Reporting of scar outcomes in the hand and wrist; a state-of-the-art literature review

Objectives The aim of this literature review was to synthesise and report current practice in evaluation and reporting of scar outcomes in hand and wrist clinical research. Methods A systematic search from inception to 2022 was conducted using three electronic databases. English language randomized controlled trials and observational cohort studies reporting standardised scar outcome measures and/or scar symptoms, appearance, impairment, function, or mental health outcomes in patients with hand and wrist scars were included. Two independent reviewers determined study eligibility and performed data extraction of a priori identified scar outcome domains. Data analysis included descriptive statistics and identification of discordance in taxonomy. Results Fifty-nine studies were included. Elective surgery cohorts were the most frequently included clinical population (n = 28; 47%) followed by burns (n = 16; 27%). Six different standardised scar outcome measures were reported by 25% of studies however only 7% of studies utilised a patient-reported measure. Scar symptoms were the most frequently reported outcome domain (81%); but taxonomy was incongruous, constructs lacked working definitions required for generalisability and outcome measurement was variable and unreported. Nineteen different measures of scar appearance and structure were reported by 30 (51%) of studies however only nine (23%) were patient-reported. Seven different hand function PROMs were reported by 25 (43%) studies. Person-centred domains including scar acceptability (12%), mental health impact (5%), and social participation (4%) were rarely reported. Conclusions This review highlights that evaluation and reporting of hand and wrist scar outcomes is not standardised, assessment methods and measures are under-reported and there is discordance in taxonomy. Evaluation is not person-centred, rather it is dependent on clinician assessment. Domains including scar acceptability, mental health, and social participation are rarely addressed. A stakeholder consensus derived hand and wrist scar core outcome measurement set will promote standardisation and underpin improvements in clinical research quality, transparency, and rigour

Neoadjuvant Paradigm for Accelerated Drug Development: An Ideal Model in Bladder Cancer

Neoadjuvant cisplatin-based combination chemotherapy for muscle-invasive bladder cancer (MIBC) has been shown to confer a survival advantage in two randomized clinical trials and a meta-analysis. Despite level 1 evidence supporting its benefit, utilization remains dismal with nearly one-half of patients ineligible for cisplatin-based therapy because of renal dysfunction, impaired performance status, and/or coexisting medical problems. This situation highlights the need for the development of novel therapies for the management of MIBC, a disease with a lethal phenotype. The neoadjuvant paradigm in bladder cancer offers many advantages for accelerated drug development. First, there is a greater likelihood of successful therapy at an earlier disease state that may be characterized by less genomic instability compared with the metastatic setting, with an early readout of activity with results determined in months rather than years. Second, pre- and post-treatment tumor tissue collection in patients with MIBC is performed as the standard of care without the need for research-directed biopsies, allowing for the ability to perform important correlative studies and to monitor tumor response to therapy in “real time.” Third, pathological complete response (pT0) predicts for improved outcome in patients with MIBC. Fourth, there is a strong biological rationale with rapidly accumulating evidence for actionable targets in bladder cancer. This review focuses on the neoadjuvant paradigm for accelerated drug development using bladder cancer as the ideal model

Mechanisms of acquired resistance to androgen receptor targeting drugs in castration-resistant prostate cancer

After initial response to androgen receptor targeting drugs abiraterone or enzalutamide, most patients develop progressive disease and therefore, castration resistant prostate cancer (CRPC) remains a terminal disease. Multiple mechanisms underlying acquired resistance have been postulated. Intratumoral androgen synthesis may resume after abiraterone treatment. A point mutation in the ligand binding domain of androgen receptor may confer resistance to enzalutamide. Emergence of androgen receptor splice variants lacking the ligand binding domain may mediate resistance to abiraterone and enzalutamide. Steroid receptors such as glucocorticoid receptor may substitute for androgen receptor. Drugs with novel mechanisms of action or combination therapy, along with biomarkers for patient selection, may be needed to improve the therapy of CRPC

Peer observation of teaching: A decoupled process

This article details the findings of research into the academic teaching staff experience of peer observation of their teaching practice. Peer observation is commonly used as a tool to enhance a teacher’s continuing professional development. Research participants acknowledged its ability to help develop their teaching practice, but they also reported that it could operate superficially as a tick box exercise, that its outcomes were frequently decoupled from formal staff development processes, and that its purpose and usefulness therefore seemed unclear. This article argues that the presence of decoupling reinforces the need to account for structural factors that can interact with peer observation of teaching to ensure it is a meaningful exercise for all teaching staff. It concludes that the published academic literature is perhaps guilty of overplaying the role of personal choice and individual tutor characteristics when addressing the complex issue that is staff disengagement with peer observation of teaching

Effects of acute exercise and learning strategy implementation on memory function

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. Background and Objectives: Long-term potentiation (LTP), the functional connectivity among neurons, is considered a mechanism of episodic memory. Both acute exercise and learning are thought to influence memory via an LTP-related mechanism. Limited research has evaluated the individual and combined effects of acute exercise and learning strategy implementation (e.g., 3-R technique, cue-integration) on memory, which was the purpose of this study. Materials and Methods: For Experiment 1, participants (n = 80; Mage = 20.9 years) were randomized into one of four experimental groups, including Exercise + Learning (E + L), Learning Only (L), Exercise Only (E), and Control Group (C; no exercise and no learning strategy implementation). The exercise stimulus involved an acute 15-min bout of lower-intensity (60% of heart rate max) walking exercise and the learning strategy involved the implementation of the 3-R technique. Experiment 2 (n = 77; Mage = 21.1 years) replicated Experiment 1 but addressed limitations (e.g., exposure level of the memory task) from Experiment 1 and employed a higher-intensity bout of exercise (77% of heart rate max). Experiment 3 (n = 80; Mage = 21.0 years) evaluated these same four experimental conditions but employed a cue-integration learning strategy and a moderate-intensity bout of acute exercise (64% of heart rate max). Results: These three experiments demonstrate that both learning techniques were effective in enhancing memory and we also provided evidence of a main effect for acute exercise (Experiment 3). However, we did not observe consistent evidence of a learning by exercise interaction effect. Conclusions: We demonstrate that both acute exercise and different learning techniques are effective in enhancing long-term memory function

Quantitative single cell determination of ERK phosphorylation and regulation in relapsed and refractory primary acute myeloid leukemia

: We investigated the constitutive activation of the MEK/ERK pathway in acute myelogenous leukemia (AML) via a flow cytometric technique to quantitate expression of phosphorylated ERK (p-ERK). A total of 42 AML samples (16 newly diagnosed, 26 relapsed/refractory) were analyzed. Normal bone marrow CD34+ cells (n = 10) had little or no expression of p-ERK, while G-CSF-mobilized CD34+ cells exhibited enhanced p-ERK levels. Markedly elevated p-ERK levels were found in 83.3% of the AML samples, with no differences observed between the newly diagnosed and relapsed/refractory samples. Treatment with a MEK inhibitor resulted in significantly decreased p-ERK levels in both the newly diagnosed and relapsed/refractory samples, which was associated with growth arrest, but not apoptosis induction. In summary, we defined conditions for the analysis of MAPK signaling in primary AML samples. Normal CD34+ cells expressed very low levels of p-ERK, and increased p-ERK levels were found in normal G-CSF-stimulated circulating CD34+ cells. Constitutively high p-ERK levels observed in the majority of AML samples suggest deregulation of this pathway that appears to be independent of disease status. The ability of ERK inhibition to promote growth arrest rather than apoptosis suggests that clinical trials of MEK/ERK inhibitors may be more effective when combined with chemotherapy

Intrinsic subtypes of high-grade bladder cancer reflect the hallmarks of breast cancer biology

The identification of molecular subtype heterogeneity in breast cancer has allowed a deeper understanding of breast cancer biology. We present evidence that there are two intrinsic subtypes of high-grade bladder cancer, basal-like and luminal, which reflect the hallmarks of breast biology. Moreover, we have developed an accurate gene set predictor of molecular subtype, the BASE47, that should allow the incorporation of subtype stratification into clinical trials. Further clinical, etiologic, and therapeutic response associations will be of interest in future investigations