bluuebunny/crossref_metadata_2025 huggingface dataset:
Anlotinib in patients with relapsed or refractory thymic epithelial tumors: a study of 50 cases
Authors: Wang Chang-Lu , Zhao Yi-Zhuo , Zhang Qin , Zeng Wan-Qin , Jia Tian-Ying , Zhu Lei , Fang Wen-Tao , Fu Xiao-Long
Published: February 2023

The optimal pharmaceutical regimen for advanced thymic epithelial tumors (TETs) remains controversial when first-line chemotherapy fails. This retrospective study aims to evaluate the efficacy and safety of anlotinib treatment for patients with relapsed and refractory TETs. Patients with progressive disease after failure of platinum-based chemotherapy were enrolled in this study. Anlotinib was orally taken once a day at an initial dose of 12 mg (10 mg when body weight <60 kg). The cycle was repeated every 3 weeks (2 weeks of treatment followed by 1-week rest). Objective response rate (ORR) and progression-free survival (PFS) were recorded as primary endpoints. There were 50 patients enrolled in this study from October 2018 to June 2021 at a median age of 50 (range 23–79) years old. Patients with thymoma and thymic carcinoma were 33 (66%) and 17 (34%), respectively. The ORR in thymoma and thymic carcinoma patients were 33% (11/33) and 41% (7/17), respectively. The median PFS (mPFS) was 7 (95% CI, 5.9–10.2) months in thymoma patients and 6 (95% CI, 4.6–9.3) months in the thymic carcinoma group. Eleven patients experienced dose reduction due to toxicities, among whom, eight patients discontinued treatment even after dose reduction. Six patients with thymoma showed myasthenia gravis deterioration during treatment, and two of them died of myasthenia gravis crisis. Anlotinib is active in patients with advanced TETs refractory to routine chemotherapy. Prescription of anlotinib to patients with myasthenia gravis should be made cautiously.
Circular RNA circ_0005667 promotes cisplatin resistance of endometrial carcinoma cells by regulating IGF2BP1 through miR-145-5p
Authors: Sun Guihua , Tian Jing , Xiao Yifang , Zeng Youling
Published: February 2023

Background

Circular RNA (circRNA) plays a significant role in cisplatin (DDP) resistance. The purpose of this study was to explore the role of circ_0005667 in DDP resistance of endometrial carcinoma (EC) cells.

Methods

The expression of circular RNA circ_0005667, microRNA-145-5p (miR-145-5p) and insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) in DDP-sensitive and DDP-resistant EC tissues and EC cells was determined by quantitative real-time PCR (qRT-PCR). The expression of apoptosis-related proteins, drug resistance-related proteins and IGF2BP1 proteins were detected by western blot. The half-maximal inhibitory concentration (IC50) of DDP was determined using a cell counting kit-8 (CCK-8) assay. For functional assays, cell proliferation, migration, invasion and cell apoptosis were determined using 5-ethynyl-2’-deoxyuridine (EdU) assay, wound healing assay, transwell assay and flow cytometry assay, respectively. The binding relationship between miR-145-5p and circ_0005667 or IGF2BP1 was verified by dual-luciferase reporter assay. A xenograft experiment was applied to clarify the functional role of circ_0005667 in vivo.

Results

Levels of circ_0005667 and IGF2BP1 were markedly increased, whereas miR-145-5p was downregulated in DDP-resistant EC tissues and cells. The circ_0005667 deficiency could enhance DDP sensitivity, inhibit cell proliferation, migration and invasion and promote cell apoptosis in DDP-resistant EC cells in vitro. Mechanistically, circ_0005667 modulated IGF2BP1 expression through sponging miR-145-5p. In addition, miR-145-5p depletion attenuated circ_0005667 silencing-induced effects in EC cells. The regulation of miR-145-5p in DDP resistance involved low IGF2BP1 expression. In vivo experiments revealed that circ_0005667 silencing could improve the sensitivity of the tumor to DDP.

Conclusion

Circ_0005667 enhanced DDP resistance in EC by elevating IGF2BP1 through sponging miR-145-5p.
Derazantinib, a fibroblast growth factor receptor inhibitor, inhibits colony-stimulating factor receptor-1 in macrophages and tumor cells and in combination with a murine programmed cell death ligand-1-antibody activates the immune environment of murine syngeneic tumor models
Authors: El Shemerly Mahmoud , Zanini Elisa , Lecoultre Marc , Walker Paul R. , Kellenberger Laurenz , Lane Heidi A. , McSheehy Paul M.J.
Published: February 2023

Derazantinib (DZB) is an inhibitor of the fibroblast growth factor receptors 1–3 (FGFRi) with similar potency against colony-stimulating factor receptor-1 (CSF1R), a protein important in the recruitment and function of tumor-associated macrophages. DZB inhibited pCSF1R in the macrophage cell line RAW264.7, and tumor cells GDM-1 and DEL, and had the same potency in HeLa cells transiently over-expressing FGFR2. DZB exhibited similar potency against pCSF1R expressed by isolated murine macrophages, but as in the cell lines, specific FGFRi were without significant CSF1R activity. DZB inhibited growth of three tumor xenograft models with reported expression or amplification of CSF1R, whereas the specific FGFRi, pemigatinib, had no efficacy. In the FGFR-driven syngeneic breast tumor-model, 4T1, DZB was highly efficacious causing tumor stasis. A murine PD-L1 antibody was without efficacy in this model, but combined with DZB, increased efficacy against the primary tumor and further reduced liver, spine and lung metastases. Immunohistochemistry of primary 4T1 tumors showed that the combination favored an antitumor immune infiltrate by strongly increasing cytotoxic T, natural killer and T-helper cells. Similar modulation of the tumor microenvironment was observed in an FGFR-insensitive syngeneic bladder model, MBT-2. These data confirm CSF1R as an important oncology target for DZB and provide mechanistic insight for the ongoing clinical trials, in which DZB is combined with the PD-L1 antibody, atezolizumab.
Therapeutic efficacy and infectious complications of CD19-targeted chimeric antigen receptor-modified T cell immunotherapy
Authors: Gao Zhilin , Lian Yu , Ti Juanjuan , Ren Ruirui , Ma Liangming
Published: February 2023

Lymphocyte depletion chemotherapy CD19-targeted chimeric antigen receptor-modified T (CAR-T) cell immunotherapy is an innovative approach for the treatment of refractory or relapsed B-cell malignancies. This method also has the occurrence of infection, and there has been no systematic analysis of infectious complications. In our study, we intend to analyze the infection in patients between day 0 and day 90 by analyzing the data of 40 patients who received CD19 CAR-T cell therapy collected in our hospital. We assessed risk factors for infection before and after treatment using Poisson and Cox regression, respectively. A cohort study was used, including patients with acute lymphocytic leukemia, chronic lymphocytic leukemia and non-Hodgkin’s lymphoma. 40 patients were infected for the first time occurred at a median of 6 days after CAR-T cell infusion, and 8 (20%) had 10 infections within 28 days after CAR-T cell infusion, on days 29 and 29. The infection density between 90 days was lower at 0.67. This resulted in an infection density of 1.19 infections per 100 days. Two patients (5%) developed invasive fungal infections and two patients (5%) developed life-threatening or fatal infections. In an adjusted model for baseline characteristics, patients with ALL, ≥4 prior antitumor regimens, and receiving the highest CAR-T cell dose had higher infection densities at 28 days. The incidence of infection was comparable to that observed in clinical trials of salvage associated with infection after CAR-T cell infusion.
A chance in hopeless cancer: 5-year complete remission after oxaliplatin-based therapy in a patient with BRCA2 mutant metastatic pancreatic cancer
Authors: Yildirim Hasan Cagri , Ismayilov Rashad , Akyildiz Arif , Guven Deniz Can , Abdurrahimli Najmaddin , Dizdar Omer , Yalcin Suayib
Published: February 2023

Pancreatic cancer is mostly metastaticat diagnosis. BReast CAncer gene (BRCA) mutations are associated with platinum sensitivity in metastatic pancreatic cancer. However, curative surgery and complete remission are infrequent. In this report, we present a 42-year-old female patient diagnosed with BRCA-mutated pancreatic cancer with liver metastases. After 12 cycles of FOLFIRINOX, liver metastases disappeared and the patient underwent pancreaticoduodenectomy. The patient has been followed in complete remission for 5 years. To the best of our knowledge, the presented case is the longest recurrence-free survival after platinum-based therapy in metastatic pancreatic cancer with BRCA mutation. Our case emphasizes that investigating BRCA gene mutations at the time of diagnosis can be life-saving in these patients.
Circular RNA SMARCA5 inhibits cholangiocarcinoma via microRNA-95-3p/tumor necrosis factor receptor associated factor 3 axis
Authors: Wang Guangxin , Gao Xia , Sun Zhijun , He Tianyou , Huang Chaogang , Li Shouwei , Long Haocheng
Published: February 2023

Enhancing research indicatedthat circular RNA (circRNA) acted a critical part in cholangiocarcinoma (CHOL) development. This research aims to discover the role of circRNA SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 5 (SMARCA5) in CHOL bio-progression, which has been proved to be downregulated in CHOL tissues. In this study, quantitative reverse transcription polymerase chain reaction was used to reveal the level and linkage of circRNA SMARCA5, miRNA-95-3p and TNF receptor-associated factor 3 gene (TRAF3) in CHOL tissues and cancer cells. The target sites of circRNA SMARCA5 and miRNA-95-3p were forecast by Starbase, and Targetscan was conducted to forecast the potential linkage points of TRAF3 and miRNA-95-3p, and which is affirmed by double luciferase reporter assay. CCK-8 and flow cytometry assay was carried to indicate cell viability. And apoptosis-related protein was counted by caspase3 activity and Western blot assay. CircRNA SMARCA5 was downregulated in CHOL cell lines and cancer samples. Besides, over-expression of SMARCA5 inhibited cell growth and promoted apoptotic rate. Dual-luciferase reporter assays presented that miRNA-95-3p could link with circRNA SMARCA5. Moreover, miRNA-95-3p was discovered highly expressed in CHOL. Interference of miRNA-95-3p repressed cell proliferation and raised the apoptosis. Importantly, TRAF3 was validated to be a downstream of miRNA-95-3p. Strengthen of miRNA-95-3p reversed the inhibitory impact of circRNA SMARCA5-plasmid transfection, and the results of miRNA-95-3p inhibitor were reversed by si-TRAF3. CircRNA SMARCA5 is involved in CHOL development by interosculating miRNA-95-3p/TRAF3 axis and may become a novel approach for treating CHOL.
Efficacy and safety of anlotinib as maintenance therapy after induction chemotherapy in extensive-stage small-cell lung cancer
Authors: Wang Na , Zhao Lu , Zhang Dou , Kong Fanming
Published: February 2023

Anlotinib has been approved as the third-line or beyond treatment regimen for patients with extensive-stage small-cell lung cancer (ES-SCLC). However, it is indistinct whether there are survival benefits of anlotinib in the maintenance therapy of ES-SCLC. Therefore, this study aims to evaluate the efficacy and safety of anlotinib monotherapy as maintenance therapy after induction chemotherapy for patients with ES-SCLC. The median progression-free survival (mPFS) was considered to be the pivotal symbol as the primary endpoint. The median overall survival (mOS) and safety were recognized as the second endpoints. Eligible patients in stable status after first-line chemotherapy would subsequently accept oral anlotinib (12 mg/d, d1-d14, every 21 days as a course). The maintenance method was continued until disease progression or unmanageable toxicity occurred. The mPFS was 7.7 months (95% CI, 7.20–8.20 months) and the mOS was 11.0 months (95% CI, 9.19–12.82 months), respectively. The most common treatment-related adverse events were hypertension (n = 9; 64.3%), fatigue (n = 6; 42.9%), followed by decreased appetite (n = 5; 35.7%), nausea (n = 5; 35.7%), weight decrease (n = 4; 28.6%), and rash (n = 4; 28.6%). There were no patients who required dose reduction because of severe adverse events. Anlotinib achieved prospective efficacy and manageable safety in the maintenance treatment of ES-SCLC. These above outcomes demonstrated that anlotinib was a tolerable and potent maintenance treatment option after induction chemotherapy in ES-SCLC.
Acquired EML4-ALK fusion and EGFR C797S in cis mutation as resistance mechanisms to osimertinib in a non-small cell lung cancer patient with EGFR L858R/T790M
Authors: Wang Liang-Sheng , Chen Shi-Qi , Zhong Xue , Jiao Xiao-Dong , Liu Ke , Qin Bao-Dong , Wu Ying , Ling Yan , Duan Xiao-Peng , Zang Yuan-Sheng
Published: February 2023

The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) dramatically improve the clinical outcomes of non-small cell lung cancer (NSCLC) patients harboring EGFR-sensitive mutations. Despite the remarkable efficacy of first-and second-generation EGFR TKIs, disease relapse is inevitable. EGFR T790M mutation is a primary contributor to the acquired resistance to first- and second-generation EGFR TKIs. Osimertinib, which is an irreversible third-generation EGFR TKI, was designed for EGFR-activating mutations as well as the EGFR T790M mutation in patients with advanced NSCLC and has demonstrated a convincing efficacy. However, acquired resistance to osimertinib after treatment inevitably occurs. The acquired resistance mechanisms to osimertinib are highly complicated and not fully understood, encompassing EGFR-dependent as well as EGFR-independent mechanisms. Treatment approaches for patients progressing from osimertinib have not been established. We present a case of a stage IV lung adenocarcinoma patient harboring EGFR L858R, acquired T790M after treatment with first-line gefitinib. She then acquired a new EML4-ALKgene fusion after treatment with osimertinib. A combination targeted therapy of osimertinib plus alectinib was initiated, with a progression-free survival of 5 months without any serious adverse reaction. After disease progression, EGFR C797S in cis was detected with a loss of the EML4-ALK fusion by targeted next-generation sequencing. Then therapy was changed to pemetrexed combined with bevacizumab plus camrelizumab, but no obvious effect was observed. The patient had achieved an overall survival of 31 months. As far as we know, this was the first reported case that an EGFR-mutant NSCLC patient-acquired ALK fusion mediating resistance to osimertinib, and sequential EGFR C797S mutation mediating resistance to combined targeted therapy with osimertinib and alectinib. Our case shows that EML4-ALK fusion is a rare but critical resistance mechanism to osimertinib, and C797S mutation in cis may be an underlying mechanism of acquired resistance mutation in double TKIs therapy. Furthermore, molecular detection and rebiopsy play important roles in the selection of therapeutic strategies when the disease progresses.
Preliminary results of randomized phase II study of etoposide plus lobaplatin or etoposide plus cisplatin with concurrent thoracic radiotherapy in the treatment of limited-stage small cell lung cancer
Authors: Wang Mengfan , Ma Zhu , Li Qingsong , Yang Wengang , Chen Xiaxia , Geng Yichao , Luo Daxian , Hu Yinxiang , Wu Bibo , Jiang Wei , Su Shengfa , Ouyang Weiwei , Lu Bing
Published: February 2023

The purpose is to compare the clinical efficacy and toxicity of etoposide plus lobaplatin (EL) or etoposide plus cisplatin (EP) with concurrent thoracic radiotherapy during the treatment of limited-stage small cell lung cancer (LS-SCLC). Forty-two patients with LS-SCLC were randomly divided into EL (n = 19) or EP (n = 23) regimens combined with thoracic intensity-modulated radiotherapy. The primary endpoint was 1-year progression-free survival (PFS) rate. The 1-, 2-, and 3-year PFS rates in the EL and EP cohorts were 50.8, 38.1, and 12.7%; and 56.5, 43.5, and 29.0%, respectively (P = 0.527), whereas the 1-, 2-, and 3-year overall survival (OS) rates were 72.2, 52.5, and 43.8%; and 73.9, 48.4, and 48.4%, respectively (P = 0.923). The hematological toxicities were similar in two cohorts. However, gastrointestinal reactions were more severe in the EP group. The incidence of nausea and vomiting in EL and EP cohorts were 31.6% vs. 73.9% (P = 0.006) and 20.1% vs. 60.9% (P = 0.009), respectively. The two cohorts did not show ≥grade 4 radiation esophagitis and ≥grade 3 radiation pneumonitis. The incidence of acute radiation esophagitis in EL group was lower (P = 0.038), both groups showed a similar incidence of radiation pneumonitis (P = 1.000). EL or EP chemotherapy with concurrent thoracic radiotherapy showed similar PFS and OS. The EL group showed milder gastrointestinal toxicity and radiation esophagitis. Radiation pneumonitis and hematological toxicity were similar in the two regimens, which can be tolerated by patients.
Circ_0091537 promotes gefitinib chemoresistance in non-small cell lung cancer by mediating the miR-520h/YAP1 network
Authors: Qu Richu , Ma Jinyu
Published: February 2023

Chemoresistance is the leading cause of poor outcomes of non-small cell lung cancer (NSCLC). Circular RNA (circRNA) plays a vital role in NSCLC resistance progression. Our study aimed to uncover the role of circRNA PDZ domain containing 8 (circ_0091537) in NSCLC with gefitinib resistance. The expression of circ_0091537, microRNA-520h (miR-520h), and Yes-associated protein 1 (YAP1) mRNA were detected using quantitative real-time PCR. Cell viability and cell proliferation were assessed by MTT assay and colony formation assay. Colony formation ability was detected by colony formation assay. Cell cycle distribution and cell apoptosis were determined by flow cytometry assay. Cell migration and cell invasion were detected by transwell assay. The potential relationship between miR-520h and circ_0091537 or YAP1 was verified by dual-luciferase reporter assay. Tumor formation assay in nude mice was performed to test the role of circ_0091537 in vivo. Circ_0091537 and YAP1 were upregulated, while miR-520h was downregulated in gefitinib-resistant NSCLC cells. Circ_0091537 knockdown inhibited gefitinib resistance in NSCLC cells and then inhibited NSCLC cell growth, migration, and invasion. MiR-520h was a target of circ_0091537, and miR-520h inhibition reversed the effects of circ_0091537 knockdown. Moreover, YAP1 was a target of miR-520h, and circ_0091537 competitively combined with miR-520h to enrich YAP1 expression. MiR-520h restoration impaired gefitinib resistance and suppressed NSCLC cell proliferation, migration, and invasion by repressing YAP1. Circ_0091537 overexpression weakened gefitinib sensitivity in vivo to promote tumor growth. Circ_0091537 strengthens gefitinib chemoresistance to promote NSCLC progression by mediating the miR-520h/YAP1 network, suggesting that circ_0091537 may be a key indicator in resistance to treatment of NSCLC.
Factors Influencing Training Transfer Among Infection Control Professionals Participating in Infectious Disease Training
Authors: Park Myonghwa , Dlamini Bonkhe Brian , Lee Hyuneung , Jeong Miri , Giap Thi-Thanh-Tinh , Jung Jihye , Bui Linh Khanh , Kim Jahyeon , Kim Jinju
Published: February 2023

Introduction:

Infectious disease training is considered vital in health care systems to improve knowledge, skills, and work performance of infection control professionals. However, the extent to which trainees effectively transfer knowledge, skills, and attitudes that they acquire through training has received little attention. This study aimed to identify factors influencing training transfer of infection control professionals receiving infectious disease training.

Methods:

This cross-sectional study selected infection control professionals who completed an infectious disease training program provided by Korea Human Resources Development Institute for Health and Welfare. A self-reported questionnaire was used to collect data on sociodemographic variables, trainee characteristics, training design, work environment, and training transfer. Data analysis was conducted using SPSS (version 26.0).

Results:

The mean age of the 139 participants was 41.45 years, and 77% were female participants. Regression analysis indicated that the following factors significantly influenced the training transfer of infection control professionals and thereby decrease morbidity and mortality: for trainee characteristics, transfer experience (β = 0.205, P = 0.012) and motivation to learn (β = 0.196, P =0.016); for training design, learning objectives (β = 0.269, P = 0.021), goals (β = 0.356, P =0.023), and methods (β = 0.365, P = 0.020); and for the work environment, supervisor support (β = 0.275, P =0.024) and colleague support (β = 0.474, P = 0.022).

Conclusion:

Future training programs for improving training transfer should focus more on strategies to improve the motivation for training transfer. Trainees should be guided on (1) how to apply training knowledge in specific clinical contexts to improve their performance and (2) potential methods to get support from their supervisors and colleagues during training.
Can the Electronic Health Record Predict Risk of Falls in Hospitalized Patients by Using Artificial Intelligence? A Meta-analysis
Authors: Hsu Yen , Kao Yung-Shuo
Published: February 2023

Because of an aging population worldwide, the increasing prevalence of falls and their consequent injuries are becoming a safety, health, and social-care issue among elderly people. We conducted a meta-analysis to investigate the benchmark of prediction power when using the EHR with artificial intelligence to predict risk of falls in hospitalized patients. The CHARMS guideline was used in this meta-analysis. We searched PubMed, Cochrane, and EMBASE. The pooled sensitivity and specificity were calculated, and the summary receiver operating curve was formed to investigate the predictive power of artificial intelligence models. The PROBAST table was used to assess the quality of the selected studies. A total of 132 846 patients were included in this meta-analysis. The pooled area under the curve of the collected research was estimated to be 0.78. The pooled sensitivity was 0.63 (95% confidence interval, 0.52–0.72), whereas the pooled specificity was 0.82 (95% confidence interval, 0.73–0.88). The quality of our selected studies was high, with most of them being evaluated with low risk of bias and low concern for applicability. Our study demonstrates that using the EHR with artificial intelligence to predict the risk of falls among hospitalized patients is feasible. Future clinical applications are anticipated.
A Comparison of Hypothesis-Driven and Data-Driven Research
Authors: Dreisbach Caitlin , Maki Katherine
Published: February 2023

Data science, bioinformatics, and machine learning are the advent and progression of the fourth paradigm of exploratory science. The need for human-supported algorithms to capture patterns in big data is at the center of personalized healthcare and directly related to translational research. This paper argues that hypothesis-driven and data-driven research work together to inform the research process. At the core of these approaches are theoretical underpinnings that drive progress in the field. Here, we present several exemplars of research on the gut-brain axis that outline the innate values and challenges of these approaches. As nurses are trained to integrate multiple body systems to inform holistic human health promotion and disease prevention, nurses and nurse scientists serve an important role as mediators between this advancing technology and the patients. At the center of person-knowing, nurses need to be aware of the data revolution and use their unique skills to supplement the data science cycle from data to knowledge to insight.
Interdisciplinary Collaboration Among Nursing and Computer Science to Refine a Pharmacogenetics Clinical Decision Support Tool Via Mobile Application
Authors: Dodson Crystal , Layman Lucas
Published: February 2023

In previous work, a prototype clinical decision support mobile application was created that accepts a patient's genomic profile information and provides information and rationale for the prescription of certain oncology medications. The response to the instrument was overwhelmingly positive by healthcare providers in the oncology field who tested the instrument. This article reports on the interdisciplinary collaboration among nursing and computer science to redesign and reimplement a new version of the instrument with expanded functionality and improved usability. This article describes the functionality, usability considerations, and usability evaluation of the instrument over three versions. The current version is Web-based and responsive to different screen sizes (desktop, tablet, mobile), features improved usability, and expands the number of gene-drug recommendations provided based on Clinical Pharmacogenetics Implementation Consortium dosing guidelines. This project represents a successful new collaboration between the nursing and computer science disciplines.
A Virtual Assistant in Vaccine Pharmacovigilance
Authors: Cavalcanti Andréia Roque de Souza , do Nascimento José William Araújo , Roque Geicianfran da Silva Lima , de Souza Rafael Roque , Queiroz Sérgio Ricardo de Melo , Correa João Antônio
Published: February 2023

This article describes the process of developing and validating a virtual assistant to perform vaccine pharmacovigilance. We performed a pilot study with a panel of 22 healthcare professionals who performed content validation of the virtual assistant prototype. Usability was tested with 126 users, using the System Usability Scale. The data analysis was performed by the agreement rate and content validity index, and the κ test was used to verify the agreement between the evaluators. The content domains of the virtual assistant achieved excellent suitability, relevance, and representativeness criteria, all greater than 86%; the content validity index ranged from 0.81 to 0.98, with an average of 0.90 and an interrater reliability index of 1.00. There was excellent interrater agreement (average κ value, 0.76). The total usability score among users was 80.1, ranging from 78.2 in group 1 (users without reactions to vaccines) to 82.1 in group 2 (users with reactions) (P = .002). The virtual assistant for vaccine pharmacovigilance obtained a satisfactory level of content validity and usability, giving greater credibility to the claim that this device provides greater surveillance and safety for patients.
Impaired autophagy activity-induced abnormal differentiation of bone marrow stem cells is related to adolescent idiopathic scoliosis osteopenia
Authors: Zhang Hongqi , Yang Guanteng , Li Jiong , Xiao Lige , Guo Chaofeng , Wang Yuxiang
Published: February 2023

Background:

Osteopenia has been well documented in adolescent idiopathic scoliosis (AIS). Bone marrow stem cells (BMSCs) are a crucial regulator of bone homeostasis. Our previous study revealed a decreased osteogenic ability of BMSCs in AIS-related osteopenia, but the underlying mechanism of this phenomenon remains unclear.

Method:

A total of 22 AIS patients and 18 age-matched controls were recruited for this study. Anthropometry and bone mass were measured in all participants. Bone marrow blood was collected for BMSC isolation and culture. Osteogenic and adipogenic induction were performed to observe the differences in the differentiation of BMSCs between the AIS-related osteopenia group and the control group. Furthermore, a total RNA was extracted from isolated BMSCs to perform RNA sequencing and subsequent analysis.

Results:

A lower osteogenic capacity and increased adipogenic capacity of BMSCs in AIS-related osteopenia were revealed. Differences in mRNA expression levels between the AIS-related osteopenia group and the control group were identified, including differences in the expression of LRRC17, DCLK1, PCDH7, TSPAN5, NHSL2, and CPT1B. Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed several biological processes involved in the regulation of autophagy and mitophagy. The Western blotting results of autophagy markers in BMSCs suggested impaired autophagic activity in BMSCs in the AIS-related osteopenia group.

Conclusion:

Our study revealed that BMSCs from AIS-related osteopenia patients have lower autophagic activity, which may be related to the lower osteogenic capacity and higher adipogenic capacity of BMSCs and consequently lead to the lower bone mass in AIS patients.
Use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers increases the risk of postoperative acute kidney injury after elective endovascular abdominal aortic aneurysm repair
Authors: Xiang Yuwei , Liu Yang , Zhao Jichun , Huang Bin , Wu Zhoupeng , Chen Xiyang
Published: February 2023

Background:

Endovascular abdominal aortic aneurysm repair (EVAR) is the major treatment for abdominal aortic aneurysm (AAA); however, EVAR still carries a considerable risk of acute kidney injury (AKI). The present study aimed to investigate the risk factors for AKI after elective EVAR procedures.

Methods:

This was a retrospective observational study. Eligible patients who underwent EVAR from September 2011 to March 2019 in West China Hospital were included. The primary outcome was the occurrence of AKI within two days after EVAR, which was defined by the Kidney Disease Improving Global Outcomes Clinical Practice Guideline. Demographics, comorbidities, medications, laboratory tests, anatomical parameters of AAA, and relative operative details were collected as variables. Univariable and multivariable logistic regression analyses were applied to identify the risk factors among variables, and covariate interactions were further assessed.

Results:

A total of 679 eligible patients were included. The incidence of postoperative AKI was 8.2% (56/679) in the whole cohort, and it was associated with a lower 5-year survival rate (63.5% vs. 80.9%; χ2 = 4.10; P = 0.043). The multivariable logistic regression showed that chronic kidney disease (OR, 5.06; 95% CI: 1.43–17.95; P = 0.012), angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) (OR, 2.60; 95% CI: 1.17–5.76; P = 0.019), and short neck (OR, 2.85; 95% CI: 1.08–7.52; P = 0.035) were independent risk factors for postoperative AKI. In the covariate interaction analysis, the effect of ACEIs/ARBs use on postoperative AKI was similar across all subgroups (P > 0.05), thereby suggesting a robust effect of ACEIs/ARBs use in all patients undergoing elective endovascular abdominal aortic aneurysm repair.

Conclusions:

Postoperative AKI was associated with lower survival rate, and the use of ACEIs/ARBs was the only adjustable independent risk factor. Clinicians should consider withdrawing ACEIs/ARBs in high-risk patients undergoing elective endovascular abdominal aortic aneurysm repair to prevent postoperative AKI.
L-Fucose inhibits the progression of cholangiocarcinoma by causing microRNA-200b overexpression
Authors: Zhu Biqiang , Zheng Jingjing , Hong Gaichao , Bai Tao , Qian Wei , Liu Jinsong , Hou Xiaohua
Published: February 2023

Background:

Cholangiocarcinoma (CCA) is a malignant biliary tract tumor with an extremely poor prognosis. There is an urgent demand to explore novel therapeutic strategies. L-fucose has been confirmed to participate in anti-inflammation and antitumor activities. However, the effect of L-fucose on the progression of CCA has not been well investigated. This study aimed to determine whether L-fucose induced the inhibition of CCA and its possible mechanism.

Methods:

The anti-growth activity was determined using Cell Counting Kit-8 assay, colony formation assays, Annexin V-fluorescein isothiocyanate/propidium iodide (FITC/PI) assay, and cell cycle analysis. The anti-metastasis activity was determined by wound healing, transwell, and invasion assays. The anti-angiogenesis activity was determined by tube formation and transwell assays. MicroRNAs that may be involved in the L-fucose-induced CCA inhibition was analyzed using bioinformatics methods. The preclinical therapeutic efficacy was mainly estimated by ultrasound in xenograft nude mouse models. Differences were analyzed via Student's t test or one-way analysis of variance.

Results:

L-Fucose induced apoptosis and G0/G1 cell cycle arrest, inhibited cell epithelial-mesenchymal transition of CCA cells, and additionally inhibited tube formation of human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner, leading to a decrease in cell proliferation, metastasis, and angiogenesis. Mechanistically, L-fucose induced microRNA-200b (miR-200b) upregulation, and mitogen-activated protein kinase 7 (MAPK7) downregulation was found to be targeted by miR-200b, with decreased cell proliferation and metastasis. Additionally, phosphorylated signal transducer and activator of transcription 3 was found to be downregulated after L-fucose treatment. Finally, in vivo experiments in CCA xenograft models also confirmed the antitumor properties of L-fucose.

Conclusion:

L-Fucose inhibited the progression of CCA via the miR-200b/MAPK7 and signal transducer and activator of transcription 3 signaling pathways.
Ideal cardiovascular health and mortality: pooled results of three prospective cohorts in Chinese adults
Authors: Zhang Yanbo , Yu Canqing , Chen Shuohua , Tu Zhouzheng , Zheng Mengyi , Lv Jun , Wang Guodong , Liu Yan , Yu Jiaxin , Guo Yu , Yang Ling , Chen Yiping , Guo Kunquan , Yang Kun , Yang Handong , Zhou Yanfeng , Jiang Yiwen , Zhang Xiaomin , He Meian , Liu Gang , Chen Zhengming , Wu Tangchun , Wu Shouling , Li Liming , Pan An
Published: February 2023

Background:

Evidence on the relations of the American Heart Association's ideal cardiovascular health (ICH) with mortality in Asians is sparse, and the interaction between behavioral and medical metrics remained unclear. We aimed to fill the gaps.

Methods:

A total of 198,164 participants without cancer and cardiovascular disease (CVD) were included from the China Kadoorie Biobank study (2004–2018), Dongfeng-Tongji cohort (2008–2018), and Kailuan study (2006–2019). Four behaviors (i.e., smoking, physical activity, diet, body mass index) and three medical factors (i.e., blood pressure, blood glucose, and blood lipid) were classified into poor, intermediate, and ideal levels (0, 1, and 2 points), which constituted 8-point behavioral, 6-point medical, and 14-point ICH scores. Results of Cox regression from three cohorts were pooled using random-effects models of meta-analysis.

Results:

During about 2 million person-years, 20,176 deaths were recorded. After controlling for demographic characteristics and alcohol drinking, hazard ratios (95% confidence intervals) comparing ICH scores of 10–14 vs. 0–6 were 0.52 (0.41–0.67), 0.44 (0.37–0.53), 0.54 (0.45–0.66), and 0.86 (0.64–1.14) for all-cause, CVD, respiratory, and cancer mortality. A higher behavioral or medical score was independently associated with lower all-cause and CVD mortality among the total population and populations with different levels of behavioral or medical health equally, and no interaction was observed.

Conclusions:

ICH was associated with lower all-cause, CVD, and respiratory mortality among Chinese adults. Both behavioral and medical health should be improved to prevent premature deaths.
Effects of anesthetic depth on postoperative pain and delirium: a meta-analysis of randomized controlled trials with trial sequential analysis
Authors: Long Yuqin , Feng Xiaomei , Liu Hong , Shan Xisheng , Ji Fuhai , Peng Ke
Published: February 2023

Background:

Whether anesthetic depth affects postoperative outcomes remains controversial. This meta-analysis aimed to evaluate the effects of deep vs. light anesthesia on postoperative pain, cognitive function, recovery from anesthesia, complications, and mortality.

Methods:

PubMed, EMBASE, and Cochrane CENTRAL databases were searched until January 2022 for randomized controlled trials comparing deep and light anesthesia in adult surgical patients. The co-primary outcomes were postoperative pain and delirium (assessed using the confusion assessment method). We conducted a meta-analysis using a random-effects model. We assessed publication bias using the Begg's rank correlation test and Egger's linear regression. We evaluated the evidence using the trial sequential analysis and Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. We conducted subgroup analyses for pain scores at different postoperative time points and delirium according to cardiac or non-cardiac surgery.

Results:

A total of 26 trials with 10,743 patients were included. Deep anesthesia compared with light anesthesia (a mean difference in bispectral index of −12 to −11) was associated with lower pain scores at rest at 0 to 1 h postoperatively (weighted mean difference = −0.72, 95% confidence interval [CI] = −1.25 to −0.18, P = 0.009; moderate-quality evidence) and an increased incidence of postoperative delirium (24.95% vs. 15.92%; risk ratio = 1.57, 95% CI = 1.28–1.91, P < 0.0001; high-quality evidence). No publication bias was detected. For the exploratory secondary outcomes, deep anesthesia was associated with prolonged postoperative recovery, without affecting neurocognitive outcomes, major complications, or mortality. In the subgroup analyses, the deep anesthesia group had lower pain scores at rest and on movement during 24 h postoperatively, without statistically significant subgroup differences, and deep anesthesia was associated with an increased incidence of delirium after non-cardiac and cardiac surgeries, without statistically significant subgroup differences.

Conclusions:

Deep anesthesia reduced early postoperative pain but increased postoperative delirium. The current evidence does not support the use of deep anesthesia in clinical practice.
Anatomical morphology of the aortic valve in Chinese aortic stenosis patients and clinical results after downsize strategy of transcatheter aortic valve replacement
Authors: Niu Guannan , Ali Walid Ben , Wang Moyang , Jilaihawi Hasan , Zhang Haitong , Zhang Qian , Ye Yunqing , Liu Xinmin , Yao Jing , Zhao Qinghao , Wang Yubin , Zhou Zheng , Zhang Lizhi , Ren Xinshuang , An Yunqiang , Lu Bin , Modine Thomas , Wu Yongjian , Song Guangyuan
Published: February 2023

Background:

The study aimed to describe the aortic valve morphology in Chinese patients underwent transcatheter aortic valve replacement (TAVR) for symptomatic severe aortic stenosis (AS), and the impact of sizing strategies and related procedural outcomes.

Methods:

Patients with severe AS who underwent TAVR were consecutively enrolled from 2012 to 2019. The anatomy and morphology of the aortic root were assessed. “Downsize” strategy was preformed when patients had complex morphology. The clinical outcomes of patients who performed downsize strategy were compared with those received annular sizing strategy. The primary outcome was device success rate, and secondary outcomes included Valve Academic Research Consortium-3 clinical outcomes variables based on 1-year follow-up.

Results:

A total of 293 patients were enrolled. Among them, 95 patients (32.4%) had bicuspid aortic valve. The calcium volume (Hounsfield Unit-850) of aortic root was 449.90 (243.15–782.15) mm3. Calcium is distributed mostly on the leaflet level. Downsize strategy was performed in 204 patients (69.6%). Compared with the patients who performed annular sizing strategy, those received downsize strategy achieved a similar device success rate (82.0% [73] vs. 83.3% [170], P = 0.79). Aortic valve gradients (downsize strategy group vs. annular sizing group, 11.28 mmHg vs. 11.88 mmHg, P = 0.64) and percentages of patients with moderate or severe paravalvular regurgitation 2.0% (4/204) vs. 4.5% (4/89), P = 0.21) were similar in the two groups at 30 days after TAVR. These echocardiographic results were sustainable for one year.

Conclusions:

Chinese TAVR patients have more prevalent bicuspid morphology and large calcium volume of aortic root. Calcium is distributed mostly on the leaflet level. Compare with annular sizing strategy, downsize strategy provided a non-inferior device success rate and transcatheter heart valve hemodynamic performance in self-expanding TAVR procedure.
New technique for in-continuity axillary and supraclavicular lymphadenectomy for advanced metastatic melanoma using intraoperative image guidance: a case report
Authors: Gajanan Kantappa , Daga Karan , Mullan Damian , Kosutic Damir
Published: February 2023

Simultaneousinvolvement of the supraclavicular and axillary lymphatic basins is known to occur in metastatic skin cancers. We present the case of a 35-year-old male with metastatic melanoma present in the right neck and axillary lymph nodes. He underwent a combined, in-continuity dissection of both basins using intraoperative ultrasound to ensure full clearance of lymph nodes from the cervicoaxillary canal, which otherwise would have been impossible to achieve without clavicle osteotomy. This allowed us to avoid a division of the clavicle and related morbidity. Postoperative imaging confirmed no residual disease, and no local recurrence subsequently. We conclude that intraoperative use of ultrasound can help guide surgeons trying to achieve clearance of metastatic disease in anatomically complex regions, avoiding unnecessary morbidity.
Pembrolizumab-induced plaque psoriasis successfully treated with risankizumab in a patient with stage IV cutaneous melanoma
Authors: Gargiulo Luigi , Ibba Luciano , Valenti Mario , Costanzo Antonio , Narcisi Alessandra
Published: February 2023

Immune checkpoint inhibitors, such as pembrolizumab and nivolumab, are monoclonal antibodies that block programmed cell death 1 (PD-1) expressed on activated CD8+ T cells and play a crucial role in the treatment of advanced melanoma. With the wide adoption of these therapies, a range of cutaneous adverse effects has been reported, such as flares of plaque psoriasis, but no specific guidelines regarding the treatment are available. We present the case of a 28-year-old male diagnosed with stage IV non-BRAFV600E mutated melanoma in 2014. After the surgery and the failure of ipilimumab and IL-2, he started immunotherapy with pembrolizumab. One month after the start of the therapy, he came to our department showing a severe flare of plaque psoriasis with a body surface area of 40% and a Psoriasis Area and Severity Index (PASI) of 28. Given the severity of the clinical picture and the contraindications to conventional systemic therapy, we decided to start biological treatment with risankizumab, an anti-IL-23 inhibitor. After just the induction phase, he showed almost skin clearance obtaining a reduction of more than 90% of the baseline PASI. Our patient’s rapid response to risankizumab enabled us to continue immunotherapy with pembrolizumab. The recognition of cutaneous signs of toxicity related to such drugs for advanced melanoma is of primary importance to start the correct treatment and continue the immunotherapy when possible.
Early Mechanical Circulatory Support for Cardiogenic Shock
Authors: Upadhrasta Sireesha , Museedi Abdulrahman , Thannoun Tariq , Chaanine Antoine H. , Le Jemtel Thierry H.
Published: February 2023

Reversal of cardiogenic shock depends on its early recognition and prompt initiation of therapy. Recognition of the clinical and hemodynamic deterioration that precedes cardiogenic shock is a crucial step in its early detection. Treatment of pre-cardiogenic shock is chiefly pharmacologic with intravenous administration of pressor, inotropic, and loop diuretic agents. Failure to reverse the preshock state with pharmacotherapy entails progression to cardiogenic shock and the need for prompt mechanical circulatory support with membrane oxygenation and possibly left ventricular decompression.
Long-term Patient and Health Service Outcomes of Ablation and Antiarrhythmic Drugs in Atrial Fibrillation: A Comparative Systematic Review
Authors: Kularatna Sanjeewa , Sharma Pakhi , Senanayake Sameera , McCreanor Victoria , Hewage Sumudu , Ngo Linh , Ranasinghe Isuru , Martin Paul , Davis Jason , Walters Tomos , McPhail Steven , Parsonage William
Published: February 2023

Atrial fibrillation (AF) is a prevalent problem worldwide and a common cause of hospitalization, poor quality of life, and increased mortality. Although several treatments are used, the use of ablation and antiarrhythmic drug therapy has increased in the past decade. However, debate continues on the most suitable option for heart rhythm control in patients. Previous studies have largely focused on short-term outcome effects of these treatments. This systematic review aims to determine the effect of ablation compared to antiarrhythmic drugs for AF on long-term patient and health service outcomes of mortality, hospitalization, and quality of life. Three databases were systematically searched—studies were included if they reported long-term outcomes of more than 12 months comparing the 2 treatments. Title and abstract screening and subsequent full-text screening was done by 2 reviewers. Data were extracted from the final studies identified. The details of the search were recorded according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses report. A total of 2224 records were identified. After removing duplicates and screening the titles and abstracts, 68 records required full-text screening. Finally, 12 papers were included in the analysis. Eight studies reported mortality indicating ablation was superior, 2 studies reported hospitalization with opposing outcomes, and 5 quality of life studies indicating ablation was a better treatment. In studies assessing long-term outcomes, beyond 12 months, following ablation or rhythm control drugs for AF, most found a lower risk of death and greater improvement in quality of life in the ablation group.
Prevention of Atrial Fibrillation After Cardiac Surgery: A Review of Literature and Comparison of Different Treatment Modalities
Authors: Halonen Jari , Kärkkäinen Jussi , Jäntti Helena , Martikainen Tero , Valtola Antti , Ellam Sten , Väliaho Eemu , Santala Elmeri , Räsänen Jenni , Juutilainen Auni , Mahlamäki Visa , Vasankari Sini , Vasankari Tommi , Hartikainen Juha
Published: February 2023

Atrial fibrillation is the most common arrhythmia to occur after cardiac surgery, with an incidence of 10% to 50%. It is associated with postoperative complications including increased risk of stroke, prolonged hospital stays and increased costs. Despite new insights into the mechanisms of atrial fibrillation, no specific etiologic factor has been identified as the sole perpetrator of the arrhythmia. Current evidence suggests that the pathophysiology of atrial fibrillation in general, as well as after cardiac surgery, is multifactorial. Studies have also shown that new-onset postoperative atrial fibrillation following cardiac surgery is associated with a higher risk of short-term and long-term mortality. Furthermore, it has been demonstrated that prophylactic medical therapy decreases the incidence of postoperative atrial fibrillation after cardiac surgery. Of note, the incidence of postoperative atrial fibrillation has not changed during the last decades despite the numerous preventive strategies and operative techniques proposed, although the perioperative and postoperative care of cardiac patients as such has improved.
Malignant Melanoma Arising in a Prolific Nevus Sebaceus With Colonization of Trichoblastoma
Authors: Kimball Kelly M. , Craig Elise , Barrick Carl , Usmani Arif
Published: February 2023

Nevus sebaceus (NS) is a cutaneous hamartoma typically found on the head and neck, with a prevalence of 0.3% in newborns. Most NS are quiescent; however, benign and malignant lesions have been reported to arise within these nevi. Malignant transformation is not common but mainly includes basal cell carcinoma and squamous cell carcinoma. Malignant melanoma arising in NS is exceedingly rare, with only 2 previously documented cases. In this article, we report the first case of malignant melanoma arising in a NS in a 68-year-old man in the United States.