Acanthosis Nigricans in a Patient with Urothelial Carcinoma Treated with PD-L1 Inhibitor Avelumab, and Secondary Adrenal Insufficiency

Acanthosis nigricans (AN) describes hyperkeratotic and hyperpigmented skin changes and its pathophysiology is linked to the activation of epidermal growth factor receptors. Current literature shows that AN is most commonly diagnosed at the time of the underlying pathology, which may occur under benign or malignant conditions. This case presentation demonstrates the occurrence of AN in a patient following the diagnosis of urothelial carcinoma and ongoing treatment with PD-L1 inhibitor immunotherapy. Subsequent investigations ruled out a secondary malignancy or disease progression; however, metabolic screening identified secondary glucocorticoid induced adrenal insufficiency. AN was persistent in this patient despite adequate treatment, which highlights its co-occurrence in both benign and paraneoplastic conditions

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Technical Report: HART Systems

For many years here in All Hallows College I have wanted to setup a centralised database for the IT Department to log all the support calls. Unfortunately as I am the only full time IT Support personnel here in the college the time was just not there to allow for this development. A few years later and I have a project for college that involves just the thing and I can kill two birds with the one stone. This project grew out of a need, a need for greater service from the IT Department. It’s very easy to lose support calls and emails when you are using a writing pad or an excel sheet between two people. With the HART System in place we can now see quickly and easily what is going on in the IT Department at any one time. We can run reports and reply by text to students who have requested support. This new system brings new efficiencies into the department and solves a business problem here in All Hallows College that has been around since the first pc arrived back in 1995

miRNAs as biomarkers of therapeutic response to HER2-targeted treatment in breast cancer: A systematic review

Breast cancer is the most common type of lethal cancer in women globally. Women have a 1 in 8 chance of developing breast cancer in their lifetime. Among the four primary molecular subtypes (luminal A, luminal B, HER2+, and triple-negative), HER2+ accounts for 20–25 % of all breast cancer and is rather aggressive. Although the treatment outcome of HER2+ breast cancer patients has been significantly improved with anti-HER2 agents, primary and acquired drug resistance present substantial clinical issues, limiting the benefits of HER2-targeted treatment. MicroRNAs (miRNAs) play a central role in regulating acquired drug resistance. miRNA are single-stranded, non-coding RNAs of around 20–25 nucleotides, known for essential roles in regulating gene expression at the post-transcriptional level. Increasing evidence has demonstrated that miRNA-mediated alteration of gene expression is associated with tumorigenesis, metastasis, and tumor response to treatment. Comprehensive knowledge of miRNAs as potential markers of drug response can help provide valuable guidance for treatment prognosis and personalized medicine for breast cancer patients

Second‐line chemotherapy in advanced biliary cancers: A retrospective, multicenter analysis of outcomes

BACKGROUND: Though gemcitabine plus platinum chemotherapy is the established first line regimen for advanced biliary tract cancer (ABC), there is no standard second line therapy. We evaluated current practice and outcomes for second line chemotherapy in patients with ABC across three US academic medical centers. METHODS: Institutional registries were reviewed to identify patients who had received second line chemotherapy for ABC from 4/2010 to 3/2015, along with demographics, diagnosis and staging, treatment history, and clinical outcomes. Overall survival from initiation of second line chemotherapy (OS2) was estimated using Kaplan-Meier methods. RESULTS: We identified 198 patients with cholangiocarcinoma (intrahepatic, 61.1% and extrahepatic, 14.1%) and gallbladder carcinoma (24.8%); 52% received at least 3 lines of systemic chemotherapy. The median OS2 11 months (95% CI 8.8-13.1). Median OS2 for intrahepatic cholangiocarcinoma was 13.4 months (95% CI: 10.7-17.8), longer than extrahepatic or gallbladder with mOS2 of 6.8 months (95% CI: 5-10.5) and 9.4 months (95% CI: 7.2-12.3), respectively (p=0.018). The median time to second line treatment failure was 2.2 (95% CI: 1.8-2.7) months, similar across tumor locations (p=0.60). CONCLUSIONS: In this large cohort of ABC patients treated across three academic medical centers after failure of first line chemotherapy, the time to treatment failure on standard therapies was short, though median OS2 was longer than has been reported previously, and over half of patients received additional lines of treatment. This multicenter collaboration represents the largest cohort studied to date of second line chemotherapy in ABC and provides a contemporary benchmark for future clinical trials

Second‐line chemotherapy in advanced biliary cancers: A retrospective, multicenter analysis of outcomes

BackgroundAlthough gemcitabine plus platinum chemotherapy is the established first-line regimen for advanced biliary cancer (ABC), there is no standard second-line therapy. This study evaluated current practice and outcomes for second-line chemotherapy in patients with ABC across 3 US academic medical centers.MethodsInstitutional registries were reviewed to identify patients who had received second-line chemotherapy for ABC from April 2010 to March 2015 along with their demographics, diagnoses and staging, treatment histories, and clinical outcomes. Overall survival from the initiation of second-line chemotherapy (OS2) was estimated with Kaplan-Meier methods.ResultsThis study identified 198 patients with cholangiocarcinoma (intrahepatic [61.1%] or extrahepatic [14.1%]) or gallbladder carcinoma (24.8%); 52% received at least 3 lines of systemic chemotherapy. The median OS2 was 11 months (95% confidence interval [CI], 8.8-13.1 months). The median OS2 for patients with intrahepatic cholangiocarcinoma was 13.4 months (95% CI, 10.7-17.8 months), which was longer than that for patients with extrahepatic cholangiocarcinoma (6.8 months; 95% CI, 5-10.6 months) or gallbladder carcinoma (9.4 months; 95% CI, 7.2-12.3 months; P = .018). The median time to second-line treatment failure was 2.2 months (95% CI, 1.8-2.7 months), and it was similar across tumor locations (P = .60).ConclusionsIn this large cohort of patients with ABC treated across 3 academic medical centers after the failure of first-line chemotherapy, the time to treatment failure on standard therapies was short, although the median OS2 was longer than has been reported previously, and more than half of the patients received additional lines of treatment. This multicenter collaboration represents the largest cohort studied to date of second-line chemotherapy for ABC and provides a contemporary benchmark for future clinical trials