Systematic Literature Review of the Prevalence and Prognostic Value of Delta-Like Ligand 3 Protein Expression in Small Cell Lung Cancer

Background: Delta-like ligand 3 (DLL3), a member of the Notch pathway, has been identified as a potential therapeutic target as it is highly expressed in small cell lung cancer (SCLC), a subtype accounting for 15% of lung cancer cases. Objective: A systematic literature review (SLR) was conducted to understand the prevalence and prognostic impact of DLL3 expression on survival of patients with SCLC and treatment response. Patients and Methods: Systematic literature searches were conducted across multiple databases to capture studies of any SCLC population that evaluated DLL3 expression. Specific outcomes of interest included prevalence of DLL3 expression, method of expression analysis, and impact on outcome, including treatment response and survival (overall, progression-free, disease-free) according to varying levels of DLL3 expression/positivity. Standard risk of bias tools were used to evaluate study quality. Results: Among the 30 included studies, the most common DLL3 testing method was immunohistochemistry (N = 26, 86.7%). For comparability, results focused on the 13 (22.3%) studies that used the Ventana DLL3 (SP347) immunohistochemistry assay. The prevalence of DLL3 positivity ranged from 80.0–93.5% for studies using a threshold of ≥ 1% of tumor cells (N = 4) and 58.3–91.1% for studies with a ≥ 25% threshold (N = 4). DLL3 expression was generally categorized as high using cutoffs of ≥ 50% (prevalence range: 45.8–79.5%; N = 6) or ≥ 75% (prevalence range: 47.3–75.6%; N = 5) of cells with positivity. Two studies used an H-score of ≥ 150 to define high DLL3 expression with prevalence ranging from 33.3–53.1%. No consistent associations were seen between DLL3 expression level and patient age, sex, smoking history, or disease stage. Two studies reported change in DLL3 expression category (high versus low) before and after chemotherapy. No statistically significant differences were reported between DLL3 expression groups and survival (overall, progression-free, or disease-free) or treatment response. Conclusions: There is a high prevalence of DLL3 expression in SCLC. Further research and analytical methods may help to characterize different populations of patients with SCLC based on DLL3 expression. While no significant prognostic factor in the included studies was identified, additional cohort studies using standardized methodology, with longer follow-up, are needed to better characterize any potential differences in patient survival or response by DLL3 expression level in SCLC.</p

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10&nbsp;years; 78.2% included were male with a median age of 37&nbsp;years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

Role of IL-28B polymorphisms in virologic response to combined pegylated interferon and ribavirin therapy in genotype 4 chronic HCV infected patients with and without cirrhosis

Background: Chronic hepatitis C virus (HCV) represents one of the common causes of chronic liver disease worldwide with Egypt having the highest prevalence, namely genotype 4. The rs12979860 CC genotype of the interleukin 28B (IL28B) polymorphisms is associated with high rates of sustained virological response to pegylated interferon and ribavirin in HCV genotype-1 patients. Data on other genotypes are more limited. Objective: We aim to evaluate the predictive power of the rs12979860 IL28B single nucleotide polymorphisms for treatment response at 3 and 6 months in chronic HCV genotype 4 Egyptian patients in relation to other predictors. Patients and methods: The study included 60 chronic HCV Egyptian patients receiving pegylated interferon and ribavirin therapy. Patients were classified into 2 groups; 30 patients with compensated cirrhosis, and 30 patients without cirrhosis. We analyzed selected pretreatment factors such as age, sex, HCV viral load, anti-schistosomal antibodies, insulin resistance, alpha fetoprotein, low and high density lipoproteins and single nucleotide polymorphisms of IL28B and tried to find out which of them influence sustained virological response. Results: In univariate analysis, CC genotype showed a significant association with sustained virological response at 6 months among the cirrhotic patients (81.8% responders had the CC genotype, 58.3% had the CT/TT genotype) (p = 0.009). While in multivariate analysis, the presence of cirrhosis showed higher risk of failed response at 3 and 6 months (p = 0.016 and 0.020 respectively). Also, positive schistosoma serology was an important negative predictor of response at 3 and 6 months in both groups (p = 0.003 and 0.001 respectively). Conclusion: In Egypt, where chronic HCV genotype 4 and schistosoma coinfection predominate, both schistosoma infection and cirrhosis are more potent than IL28B polymorphisms as strong baseline negative predictors of hepatitis C treatment response