Nicotinamide for Skin-Cancer Chemoprevention in Transplant Recipients.

Background: Immunosuppressed organ-transplant recipients have an increased incidence of, and mortality from, skin cancer. Nicotinamide (vitamin B) enhances the repair of ultraviolet (UV) radiation-induced DNA damage, reduces the cutaneous immunosuppressive effects of UV radiation, and reduces the incidence of keratinocyte cancers (including squamous-cell and basal-cell carcinomas) and actinic keratoses among high-risk immunocompetent patients. Whether oral nicotinamide is useful for skin-cancer chemoprevention in organ-transplant recipients is unclear.

Transferring patients from high-dose methadone to buprenorphine: A retrospective case series.

Objective: Transferring from methadone to buprenorphine can be difficult, -particularly at higher methadone doses. Precipitated withdrawal (PW) and severe opioid withdrawal can compromise transfers and limited data guide high-dose transfers. This study describes processes and outcomes of transfers to buprenorphine from methadone.

Tumor-Infiltrating Lymphocyte Therapy or Ipilimumab in Advanced Melanoma.

Background: Immune checkpoint inhibitors and targeted therapies have dramatically improved outcomes in patients with advanced melanoma, but approximately half these patients will not have a durable benefit. Phase 1-2 trials of adoptive cell therapy with tumor-infiltrating lymphocytes (TILs) have shown promising responses, but data from phase 3 trials are lacking to determine the role of TILs in treating advanced melanoma.

Methods: In this phase 3, multicenter, open-label trial, we randomly assigned patients with unresectable stage IIIC or IV melanoma in a 1:1 ratio to receive TIL or anti-cytotoxic T-lymphocyte antigen 4 therapy (ipilimumab at 3 mg per kilogram of body weight).

Long-Term Outcomes After Atrial Switch Operation for Transposition of the Great Arteries.

Background: For patients with d-loop transposition of the great arteries (d-TGA) with a systemic right ventricle after an atrial switch operation, there is a need to identify risks for end-stage heart failure outcomes.

Objectives: The authors aimed to determine factors associated with survival in a large cohort of such individuals.

Methods: This multicenter, retrospective cohort study included adults with d-TGA and prior atrial switch surgery seen at a congenital heart center.

The norepinephrine reuptake inhibitor reboxetine alone reduces obstructive sleep apnea severity: a double-blind, placebo-controlled, randomized crossover trial.

Study Objectives: Recent findings indicate that noradrenergic and muscarinic processes are crucial for pharyngeal muscle control during sleep. However, to date, reductions in obstructive sleep apnea (OSA) severity have only been detected when noradrenergic agents are combined with an antimuscarinic. Accordingly, this study aimed to determine if reboxetine alone and combined with oxybutynin reduces OSA severity.

Efficacy of a digital cognitive behavioral therapy for insomnia in people with low back pain: a feasibility randomized co-twin and singleton-controlled trial.

Background: Digital cognitive behavioral therapy for insomnia (CBT-i) in people with low back pain (LBP) may be efficacious in improving both sleep and pain; and twin trial designs provide greater precision of treatment effects by accounting for genetic and early environmental factors. We aimed to determine the feasibility of a trial investigating the efficacy of a digital CBT-i program in people with comorbid symptoms of insomnia and LBP, in twins and people from the general community (singletons).

Methods: Thirty-two twins (16 pairs) and 66 singletons with comorbid symptoms of insomnia and LBP (> 6 weeks duration) were randomized to digital CBT-i (intervention) or educational program (control) for 6 weeks.

Predictors of Sentinel Lymph Node Metastasis in Patients with Thin Melanoma: An International Multi-institutional Collaboration.

Background: Consideration of sentinel lymph node biopsy (SLNB) is recommended for patients with T1b melanomas and T1a melanomas with high-risk features; however, the proportion of patients with actionable results is low. We aimed to identify factors predicting SLNB positivity in T1 melanomas by examining a multi-institutional international population.

Methods: Data were extracted on patients with T1 cutaneous melanoma who underwent SLNB between 2005 and 2018 at five tertiary centers in Europe and Canada.

Survey of brachytherapy training experience among radiation oncology trainees and fellows in the Royal Australian and New Zealand College of Radiologists (RANZCR).

Introduction: To evaluate brachytherapy training experience among trainees and fellows trained through the Royal Australian and New Zealand College of Radiologists (RANZCR).

Methods: All current trainees and fellows (who obtained fellowship from 2015 onwards) were sent an online anonymous questionnaire on various aspects of brachytherapy training, including number of cases observed/ performed, opinions on brachytherapy assessment during training, barriers to brachytherapy training and future role of brachytherapy.

Results: The overall survey response rate was 24% (40/161 trainees, 30/126 fellows).

Extended Versus Standard Antibiotic Course Duration in Children <5 Years of Age Hospitalized With Community-acquired Pneumonia in High-risk Settings: Four-week Outcomes of a Multicenter, Double-blind, Parallel, Superiority Randomized Controlled Trial.

Background: High-level evidence is limited for antibiotic duration in children hospitalized with community-acquired pneumonia (CAP) from First Nations and other at-risk populations of chronic respiratory disorders. As part of a larger study, we determined whether an extended antibiotic course is superior to a standard course for achieving clinical cure at 4 weeks in children 3 months to ≤5 years old hospitalized with CAP.

Methods: In our multinational (Australia, New Zealand, Malaysia), double-blind, superiority randomized controlled trial, children hospitalized with uncomplicated, radiographic-confirmed, CAP received 1-3 days of intravenous antibiotics followed by 3 days of oral amoxicillin-clavulanate (80 mg/kg, amoxicillin component, divided twice daily) and then randomized to extended (13-14 days duration) or standard (5-6 days) antibiotics.

My pathway to a career in neuropathology.

(No abstract).

Narrow doorways alter brain connectivity and step patterns in isolated REM sleep behaviour disorder.

Background: Motor impairments in those with isolated REM sleep behaviour disorder (iRBD) significantly increases the likelihood of developing Lewy body disease (e.g. Parkinson's disease and Dementia with Lewy Bodies).

Evaluation of pharmacogenomics and hepatic nuclear imaging-related covariates by population pharmacokinetic models of irinotecan and its metabolites.

Background: Body surface area (BSA)-based dosing of irinotecan (IR) does not account for its pharmacokinetic (PK) and pharmacodynamic (PD) variabilities. Functional hepatic nuclear imaging (HNI) and excretory/metabolic/PD pharmacogenomics have shown correlations with IR disposition and toxicity/efficacy. This study reports the development of a nonlinear mixed-effect population model to identify pharmacogenomic and HNI-related covariates that impact on IR disposition to support dosage optimization.

The self-peptide repertoire plays a critical role in transplant tolerance induction.

While direct allorecognition underpins both solid organ allograft rejection and tolerance induction, the specific molecular targets of most directly alloreactive CD8+ T cells have not been defined. In this study, we used a combination of genetically engineered major histocompatibility complex class I (MHC I) constructs, mice with a hepatocyte-specific mutation in the class I antigen-presentation pathway, and immunopeptidomic analysis to provide definitive evidence for the contribution of the peptide cargo of allogeneic MHC I molecules to transplant tolerance induction. We established a systematic approach for the discovery of directly recognized pMHC epitopes and identified 17 strongly immunogenic H-2Kb-associated peptides recognized by CD8+ T cells from B10.

Contemporary management of locoregionally advanced melanoma in Australia and New Zealand and the role of adjuvant systemic therapy.

Australia and New Zealand have the highest incidence and mortality rates for melanoma in the world. Local surgery is still the standard treatment of primary cutaneous melanoma, and it is therefore important that surgeons understand the optimal care pathways for patients with melanoma. Accurate staging is critical to ensure a reliable assessment of prognosis and to guide treatment selection.

Methods used to attribute costs avoided from pharmacist interventions in acute care: A scoping review.

Purpose: Cost-avoidance studies are common in pharmacy practice literature. This scoping review summarizes, critiques, and identifies current limitations of the methods that have been used to determine cost avoidance associated with pharmacists' interventions in acute care settings.

Methods: An Embase and MEDLINE search was conducted to identify studies that estimated cost avoidance from pharmacist interventions in acute care settings.

Right ventricular myocardial deoxygenation in patients with pulmonary artery hypertension.

Background: In pulmonary arterial hypertension (PAH), progressive right ventricular (RV) dysfunction is believed to be largely secondary to RV ischaemia. A recent pilot study has demonstrated the feasibility of Oxygen-sensitive (OS) cardiovascular magnetic resonance (CMR) to detect in-vivo RV myocardial oxygenation. The aims of the present study therefore, were to assess the prevalence of RV myocardial ischaemia and relationship with RV myocardial interstitial changes in PAH patients with non-obstructive coronaries, and corelate with functional and haemodynamic parameters.

Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19.

Background: The efficacy of interleukin-6 receptor antagonists in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear.

Methods: We evaluated tocilizumab and sarilumab in an ongoing international, multifactorial, adaptive platform trial. Adult patients with Covid-19, within 24 hours after starting organ support in the intensive care unit (ICU), were randomly assigned to receive tocilizumab (8 mg per kilogram of body weight), sarilumab (400 mg), or standard care (control).

New cardiovascular prevention guidelines: How to optimally manage dyslipidaemia and cardiovascular risk in 2021 in patients needing secondary prevention?

Elevated low-density lipoprotein cholesterol (LDL-C) is a principally modifiable cause of atherosclerotic cardiovascular disease; accordingly, recent European and US multisociety dyslipidaemia guidelines emphasise the importance of lowering LDL-C to reduce cardiovascular risk. This review provides perspectives on established and emerging agents that reduce LDL-C to help providers synthesize the abundance of new evidence related to prevention of cardiovascular disease. We provide hypothetical cases of patients with different cardiovascular risk factors and medical histories to illustrate application of current lipid-lowering guidelines in various clinical settings.

Precaval recurrent endometrial cancer treated with en-bloc resection of the inferior vena cava and reconstruction using bovine pericardium. A case report and review of the literature.

•Bovine pericardium for IVC reconstruction has significant advantages comparing to vascular ligation, autogenous or PTFE grafts.•En-bloc resection of metastatic precaval lymph nodes and reconstruction of the IVC is feasible.•Recurrence of endometrial cancer at para-aortic lymph nodes is good candidate for secondary cytoreduction with MDT approach.

Glomangiomyoma of the clitoris: A case report and literature review.

Glomus tumor is an uncommon, benign, soft-tissue lesion in which the cells recapitulate the structure of the normal modified smooth muscle cells of the glomus body. Glomus tumors usually occur in tissues that normally contain glomus bodies; only rarely can they develop in sites where glomus bodies are normally sparse or absent. There are three subtypes of glomus tumor, with glomangiomyoma being the rarest.