A Dedicated Menopausal After Cancer Clinic May Improve Adherence to Endocrine Therapy For Breast Cancer: A Population Based Study.

Purpose: To examine utilization of a dedicated menopause symptoms after cancer clinic (MSAC) and to determine whether women referred to the MSAC for management of severe hot flush symptoms are more likely to adhere to endocrine therapy compare to those with severe symptoms not referred to MSAC.

Patients And Methods: Breast cancer patients prescribed endocrine therapy with a diagnosis of estrogen-receptor positive breast cancer between January 2003 and December 2011 were identified from the Royal Perth Hospital Breast Unit database. Details of breast cancer pathology, endocrine therapy, endocrine therapy related side effects, referral to MSAC and patient reported adherence to endocrine therapy for up to 4 years were ascertained from the database and medical records systems.

An evaluation of durvalumab across the spectrum of urothelial carcinoma.

Introduction: Urothelial carcinoma is a common malignancy affecting the urinary system, with the spectrum of disease encompassing non-muscle invasive, muscle-invasive and metastatic disease. On a background of almost half a century of immunogenic management with BCG, various immune checkpoint inhibitors, including durvalumab, have now demonstrated clinical efficacy in the treatment of urothelial carcinoma.

Areas Covered: This article reviews the available literature on durvalumab in the treatment of urothelial carcinoma for all stages of the disease including mechanisms of action, pharmacokinetics, efficacy and safety and covers a broad portfolio of reported and ongoing trials.

BMP4-Induced Suppression of Breast Cancer Metastasis Is Associated with Inhibition of Cholesterol Biosynthesis.

We reported previously that in preclinical models, BMP4 is a potent inhibitor of breast cancer metastasis and that high BMP4 protein levels predict favourable patient outcomes. Here, we analysed a breast cancer xenograft with or without enforced expression of BMP4 to gain insight into the mechanisms by which BMP4 suppresses metastasis. Transcriptomic analysis of cancer cells recovered from primary tumours and phosphoproteomic analyses of cancer cells exposed to recombinant BMP4 revealed that BMP4 inhibits cholesterol biosynthesis, with many genes in this biosynthetic pathway being downregulated by BMP4.

COVID-19 in children: Clinical presentation and hospital course at a district hospital in South Africa.

Unlabelled: Limited data exist on South African children hospitalised with COVID-19 in district hospitals. We describe the presentation and outcomes of children admitted to a level 1 and 2 hospital and compare this with children admitted to a level 2 and 3 hospital.

Contribution: This study highlights that young age is an important risk factor for hospitalisation with severe COVID-19.

Unleashing anti-tumour immunity: dietary restriction and exercise interventions adjunct to chemotherapy for cancer patients.

Conventional chemotherapies can stimulate the immune system by increasing tumour antigenicity (e.g., neoantigen exposure to immune cells) and altering adjuvanticity in the tumour (e.

Enhancing circulatory myokines and extracellular vesicle uptake with targeted exercise in patients with prostate cancer (the MYEX trial): a single-group crossover study.

Introduction: Physical activity is associated with improved disease progression and cancer-specific survival in patients with prostate cancer (PCa). However, the mechanisms underlying these associations remain unclear, while the relative impact of exercise modes is unknown. This study aims to examine the differential impact of exercise mode on tumour-suppressive skeletal muscle-associated systemic molecules as well as their delivery mechanism.

Eribulin in breast cancer: Current insights and therapeutic perspectives.

Eribulin is a non-taxane synthetic analogue approved in many countries as third-line treatment for the treatment of patients with metastatic breast cancer. In addition to its mitotic property, eribulin has non-mitotic properties including but not limited to, its ability to induce phenotypic reversal of epithelial to mesenchymal transition, vascular remodelling, reduction in immunosuppressive tumour microenvironment. Since approval, there has been a surge in studies investigating the application of eribulin as an earlier-line treatment and also in combination with other agents such as immunotherapy and targeted therapy across all breast cancer sub-types, including hormone receptor positive, HER2 positive and triple negative breast cancer, many demonstrating promising activity.

Clinical spectrum of disease and outcomes in children with Omicron SARS-COV-2 infection in Cape Town, South Africa.

Introduction: Children with underlying comorbidities and infants are most severely affected by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, including in low- and middle-income countries with a high prevalence of HIV and TB. We describe the clinical presentation of SARS-CoV-2 infection in children during the Omicron wave, in Cape Town, South Africa.

Methods: We analysed routine care data from a prospective cohort of children aged 0-13 years, with a positive SARS-CoV-2 real-time reverse-transcription polymerase chain reaction (rRT-PCR) or SARS-CoV-2 antigen test, admitted to Tygerberg Hospital between 1 November 2021 until 1 March 2022.

Designing a Smartphone-Based Pulse Oximeter for Children in South Africa (Phefumla Project): Qualitative Analysis of Human-Centered Design Workshops With Health Care Workers.

Background: Pulse oximeters noninvasively measure blood oxygen levels, but these devices have rarely been designed for low-resource settings and are inconsistently available at outpatient clinics.

Objective: The Phefumla project aims to develop and validate a pediatric smartphone-based pulse oximeter designed specifically for this context. We present the process of human-centered oximeter design with health care workers in South Africa.

Loss of tumor-derived SMAD4 enhances primary tumor growth but not metastasis following BMP4 signalling.

Background: Bone morphogenetic protein 4 (BMP4) is a potent inhibitor of breast cancer metastasis. However, a tumor-promoting effect of BMP4 is reported in other tumor types, especially when SMAD4 is inactive.

Methods: To assess the requirement for SMAD4 in BMP4-mediated suppression of metastasis, we knocked down SMAD4 in two different breast tumors and enforced SMAD4 expression in a third line with endogenous SMAD4 deletion.

Comparing fluorodeoxyglucose positron emission tomography with computed tomography in staging for nodal and distant metastasis in urothelial/bladder cancer.

Objectives: We aim to assess the clinical value of F-fluorodeoxyglucose positron (F-FDG-PET) scan in detecting nodal and distant metastasis compared with computed tomography (CT) scan in patients with urothelial carcinoma or bladder cancer, aiming to improve staging accuracy and thereby better prognosticate and determine therapy.

Methods: A retrospective review of 75 patients with invasive bladder cancer (≥T1) who were staged with both CT and F-FDG-PET within an 8-week interval was performed for the period between 2015 and 2020. Seventy-two per cent (54/75) had formal pelvic lymph node (LN) dissection or biopsy of lesions suspicious for metastases.

[Lu]Lu-PSMA-617 plus enzalutamide in patients with metastatic castration-resistant prostate cancer (ENZA-p): an open-label, multicentre, randomised, phase 2 trial.

Background: Enzalutamide and lutetium-177 [Lu]Lu-prostate-specific membrane antigen (PSMA)-617 both improve overall survival in patients with metastatic castration-resistant prostate cancer. Androgen and PSMA receptors have a close intracellular relationship, with data suggesting complementary benefit if targeted concurrently. In this study, we assessed the activity and safety of enzalutamide plus adaptive-dosed [Lu]Lu-PSMA-617 versus enzalutamide alone as first-line treatment for metastatic castration-resistant prostate cancer.

The socioeconomic impact of the COVID-19 lockdown on families affected by childhood respiratory illnesses in Cape Town, South Africa.

The COVID-19 pandemic impacted families globally, directly and indirectly. Children presenting with respiratory illnesses are affected by emerging health systems and socioeconomic changes in the COVID-19 era. We explored the socioeconomic impacts of the COVID-19 lockdown on families with a respiratory illness diagnosed in their child in Cape Town, South Africa.

The SUB-urothelial DUrvalumab InjEction-1 (SUBDUE-1) trial: first-in-human trial in patients with bladder cancer.

Objectives: To assess the safety of sub-urothelial injection of durvalumab and examine the impact on tissue and circulating immune cell populations.

Patients And Methods: The patients were chemotherapy and immunotherapy naïve (bacille Calmette-Guérin allowed) with non-metastatic muscle-invasive bladder cancer or non-muscle-invasive bladder cancer planned for radical cystectomy (RC). The study was a Phase Ib 3 + 3 dose-escalation design with sub-urothelial injection of durvalumab at three pre-determined doses (25, 75, 150 mg) diluted in 25 mL normal saline, injected at 25 locations (25 × 1 mL injections), at least 2 weeks before RC.

Bone mineral density fall during aromatase inhibitor treatment may predict lower breast cancer recurrence.

Purpose: Aromatase inhibitors (AIs) are associated with reduction in bone mineral density (BMD). The use of bone strengthening agents zoledronic acid and denosumab are associated with improved breast cancer outcomes for post-menopausal patients treated with AIs. This study investigates whether change in BMD with AI therapy is associated with breast cancer recurrence.

Overall survival with [Lu]Lu-PSMA-617 versus cabazitaxel in metastatic castration-resistant prostate cancer (TheraP): secondary outcomes of a randomised, open-label, phase 2 trial.

Background: The TheraP study reported improved prostate-specific antigen responses with lutetium-177 [Lu]Lu-PSMA-617 versus cabazitaxel in men with metastatic castration-resistant prostate cancer progressing after docetaxel. In this Article, we report the secondary outcome of overall survival with mature follow-up, and an updated imaging biomarker analysis. We also report the outcomes of participants excluded due to ineligibility on gallium-68 [Ga]Ga-PSMA-11 and 2-[F]fluoro-2-deoxy-D-glucose (2-[F]FDG) PET-CT.

Competencies of junior medical doctors in managing seriously ill and injured children: time to rethink our current training approach?

Background: The correct treatment of very ill and injured children is critical, yet little is known about the competencies of South African (SA) junior doctors in managing these children.

Methods: This survey documents SA junior doctors' reported resuscitation training opportunities, experience, skills and knowledge.

Results: A total of 118 doctors (interns, medical officers and registrars) from paediatric departments affiliated with 7 medical schools, participated.

Stromal inflammation, fibrosis and cancer: An old intuition with promising potential.

It is now well established that the biology of cancer is influenced by not only malignant cells but also other components of the tumour microenvironment. Chronic inflammation and fibrosis have long been postulated to be involved in carcinogenesis. Chronic inflammation can promote tumorigenesis growth factor/cytokine-mediated cellular proliferation, apoptotic resistance, immunosuppression; and free-radical-induced oxidative deoxyribonucleic acid damage.

Eyes for Ears: Usage and Efficacy of a Podcast for Ophthalmic Education.

Purpose: To characterize listenership and perceived educational impact of the ophthalmic podcast "Eyes for Ears".

Methods: A cross-sectional, internet-distributed, 9-question Qualtrics survey was made available to podcast listeners. Listenership metrics were analyzed from the podcast host platform.

A phase 1 study in healthy participants to characterize the safety and pharmacology of inclacumab, a fully human anti-P-selectin antibody, in development for treatment of sickle cell disease.

Purpose: We evaluated the safety, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of intravenous (IV) inclacumab, a fully human IgG4 anti-P-selectin monoclonal antibody in development for the treatment of sickle cell disease, at doses up to and exceeding those previously tested in healthy individuals.

Methods: In this phase 1, open-label, single-ascending-dose study, 15 healthy participants were enrolled into cohorts receiving 20 mg/kg (n = 6) or 40 mg/kg (n = 9) IV inclacumab and observed for up to 29 weeks post-dose. Safety, PK parameters, thrombin receptor-activating peptide (TRAP)-activated platelet-leukocyte aggregate (PLA) formation, P-selectin inhibition, plasma soluble P-selectin, and anti-drug antibodies were characterized.

Unpacking the Complexity of Epithelial Plasticity: From Master Regulator Transcription Factors to Non-Coding RNAs.

Cellular plasticity in cancer enables adaptation to selective pressures and stress imposed by the tumor microenvironment. This plasticity facilitates the remodeling of cancer cell phenotype and function (such as tumor stemness, metastasis, chemo/radio resistance), and the reprogramming of the surrounding tumor microenvironment to enable immune evasion. Epithelial plasticity is one form of cellular plasticity, which is intrinsically linked with epithelial-mesenchymal transition (EMT).