Adjuvant nivolumab for stage III/IV melanoma: evaluation of safety outcomes and association with recurrence-free survival.

Background: Several therapeutic options are now available in the adjuvant melanoma setting, mandating an understanding of their benefit‒risk profiles in order to make informed treatment decisions. Herein we characterize adjuvant nivolumab select (immune-related) treatment-related adverse events (TRAEs) and evaluate possible associations between safety and recurrence-free survival (RFS) in the phase III CheckMate 238 trial.

Methods: Patients with resected stage IIIB-C or IV melanoma received nivolumab 3 mg/kg every 2 weeks (n=452) or ipilimumab 10 mg/kg every 3 weeks for four doses and then every 12 weeks (n=453) for up to 1 year or until disease recurrence, unacceptable toxicity, or consent withdrawal.

Payments reported by the pharmaceutical industry in Ireland from 2015 to 2019: An observational study.

Background: The pharmaceutical industry makes large numbers of payments to healthcare organisations (HCOs) and healthcare professionals (HCPs). Ireland has a large pharmaceutical industry presence and national debate on legislating for greater industry payment transparency. This study characterises payments in Ireland to HCPs and HCOs during 2015-2019, and the content, consistency and methodology of the data source.

Detection of SARS-CoV-2-Specific IgA in the Human Milk of COVID-19 Vaccinated Lactating Health Care Workers.

In 2019, a deadly virus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for coronavirus disease 2019 (COVID-19), emerged. In December 2020, two mRNA-based COVID-19 vaccines were approved for use in the United States, which provide immunity to those receiving the vaccine. Maternally derived antibodies are a key element of infants' immunity.

TMB and Inflammatory Gene Expression Associated with Clinical Outcomes following Immunotherapy in Advanced Melanoma.

Outcomes for patients with melanoma have improved over the past decade as a result of the development and FDA approval of immunotherapies targeting cytotoxic T lymphocyte antigen-4 (CTLA-4), programmed death-1 (PD-1), and programmed death ligand 1 (PD-L1). However, these therapies do not benefit all patients, and an area of intensive research investigation is identifying biomarkers that can predict which patients are most likely to benefit from them. Here, we report exploratory analyses of the associations of tumor mutational burden (TMB), a 4-gene inflammatory gene expression signature, and mutation status with tumor response, progression-free survival, and overall survival in patients with advanced melanoma treated as part of the CheckMate 066 and 067 phase III clinical trials evaluating immuno-oncology therapies.

Trajectories of clinical and laboratory characteristics associated with COVID-19 in hemodialysis patients by survival.

Introduction: The clinical impact of COVID-19 has not been established in the dialysis population. We evaluated the trajectories of clinical and laboratory parameters in hemodialysis (HD) patients.

Methods: We used data from adult HD patients treated at an integrated kidney disease company who received a reverse transcription polymerase chain reaction (RT-PCR) test to investigate suspicion of a severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection between May 1 and September 1, 2020.

Real-time prediction of intradialytic relative blood volume: a proof-of-concept for integrated cloud computing infrastructure.

Background: Inadequate refilling from extravascular compartments during hemodialysis can lead to intradialytic symptoms, such as hypotension, nausea, vomiting, and cramping/myalgia. Relative blood volume (RBV) plays an important role in adapting the ultrafiltration rate which in turn has a positive effect on intradialytic symptoms. It has been clinically challenging to identify changes RBV in real time to proactively intervene and reduce potential negative consequences of volume depletion.

Strong yet incomplete reproductive isolation in is not contradicted by other lines of evidence: A reply to Toews et al.

Toews et al. assert that strong reproductive isolation in is inconsistent with other lines of evidence. Here, we discuss how strong yet incomplete reproductive isolation is consistent with other results from this system.

GPs' perceptions of their relationship with the pharmaceutical industry: a qualitative study.

Background: The pharmaceutical industry invests heavily in promoting medications to physicians. This promotion may influence physicians' prescribing behaviour and lead to inappropriately increased prescribing rates.

Aim: To understand GPs' experience of interacting with the pharmaceutical industry, and explore their views and perceptions of the impact of this interaction in general practice in Ireland.

Machine learning directed interventions associate with decreased hospitalization rates in hemodialysis patients.

Background: An integrated kidney disease company uses machine learning (ML) models that predict the 12-month risk of an outpatient hemodialysis (HD) patient having multiple hospitalizations to assist with directing personalized interdisciplinary interventions in a Dialysis Hospitalization Reduction Program (DHRP). We investigated the impact of risk directed interventions in the DHRP on clinic-wide hospitalization rates.

Methods: We compared the hospital admission and day rates per-patient-year (ppy) from all hemodialysis patients in 54 DHRP and 54 control clinics identified by propensity score matching at baseline in 2015 and at the end of the pilot in 2018.

Sigmoid volvulus: definitive surgery is safe and should be considered in all instances.

Background: Acute sigmoid volvulus (ASV) represents a small but significant portion of cases of large bowel obstruction, especially in the elderly and co-morbid. Given the characteristics of the patient cohort most commonly affected, a non-operative/conservative approach is often undertaken but is associated with a high rate of recurrence.

Objective: We sought to evaluate outcomes for those patients who underwent non-operative management, emergency surgery or staged, semi-elective surgery following decompression for ASV at our institution.

Selective blood-brain barrier permeabilization of brain metastases by a type 1 receptor-selective tumor necrosis factor mutein.

Background: Metastasis to the brain is a major challenge with poor prognosis. The blood-brain barrier (BBB) is a significant impediment to effective treatment, being intact during the early stages of tumor development and heterogeneously permeable at later stages. Intravenous injection of tumor necrosis factor (TNF) selectively induces BBB permeabilization at sites of brain micrometastasis, in a TNF type 1 receptor (TNFR1)-dependent manner.

A protocol for the evaluation of the process and impact of embedding formal and experiential Public and Patient Involvement training in a structured PhD programme.

Background: Incorporating Public and Patient Involvement (PPI) into doctoral research is valued by PhD scholars. The importance of providing early career researchers with appropriate education and training to develop skills to conduct meaningful involvement has been articulated. The Collaborative Doctoral Award in MultiMorbidity (CDA-MM) PhD programme embedded formal PPI training as a postgraduate education component.

Clinical outcomes of patients with corticosteroid refractory immune checkpoint inhibitor-induced enterocolitis treated with infliximab.

Introduction: Immune checkpoint inhibitors (CPIs) have changed the treatment landscape for many cancers, but also cause severe inflammatory side effects including enterocolitis. CPI-induced enterocolitis is treated empirically with corticosteroids, and infliximab (IFX) is used in corticosteroid-refractory cases. However, robust outcome data for these patients are scarce.

Severe progressive scarring pembrolizumab-induced lichen planopilaris in a patient with metastatic melanoma.

Lichenoid reactions are one of the many cutaneous immune-related adverse events seen with the use of immune checkpoint inhibitors, particularly anti-PD1 inhibitors. We present a rare care of severe lichen planopilaris secondary to pembrolizumab, with progression even after cessation of immunotherapy. It is important to recognise the significant long-term impact of these cutaneous adverse effects on patient's quality of life.

Re-induction ipilimumab following acquired resistance to combination ipilimumab and anti-PD-1 therapy.

Purpose: Combination immunotherapy with nivolumab and ipilimumab has a high initial response rate in advanced melanoma; however, up to 55% of patients later progress. The efficacy and safety of ipilimumab re-induction in the setting of acquired resistance (AR) to combination immunotherapy is unknown.

Methods: Patients with advanced melanoma who initially achieved a complete response, partial response or sustained stable disease to induction combination immunotherapy then progressed and were reinduced with ipilimumab (alone or in combination with anti-PD-1) and were analysed retrospectively.

Hyperacute toxicity with combination ipilimumab and anti-PD1 immunotherapy.

Background: Combination ipilimumab and nivolumab is approved for several malignancies. Toxicity most often occurs 6-10 weeks into treatment. Whether very early toxicity is harder to manage or influences efficacy is unknown.

5-Year Outcomes with Cobimetinib plus Vemurafenib in BRAFV600 Mutation-Positive Advanced Melanoma: Extended Follow-up of the coBRIM Study.

Purpose: The randomized phase III coBRIM study (NCT01689519) demonstrated improved progression-free survival (PFS) and overall survival (OS) with addition of cobimetinib to vemurafenib compared with vemurafenib in patients with previously untreated BRAFV600 mutation-positive advanced melanoma. We report long-term follow-up of coBRIM, with at least 5 years since the last patient was randomized.

Patients And Methods: Eligible patients were randomized 1:1 to receive either oral cobimetinib (60 mg once daily on days 1-21 in each 28-day cycle) or placebo in combination with oral vemurafenib (960 mg twice daily).

Radiation Therapy for Brain Metastases: A Systematic Review.

Purpose: This evidence report synthesizes the available evidence on radiation therapy for brain metastases.

Methods And Materials: The literature search included PubMed, EMBASE, Web of Science, Scopus, CINAHL, clinicaltrials.gov, and published guidelines in July 2020; independently submitted data, expert consultation, and contacting authors.

Exercise Improves Cancer-free Survival and Health Span in a Model of Radiation-induced Cancer.

Introduction: Radiation therapy increases the risk of secondary malignancy and morbidity in cancer survivors. The role of obesity and exercise training in modulating this risk is not well understood. As such, we used a preclinical model of radiation-induced malignancy to investigate whether diet-induced obesity and/or endurance exercise training altered lifelong survival, cancer incidence, and morbidity.

Safety of vaccines used for routine immunization in the United States: An updated systematic review and meta-analysis.

Background: Understanding the safety of vaccines is critical to inform decisions about vaccination. Our objective was to conduct a systematic review of the safety of vaccines recommended for children, adults, and pregnant women in the United States.

Methods: We searched the literature in November 2020 to update a 2014 Agency for Healthcare Research and Quality review by integrating newly available data.

Allocation of scarce resources in a pandemic: rapid systematic review update of strategies for policymakers.

Objective: In pandemics like COVID-19, the need for medical resources quickly outpaces available supply. policymakers need strategies to inform decisions about allocating scarce resources.

Study Design And Setting: We updated a systematic review on evidence-based approaches and searched databases through May 2020 for evaluation of strategies for policymakers.

Cytokine release syndrome in a patient with colorectal cancer after vaccination with BNT162b2.

Patients with cancer are currently prioritized in coronavirus disease 2019 (COVID-19) vaccination programs globally, which includes administration of mRNA vaccines. Cytokine release syndrome (CRS) has not been reported with mRNA vaccines and is an extremely rare immune-related adverse event of immune checkpoint inhibitors. We present a case of CRS that occurred 5 d after vaccination with BTN162b2 (tozinameran)-the Pfizer-BioNTech mRNA COVID-19 vaccine-in a patient with colorectal cancer on long-standing anti-PD-1 monotherapy.