A phase I dose escalation study of the HIF-2 alpha inhibitor DFF332 in patients with advanced clear cell renal cell carcinoma.

Background: Mutations or silencing of the von Hippel Lindau (VHL) tumor suppressor gene accumulates hypoxia-inducible factors (HIFs). HIF-2α is implicated in the oncogenesis of ~50% of patients with clear cell renal cell carcinoma (ccRCC) but, has been considered "undruggable". DFF332, an orally administered novel allosteric inhibitor of HIF-2α showed dose-dependent antitumor efficacy in preclinical models of ccRCC.

Cigarette smoking is associated with reduced neuroinflammation and better cognitive control in people living with HIV.

People living with HIV (HIV+) are roughly twice as likely to smoke cigarettes (Smok+) as the general population. With the advent of effective antiretroviral therapies, it is increasingly important to understand the effects of chronic HIV infection and cigarette smoking on brain function and cognition since HIV+ individuals have heightened neuroinflammation and cognitive deficits even with such therapies. Based on prior studies demonstrating that smoking reduces a marker for neuroinflammation in HIV- individuals, we hypothesized that HIV+/Smok+ individuals would have less neuroinflammation and better cognitive control than HIV+/Smok- individuals.

Preclinical and clinical evaluation through serial colonoscopic evaluation of neratinib-induced diarrhea in HER2-positive breast cancer-A pilot study.

The irreversible pan-HER tyrosine kinase inhibitor neratinib is approved for patients with HER2-positive, early-stage and metastatic breast cancer (BC). Neratinib-associated diarrhea is the most common reason for early discontinuation. Preclinical studies identified mechanisms of neratinib-induced diarrhea and rationale for prophylactic and preventive measures.

Androgen Receptor Splice Variant 7 in Asian Patients With Metastatic Castration-Resistant Prostate Cancer.

Purpose: Androgen receptor splice variant 7 (ARV-7) is a resistance mechanism to hormonal therapy in metastatic castrate-resistant prostate cancer (mCRPC). It has been associated with poor outcomes. On progression to castrate resistance, ARV-7 positivity has been identified in global populations at an incidence of 17.

A Cost-Consequence Analysis of Nutritional Interventions Used in Hospital Settings for Older Adults with or at Risk of Malnutrition.

Background: Malnutrition is a significant and prevalent issue in hospital settings, associated with increased morbidity and mortality, longer hospital stays, higher readmission rates, and greater healthcare costs. Despite the potential impact of nutritional interventions on patient outcomes, there is a paucity of research focusing on their economic evaluation in the hospital setting. This study aims to fill this gap by conducting a cost-consequence analysis (CCA) of nutritional interventions targeting malnutrition in the hospital setting.

A Conceptual Study on Characterizing the Complexity of Nutritional Interventions for Malnourished Older Adults in Hospital Settings: An Umbrella Review Approach.

Introduction: Malnutrition is a widespread and intricate issue among hospitalized adults, necessitating a wide variety of nutritional strategies to address its root causes and repercussions. The primary objective of this study is to systematically categorize nutritional interventions into simple or complex, based on their resource allocation, strategies employed, and predictors of intervention complexity in the context of adult malnutrition in hospital settings.

Methods: A conceptual evaluation of 100 nutritional intervention studies for adult malnutrition was conducted based on data from a recent umbrella review (patient population of mean age > 60 years).

The Clinical and Cost-Effectiveness of an Individualized Nutritional CAre (INCA) Bundle versus Standard Care for Adults with Pressure Injuries Receiving Home Nursing Services: A Protocol for a Cluster Randomized and Pragmatic Clinical Trial with an Economic Evaluation.

Background: Pressure injuries (PIs) represent a significant healthcare challenge in Singapore among the aging population. These injuries contribute to increased morbidity, mortality, and healthcare expenditure. Existing research predominantly explores single-component interventions in hospital environments, often yielding limited success.

Management of Metastatic Urothelial Carcinoma in Emerging Markets (EM): An Expert Opinion.

Urothelial carcinoma (UC) is the 10 most common cancer globally with an almost 4 times higher prevalence in men. The main risk factors for development of urothelial carcinoma are advanced age, smoking, arsenic contamination, exposure to carcinogens. Metastatic urothelial carcinoma (mUC) has overall poor prognosis with a 5-year overall survival rate of only < 5%.

Global Registry of Acute Coronary Events Score Underestimates Post-Acute Coronary Syndrome Mortality among Cancer Patients.

Background Patients with prior cancer are at increased risk of acute coronary syndrome (ACS) with poorer post-ACS outcomes. We aimed to ascertain if the Global Registry of Acute Coronary Events (GRACE) score accurately predicts mortality risk among patients with ACS and prior cancer. Methods We linked nationwide ACS and cancer registries from 2007 to 2018 in Singapore.

A review of strategies to overcome immune resistance in the treatment of advanced prostate cancer.

Immunotherapy has become integral in cancer therapeutics over the past two decades and is now part of standard-of-care treatment in multiple cancer types. While various biomarkers and pathway alterations such as dMMR and AR-V7 have been identified in advanced prostate cancer to predict immunotherapy responsiveness, the vast majority of prostate cancer remain intrinsically immune-resistant, as evidenced by low response rates to anti-PD(L)1 monotherapy. Since regulatory approval of the vaccine therapy sipuleucel-T in the biomarker-unselected population, there has not been much success with immunotherapy treatment in advanced prostate cancer.

Behavioural strategies to reduce obesity among lower socio-economic adults living in high-income countries: a Grades of Recommendation, Assessment, Development and Evaluation-assessed systematic review and meta-analysis of randomised controlled trials.

Adult obesity disproportionately affects lower socio-economic groups in high-income countries and perpetuates health inequalities, imposing health and socio-economic burden. This review evaluates the effectiveness of behavioural strategies in reducing weight and cardiovascular disease (CVD) risks among low-income groups based in high-income countries. We searched major databases for randomised controlled trials published between 1 November 2011 and 1 May 2023.

Management of Craniosynostosis in Lethal Perinatal Hypophosphatasia.

Although perinatal lethal hypophosphatasia (HPP) was once a disease with a universally poor prognosis, it has now become a rare but treatable condition with the advent of enzyme replacement therapy with asfotase alfa. As a result, a greater population of patients with perinatal HPP are presenting with abnormal head shape and craniosynostosis. The authors present here 3 cases of perinatal lethal HPP, 1 treated with traditional open cranial vault remodeling and 2 treated utilizing distraction osteogenesis techniques.

An Umbrella Review and Meta-analysis of Interventions, Excluding Enteral and Parenteral Nutrition, Initiated in the Hospital for Adults with or at Risk of Malnutrition.

Background: Multiple systematic reviews and meta-analyses (SRMAs) on various nutritional interventions in hospitalized patients with or at risk of malnutrition are available, but disagreements among findings raise questions about their validity in guiding practice.

Objectives: We conducted an umbrella review (a systematic review of systematic reviews in which all appropriate studies included in SRMAs are combined) to assess the quality of reviews, identify the types of interventions available (excluding enteral and parenteral nutrition), and re-analyze the effectiveness of interventions.

Methods: The databases MEDLINE/PubMed, CINAHL, Embase, The Cochrane Library, and Google Scholar were searched.

The Evolution of the Reconstructive Strategy for Elbow Flexion for Acute C5, C6 Brachial Plexus Injuries over Two Decades.

Background:  Over the course of the past two decades, improved outcomes following brachial plexus reconstruction have been attributed to newer nerve transfer techniques. However, key factors aside from surgical techniques have brought improved consistency to elbow flexion techniques in the latter decade.

Methods:  One-hundred seventeen patients who underwent brachial plexus reconstruction from 1996 to 2006 were compared with 120 patients from 2007 to 2017.

Outcomes and prognostic predictors of Lu-177 PSMA radioligand therapy in metastatic castration-resistant prostate cancer (Asian Population Study).

Aim: Lutetium-177 (Lu-177) prostate-specific membrane antigen radioligand therapy (PSMA-RLT) is a promising therapy for metastatic castration-resistant prostate cancer (mCRPC), but there is limited data of its efficacy and safety in Asian population. We aim to explore the clinical outcomes of Lu-177 PSMA-RLT in this population.

Methods: We evaluated 84 patients with progressive mCRPC receiving Lu-177 PSMA-RLT between 9 May 2018 and 21 February 2022.

An approach to genetic testing in patients with metastatic castration-resistant prostate cancer in Singapore.

Introduction: There has been a rapid evolution in the treatment strategies for metastatic castration-resistant prostate cancer (mCRPC) following the identification of targetable mutations, making genetic testing essential for patient selection. Although several international guidelines recommend genetic testing for patients with mCRPC, there is a lack of locally endorsed clinical practice guidelines in Singapore.

Method: A multidisciplinary specialist panel with representation from medical and radiation oncology, urology, pathology, interventional radiology, and medical genetics discussed the challenges associated with patient selection, genetic counselling and sample processing in mCRPC.

Quantifying the changes in the tumour vascular micro-environment in spinal metastases treated with stereotactic body radiotherapy - a single arm prospective study.

Background: The primary objective was to quantify changes in vascular micro-environment in spinal metastases (SM) patients treated with stereotactic body radiotherapy (SBRT) with multi-parametric dynamic contrast enhanced (DCE) magnetic resonance imaging (MRI). The secondary objective was to study plasma biomarkers related to endothelial apoptosis.

Patients And Methods: Patients were imaged with DCE-MRI at baseline/1-week/12-weeks post-SBRT.