bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a metric Healthy Eating Index-2015 and comparison with the Healthy Eating Index-2015 for the evaluation of dietary quality
Authors: Kohl Jan , Hohberg Vivien , Hauff Pascal , Lang Céline , Faude Oliver , Gollhofer Albert , König Daniel
Published: August 2022

Background

Diet quality indices can provide important information about relationships between diet and health independent of energy balance. The Healthy Eating Index-2015 (HEI-2015) is widely used and has been extensively evaluated. However, due to imperial units the HEI-2015 is difficult to apply in countries with metric systems. Our objective was to develop a metric version of the HEI-2015 and compare it to the original. The metric Healthy Eating Index-2015 (mHEI-2015) is intended to simplify the application of a dietary quality index in countries using the metric system.

Methods

We developed a metric database logic following the methodology of the HEI-2015, which allows the application to metric databases and was applied to Food Patterns Equivalents Database (FPED). The HEI-2015 was calculated for the National Health and Nutrition Examination Survey (NHANES) 2017-2018 and the scoring standards for each component of the mHEI-2015 was calibrated against it. For the assessment of agreement between indices, HEI-2015 and mHEI-2015 were calculated for NHANES 2015-2016 and a Bland–Altman plot was created.

Results

Healthy Eating Index-2015 and mHEI-2015 for the NHANES 2015-2016 averaged 52.5 ± 13.5 and 52.6 ± 13.2, respectively. The total scores as well as component scores of the indices were strongly correlated. The Bland–Altman plot revealed a high agreement of the total scores. An illustrated analysis of six different menu plans showed only minor differences between the HEI-2015 and mHEI-2015 component scores.

Conclusion

The mHEI-2015 allows for superior analysis of metric dietary data to better examine the relationship between chronic diseases and diet. The streamlined metric methodology enables straightforward application to metric food databases and thus the development of country-specific indices.
Hapten designs based on aldicarb for the development of a colloidal gold immunochromatographic quantitative test strip
Authors: Shen Hong , Wan Yuping , Wu Xiaosheng , Zhang Yu , Li Jingwen , Cui Tingting , Sun Han , Cui Haifeng , He Kailun , Hui Guangpeng , Chen Xu , Liu Guoqiang , Du Meihong
Published: August 2022

The common carbamate insecticide aldicarb is considered one of the most acutely toxic pesticides. Herein, rational design was used to synthesize two haptens with spacers of different carbon chain lengths. The haptens were then used to immunize mice. The antibodies obtained were evaluated systematically, and a colloidal gold immunochromatographic strip was developed based on an anti-aldicarb monoclonal antibody. The 50% inhibition concentration and linear range of anti-aldicarb monoclonal antibody immunized with Hapten 1 were 0.432 ng/mL and 0.106–1.757 ng/mL, respectively. The cross-reactivities for analogs of aldicarb were all <1%. The limit of detection of the colloidal gold immunochromatographic strip was 30 μg/kg, and the average recoveries of aldicarb ranged from 80.4 to 110.5% in spiked samples. In the analysis of spiked samples, the test strip could accurately identify positive samples detected by the instrumental method in the GB 23200.112-2018 standard but produced some false positives for negative samples. This assay provides a rapid and accurate preliminary screening method for the determination of aldicarb in agricultural products and environments.
Association of dietary and nutrient patterns with systemic inflammation in community dwelling adults
Authors: Wang Yoko Brigitte , Page Amanda J. , Gill Tiffany K. , Melaku Yohannes Adama
Published: August 2022

Purpose

Evidence investigating associations between dietary and nutrient patterns and inflammatory biomarkers is inconsistent and scarce. Therefore, we aimed to determine the association of dietary and nutrient patterns with inflammation.

Methods

Overall, 1,792 participants from the North-West Adelaide Health Study were included in this cross-sectional study. We derived dietary and nutrient patterns from food frequency questionnaire data using principal component analysis. Multivariable ordinal logistic regression determined the association between dietary and nutrient patterns and the grade of inflammation (normal, moderate, and severe) based on C-reactive protein (CRP) values. Subgroup analyses were stratified by gender, obesity and metabolic health status.

Results

In the fully adjusted model, a plant-sourced nutrient pattern (NP) was strongly associated with a lower grade of inflammation in men (ORQ5vsQ1 = 0.59, 95% CI: 0.38–0.93, p-trend = 0.08), obesity (ORQ5vsQ1 = 0.43; 95% CI: 0.24–0.77, p-trend = 0.03) and metabolically unhealthy obesity (ORQ5vsQ1 = 0.24; 95% CI: 0.11–0.52, p-trend = 0.01). A mixed NP was positively associated with higher grade of inflammation (ORQ5vsQ1 = 1.35; 95% CI: 0.99–1.84, p-trend = 0.03) in all participants. A prudent dietary pattern was inversely associated with a lower grade of inflammation (ORQ5vsQ1 = 0.72, 95% CI: 0.52–1.01, p-trend = 0.14). In contrast, a western dietary pattern and animal-sourced NP were associated with a higher grade of inflammation in the all participants although BMI attenuated the magnitude of association (ORQ5vsQ1 = 0.83, 95% CI: 0.55–1.25; and ORQ5vsQ1 = 0.94, 95% CI: 0.63–1.39, respectively) in the fully adjusted model.

Conclusion

A plant-sourced NP was independently associated with lower inflammation. The association was stronger in men, and those classified as obese and metabolically unhealthy obese. Increasing consumption of plant-based foods may mitigate obesity-induced inflammation and its consequences.
Lentinan-functionalized selenium nanoparticles induce apoptosis and cell cycle arrest in human colon carcinoma HCT-116 cells
Authors: Gao Xiong , Yao Yanting , Chen Xujie , Lin Xiaorong , Yang Xiaobing , Ho Chi-Tang , Li Bin , Chen Zhongzheng
Published: August 2022

Selenium nanoparticles (SeNPs) have gained extensive attention for their excellent biological activity and low toxicity. However, SeNPs are extremely liable to aggregate into non-bioactive or gray elemental selenium, which limits their application in the biomedicine field. This study aimed to prepare stable SeNPs by using lentinan (LNT) as a template and evaluate its anti-colon cancer activity. The average particle diameter of obtained lentinan-selenium nanoparticles (LNT-SeNPs) was approximately 59 nm and presented zero-valent, amorphous, and spherical structures. The monodisperse SeNPs were stabilized by LNT through hydrogen bonding interactions. LNT-SeNPs solution remained highly stable at 4°C for at least 8 weeks. The stability of LNT-SeNPs solution sharply decreased under high temperature and strong acidic conditions. LNT-SeNPs showed no obvious cytotoxic effect on normal cells (IEC-6) but significantly inhibited the proliferation of five colon cancer cells (HCT-116, HT-29, Caco-2, SW620, and CT26). Among them, LNT-SeNPs exhibited the highest sensitivity toward HCT-116 cells with an IC50 value of 7.65 μM. Also, LNT-SeNPs displayed better cancer cell selectivity than sodium selenite and selenomethionine. Moreover, LNT-SeNPs promoted apoptosis of HCT-116 cells through activating mitochondria-mediated apoptotic pathway. Meanwhile, LNT-SeNPs induced cell cycle arrest at G0/G1 phase in HCT-116 cells via modulation of cell cycle regulatory proteins. The results of this study indicated that LNT-SeNPs possessed strong potential application in the treatment of colorectal cancer (CRC).
COVID-19 vaccination in advanced skin cancer patients receiving systemic anticancer treatment: A prospective singlecenter study investigating seroconversion rates
Authors: Lodde Georg C. , Fiedler Melanie , Dittmer Ulf , Placke Jan-Malte , Jansen Philipp , Becker Jürgen C. , Zimmer Lisa , Livingstone Elisabeth , Schadendorf Dirk , Sondermann Wiebke , Ugurel Selma
Published: August 2022

Background

COVID-19 vaccination reduces risk of SARS-CoV-2 infection, COVID-19 severity and death. However, the rate of seroconversion after COVID-19 vaccination in cancer patients requiring systemic anticancer treatment is poorly investigated. The aim of the present study was to determine the rate of seroconversion after COVID-19 vaccination in advanced skin cancer patients under active systemic anticancer treatment.

Methods

This prospective single-center study of a consecutive sample of advanced skin cancer patients was performed from May 2020 until October 2021. Inclusion criteria were systemic treatment for advanced skin cancer, known COVID-19 vaccination status, repetitive anti-SARS-CoV-2-S IgG serum quantification and first and second COVID-19 vaccination. Primary outcome was the rate of anti-SARS-CoV-2-S IgG seroconversion after complete COVID-19 vaccination.

Results

Of 60 patients with advanced skin cancers, 52 patients (86.7%) received immune checkpoint inhibition (ICI), seven (11.7%) targeted agents (TT), one (1.7%) chemotherapy. Median follow-up time was 12.7 months. During study progress ten patients had died from skin cancer prior to vaccination completion, six patients were lost to follow-up and three patients had refused vaccination. 41 patients completed COVID-19 vaccination with two doses and known serological status. Of those, serum testing revealed n=3 patients (7.3%) as anti-SARS-CoV-2-S IgG positive prior to vaccination, n=32 patients (78.0%) showed a seroconversion, n=6 patients (14.6%) did not achieve a seroconversion. Patients failing serological response were immunocompromised due to concomitant hematological malignancy, previous chemotherapy or autoimmune disease requiring immunosuppressive comedications. Immunosuppressive comedication due to severe adverse events of ICI therapy did not impair seroconversion following COVID-19 vaccination. Of 41 completely vaccinated patients, 35 (85.4%) were under treatment with ICI, five (12.2%) with TT, and one (2.4%) with chemotherapy. 27 patients (65.9%) were treated non adjuvantly. Of these patients, 13 patients had achieved objective response (complete/partial response) as best tumor response (48.2%).

Conclusion and relevance

Rate of anti-SARS-CoV-2-S IgG seroconversion in advanced skin cancer patients under systemic anticancer treatment after complete COVID-19 vaccination is comparable to other cancer entities. An impaired serological response was observed in patients who were immunocompromised due to concomitant diseases or previous chemotherapies. Immunosuppressive comedication due to severe adverse events of ICI did not impair the serological response to COVID-19 vaccination.
Periodontal disease and cancer risk: A nationwide population-based cohort study
Authors: Kim Eun Hwa , Nam Sunghyun , Park Chung Hyun , Kim Yitak , Lee Myeongjee , Ahn Joong Bae , Shin Sang Joon , Park Yu Rang , Jung Hoi In , Kim Baek-Il , Jung Inkyung , Kim Han Sang
Published: August 2022

Background

Although emerging evidence suggests that periodontitis might increase the risk of cancer, comorbidity and lifestyle behaviors, such as smoking and body mass index (BMI), may have confounded this reported association. This study aimed to investigate whether chronic periodontitis is associated with cancer risk using a large, nationwide database.

Methods

We conducted a population-based, retrospective cohort study using data from the Korean National Health Insurance Cohort Database obtained between January 2003 and December 2015. We included 713,201 individuals without a history of cancer who were followed up to 10 years. Confounding factors included demographic factors (age, sex, income, and residential area), lifestyle behaviors (smoking history and BMI), and comorbidities, such as hypertension, diabetes, heart failure, and pulmonary disease, using the Charlson Comorbidity Index. Multivariable Cox regression analysis was applied to estimate the adjusted hazard ratio (aHR) for cancer risk.

Results

Of the 713,201 participants, 53,075 had periodontitis and were placed in the periodontitis group; the remaining 660,126 individuals were included as the control group. Overall, the cumulative incidence of cancer in the periodontitis group was 2.2 times higher than that in the control group. The periodontitis group had an increased risk of total cancer compared to the control group after adjusting for age, sex, comorbidities, BMI, and smoking history (aHR, 1.129; 95% confidence interval [CI], 1.089-1.171; P<0.0001). When examining specific cancer types, significant associations were also observed between periodontitis and stomach cancer (aHR, 1.136; 95% CI, 1.042-1.239; P=0.0037), colon cancer (aHR, 1.129; 95% CI, 1.029-1.239; P=0.0105), lung cancer (aHR, 1.127; 95% CI, 1.008-1.260; P=0.0353), bladder cancer (aHR, 1.307; 95% CI, 1.071-1.595; P=0.0085), thyroid cancer (aHR, 1.191; 95% CI, 1.085-1.308; P=0.0002), and leukemia (aHR, 1.394; 95% CI, 1.039-1.872; P=0.0270). There was no significant association between the development of secondary malignancy and periodontitis in cancer survivors who were alive 5 years after they were diagnosed with the primary malignancy.

Conclusions

Periodontal disease, including periodontitis, was associated with increased risk of cancer, which persisted after controlling for confounding factors. Further prospective research is warranted to establish a causal relationship.
Is ICI-based therapy better than chemotherapy for metastatic NSCLC patients who develop EGFR-TKI resistance? A real-world investigation
Authors: Cheng Yajie , Yang Bin , Ouyang Wen , Jie Chen , Zhang Wei , Chen Gang , Zhang Junhong , Yu Jing , Xie Conghua
Published: August 2022

Purpose

To evaluate the outcomes of immune checkpoint inhibitor (ICI)-based treatments versus classical chemotherapy for metastatic non-small cell lung cancer (NSCLC) patients who develop epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) resistance and to explore the population that may benefit from ICI-based therapy.

Materials and methods

All patients who had previously received EGFR-TKI therapy at two cancer centers in China and developed resistance to targeted therapies were included. Progression-free survival (PFS) and overall survival (OS) were utilized to evaluate the outcomes of the study cohort.

Results

A total of 132 patients were included. The median follow-up time for this cohort was 21.7 months (IQR, 14.8–28.8 months), calculated from the date of EGFR-TKI resistance. The median PFS and OS were 4.9 months (IQR, 2.8–9.2) and 13.5 months (IQR, 6.6–26.5 months), respectively. Multivariate analysis showed that ICI-based therapy could significantly improve OS when compared to the classic chemotherapy (hazard ratio [HR], 0.55; 95% CI, 0.34–0.88; P = 0.01) after adjusting for variables such as gender, age, mutation status, and brain or liver metastasis status. The combined modality of ICI plus chemotherapy could offer a long-term OS benefit in most subgroups, such as young (<65 years) patients, and those without secondary T790M mutations or absence of liver and brain metastases, and the populations with good Eastern Cooperative Oncology Group (ECOG) scores.

Conclusion

For patients presenting with EGFR-TKI resistance, ICI-based therapy could offer a more favorable survival than classical chemotherapy. The combination of ICI with chemotherapy may be the optimal modality for those with good ECOG PS scores.
Application of a combined radiomics nomogram based on CE-CT in the preoperative prediction of thymomas risk categorization
Authors: Dong Wentao , Xiong Situ , Lei Pinggui , Wang Xiaolian , Liu Hao , Liu Yangchun , Zou Huachun , Fan Bing , Qiu Yingying
Published: August 2022

Objective

This study aimed to establish a combined radiomics nomogram to preoperatively predict the risk categorization of thymomas by using contrast-enhanced computed tomography (CE-CT) images.

Materials and Methods

The clinical, pathological, and CT data of 110 patients with thymoma (50 patients with low-risk thymomas and 60 patients with high-risk thymomas) collected in our Hospital from July 2017 to March 2022 were retrospectively analyzed. The study subjects were randomly divided into the training set (n = 77) and validation set (n = 33) in a 7:3 ratio. Radiomics features were extracted from the CT images, and the least absolute shrinkage and selection operator (LASSO) algorithm was performed to select 13 representative features. Five models, including logistic regression (LR), support vector machine (SVM), random forest (RF), decision tree (DT), and gradient boosting decision tree (GBDT) were constructed to predict thymoma risks based on these features. A combined radiomics nomogram was further established based on the clinical factors and radiomics scores. The performance of the models was evaluated using receiver operating characteristic (ROC) curve, DeLong tests, and decision curve analysis.

Results

Maximum tumor diameter and boundary were selected to build the clinical factors model. Thirteen features were acquired by LASSO algorithm screening as the optimal features for machine learning model construction. The LR model exhibited the highest AUC value (0.819) among the five machine learning models in the validation set. Furthermore, the radiomics nomogram combining the selected clinical variables and radiomics signature predicted the categorization of thymomas at different risks more effectively (the training set, AUC = 0.923; the validation set, AUC = 0.870). Finally, the calibration curve and DCA were utilized to confirm the clinical value of this combined radiomics nomogram.

Conclusion

We demonstrated the clinical diagnostic value of machine learning models based on CT semantic features and the selected clinical variables, providing a non-invasive, appropriate, and accurate method for preoperative prediction of thymomas risk categorization.
Selection of the surgical approach for patients with cStage IA lung squamous cell carcinoma: A population-based propensity score matching analysis
Authors: Shao Shengteng , Song Guisong , Wang Yuanyong , Yi Tengfei , Li Shuo , Chen Fuhui , Li Yang , Liu Xiaotong , Han Bin , Liu Yuhong
Published: August 2022

Background

This study aimed to conduct a comparative analysis of the survival rates after segmentectomy, wedge resection, or lobectomy in patients with cStage IA lung squamous cell carcinoma (SCC).

Methods

We enrolled 4,316 patients who had cStage IA lung SCC from the Surveillance, Epidemiology, and End Results (SEER) database. The Cox proportional hazards model was conducted to recognize the potential risk factors for overall survival (OS) and lung cancer-specific survival (LCSS). To eliminate potential biases of included patients, the propensity score matching (PSM) method was used. OS and LCSS rates were compared among three groups stratified according to tumor size.

Results

Kaplan–Meier analyses revealed no statistical differences in the rates of OS and LCSS between wedge resection (WR) and segmentectomy (SG) groups for patients who had cStage IA cancers. In patients with tumors ≤ 1 cm, LCSS favored lobectomy (Lob) compared to segmentectomy (SG), but a similar survival rate was obtained for wedge resection (WR) and lobectomy (Lob). For patients with tumors sized 1.1 to 2 cm, lobectomy had improved OS and LCSS rates compared to the segmentectomy or wedge resection groups, with the exception of a similar OS rate for lobectomy and segmentectomy. For tumors sized 2.1 to 3 cm, lobectomy had a higher rate of OS or LCSS than wedge resection or segmentectomy, except that lobectomy conferred a similar LCSS rate compared to segmentectomy. Multivariable analyses showed that patients aged ≥75 and tumor sizes of >2 to ≤3 cm were potential risk factors for OS and LCSS, while lobectomy and first malignant primary indicator were considered protective factors. The Cox proportional analysis also confirmed that male patients aged ≥65 to <75 were independent prognostic factors that are indicative of a worse OS rate.

Conclusions

The tumor size can influence the surgical procedure recommended for individuals with cStage IA lung SCC. For patients with tumors ≤1 cm, lobectomy is the recommended approach, and wedge resection or segmentectomy might be an alternative for those who cannot tolerate lobectomy if adequate surgical margin is achievable and enough nodes are sampled. For tumors >1 to ≤3 cm, lobectomy showed better survival outcomes than sublobar resection. Our findings require further validation by randomized controlled trial (RCT) or other evidence.
Effects of Wee1 inhibitor adavosertib on patient-derived high-grade serous ovarian cancer cells are multiple and independent of homologous recombination status
Authors: Roering Pia , Siddiqui Arafat , Heuser Vanina D. , Potdar Swapnil , Mikkonen Piia , Oikkonen Jaana , Li Yilin , Pikkusaari Sanna , Wennerberg Krister , Hynninen Johanna , Grenman Seija , Huhtinen Kaisa , Auranen Annika , Carpén Olli , Kaipio Katja
Published: August 2022

Objective

A major challenge in the treatment of platinum-resistant high-grade serous ovarian cancer (HGSOC) is lack of effective therapies. Much of ongoing research on drug candidates relies on HGSOC cell lines that are poorly documented. The goal of this study was to screen for effective, state-of-the-art drug candidates using primary HGSOC cells. In addition, our aim was to dissect the inhibitory activities of Wee1 inhibitor adavosertib on primary and conventional HGSOC cell lines.

Methods

A comprehensive drug sensitivity and resistance testing (DSRT) on 306 drug compounds was performed on three patient-derived genetically unique HGSOC cell lines and two commonly used ovarian cancer cell lines. The effect of adavosertib on the cell lines was tested in several assays, including cell-cycle analysis, apoptosis induction, proliferation, wound healing, DNA damage, and effect on nuclear integrity.

Results

Several compounds exerted cytotoxic activity toward all cell lines, when tested in both adherent and spheroid conditions. In further cytotoxicity tests, adavosertib exerted the most consistent cytotoxic activity. Adavosertib affected cell-cycle control in patient-derived and conventional HGSOC cells, inducing G2/M accumulation and reducing cyclin B1 levels. It induced apoptosis and inhibited proliferation and migration in all cell lines. Furthermore, the DNA damage marker γH2AX and the number of abnormal cell nuclei were clearly increased following adavosertib treatment. Based on the homologous recombination (HR) signature and functional HR assays of the cell lines, the effects of adavosertib were independent of the cells' HR status.

Conclusion

Our study indicates that Wee1 inhibitor adavosertib affects several critical functions related to proliferation, cell cycle and division, apoptosis, and invasion. Importantly, the effects are consistent in all tested cell lines, including primary HGSOC cells, and independent of the HR status of the cells. Wee1 inhibition may thus provide treatment opportunities especially for patients, whose cancer has acquired resistance to platinum-based chemotherapy or PARP inhibitors.
Alterations in the gastric microbiota and metabolites in gastric cancer: An update review
Authors: Lei Changzhen , Gong Daojun , Zhuang Bo , Zhang Zhiwei
Published: August 2022

Gastric cancer (GC) is one of the leading causes of cancer mortality worldwide. Numerous studies have shown that the gastric microbiota can contribute to the occurrence and development of GC by generating harmful microbial metabolites, suggesting the possibility of discovering biomarkers. Metabolomics has emerged as an advanced promising analytical method for the analysis of microbiota-derived metabolites, which have greatly accelerated our understanding of host-microbiota metabolic interactions in GC. In this review, we briefly compiled recent research progress on the changes of gastric microbiota and its metabolites associated with GC. And we further explored the application of metabolomics and gastric microbiome association analysis in the diagnosis, prevention and treatment of GC.
Sirolimus combined with interferon-alpha 2b therapy for giant hepatic epithelioid hemangioendothelioma: a case report
Authors: Liu Xiaolei , Zhou Ruiquan , Si Shuang , Liu Liguo , Yang Shiwei , Han Dongdong , Tan Haidong
Published: August 2022

Hepatic epithelioid hemangioendothelioma (HEH) is a very rare tumor originated from vascular endothelial cells, with unpredictable malignancy. No standard treatment has been established yet. Although surgical resection and liver transplantation have been reported to be effective treatments with favorable long-term outcomes, the multiple intrahepatic lesions or extrahepatic metastasis makes these procedures unsuitable to most patients. Sirolimus was reported to be an effective drug for epithelioid hemangioendothelioma but only about 10% achieved partial response. Interferon-alpha 2b (IFN-a 2b) has also been used for the treatment of HEH, and the rate of tumor regression was more than 50%. Here, we report a HEH patient with giant intrahepatic tumor (>15cm), who achieved partial response after the combined therapy of sirolimus and IFN-a 2b. The giant intrahepatic lesion (>15 cm) regressed obviously after 8 months treatment and no severe adverse event was reported. The good response and safety of combined therapy with sirolimus and IFN-a 2b provide a promising guidance for future clinical study.
Colon cancer patient with long-term colon stent placement: Case report and literature review
Authors: Huang Qing , Zou Min-hong , Liang Wen-long , Wei Jian-chang , Xie Jie-feng , Li Yong-Qiang , Li Wang-lin , Cao Jie
Published: August 2022

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer mortality globally. Large bowel obstruction (occurring in 15-30% of patients with CRCs) accounts for approximately 80% of medical emergencies related to CRC. Currently, there is no standard treatment of this condition. The European Society of Gastrointestinal Endoscopy (ESGE) recommends self-expandable metal stent (SEMS) as a bridge (two weeks) to surgery for left-sided obstructing colon cancer. In the present report, we describe an 81-year-old male with colon cancer who underwent colon stent placement for 32 months, but later underwent radical resection. A follow-up of more than four-months revealed that his condition was normal. The history as well as application and advantages of SEMS are discussed in this report.
Clinical relevance of the combined analysis of circulating tumor cells and anti-tumor T-cell immunity in metastatic breast cancer patients
Authors: Muraro Elena , Del Ben Fabio , Turetta Matteo , Cesselli Daniela , Bulfoni Michela , Zamarchi Rita , Rossi Elisabetta , Spazzapan Simon , Dolcetti Riccardo , Steffan Agostino , Brisotto Giulia
Published: August 2022

Background

Metastatic breast cancer (mBC) is a heterogeneous disease with varying responses to treatments and clinical outcomes, still requiring the identification of reliable predictive biomarkers. In this context, liquid biopsy has emerged as a powerful tool to assess in real-time the evolving landscape of cancer, which is both orchestrated by the metastatic process and immune-surveillance mechanisms. Thus, we investigated circulating tumor cells (CTCs) coupled with peripheral T-cell immunity to uncover their potential clinical relevance in mBC.

Methods

A cohort of 20 mBC patients was evaluated, before and one month after starting therapy, through the following liquid biopsy approaches: CTCs enumerated by a metabolism-based assay, T-cell responses against tumor-associated antigens (TAA) characterized by interferon-γ enzyme-linked immunosorbent spot (ELISpot), and the T-cell receptor (TCR) repertoire investigated by a targeted next-generation sequencing technique. TCR repertoire features were characterized by the Morisita’s overlap and the Productive Simpson Clonality indexes, and the TCR richness. Differences between groups were calculated by Fisher’s, Mann-Whitney or Kruskal-Wallis test, as appropriate. Prognostic data analysis was estimated by Kaplan-Meier method.

Results

Stratifying patients for their prognostic level of 6 CTCs before therapy, TAA specific T-cell responses were detected only in patients with a low CTC level. By analyzing the TCR repertoire, the highest TCR clonality was observed in the case of CTCs under the cut-off and a positive ELISpot response (p=0.03). Whereas, at follow-up, patients showing a good clinical response coupled with a low number of CTCs were characterized by the most elevated TCR clonality (p<0.05). The detection of CTCs≥6 in at least one time-point was associated with a lower TCR clonality (p=0.02). Intriguingly, by combining overall survival analysis with TCR repertoire, we highlighted a potential prognostic role of the TCR clonality measured at follow-up (p=0.03).

Conclusion

These data, whether validated in a larger cohort of patients, suggest that the combined analysis of CTCs and circulating anti-tumor T-cell immunity could represent a valuable immune-oncological biomarker for the liquid biopsy field. The clinical application of this promising tool could improve the management of mBC patients, especially in the setting of immunotherapy, a rising approach for BC treatment requiring reliable predictive biomarkers.
Survival benefit of thermal ablation therapy for patients with stage II-III non-small cell lung cancer: A propensity-matched analysis
Authors: Yang Wei-Yu , He Yu , Hu Qikang , Peng Muyun , Zhang Zhe , Xie Shouzhi , Yu Fenglei
Published: August 2022

Background

Thermal ablation (TA) is considered a safe alternative to surgical resection for the treatment of non-small cell lung cancer (NSCLC). While previous studies have shown that TA is beneficial for stage I NSCLC patients, however, few have reported on TA efficacy in patients with stage II-III NSCLC. The current study investigated the impact of TA on the overall survival (OS) and cancer-specific survival (CSS) of patients with stage II-III NSCLC.

Methods

Data on patients with stage II-III NSCLC who did not undergo surgical resection between 2004 and 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM), Kaplan-Meier survival curves, and Cox regression were used for statistical analyses.

Results

A total of 57,959 stage II-III NSCLC patients who did not undergo surgical resection were included in this study, 261 of whom received TA. Overall, TA was associated with a longer OS (p = 0.035) and CSS (p = 0.005) than non-ablation. After 1:3 PSM, 252 patients receiving TA and 732 patients not receiving ablation were enrolled in the matched cohort. The OS (p = 0.047) and CSS (p = 0.029) remained higher in the TA group than in the non-ablation group after PSM. Cox regression analysis showed that age, sex, primary tumor site, pathological type, tumor size, radiotherapy, chemotherapy, and thermal ablation were independently associated with OS and CSS (p <0.05). Subgroup analysis found that the advantages of TA were more pronounced among individuals ≥70 years of age, with tumor size ≤3.0 cm, or who did not receive radiotherapy.

Conclusion

TA could be an effective alternative treatment for stage II-III NSCLC patients unsuitable for surgical resection, particularly those ≥70 years of age, with tumor size ≤3.0 cm, or who have not received radiotherapy.
Clinical impact of inferior mesenteric vein preservation during left hemicolectomy with low ligation of the inferior mesenteric artery for distal transverse and descending colon cancers: A comparative study based on computed tomography
Authors: Suh Jung Wook , Park Jihoon , Lee Jeehye , Yang In Jun , Ahn Hong-Min , Oh Heung-Kwon , Kim Duck-Woo , Kang Sung-Bum
Published: August 2022

Purpose

Presence of a long remnant sigmoid colon after left hemicolectomy with inferior mesenteric vein (IMV) ligation for distal transverse and descending colon cancers may be a risk factor for venous ischemia. This study aimed to evaluate the clinical impact of IMV preservation in patients who underwent left hemicolectomy with inferior mesenteric artery (IMA) preservation.

Methods

We included 155 patients who underwent left hemicolectomy with IMA preservation for distal transverse and descending colon cancers from 2003 to 2020. Technical success of IMV preservation was determined by assessing pre- and post-operative patency of the IMV on computed tomography (CT) by an abdominal radiologist. Intestinal complications comprising ulceration, stricture, venous engorgement, and colitis in remnant colon were compared between the IMV preservation and ligation groups.

Results

IMV was preserved in 22 (14.2%) and ligated in 133 (85.8%) patients. Surgical time, postoperative recovery outcomes, and number of harvested lymph nodes were similar in both groups. The technical success of IMV preservation was 81.8%. Intestinal complications were less common in the preservation group than in the IMV ligation group (4.5% vs. 23.3%, P=0.048). The complications in the IMV ligation group were anastomotic ulcer (n=2), anastomotic stricture (n=4), venous engorgement of the remnant distal colon (n=4), and colitis in the distal colon (n=21).

Conclusions

IMV preservation may be beneficial after left hemicolectomy with IMA preservation for distal transverse and descending colon cancers. We suggest that IMV preservation might be considered when long remnant sigmoid colon is expected during left hemicolectomy with low ligation of IMA.
The value of combined PET/MRI, CT and clinical metabolic parameters in differentiating lung adenocarcinoma from squamous cell carcinoma
Authors: Tang Xin , Wu Jiaojiao , Liang Jiangtao , Yuan Changfeng , Shi Feng , Ding Zhongxiang
Published: August 2022

Objective

This study aimed to study the diagnostic efficacy of positron emission tomography (PET)/magnetic resonance imaging (MRI), computed tomography (CT) and clinical metabolic parameters in predicting the histological classification of lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC).

Methods

PET/MRI, CT and clinical metabolic data of 80 patients with lung ADC or SCC were retrospectively collected. According to the pathological results from surgery or fiberscopy, the patients were diagnosed with lung ADC (47 cases) or SCC (33 cases). All 80 patients were divided into a training group (64 cases), an internal testing group (8 cases) and an external testing group (8 cases) in the ratio of 8:1:1. Nine models were constructed by integrating features from different modalities. The Gaussian classifier was used to differentiate ADC and SCC. The prediction ability was evaluated using the receiver operating characteristic curve. The area under the curve (AUC) of the models was compared using Delong’s test. Based on the best composite model, a nomogram was established and evaluated with a calibration curve, decision curve and clinical impact curve.

Results

The composite model (PET/MRI + CT + Clinical) owned the highest AUC values in the training, internal testing and external testing sets, respectively. In the training set, significant differences in the AUC were found between the composite model and other models except for the PET/MRI + CT model. The calibration curves showed good consistency between the predicted output and actual disease. The decision curve analysis and clinical impact curves demonstrated that the composite model increased the clinical net benefit for predicting lung cancer subtypes.

Conclusion

The composite prediction model of PET/MRI + CT + Clinical better distinguished ADC from SCC pathological subtypes preoperatively and achieved clinical benefits, thus providing an accurate clinical diagnosis.
The prognostic potential of fragmented CK18 serum levels in HCC patients reflecting disease progression and overall hepatocyte damage
Authors: Eguchi Akiko , Iwasa Motoh , Tamai Yasuyuki , Yamada Minori , Okuno Koji , Shigefuku Ryuta , Yoshikawa Kyoko , Tempaku Mina , Sakaguchi Koji , Tanaka Hideaki , Sugimoto Kazushi , Kobayashi Yoshinao , Yamaguchi Tetsuji , Nakagawa Hayato
Published: August 2022

Background

Fragmented cytokeratin 18 (fCK18) is released from damaged hepatocytes undergoing apoptosis and is recognized as a liver condition biomarker. We have developed a highly sensitive serum fCK18 CLEIA and reported that serum levels of this caspase-derived protein were significantly associated with hepatocyte ballooning, thus assisting in the accurate diagnosis of nonalcoholic steatohepatitis (NASH). We aim to investigate serum fCK18 levels in a variety of chronic liver diseases and to explore its potential as a prognostic marker of survival in hepatocellular carcinoma (HCC) patients.

Methods

Serum fCK18 levels were measured using a highly sensitive CLEIA in 497 chronic liver disease patients (297 outpatients and 200 hospitalized with HCC).

Results

In 497 chronic liver disease patients, serum fCK18 levels were significantly correlated with overall liver condition, including ALT, FIB-4 index and albumin-bilirubin (ALBI) score and were significantly increased in patients with HCC. In 200 HCC patients, serum fCK18 levels were significantly correlated with alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP), and were significantly associated with HCC stage, whereas FIB-4 index and ALBI score were not changed based on HCC stage. The Survival group had significantly lower levels of serum fCK18, AFP, DCP, FIB-4 index and ALBI score. A ROC analysis yield area under the curve (AUC) value of 0.728 for serum fCK18 is a significantly high value when compared to AUC measurements for other factors. Notably, AUROC values for serum fCK18 levels were constant in the short- and long-term by time-dependent ROC analysis for the prediction of HCC patient survival. HCC patients with serum fCK18 measured at < 1.15 ng/mL, AFP < 7.7 ng/mL, DCP < 133 mAU/mL, ALBI score < -2.97 or FIB-4 index < 6.4 had significantly longer rates of survival when compared to patients with values exceeding these thresholds. Serum fCK18 (HR, 3.5; P < 0.0001), DCP (HR, 3.2; P < 0.0001) and Barcelona Clinic Liver Cancer (BCLC) (HR, 2.4; P = 0.001) values were independent predictors of patient survival. [Conclusion] Serum fCK18 levels reflect overall liver function, the level of liver fibrosis and the progression of HCC, and are a potential predictor of survival in HCC patients.
Acute retinal necrosis: A mini review
Authors: Hoogewoud Florence , Rossi Daniele C. , Stappler Theodor , Guex-Crosier Yan
Published: August 2022

Acute retinal necrosis is a rare but potentially devastating disease. Even in the era of modern medicine, retinal detachment is a frequent complication leading to vison loss, as well as phthisis bulbi. Whereas IV acyclovir still remains the standard of care, high doses of valacyclovir with/without additional intravitreal injections of foscarnet have been used. In an attempt to reduce the retinal detachment rate, prophylactic laser treatment and early vitrectomy have been proposed. In this article, we aim to review current diagnostic and treatment modalities.
The association of cesarean section with overweight and neurodevelopment of Chinese children aged 1–5 months
Authors: Zheng Xiaoguo , Li Ruili , Wang Lihong , Yang Huimin , Li Linlin , Cui Jiayin , Zhao Wenhua , Yang Zhenyu , Zhang Qian , Xu Tao , Wang Yuying , Chen Bowen
Published: August 2022

Objective

The purpose of this survey was to explore the association of delivery mode with overweight and neurodevelopment of Chinese infants aged 1–5 months.

Materials and methods

This study was based on a cross-sectional survey. Data for this study were obtained from the Children’s Nutrition and Health System Survey in China which was conducted from 2019 to 2020. Characteristics of parents and children and the delivery mode were obtained using interview-administered questionnaires. Body mass index-for age z-score (BMI z) was calculated using World Health Organization (WHO) child growth standards. Children’s neurodevelopment was assessed by a trained child health care physician using the Child Psychological Development Scale. The association of delivery mode with infant overweight was analyzed using a multivariable logistic regression model. We conducted a multivariable linear regression model to explore the relationship between delivery modes with neurodevelopment.

Results

In total, the present analysis included 1,347 children aged 1–5 months, 35.61% were born via cesarean section, of which 15.21% were overweight. After adjustment for infant characteristics and parental factors, the cesarean section was significantly related with the likehood of being overweight [OR = 1.95; 95% confidence interval (CI): 1.27 to 2.98]. Children born via cesarean section had a 3.41-point decrease in gross motor development (β = −3.41; 95% CI: −5.77 to −1.05), a 3.65-point decrease in fine motor development (β = −3.65; 95% CI: −6.03 to −1.28), and a 2.96-point in language development (β = −2.96; 95% CI: −5.20 to −0.73), a 1.65-point in total development (β = −1.65; 95% CI: −3.17 to −0.14) compared with those who were vaginal birth.

Conclusion

In our study population, cesarean section was associated with overweight and neurodevelopment outcomes. The cesarean section might increase the likehood of infant overweight, and might decrease the developmental scores of gross motor, fine motor and language. Further studies should be conducted to verify the associations and explore the possible mechanisms.
Case report: Fluctuating tumor markers in a boy with gonadotropin-releasing hormone-independent precocious puberty induced by a pineal germ cell tumor
Authors: Cattoni Alessandro , Albanese Assunta
Published: August 2022

GnRH-independent precocious puberty (GIPP) can be the presenting clinical picture experienced by patients with secreting germ cell tumor (GCT). Indeed, as luteinizing hormone (LH) and human chorionic gonadotropin (hCG) share identical α-subunits and similar β-subunits, an increased secretion of β-hCG may result in a precocious activation of Leydig cells. Though the co-occurrence of raised β-hCG levels and signs of precocious virilization usually prompts a complete oncological work-up, the diagnostic and therapeutic management of GCT-induced GIPP may be challenging. We report the case of a 6.2 year-old boy presenting with clinical and biochemical findings consistent with GIPP (discrepancy between overt virilization and pre-pubertal testicular volume, suppressed gonadotropins and remarkably raised testosterone). Brain imaging detected a bilobed cyst of the pineal gland, while serum and cerebrospinal baseline assessment initially ruled out raised alpha-fetoprotein or β-hCG levels. Nevertheless, a strict biochemical follow-up highlighted a fluctuant trend of tumor markers, with a more aggressive behavior and recurrent erections occurring as a result of unpredictable phases of raised testosterone and serum/cerebrospinal β-hCG, followed by sudden spontaneous decrease. Accordingly, a secreting pineal GCT was suspected. Given the fluctuating trend of tumor markers, surgery was initially kept on hold and a combined treatment with bicalutamide (androgen receptor blocker) and anastrozole (aromatase inhibitor) was undertaken in order to prevent the patient from experiencing further virilization and excessive bone age maturation. Subsequently, a progression in the size of the pineal tumor prompted surgical resection and a diagnosis of secreting GCT was histologically confirmed. Accordingly, the patient was started on adjuvant chemo- and radiotherapy. Antineoplastic treatment was followed by persistent and remarkable decrease of tumor markers and by a complete pubertal arrest. We reported the challenging diagnosis of a secreting pineal GCT in a patient with GIPP and a fluctuating trend of tumor markers, testosterone levels and associated clinical signs, hence prompting the indication for a systematic assessment and a strict monitoring whenever a patient with GnRH-independent precocious puberty shows clinical or radiological markers potentially consistent with a GCT.
Prediction nomogram for evaluating the probability of postoperative fever in children with acute appendicitis
Authors: Chen Yang , Ren Feng , Xiao Dong , Guan Ai-hui , Zhu Le-dao , Ma Xiao-peng , Wang Zhi-yong
Published: August 2022

Objective

The purpose of this study was to establish a predictive model of postoperative fever in children with acute appendicitis through retrospective analysis, and the prediction ability of the model is demonstrated by model evaluation and external validation.

Methods

Medical records information on children undergoing surgery for acute appendicitis within 2 years were retrospectively collected, prospective collection was performed for external validation in the next 3 months. The patients were divided into two groups according to whether the postoperative body temperature exceeded 38.5°C. Multivariate logistic regression analysis was used to determine independent risk factors and develop regression equations and nomogram. ROC curve, calibration curve and decision curve were made for model evaluation. Finally, the clinical implication of the prediction model was clarified by associating postoperative fever with prognosis.

Results

High risk factors of postoperative fever included in the prediction model were onset time (X1), preoperative temperature (X2), leukocyte count (X3), C-reactive protein (X4) and operation time (X5). The regression equation is logit (P) = 0.005X1+0.166X2+0.056X3+0.004X4+0.005X5-9.042. ROC curve showed that the area under the curve (AUC) of the training set was 0.660 (0.621, 0.699), and the AUC of the verification set was 0.712 (0.639, 0.784). The calibration curve suggested that the prediction probability was close to the actual probability. Decision curve analysis (DCA) showed that patients could benefit from clinician’s judgment. Furthermore, prognostic analysis showed children presenting with postoperative fever had the more duration of postoperative fever, hospitalization stays and cost, except for rehospitalization.

Conclusion

All the results revealed that the model had good predictive ability. Pediatricians can calculate the probability of postoperative fever and make timely interventions to reduce pain for children and parents.
Generalised weibull model-based approaches to detect non-constant hazard to signal adverse drug reactions in longitudinal data
Authors: Sauzet Odile , Cornelius Victoria
Published: August 2022

Pharmacovigilance is the process of monitoring the emergence of harm from a medicine once it has been licensed and is in use. The aim is to identify new adverse drug reactions (ADRs) or changes in frequency of known ADRs. The last decade has seen increased interest for the use of electronic health records (EHRs) in pharmacovigilance. The causal mechanism of an ADR will often result in the occurrence being time dependent. We propose identifying signals for ADRs based on detecting a variation in hazard of an event using a time-to-event approach. Cornelius et al. proposed a method based on the Weibull Shape Parameter (WSP) and demonstrated this to have optimal performance for ADRs occurring shortly after taking treatment or delayed ADRs, and introduced censoring at varying time points to increase performance for intermediate ADRs. We now propose two new approaches which combined perform equally well across all time periods. The performance of this new approach is illustrated through an EHR Bisphosphonates dataset and a simulation study. One new approach is based on the power generalised Weibull distribution (pWSP) introduced by Bagdonavicius and Nikulin alongside an extended version of the WSP test, which includes one censored dataset resulting in improved detection across time period (dWSP). In the Bisphosphonates example, the pWSP and dWSP tests correctly signalled two known ADRs, and signal one adverse event for which no evidence of association with the drug exist. A combined test involving both pWSP and dWSP is reliable independently of the time of occurrence of ADRs.