inducing relatively high medical expenditure. A total of 47,393 lung cancer inpatients were included in this study, with 38,697 (81.7%) of them at least using one kind of TCM approach. The per inpatient medical cost of TCM users was RMB18,798 (USD2,830), which was 65.2% significantly higher than that of TCM nonusers (P < 0.001). The medication cost, conventional medication cost, and nonpharmacy cost of TCM users were all higher than TCM nonusers, illustrating the higher medical cost of TCM users was not induced by TCM only. With confounding factors fixed, there was a positive correlation between TCM cost and conventional medication cost, nonpharmacy cost (Coef. 0.283 and 0.211, all P < 0.001), indicting synchronous increase of TCM costs and conventional medication cost for TCM users. The use of TCM could not offset the utilization of conventional medicine, demonstrating TCM mainly played a complementary role but not an alternative role in the inpatient treatment of lung cancer. A joint Clinical Guideline that could balance the use of TCM and Conventional medicine should be developed for the purpose of reducing economic burden for lung cancer inpatients.

DM-MOGA a multi-objective optimization genetic algorithm for identifying disease modules of non-small cell lung cancer.

Constructing molecular interaction networks from microarray data and then identifying disease module biomarkers can provide insight into the underlying pathogenic mechanisms of non-small cell lung cancer. A promising approach for identifying disease modules in the network is community detection. In order to identify disease modules from gene co-expression networks, a community detection method is proposed based on multi-objective optimization genetic algorithm with decomposition. The method is named DM-MOGA and possesses two highlights. First, the boundary correction strategy is designed for the modules obtained in the process of local module detection and pre-simplification. Second, during the evolution, we introduce Davies-Bouldin index and clustering coefficient as fitness functions which are improved and migrated to weighted networks. In order to identify modules that are more relevant to diseases, the above strategies are designed to consider the network topology of genes and the strength of connections with other genes at the same time. Experimental results of different gene expression datasets of non-small cell lung cancer demonstrate that the core modules obtained by DM-MOGA are more effective than those obtained by several other advanced module identification methods. The proposed method identifies disease-relevant modules by optimizing two novel fitness functions to simultaneously consider the local topology of each gene and its connection strength with other genes. The association of the identified core modules with lung cancer has been confirmed by pathway and gene ontology enrichment analysis.

Autologous T cell therapy for MAGE-A4

Affinity-optimized T cell receptors can enhance the potency of adoptive T cell therapy. Afamitresgene autoleucel (afami-cel) is a human leukocyte antigen-restricted autologous T cell therapy targeting melanoma-associated antigen A4 (MAGE-A4), a cancertestis antigen expressed at varying levels in multiple solid tumors. We conducted a multicenter, dose-escalation, phase 1 trial in patients with relapsedrefractory metastatic solid tumors expressing MAGE-A4, including synovial sarcoma (SS), ovarian cancer and head and neck cancer ( NCT03132922 ). The primary endpoint was safety, and the secondary efficacy endpoints included overall response rate (ORR) and duration of response. All patients (N 38, nine tumor types) experienced Grade ≥3 hematologic toxicities 55% of patients (90% Grade ≤2) experienced cytokine release syndrome. ORR (all partial response) was 24% (938), 716 (44%) for SS and 222 (9%) for all other cancers. Median duration of response was 25.6 weeks (95% confidence interval (CI) 12.286, not reached) and 28.1 weeks (95% CI 12.286, not reached) overall and for SS, respectively. Exploratory analyses showed that afami-cel infiltrates tumors, has an interferon-γ-driven mechanism of action and triggers adaptive immune responses. In addition, afami-cel has an acceptable benefit-risk profile, with early and durable responses, especially in patients with metastatic SS. Although the small trial size limits conclusions that can be drawn, the results warrant further testing in larger studies.

Robust single-cell matching and multimodal analysis using shared and distinct features.

The ability to align individual cellular information from multiple experimental sources is fundamental for a systems-level understanding of biological processes. However, currently available tools are mainly designed for single-cell transcriptomics matching and integration, and generally rely on a large number of shared features across datasets for cell matching. This approach underperforms when applied to single-cell proteomic datasets due to the limited number of parameters simultaneously accessed and lack of shared markers across these experiments. Here, we introduce a cell-matching algorithm, matching with partial overlap (MARIO) that accounts for both shared and distinct features, while consisting of vital filtering steps to avoid suboptimal matching. MARIO accurately matches and integrates data from different single-cell proteomic and multimodal methods, including spatial techniques and has cross-species capabilities. MARIO robustly matched tissue macrophages identified from COVID-19 lung autopsies via codetection by indexing imaging to macrophages recovered from COVID-19 bronchoalveolar lavage fluid by cellular indexing of transcriptomes and epitopes by sequencing, revealing unique immune responses within the lung microenvironment of patients with COVID.

Tumor-intrinsic IRE1α signaling controls protective immunity in lung cancer.

IRE1α-XBP1 signaling is emerging as a central orchestrator of malignant progression and immunosuppression in various cancer types. Employing a computational XBP1s detection method applied to TCGA datasets, we demonstrate that expression of the XBP1s mRNA isoform predicts poor survival in non-small cell lung cancer (NSCLC) patients. Ablation of IRE1α in malignant cells delays tumor progression and extends survival in mouse models of NSCLC. This protective effect is accompanied by alterations in intratumoral immune cell subsets eliciting durable adaptive anti-cancer immunity. Mechanistically, cancer cell-intrinsic IRE1α activation sustains mPGES-1 expression, enabling production of the immunosuppressive lipid mediator prostaglandin E

Thiolate DNAzymes on Gold Nanoparticles for Isothermal Amplification and Detection of Mesothelioma-derived Exosomal PD-L1 mRNA.

Catalytic DNAzymes have been used for isothermal amplification and rapid detection of nucleic acids, holding the potential for point-of-care testing applications. However, when Subzymes (universal substrate and DNAzyme) are tethered to the polystyrene magnetic microparticles via biotin-streptavidin bonds, the residual free Subzymes are often detached from the microparticle surface, which causes a significant degree of false positives. Here, we attached dithiol-modified Subzyme to gold nanoparticle and improved the limit of detection (LoD) by 200 times compared to that using magnetic microparticles. As a proof of concept, we applied our new method for the detection of exosomal programed cell-death ligand 1 (PD-L1) RNA. As the classical immune checkpoint, molecule PD-L1, found in small extracellular vesicles (sEVs, traditionally called exosomes), can reflect the antitumor immune response for predicting immunotherapy response. We achieved the LoD as low as 50 fM in detecting both the RNA homologous to the PD-L1 gene and exosomal PD-L1 RNAs extracted from epithelioid and nonepithelioid subtypes of mesothelioma cell lines, which only takes 8 min of reaction time. As the first application of isothermal DNAzymes for detecting exosomal PD-L1 RNA, this work suggests new point-of-care testing potentials toward clinical translations.

RGD-decorated PLGA nanoparticles improved effectiveness and safety of cisplatin for lung cancer therapy.

Upon extensive pharmaceutical and biomedical research to treat lung cancer indicates that lung cancer remains one of the deadliest diseases and the leading cause of death in men and women worldwide. Lung cancer remains untreated and has a high mortality rate due to the limited potential for effective treatment with existing therapies. This highlights the urgent need to develop an effective, precise and sustainable solutions to treat lung cancer. In this study, we developed RGD receptor-targeted PLGA nanoparticles for the controlled and targeted co-delivery of cisplatin (CDDP) and upconversion nanoparticles (UCNP) in lung cancer therapy. Pluronic F127-RGD conjugate was synthesized by carbodiimide chemistry method and the conjugation was confirmed by FTIR and

Serum-derived exosomal miR-125a-3p predicts the response to anti-programmed cell death-1programmed cell death-ligand 1 monotherapy in patients with non-small cell lung cancer.

Versatile biomarkers for immune checkpoint inhibitors (ICI) efficacy in patients with cancer remain to be identified. Liquid biopsy using serum-derived exosomal microRNAs (miRNAs) are widely investigated as diagnostic and therapeutic outcome predictors in patients with cancer. However, exosomal miRNAs linked to the response to ICI in patients with non-small cell lung cancer (NSCLC) remain elusive thus far. The value of serum-derived exosomal miRNAs in predicting the effect of anti-programmed cell death-1 (PD-1)anti-programmed cell death-ligand 1 (PD-L1) monotherapy in 41 patients with advanced NSCLC was assessed. We performed functional analysis of candidate miRNAs using NSCLC cell lines. Exosomal miR-125a-3p was associated with response to treatment with ICI. Exosomal miR-125a-3p was more useful in predicting response to ICI versus tumoral PD-L1 in patients with low PD-L1 expression <50 %). Moreover, high expression of miR-125a-3p was associated with worse progression-free and overall survival. In H1975 and H441 cells, induction of miR-125a-3p regulated PD-L1 expression via suppression of neuregulin 1 (NRG1). Exosomal miR-125a-3p is a potential predictor of response to anti-PD-1PD-L1 therapy in advanced NSCLC patients with low PD-L1 expression.

Induction Immune Checkpoint Inhibitors and Chemotherapy Before Definitive Chemoradiation Therapy for Patients With Bulky Unresectable Stage III Non-Small Cell Lung Cancer.

In the era of immunotherapy, the treatment for bulky, locally advanced non-small cell lung cancer (LA-NSCLC) remains challenging. This study explored the feasibility of induction immune checkpoint inhibitors (ICIs) plus chemotherapy before definitive chemoradiation therapy (CRT) for bulky LA-NSCLC. Patients with bulky, unresectable stage III NSCLC (primary tumor ≥5 cm in greatest dimension or metastatic lymph nodes ≥2 cm in shortest diameter) receiving ICIs and chemotherapy before CRT from 2018 to 2022 were identified. Survival outcomes and toxic effects were analyzed. Radiation therapy plans on computed tomography images before and after 2 cycles of induction chemoimmunotherapy were simulated to evaluate dosimetric outcomes. Seventy-five patients were included. One- and 2-year overall-survival (OS) rates were 91.5% (95% CI, 85.2%-98.3%) and 75.1% (95% CI, 64.1%-88.0%), respectively. One- and 2-year progression-free-survival (PFS) rates were 85.8% (95% CI, 78.0%-94.4%) and 64.2% (95% CI, 52.5%-78.6%), respectively. Median OS was not reached (NR). Median PFS was 30.6 months (95% CI, 25.9 months to NR). Grade 2 and ≥3 pneumonitis occurred in 26.7% and 9.3% of patients, respectively. Grade ≥3 pneumonitis was significantly associated with poorer OS (P .003) and PFS (P .018). Treatment discontinuation was significantly associated with shorter OS (P .023) and PFS (P .047). Patients with consolidation ICIs exhibited numerically better OS than those without consolidation ICIs (2-year OS, 85.8% vs 64.2% P .170). The objective response rate was 76.1% for induction treatment and 86.7% for induction treatment plus CRT. The disease control rate after 2 cycles of induction therapy was significantly greater than after 4 (P .046) or more cycles (P .025). Simulated radiation plans indicated that all target volumes, mean lung dose, and volume of lung parenchyma receiving ≥5 Gy, ≥20 Gy, and ≥30 Gy significantly decreased after 2 cycles (all P < .005). Two cycles of induction ICIs plus chemotherapy before definitive CRT were feasible for bulky LA-NSCLC, with significant tumor reduction and normal lung protection. Further investigations on CRT combined with induction and consolidation ICIs are warranted.

3D SAACNet with GBM for the classification of benign and malignant lung nodules.

In view of the low diagnostic accuracy of the current classification methods of benign and malignant pulmonary nodules, this paper proposes a 3D segmentation attention network integrating asymmetric convolution (SAACNet) classification model combined with a gradient boosting machine (GBM). This can make full use of the spatial information of pulmonary nodules. First, the asymmetric convolution (AC) designed in SAACNet can not only strengthen feature extraction but also improve the networks robustness to object flip and rotation detection and improve network performance. Second, the segmentation attention network integrating AC (SAAC) block can effectively extract more fine-grained multiscale spatial information while adaptively recalibrating multidimensional channel attention weights. The SAACNet also uses a dual-path connection for feature reuse, where the model makes full use of features. In addition, this article makes the loss function pay more attention to difficult and misclassified samples by adding adjustment factors. Third, the GBM is used to splice the nodule size, originally cropped nodule pixels, and the depth features learned by SAACNet to improve the prediction accuracy of the overall model. A comprehensive ablation experiment is carried out on the public dataset LUNA16 and compared with other lung nodule classification models. The classification accuracy (ACC) is 95.18%, and the area under the curve (AUC) is 0.977. The results show that this method effectively improves the classification performance of pulmonary nodules. The proposed method has advantages in the classification of benign and malignant pulmonary nodules, and it can effectively assist radiologists in pulmonary nodule classification.

Preoperative PET-SUVmax and volume based PET parameters of the primary tumor fail to predict nodal upstaging in early-stage lung cancer.

Accurate nodal staging is of utmost importance in patients with lung cancer. FDG-PETCT imaging is now part of the routine staging. Despite thorough preoperative staging nodal upstaging still occurs in early-stage lung cancer. However, the predictive value of preoperative PET metrics of the primary tumor on nodal upstaging remains to be unexplored. Our aim was to assess the association of these preoperative PET-parameters with nodal upstaging in histologically confirmed lung adenocarcinoma and squamous cell carcinoma. From January 2016 to November 2018, 500 patients with pT1-T2cN0 lung cancer received an anatomical resection with curative intent. 171 patients with adenocarcinoma and squamous cell carcinoma and available PET-CTs were retrospectively included. We analyzed the the association of nodal upstaging with preoperative PET-SUVmax and metabolic PET metrics including total lesion glycolysis (TLG) and metabolic tumor volume (MTV) with different defined thresholds. High values of preoperative PET-SUVmax of the primary tumor were associated with squamous cell carcinoma (p < 0.0001) and with larger tumors (p < 0.0001). Increased preoperative C-reactive protein levels (<1mgdL) correlated significantly with high preoperative PET-SUVmax values (p < 0.0001). No significant relationship between PET-SUVmax and lactate dehydrogenase activity (p 0.6818), white blood cell count (p 0.7681), gender (p 0.1115) or age (p 0.9284) was observed. Nodal upstaging rate was 14.0 % with 8.8 % N1 and 5.3 % N2 upstaging. Tumor size (p 0.0468) and number of removed lymph nodes (p 0.0461) were significant predictors of nodal upstaging but no significant association was found with histology or PET parameters. Of note, increased MTV - regardless of the threshold - tended to associate with nodal upstaging. Early-stage lung cancer patients with squamous histology and T2 tumors presented increased preoperative PET-SUVmax values. Nevertheless, beyond tumor size and number of removed lymph nodes neither SUVmax nor metabolic PET parameters MTV and TLG were significant predictors of nodal upstaging.

Comparison of dual-energy CT with positron emission tomography for lung perfusion imaging in patients with non-small cell lung cancer.

Cosmetic Results and Side Effects of Accelerated Partial-Breast Irradiation Versus Whole-Breast Irradiation for Low-Risk Invasive Carcinoma of the Breast The Randomized Phase III IRMA Trial.

The results in terms of side effects vary among the published accelerated partial-breast irradiation (APBI) studies. Here, we report the 5-year results for cosmetic outcomes and toxicity of the IRMA trial. We ran this randomized phase III trial in 35 centers. Women with stage I-IIA breast cancer treated with breast-conserving surgery, age ≥ 49 years, were randomly assigned 11 to receive either whole-breast irradiation (WBI) or external beam radiation therapy APBI (38.5 Gy10 fraction twice daily). Patients and investigators were not masked to treatment allocation. The primary end point was ipsilateral breast tumor recurrence. We hereby present the analysis of the secondary outcomes, cosmesis, and normal tissue toxicity. All side effects were graded with the Radiation Therapy Oncology GroupEuropean Organisation for Research and Treatment of Cancer Radiation Morbidity Scoring Schema. Analysis was performed with both intention-to-treat and as-treated approaches. Between March 2007 and March 2019, 3,309 patients were randomly assigned to 1,657 WBI and 1,652 APBI 3,225 patients comprised the intention-to-treat population (1,623 WBI and 1,602 APBI). At a median follow-up of 5.6 (interquartile range, 4.0-8.4) years, adverse cosmesis in the APBI patients was higher than that in the WBI patients at 3 years (12.7% External beam radiation therapy-APBI with a twice-daily IRMA schedule was associated with increased rates of late moderate soft tissue and bone toxicities, with a slight decrease in patient-reported cosmetic outcomes at 5 years when compared with WBI, although overall toxicity was in an acceptable range.

Secondary Neoplasms After Hematopoietic Cell Transplant for Sickle Cell Disease.

To report the incidence and risk factors for secondary neoplasm after transplantation for sickle cell disease. Included are 1,096 transplants for sickle cell disease between 1991 and 2016. There were 22 secondary neoplasms. Types included leukemiamyelodysplastic syndrome (MDS n 15) and solid tumor (n 7). Fine-Gray regression models examined for risk factors for leukemiaMDS and any secondary neoplasm. The 10-year incidence of leukemiaMDS was 1.7% (95% CI, 0.90 to 2.9) and of any secondary neoplasm was 2.4% (95% CI, 1.4 to 3.8). After adjusting for other risk factors, risks for leukemiaMDS (hazard ratio, 22.69 95% CI, 4.34 to 118.66 Low-intensity regimens rely on tolerance induction and establishment of mixed-donor chimerism. Persistence of host cells exposed to low-dose radiation triggering myeloid malignancy is one plausible etiology. Pre-existing myeloid mutations and prior inflammation may also contribute but could not be studied using our data source. Choosing conditioning regimens likely to result in full-donor chimerism may in part mitigate the higher risk for leukemiaMDS.

Pan-cancer Landscape of Programmed Death Ligand-1 and Programmed Death Ligand-2 Structural Variations.

Programmed cell death protein-1 (PD-1) receptor and ligand interactions are the target of immunotherapies for more than 20 cancer types. Biomarkers that predict response to immunotherapy are microsatellite instability, tumor mutational burden, and programmed death ligand-1 (PD-L1) immunohistochemistry. Structural variations (SVs) in PD-L1 ( We analyzed sequencing data from cancer cases with Using data sets encompassing 300,000 tumors, we curated 486 cases with SVs in PD-L1 and PD-L2 and observed consistent breakpoint patterns, or hotspots. Leveraging The Cancer Genome Atlas, we observed significant upregulation in Our findings show that the 3-UTR is frequently affected, and that SVs are associated with increased expression of ligands and immune signatures. Retrospective evidence from curated studies suggests this genomic alteration could help identify candidates for PD-1PD-L1 immunotherapy. We expect these findings will better define

High-Dose Once-Daily Thoracic Radiotherapy in Limited-Stage Small-Cell Lung Cancer CALGB 30610 (Alliance)RTOG 0538.

Although level 1 evidence supports 45-Gy twice-daily radiotherapy as standard for limited-stage small-cell lung cancer, most patients receive higher-dose once-daily regimens in clinical practice. Whether increasing radiotherapy dose improves outcomes remains to be prospectively demonstrated. This phase III trial, CALGB 30610RTOG 0538 (ClinicalTrials.gov identifier NCT00632853), was conducted in two stages. In the first stage, patients with limited-stage disease were randomly assigned to receive 45-Gy twice-daily, 70-Gy once-daily, or 61.2-Gy concomitant-boost radiotherapy, starting with either the first or second (of four total) chemotherapy cycles. In the second stage, allocation to the 61.2-Gy arm was discontinued following planned interim toxicity analysis, and the study continued with two remaining arms. The primary end point was overall survival (OS) in the intention-to-treat population. Trial accrual opened on March 15, 2008, and closed on December 1, 2019. All patients randomly assigned to 45-Gy twice-daily (n 313) or 70-Gy once-daily radiotherapy (n 325) are included in this analysis. After a median follow-up of 4.7 years, OS was not improved on the once-daily arm (hazard ratio for death, 0.94 95% CI, 0.76 to 1.17 Although 45-Gy twice-daily radiotherapy remains the standard of care, this study provides the most robust information available to help guide the choice of thoracic radiotherapy regimen for patients with limited-stage small-cell lung cancer.

First-, Second-, and Third-Generation Radiolabeled Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Positron Emission Tomography State of the Art, a Systematic Review.

Radiotheranostics in oncology Making precision medicine possible.

A quintessential setting for precision medicine, theranostics refers to a rapidly evolving field of medicine in which disease is diagnosed followed by treatment of disease-positive patients using tools for the therapy identical or similar to those used for the diagnosis. Against the backdrop of only-treat-when-visualized, the goal is a high therapeutic index with efficacy markedly surpassing toxicity. Oncology leads the way in theranostics innovation, where the approach has become possible with the identification of unique proteins and other factors selectively expressed in cancer versus healthy tissue, advances in imaging technology able to report these tissue factors, and major understanding of targeting chemicals and nanodevices together with methods to attach labels or warheads for imaging and therapy. Radiotheranostics-using radiopharmaceuticals-is becoming routine in patients with prostate cancer and neuroendocrine tumors who express the proteins PSMA (prostate-specific membrane antigen) and SSTR2 (somatostatin receptor 2), respectively, on their cancer. The palpable excitement in the field stems from the finding that a proportion of patients with large metastatic burden show complete and partial responses, and this outcome is catalyzing the search for more radiotheranostics approaches. Not every patient will benefit from radiotheranostics but, for those who cross the target-detected line, the likelihood of response is very high.

Pustular Lichenoid Eruptions Induced by Immune Checkpoint Inhibitors Two Case Reports and a Review of the Literature.

Immune checkpoint inhibitors (ICIs) have become the standard treatment for many types of cancer. After several years of using these therapies, many adverse events related to ICIs have been observed. Dermatologic toxicities such as nonspecific morbilliform rash, vitiligo, Stevens-Johnson syndrometoxic epidermal necrolysis, and more rarely, lichenoid eruptions have been described in the literature. We report 2 cases of pustular lichenoid eruptions, 1 in a patient with nonsmall cell lung carcinoma and 1 in a patient with metastatic melanoma, induced by pembrolizumab and nivolumab, respectively. The 2 patients were treated with topical corticosteroids, and complete healing of lesions was slowly obtained. Due to the severity of the cutaneous eruptions, pembrolizumab and nivolumab were discontinued. We identified 6 cases of pustular lichenoid eruptions induced by ICIs in the published literature and in the French Pharmacovigilance Database and reviewed their main clinical features and courses.

Healthy Eating Patterns and Risk of Total and Cause-Specific Mortality.

The current Dietary Guidelines for Americans recommend multiple healthy eating patterns. However, few studies have examined the associations of adherence to different dietary patterns with long-term risk of total and cause-specific mortality. To examine the associations of dietary scores for 4 healthy eating patterns with risk of total and cause-specific mortality. This prospective cohort study included initially healthy women from the Nurses Health Study (NHS 1984-2020) and men from the Health Professionals Follow-up Study (HPFS 1986-2020). Healthy Eating Index 2015 (HEI-2015), Alternate Mediterranean Diet (AMED) score, Healthful Plant-based Diet Index (HPDI), and Alternate Healthy Eating Index (AHEI). The main outcomes were total and cause-specific mortality overall and stratified by race and ethnicity and other potential risk factors. The final study sample included 75 230 women from the NHS (mean SD baseline age, 50.2 7.2 years) and 44 085 men from the HPFS (mean SD baseline age, 53.3 9.6 years). During a total of 3 559 056 person-years of follow-up, 31 263 women and 22 900 men died. When comparing the highest with the lowest quintiles, the pooled multivariable-adjusted HRs of total mortality were 0.81 (95% CI, 0.79-0.84) for HEI-2015, 0.82 (95% CI, 0.79-0.84) for AMED score, 0.86 (95% CI, 0.83-0.89) for HPDI, and 0.80 (95% CI, 0.77-0.82) for AHEI (P < .001 for trend for all). All dietary scores were significantly inversely associated with death from cardiovascular disease, cancer, and respiratory disease. The AMED score and AHEI were inversely associated with mortality from neurodegenerative disease. The inverse associations between these scores and risk of mortality were consistent in different racial and ethnic groups, including Hispanic, non-Hispanic Black, and non-Hispanic White individuals. In this cohort study of 2 large prospective cohorts with up to 36 years of follow-up, greater adherence to various healthy eating patterns was consistently associated with lower risk of total and cause-specific mortality. These findings support the recommendations of Dietary Guidelines for Americans that multiple healthy eating patterns can be adapted to individual food traditions and preferences.

Role of AIM2 Gene Knockdown Mechanism in Diabetic Cardiomyopathy an In Vivo and Ex Vivo Study.

Chronic hyperglycemia induces reactive oxygen species that have an essential function in tissue injuries in cases of diabetic cardiomyopathy. The mechanism of the absent in melanoma 2 (AIM2)-associated inflammasome response in diabetic cardiomyopathy is unknown. Therefore, this study was performed to investigate the role of AIM2 and its molecular mechanisms. Diabetic rats received 1 × 10

Systematically analyzed molecular characteristics of lung adenocarcinoma using metabolism-related genes classification.

High heterogeneity of lung adenocarcinoma (LUAD) is a major clinical challenge. This study aims to characterize the molecular features of LUAD through classification based on metabolism-related genes. A total of 500 LUAD samples from The Cancer Genome Atlas (TCGA) and 612 from Gene Expression Omnibus (GEO) were integrated with 2,753 metabolism-related genes to determine the molecular classification. Systematic bioinformatics analysis was used to conduct correlation analysis between metabolism-related classification and molecular characteristics of LUAD. LUAD patients were divided into three molecular clusters (C1-C3). Survival analysis revealed that C1 and C2 showed good and poor prognoses, respectively. Associational analysis of classification and molecular characteristics revealed that C1 was associated with low pathological stage, metabolic pathways, high metabolic process, active immune process and checkpoint, sensitive drug response, as well as a low genetic mutation. Nevertheless, C2 was associated with high pathological stage, carcinogenic pathways, low metabolic process, inactive immune signatures, resistant drug response, and frequent genetic mutation. Eventually, a classifier with 60 metabolic genes was constructed, confirming the robustness of molecular classification on LUAD. Our findings promote the understanding of LUAD molecular characteristics, and the research data may be used for providing information be helpful for clinical diagnosis and treatment.

Pan-cancer molecular analysis of EGFR large fragment deletion in the Asian population.

Large fragment deletion (LFD) of EGFR was associated with carcinogenesis in many types of cancers. However, the molecular features of EGFR-LFD have not been studied in the Asian cancer population. Here we retrospectively analyzed the targeted sequencing data from a large cancer database. EGFR-LFD was detected at a frequency of 0.03% with EGFRvIII being the most frequently observed LFD. TERTp variants were identified in 60% of the cases. TP53 alterations (33%) were mutually exclusive with TERTp variants and coexisted with EGFR-LFD in lung cancer and colorectal cancer. EGFR amplification (67%) and chromosome 10p deletion (53%) were the most focal-level and arm-level CNV in this cohort. EGFR exon2-17 skipping was found in the tumor tissue of one patient after progressing on osimertinib. Our study provided valuable insights into the distribution and molecular characteristics of EGFR-LFD, hoping to shed light on the treatment management for EGFR-LFD carriers.

Disparities in cancer incidence by rurality in California.

Cancer rates in rural areas across the United States have different patterns than in urban areas. This study examines associations between rurality and incidence for the top five cancers in California and evaluates whether these associations vary jointly by sex, race, and ethnicity. We use 2015-2019 California Cancer Registry data to compare incidence rate ratios (IRRs) and trends for breast, prostate, lung, colorectal, and skin (melanoma) cancers. We leverage census tract aggregation zones and seven levels of % rural population (0%, >0-<10%, 10-<20%, 20-<30%, 30-<40%, 40-<50%, and 50%). Zones with higher proportions of rural population were significantly associated with lower incidence of female breast cancer and prostate cancer, though the trends were not significant overall. Zones with higher proportions of rural population were significantly associated with higher incidence of lung cancer and melanoma. There were no statistically significant trends for colorectal cancer overall. Comparing areas with ≥50% rural population with areas with 0% rural population, the IRR for lung cancer in Hispanic females was higher (IRR 1.43, 95% CI (1.17, 1.74)) than in Hispanic males (IRR 0.90, 95% CI (0.72, 1.11)). Also in areas with ≥50% rural population, the IRR for melanoma was higher in Hispanic females (IRR 1.75, 95% CI (1.23, 2.45)) than non-Hispanic White females (IRR 0.87 95% CI (0.80, 0.95)). Our findings show that rurality is associated with cancer incidence and underscore the importance of examining rural disparities jointly with sex, race and ethnicity by cancer site.

A network meta-analysis of immunotherapy-based treatments for advanced nonsquamous non-small cell lung cancer.

LINC00669 promotes lung adenocarcinoma growth by stimulating the Wntβ-catenin signaling pathway.

Lung cancer poses severe threats to human health. It is indispensable to discover more druggable molecular targets. We identified a novel dysregulated long non-coding RNA (lncRNA), LINC00669, in lung adenocarcinoma (LUAD) by analyzing the TCGA and GEO databases. Pan-cancer analysis indicated significantly upregulated LINC00669 across 33 cancer types. GSEA revealed a tight association of LINC00669 with the cell cycle. We next attempted to improve the prognostic accuracy of this lncRNA by establishing a risk signature in reliance on cell cycle genes associated with LINC00669. The resulting risk score combined with LINC00669 and stage showed an AUC of 0.746. The risk score significantly stratified LUAD patients into low- and high-risk subgroups, independently predicting prognosis. Its performance was verified by nomogram (C-index 0.736) and decision curve analysis. Gene set variation analysis disclosed the two groups molecular characteristics. We also evaluated the tumor immune microenvironment by dissecting 28 infiltrated immune cells, 47 immune checkpoint gene expressions, and immunophenoscore within the two subgroups. Furthermore, the risk signature could predict sensitivity to immune checkpoint inhibitors and other anticancer therapies. Eventually, in vitro and in vivo experiments were conducted to validate LINC00669s function using qRT-PCR, CCK8, flow cytometry, western blot, and immunofluorescence staining. The gain- and loss-of-function study substantiated LINC00669s oncogenic effects, which stimulated non-small cell lung cancer cell proliferation but reduced apoptosis via activating the Wntβ-catenin pathway. Its oncogenic potentials were validated in the xenograft mouse model. Overall, we identified a novel oncogenic large intergenic non-coding RNA (lincRNA), LINC00669. The resulting signature may facilitate predicting prognosis and therapy responses in LUAD.

Phase 1 study of DS-1205c combined with gefitinib for EGFR mutation-positive non-small cell lung cancer.

Tyrosine kinase inhibitors (TKIs) are effective for the treatment of non-small cell lung cancer (NSCLC) patients with activating mutations of the epidermal growth factor receptor (EGFR), but responses are not durable as tumors develop resistance. DS-1205c is a novel, specific, orally bioavailable, small-molecule AXL receptor TKI. In preclinical studies, DS-1205c restored TKI antitumor activity in a TKI acquired-resistance EGFR-mutant NSCLC tumor xenograft model. This first-in-human, multicenter, open-label Phase 1 study (registered at ClinicalTrials.gov NCT03599518) primarily evaluated the safety and tolerability of combination therapy with DS-1205c and gefitinib in Japanese patients with metastatic or unresectable EGFR-mutant NSCLC and tumor progression during treatment with EGFR-TKIs. Patients (n 20) received DS-1205c monotherapy (200-1200 mg twice daily BID) in a 7-day safety monitoring period before combination DS-1205cgefitinib (250 mg once daily) in 21-day cycles. The observed common treatment-emergent adverse events (TEAEs) were increased aspartate aminotransferase (35%), increased alanine aminotransferase (30%), rash maculo-papular (30%), and diarrhea (25%). No serious TEAEs were reported. Plasma concentrations and pharmacokinetic parameters of DS-1205a (free form of DS-1205c) were unaffected by concomitant administration of gefitinib. No patient achieved a complete or partial response and 5 patients (25%) had stable disease. DS-1205c was generally safe and well tolerated at all dose levels, but the safety profile of ≤800 mg BID was more favorable than 1200 mg BID. The recommended dose for dose-expansion cohorts of DS-1205c in combination therapy with gefitinib was 800 mg BID.

Cigarette smoke condensate induces centrosome clustering in normal lung epithelial cells.

Unlike normal cells, cancer cells frequently have multiple centrosomes that can cluster to form bipolar mitotic spindles and allow for successful cell division. Inhibiting centrosome clustering, therefore, holds therapeutic promise to promote cancer cell-specific cell death. We used confocal microscopy, real-time PCR, siRNA knockdown, and western blot to analyze centrosome clustering and declustering using normal lung bronchial epithelial and nonsmall-cell lung cancer (NSCLC) cell lines. Also, we used Ingenuity Pathway Analysis software to identify novel pathways associated with centrosome clustering. In this study, we found that exposure to cigarette smoke condensate induces centrosome amplification and clustering in human lung epithelial cells. We observed a similar increase in centrosome amplification and clustering in unexposed NSCLC cell lines which may suggest a common underlying mechanism for lung carcinogenesis. We identified a cyclin D2-mediated centrosome clustering pathway that involves a sonic hedgehog-forkhead box protein M1 axis which is critical for mitosis. We also observed that cyclin D2 knockdown induced multipolar mitotic spindles that could eventually lead to cell death. Here we report a novel role of cyclin D2 in the regulation of centrosome clustering, which could allow the identification of tumors sensitive to cyclin D2 inhibitors. Our data reveal a pathway that can be targeted to inhibit centrosome clustering by interfering with the expression of cyclin D2-associated genes.

Real-world analysis of the prognostic value of EGFR mutation detection in plasma ctDNA from patients with advanced non-small cell lung cancer.

The plasma sample has emerged as a promising surrogate sample for EGFR mutation detection in advanced non-small cell lung cancer (NSCLC). In clinical practice, whether EGFR variants in baseline plasma ctDNA of advanced NSCLC can predict prognosis in addition to guiding targeted therapy remains to be further explored. In total, 315 NSCLC patients were retrospectively enrolled. EGFR mutation data from tissue detected by ARMS-PCR and paired plasma samples within 1 month of admission detected by SuperARMS or ARMS-PCR were collected. The correlation between baseline plasma ctDNA EGFR mutation status and survival was compared. EGFR mutation detection rates in tumor samples and plasma samples were 65.1% (205315) and 43.8% (138315). Referred to tissue results, the consistent rate of test ctDNA EGFR alteration by SuperARMS was higher than that detected by ARMS (79.5% vs. 69.0%, p 0.04), either in stage I-IIIA patients (85.7% vs. 50.0%, p 0.4) or stage IIIB-IV patients (79.1% vs. 69.4%, p 0.04). Patients treatment status and pathological subtype were the two factors that affected plasma ctDNA EGFR alteration detection accuracy. The concordance in non-adenocarcinoma patients was obviously higher than that in adenocarcinoma (p 0.02), and the concordance in treatment naïve patients was significantly higher than that in relapse patients (p 0.047). In treatment naïve patients, the median PFS (mPFS) in plasma ctDNA EGFR-positive patients was shorter than that in plasma ctDNA EGFR negative patients (7.0 vs. 10.0 months, p 0.01). In relapsed patients, the mPFS in plasma ctDNA EGFR-positive patients was 9.0 months versus 11.0 months in plasma ctDNA EGFR negative patients (p 0.1). A plasma sample could be an alternative for a molecular test when tissue samples was unavailable. The SuperARMS-PCR detection method has high sensitivity in real-world clinical practice. Furthermore, in patients with stage IIIB-IV, baseline plasma ctDNA EGFR mutation positivity not only guides targeted therapy but also predicts a worse prognosis.

Changing Smoking Behavior and Epigenetics A Longitudinal Study of 4,432 Individuals From the General Population.

Hypomethylation of the aryl hydrocarbon receptor repressor (AHRR) gene indicates long-term smoking exposure and might therefore be a monitor for smoking-induced disease risk. However, studies of individual longitudinal changes in AHRR methylation are sparse. How does the recovery of AHRR methylation depend on change in smoking behaviors and demographic variables This study included 4,432 individuals from the Copenhagen City Heart Study with baseline and follow-up blood samples and smoking information collected approximately 10 years apart. AHRR methylation at the cg05575921 site was measured in bisulfite-treated leukocyte DNA. Four smoking groups were defined persistent never smokers (Never-Never), persistent former smokers (Former-Former), interim quitters (Current-Former), and individuals who smoked at both baseline and follow-up (Current-Current). Methylation recovery was defined as the increase in AHRR methylation between baseline and follow-up examination. Methylation recovery was highest among quitters with a median methylation recovery of 5.58% (interquartile range, 1.79 9.15) vs 1.64% (interquartile range, -1.88 4.96) in the Current-Current group (P < 0.0001). In individuals who quit smoking, higher age was associated with lower methylation recovery (P < 0.0001). In quitters aged > 65 years, methylation recovery was 5.9% at 5.6 years after quitting methylation recovery was 8.5% after 2.8 years for quitters aged < 55 years. AHRR methylation recovered after individuals quit smoking, and recovery was more pronounced and occurred faster in younger than in older interim quitters.

Health-Related Quality of Life Following Robotic-Assisted or Video-Assisted Lobectomy in Patients With Non-Small Cell Lung Cancer Results From the RVlob Randomized Clinical Trial.

Robot-assisted lobectomy (RAL) is increasingly used as an alternative to video-assisted lobectomy (VAL) for resectable non-small cell lung cancer (NSCLC). However, there is little evidence of any difference in postoperative health-related quality of life (HRQoL) between these two approaches. Is RAL superior to VAL in improving quality of life in patients with resectable NSCLC We performed a single-center, open-label randomized clinical trial from May 2017 to May 2020 with 320 enrolled patients undergoing RAL or VAL for resectable NSCLC (RVlob trial NCT03134534). Postoperative pain was evaluated by visual analog score or numeric rating score on postoperative day 1 and at weeks 4, 24, and 48. The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30), EORTC Quality of Life Questionnaire in Lung Cancer (QLQ-LC13), and the European Quality of Life 5 Dimensions (EQ-5D) questionnaire were also administered at weeks 4, 24, and 48 after surgery. One hundred and fifty-seven patients underwent RAL and 163 underwent VAL. The mean pain score of patients after RAL was significantly lower at week 4 (2.097 ± 0.111 vs 2.431 ± 0.108 P .032). QLQ-C30 and QLQ-LC13 summary scores (P > .05) were similar for both RAL and VAL during the first 48 weeks of follow-up. HRQoL scores assessed with the EQ-5D questionnaire were also comparable between the two groups (P > .05) during the whole study period. Both RAL and VAL showed satisfactory and comparable HRQoL and postoperative pain up to 48 weeks after surgery, despite some minor statistical differences at week 4. ClinicalTrials.gov No. NCT03134534 URL www. gov.

Design, synthesis, antitumor activity and ct-DNA binding study of photosensitive drugs based on porphyrin framework.

Photodynamic therapy is a promising novel tumor treatment method. In this study, novel porphyrin-chrysin photosensitizer derivatives were synthesized. Most of the compounds showed antitumor activity against human cervical cancer HeLa cells and human lung cancer A549 cells, among which compound 4c had the best photodynamic therapy effect on HeLa cells and A549 cells, with IC

Generation of the novel anti-FXYD5 monoclonal antibody and its application to the diagnosis of pancreatic and lung cancer.

Despite recent advances in cancer treatments, pancreatic cancer has a dismal prognosis globally. Early detection of cancer cells and effective treatments for recalcitrant tumors are required, but the innovative therapeutic tools remain in development. Cancer-specific antigens expressed only on cancer cells may help resolve these problems, and antibodies to such antigens have potential in basic research and clinical applications. To generate specific antibodies that bind to proteins expressed on the surface of pancreatic cancer cells, we immunized mice with human pancreatic cancer MIA PaCa-2 cells, and isolated a hybridoma that produces a monoclonal antibody (mAb), named 12-13.8. This antibody was applied to molecular biological experiments such as immunocytochemistry, immunoblotting, flow cytometry, and immunoprecipitation. In addition, we showed that mAb 12-13.8 could accumulate in tumors, through in vivo experiments using cancer-bearing mice. Immunohistochemical staining of pancreatic and lung tumor tissues indicated that the increase of the staining strength by mAb 12-13.8 positively and inversely correlated with the patients cancer recurrence and survival rate, respectively. We identified the FXYD5 protein as the target protein of mAb 12-13.8, by a human protein array screening system. The FXYD5 protein is overexpressed in various types of cancer and is modified by O-linked glycosylation. We confirmed the binding of the FXYD5 protein to mAb 12-13.8 by using FXYD5-knockout MIA PaCa-2 cells, and detailed epitope mapping identified amino acid residues 45-52 as the minimal peptide sequence. Our results indicate that mAb 12-13.8 could be a valuable tool for FXYD5 studies, and useful in diagnostic and drug delivery applications for cancer patients.

Ultrasound-mediated mesoporous silica nanoparticles loaded with PDLIM5 siRNA inhibit gefitinib resistance in NSCLC cells by attenuating EMT.

Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKIs) was one of the main drugs in the treatment of non-small cell lung cancer (NSCLC). Previous studies had demonstrated that PDZ and LIM Domain 5 (PDLIM5) played an important role in EGFR TKIs resistance. However, there was no feasible method to eliminate EGFR TKIs resistance by suppressing this gene. Here, we formulated a novel mesoporous silica-loaded PDLIM5 siRNA (Small interfering RNA) nanoplatforms. The results have shown that PDLIM5 siRNA could be effectively bound to the nanoplatforms and had good biocompatibility. Further exploration suggested that the nano-platform combined with ultrasonic irradiation could be very effective for siRNA delivery and ultrasound imaging. Moreover, Epithelial-mesenchymal transformation (EMT) changes occurred in PC-9 Gefitinib resistance (PC-9GR) cells during the development of drug resistance. When PDLIM5 siRNA entered PC-9GR cells, the sensitivity of drug-resistant cells to gefitinib could be restored through the transforming growth factor-β (TGF-β)EMT pathway. Therefore, PDLIM5 may be an important reason for the resistance of NSCLC cells to gefitinib, and this nanoplatform may become a novel treatment for EGFR TKIs resistance in NSCLC patients.

Feasibility of shape-sensing robotic-assisted bronchoscopy for biomarker identification in patients with thoracic malignancies.

Molecular diagnostic assays require samples with high nucleic acid content to generate reliable data. Similarly, programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) requires samples with adequate tumor content. We investigated whether shape-sensing robotic-assisted bronchoscopy (ssRAB) provides adequate samples for molecular and predictive testing. We retrospectively identified diagnostic samples from a prospectively collected database. Pathologic reports were reviewed to assess adequacy of samples for molecular testing and feasibility of PD-L1 IHC. Tumor cellularity was quantified by an independent pathologist using paraffin-embedded sections. Univariable and multivariable linear regression models were constructed to assess associations between lesion- and procedure-related variables and tumor cellularity. In total, 128 samples were analyzed 104 primary lung cancers and 24 metastatic lesions. On initial pathologic assessment, ssRAB samples were deemed to be adequate for molecular testing in 84% of cases on independent review of cellular blocks, median tumor cellularity was 60% (interquartile range, 25%-80%). Hybrid capture-based next-generation sequencing was successful for 25 of 26 samples (96%), polymerase chain reaction-based molecular testing (Idylla Biocartis) was successful for 49 of 52 samples (94%), and PD-L1 IHC was successful for 61 of 67 samples (91%). Carcinoid and small cell carcinoma histologic subtype and adequacy on rapid on-site evaluation were associated with higher tumor cellularity. The ssRAB platform provided adequate tissue for next-generation sequencing, polymerase chain reaction-based molecular testing, and PD-L1 IHC in >80% of cases. Tumor histology and adequacy on intraoperative cytologic assessment might be associated with sample quality and suitability for downstream assays.

Opportunities and Challenges of Computed Tomography Coronary Angiography in the Investigation of Chest Pain in the Emergency Department-A Narrative Review.

Chest pain is one of the most common presentations to emergency departments. However, only 5.1% will be diagnosed with an acute coronary syndrome, representing considerable time and expense in the diagnosis and investigation of the patients eventually found not to be suffering from an acute coronary syndrome. PubMed and Medline databases were searched with variations of the terms chest pain, emergency department, computed tomography coronary angiography. After review, 52 articles were included. Computed tomography coronary angiography (CTCA) is a class I endorsement for investigating chest pain in major international societal guidelines. CTCA offers excellent sensitivity and negative predictive value in identifying patients with coronary disease, with prognostic data impacting patient management. If CTCA is to be applied to all comers, it is pertinent to discuss the advantages and potential pitfalls if use in the Australian system is to be increased.

Evaluation of Routine Ear, Nose, and Throat Screening in Heart Transplant Candidates A Retrospective Cohort Study.

Patients with end-stage heart failure refractory to medication can be treated with a heart transplant (HTx). These patients are subjected to a preoperative screening procedure according to International Society for Heart and Lung Transplantation guidelines. Additionally, in our hospital, a routine ear, nose, and throat (ENT) screening is performed, directed toward the identification of asymptomatic infections and head and neck neoplasms. There are no studies demonstrating that this screening has additional value in these patients. To investigate the yield of protocolled ENT screening in candidates for HTx, we retrospectively reviewed the medical records of patients who were subjected to the screening procedure between 2012 and 2020. The study population consisted of 251 patients of whom 177 (70.5%) were male with a median age of 52 years (IQR, 45-59 years). Ten patients (4.0%) were diagnosed with an infection (sinus) or a neoplasm, resulting in a number needed to screen of 25. In all cases, ENT consultation or sinus radiography did not influence the decision to list patients for HTx. Furthermore, no major ENT infections or occurrence of de novo head and neck malignant neoplasm were observed during follow-up after HTx. The clinically relevant yield of protocolled ENT screening in candidates for HTx is low. Based on these findings, we believe that only patients with abnormal findings on a routine sinus computed tomography scan andor specific ENT complaints should be referred to an otorhinolaryngologist.

Computed tomography radiomics in growth prediction of pulmonary ground-glass nodules.

Individualized follow-up of pulmonary ground-glass nodules (GGNs) remains challenging in clinical practice. Accurate prediction of the growth or long-term stability of persistent GGNs is essential to optimize the follow-up intervals. In this retrospective study, 253 patients with 1115 computed tomography (CT) images were recruited. In total, 1115 CT images were randomized into training (70%) and validation sets (30%). We developed models for the growth or long-term stable prediction of GGNs using radiomics and clinical features. We evaluated the prediction accuracy of the models using receiver operating characteristic (ROC) curve analysis, and the areas under the curve (AUCs) were established. The ROC curves of the models were compared using the DeLong method. The growth and stable groups contained 535 and 580 GGNs, respectively. Traditional radiographic features have limited value in the prediction of growth or long-term stability of GGNs. The prediction nomogram model combining radiomics and clinical features (size, location, and age) yielded the best AUC in both the training and validation sets (AUC 0.843 and 0.824, respectively). The radiomics model outperformed the clinical model in both sets (AUC 0.836 vs 0.772 and 0.818 vs 0.735, respectively). The radiomics signature and nomogram model achieved similar AUCs (Delong test, training set P 0.09 validation set P 0.37). We developed and validated a nomogram model combining radiomics signature, size, age, and location to predict the growth or long-term stability of GGNs. The model achieved good performance and may provide a basis for the improvement of follow-up management of GGNs.

Icariside II potentiates the anti-PD-1 antitumor effect by reducing chemotactic infiltration of myeloid-derived suppressor cells into the tumor microenvironment via ROS-mediated inactivation of the SRCERKSTAT3 signaling pathways.

Immune checkpoint blockade agents, such as anti-PD-1 antibodies, show promising antitumor efficacy but only a limited response in patients with non-small cell lung cancer (NSCLC). Icariside II (IS), a metabolite of Herba Epimedii, is a COX-2 and EGFR inhibitor that can enhance the anti-PD-1 effect. This study aimed to evaluate the antitumor effect of IS in combination with anti-PD-1 and explore the underlying mechanism. Tumor growth was assessed in Lewis Lung Cancer (LLC) tumor-bearing mice in seven groups (control, IS 20 mgkg, IS 40 mgkg, anti-PD-1, IS 20 mgkganti-PD-1, IS 40 mgkganti-PD-1, ERK inhibitoranti-PD-1). Tumor-infiltrating immune cells were measured by flow cytometry. The mechanisms were explored by tumor RNA-seq and validated in LLC cells through molecular biological experiments using qRT‒PCR, ELISA, and western blotting. Animal experiments showed that IS in combination with anti-PD-1 further inhibited tumor growth and remarkably reduced the infiltration of myeloid-derived suppressor cells (MDSCs) into the tumor compared with anti-PD-1 monotherapy. RNA-seq and in vitro experiments showed that IS suppressed the chemotactic migration of MDSCs by downregulating the expression of CXC chemokine ligands 2 (CXCL2) and CXCL3. Moreover, IS promoted reactive oxygen species (ROS) generation and inhibited the activation of SRCERKSTAT3 in LLC cells, which are upstream signaling pathways of these chemokines. IS potentiates the anti-PD-1 anti-tumor effect by reducing chemotactic infiltration of the myeloid-derived suppressor cell into the tumor microenvironment, via ROS-mediated inactivation of SRCERKSTAT3 signaling pathways.

The clinical application of

Brain metastases (BMs) of lung cancer are common malignant intracranial tumours associated with severe neurological symptoms and an abysmal prognosis. Prostate-specific membrane antigen (PSMA) has been reported to express significantly in a variety of solid tumours. However, the clinical applications of