Evaluation of urological and gynecological surgeons as force multipliers for mass Casualty trauma care.

BACKGROUND: The clinical demands of mass casualty events strain even the most well-equipped trauma centers and are especially challenging in resource-limited rural, remote, or austere environments. Gynecologists and urologists care for patients with pelvic and abdominal injuries, but the extent to which they are able to serve as "force multipliers" for trauma care is unclear. This study examined the abilities of urologists and gynecologists to perform 32 trauma procedures after mentored training by expert trauma educators to inform the potential for these specialists to independently care for trauma patients. METHODS: Urological (6), gynecological surgeons (6), senior (PGY5) general surgery residents (6), and non-trauma trained general surgeons (8) completed a rigorous trauma training program (ASSET+). All participants were assessed in their trauma knowledge and surgical abilities performing 32 trauma procedures pre/post mentored training by expert trauma surgeons. Performance benchmarks were set for knowledge (80%) and independent, accurate completion of all procedural components within a realistic time window (90%). RESULTS: General surgery participants demonstrated greater trauma knowledge than gynecologists and urologists; however, none of the specialties reached the 80% benchmark. Pre-training, general surgery and urology participants outperformed gynecologists for overall procedural abilities. Post-training, only general surgeons met the 90% benchmark. Post-hoc analysis revealed no differences between the groups performing most pelvic and abdominal procedures, however knowledge associated with decision making and judgment in the provision of trauma care was significantly below the benchmark for gynecologists and urologists, even after training. CONCLUSION: For physiologically stable patients with traumatic injuries to the abdomen, pelvis or retroperitoneum, these specialists might be able to provide appropriate care; however, they would best benefit trauma patients in the capacity of highly skilled assisting surgeons to trauma specialists. These specialists should not be considered for solo resuscitative surgical care. LEVEL OF EVIDENCE: Therapeutic/Care Management, Level III/IV.

Use of a novel microbiome modulator improves anticancer immunity in a murine model of malignant pleural mesothelioma.

Objective: Malignant pleural mesothelioma is a fatal disease and a clinical challenge, as few effective treatment modalities are available. Previous evidence links the gut microbiome to the host immunoreactivity to tumors. We thus evaluated the impact of a novel microbiome modulator compound (MMC) on the gut microbiota composition, tumor immune microenvironment, and cancer control in a model of malignant pleural mesothelioma. Methods: Age- and weight-matched immunocompetent (n = 23) or athymic BALB/c mice (n = 15) were randomly assigned to MMC or no treatment (control) groups. MMC (31 ppm) was administered through the drinking water 14 days before AB12 malignant mesothelioma cell inoculation into the pleural cavity. The impact of MMC on tumor growth, animal survival, tumor-infiltrating leucocytes, gut microbiome, and fecal metabolome was evaluated and compared with those of control animals. Results: The MMC delayed tumor growth and significantly prolonged the survival of immunocompetent animals (P = .0015) but not that of athymic mice. The improved tumor control in immunocompetent mice correlated with increased infiltration of CD3+CD8+GRZB+ cytotoxic T lymphocytes in tumors. Gut microbiota analyses indicated an enrichment in producers of short chain fatty acids in MMC-treated animals. Finally, we observed a positive correlation between the level of fecal short chain fatty acids and abundance of tumor-infiltrating cytotoxic T cells in malignant pleural mesothelioma. Conclusions: MMC administration boosts antitumor immunity, which correlates with a change in gut microbiome and metabolome. MMC may represent a valuable treatment option to combine with immunotherapy in patients with cancer.

Missing in action: A bibliometric analysis of military research in the medical literature since 1950.

BACKGROUND: Top-tier general and specialty scientific journals serve as a bellwether for national research priorities. We hypothesize that military-relevant publications are underrepresented in the scientific literature and that such publications decrease significantly during peacetime. METHODS: We identified high impact journals in the fields of Medicine, Surgery and Critical Care and developed Boolean searches for military-focused topics using National Library of Medicine Subject Headings terms. A PubMed search from 1950 to 2020 returned the number of research publications in relevant journals and the rate of military-focused publications by year. Rates of military publications were compared between peacetime and wartime. Publication rate trends were modeled with a quadratic function controlling for the start of active conflict and total casualty numbers. Baseline proportions of military physicians relative to the civilian sector served to estimate expected publication rates. Comparisons were performed using Pearson's Chi Square and Mann-Whitney U test, with p < 0.05 considered a significant difference. RESULTS: From 1950 to 2020, a total of 716,340 manuscripts were published in the journals queried. Of these, military-relevant manuscripts totaled 4,052 (0.57%). We found a significant difference in the rate of publication during times of peace and times of war (0.40% vs. 0.69%, p < 0.001). Subgroup analysis found significantly reduced rates of publication in medical and critical care journals during peacetime. For each conflict, the percentage of military-focused publications peaked during periods of war but then receded below baseline levels within a median of 2.5 years (interquartile range 1.5-3.8 years) during peacetime. The proportion of military-focused publications never reached the current proportion of military physicians in the workforce. CONCLUSION: There is marked reduction in rates of publication for military-focused articles in high impact journals during peacetime. Military-focused articles are underrepresented in high-impact journals. Investigators of military-relevant topics and editors of high-impact journals should seek to close this gap.

From Blur to Brilliance: The Ascendance of Advanced Microscopy in Neuronal Cell Biology.

The intricate network of the brain's neurons and synapses poses unparalleled challenges for research, distinct from other biological studies. This is particularly true when dissecting how neurons and their functional units work at a cell biological level. While traditional microscopy has been foundational, it was unable to reveal the deeper complexities of neural interactions. However, an imaging renaissance has transformed our capabilities. Advancements in light and electron microscopy, combined with correlative imaging, now achieve unprecedented resolutions, uncovering the most nuanced neural structures. Maximizing these tools requires more than just technical proficiency. It is crucial to align research aims, allocate resources wisely, and analyze data effectively. At the heart of this evolution is interdisciplinary collaboration, where various experts come together to translate detailed imagery into significant biological insights. This review navigates the latest developments in microscopy, underscoring both the promise of and prerequisites for bending this powerful tool set to understanding neuronal cell biology.

Moving from conventional to adaptive risk stratification for oropharyngeal cancer.

Oropharyngeal cancer (OPC) poses a complex therapeutic dilemma for patients and oncologists alike, made worse by the epidemic increase in new cases associated with the oncogenic human papillomavirus (HPV). In a counterintuitive manner, the very thing which gives patients hope, the high response rate of HPV-associated OPC to conventional chemo-radiation strategies, has become one of the biggest challenges for the field as a whole. It has now become clear that for ~30-40% of patients, treatment intensity could be reduced without losing therapeutic efficacy, yet substantially diminishing the acute and lifelong morbidity resulting from conventional chemotherapy and radiation. At the same time, conventional approaches to de-escalation at a population (selected or unselected) level are hampered by a simple fact: we lack patient-specific information from individual tumors that can predict responsiveness. This results in a problematic tradeoff between the deleterious impact of de-escalation on patients with aggressive, treatment-refractory disease and the beneficial reduction in treatment-related morbidity for patients with treatment-responsive disease. True precision oncology approaches require a constant, iterative interrogation of solid tumors prior to and especially during cancer treatment in order to tailor treatment intensity to tumor biology. Whereas this approach can be deployed in hematologic diseases with some success, our ability to extend it to solid cancers with regional metastasis has been extremely limited in the curative intent setting. New developments in metabolic imaging and quantitative interrogation of circulating DNA, tumor exosomes and whole circulating tumor cells, however, provide renewed opportunities to adapt and individualize even conventional chemo-radiation strategies to diseases with highly variable biology such as OPC. In this review, we discuss opportunities to deploy developing technologies in the context of institutional and cooperative group clinical trials over the coming decade.

The provision of general surgery in rural Australia: a narrative review.

Rural surgery is most commonly provided by general surgeons to the 29% of people (7 million) living in rural Australia. The provision of rural general surgery to enable equitable and safe surgical care for rural Australians is a multifaceted issue concerning recruitment, training, retention, surgical procedures and surgical outcomes. Sustaining the rural general surgical workforce will be dependent upon growing an increased number of resident rural general surgeons, as well as changed models of care, with a need for ongoing review to track the outcomes of these changes. To increase recruitment, rural general surgical training must improve to be less stressful for trainees and to be incorporated alongside a rural-facing generalist curriculum. Rural general surgical outcomes (excluding some oncology conditions) achieve comparable results to metropolitan centres. Access to, and outcomes of, surgical oncology services continues to be inequitable for rural Australians and should be a major focus for improved service delivery.

Prevalence of Renal Neoplasia in Autosomal Dominant Polycystic Kidney Disease: Systematic Review and Meta-analysis.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited condition, however its relationship with renal cell carcinoma (RCC) remains unclear. This paper aims to establish the prevalence of RCC and its subtypes amongst ADPKD patients. METHODS: A database search was conducted to retrieve studies reporting RCC occurrence within ADPKD patients until July 2023. Key outcomes included number and subtype of RCC cases, and number of RCCs presenting incidentally. A random-effects meta-analysis was performed. RESULTS: Our search yielded 569 articles, 16 met the inclusion criteria. Nephrectomy specimens from 1,147 ADPKD patients were identified. Of studies reporting per-kidney results (n = 13), 73 RCCs were detected amongst 1,493 kidneys, equating to a per-kidney prevalence of 4.3% (95% CI, 3.1 to 5.7, I2 = 15.7%). 75 ADPKD patients were found to have RCC (75/1147), resulting in a per-person prevalence of 5.7% (95% CI, 3.7 to 7.9, I2 = 40.3%) (n = 16). As 7 patients had bilateral disease, 82 RCCs were detected in total. Of these, 39 were clear cell RCC, 35 were papillary and 8 were other. As such, papillary RCCs made up 41.1% (95% CI, 25.9 to 56.9, I2 = 18.1%) of detected cancers. The majority of RCCs were detected incidentally (72.5% [95% CI, 43.7 to 95.1, I2 = 66.9%]). CONCLUSION: ADPKD appears to be associated with the papillary RCC subtype. The clinical implications of these findings are unclear, however may become apparent as outcomes and life expectancy amongst APDKD patients improve.

Vasovasostomy: A systematic review and meta-analysis comparing macroscopic, microsurgical, and robot-assisted microsurgical techniques.

BACKGROUND AND OBJECTIVES: Vasovasostomy is a cost-effective procedure for the reversal of vasectomy. A water-tight adequately blood-supplied mucosal anastomosis is required for better outcomes. This review aimed to compare the outcome of vasovasostomy performed by three different techniques: macroscopic, pure microsurgical, and robot-assisted microsurgical techniques. METHODS: Scopus, Web of Science, PubMed, Embase, and Cochrane library databases were searched for relevant studies from January 1901 to June 2023. We conducted our quantitative syntheses using the inverse variance method in OpenMeta software. The study's protocol was registered on PROSPERO. RESULTS: This review involved 95 studies of different designs, with a total sample size of 48,132. The majority of operations were performed bilaterally, and participants were monitored for up to 10 years. The pooled patency rate was the highest following robot-assisted vasovasostomy (94.4%), followed by pure microsurgical vasovasostomy (87.5%), and macroscopic vasovasostomy (83.7%). The pooled pregnancy rate following purely microsurgical vasovasostomy was higher than that of macroscopic vasovasostomy (47.4 vs. 43.7%). Definitive pregnancy rates in robotic vasovasostomy are yet to be determined. CONCLUSION: Patency outcomes for vasovasostomy were best with robot-assisted microsurgical technique, followed by pure microsurgical technique, and conventional macroscopic technique. Further investigations of robot-assisted microsurgical vasovasostomy outcomes and randomized control trials are required to support this evidence.

Pre-rehabilitation interventions for patients with head and neck cancers: A systematic review and meta-analysis.

OBJECTIVE: To investigate the effect of pre-rehabilitation interventions such as nutrition and exercise for patients with head and neck cancer (HNC). METHODS: Web of Science, PubMed, Scopus, Google Scholar, and Cochrane databases were searched up to December 2022. Quality of life, length of hospital stay, postoperative complications, change in body mass index or muscle mass, and functional assessments were the primary outcomes. PRISMA guidelines were adhered to, and the study was registered on PROSPERO. The Cochrane Collaboration tool and Newcastle Ottawa scale assessed the quality of included studies. Pooled data are presented as odds ratios (OR) and 95% confidence intervals (CI). Analysis was conducted using RevMan5.4. RESULTS: A total of 31 articles were included for quantitative analysis and 15 for qualitative synthesis. Nutrition alone resulted in significant weight retention (2.60; 2.32, 2.88, p < 0.00001), length of stay (-4.00; -6.87, -1.13), p = 0.0006) and complications (0.64; 0.49, 0.83, p = 0.0009). Nutrition and psychoeducation resulted in a significant reduction in mortality rate (0.70; 0.49, 1.00, p = 0.05 and 0.60; 0.48, 0.74, p < 0.00001), and exercise resulted in a significant reduction in dysphagia (0.55; 0.35, 0.87, p = 0.01). Exercise with nutrition resulted in significant improvements in weight loss, length of stay, complications, and dysphagia. Randomized controlled trials (RCTs) had a moderate risk of bias and cohort studies were of fair to good quality. CONCLUSION: Prehabilitation programs based on exercise, nutrition, or psychoeducation demonstrated improved post-interventional outcomes in HNC, such as quality of life, and mortality and morbidity. Studies with longer follow-ups and larger sample sizes, and investigations comparing nutritional supplements with exercise programs are needed.

Effectiveness of wheelchair skills training for improving manual wheelchair mobility in children and adolescents: protocol for a multicenter randomized waitlist-controlled trial.

BACKGROUND: Self-directed mobility during childhood can influence development, social participation, and independent living later in life. For children who experience challenges with walking, manual wheelchairs (MWCs) provide a means for self-directed mobility. An effective MWC skills training program exists for adults, but controlled trials have not yet been documented in children and adolescents. This paper outlines the protocol for a multi-centre randomized wait-list controlled trial. The primary objective is to test the hypothesis that children and adolescents who receive MWC skills training will have higher MWC skills capacity compared to children and adolescents in the control group who receive usual care. The secondary objectives are to explore the influence of MWC skills training in children and adolescents (MWC use self-efficacy and satisfaction with participation in meaningful activities), and parents (perceived MWC skills); and to measure retention three months later. METHODS: A multi-centre, parallel-group, single-blind randomized wait-list controlled trial will be conducted. A sample of 60 children and adolescents who use MWCs will be recruited in rehabilitation centres, specialized schools, and the communities of three Canadian cities. Participants will be randomized (1:1) to the experimental (Wheelchair Skills Training Program [WSTP]) or wait-list control group (usual care). Performance-based and self-report measures will be completed at baseline (T1), three months (post-intervention, T2), and three months post-intervention (T3). The primary outcome will be MWC skills capacity post-intervention. Secondary outcomes will be MWC use self-efficacy and satisfaction with participation of the child/adolescent, and parent-perceived MWC skills. The WSTP will consist of 12 sessions, 45-60 min each, delivered 1-2 times per week by trained personnel with health professions education. Training will be customized according to the child's baseline skills and participation goals that require the use of the MWC. The wait-list control group will receive usual care for 3 months and then receive the WSTP after completing T2 evaluations. Data will be analysed using ANCOVA (controlling for baseline scores). DISCUSSION: MWC skills training may be one way to improve self-directed mobility and related outcomes for children and adolescents. The results of this multi-centre randomized wait-list controlled trial will allow for the effectiveness of the intervention to be evaluated in a variety of clinical contexts and geographical regions. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05564247, Version October 3, 2022.

Effects of the WHO 8-step wheelchair-service-delivery process on wheelchair users in El Salvador: a cohort study.

PURPOSE: To test the hypotheses that, after the delivery of manual wheelchairs following the WHO 8-step service-delivery process, wheelchair-related health and quality of life, wheelchair skills, wheelchair use, and poverty probability would improve; and that the number of wheelchair repairs required, adverse events, caregiver burden, and the level of assistance provided would decrease. METHODS: This was a longitudinal, prospective within-subject study including 247 manual wheelchair users, and 119 caregivers, in El Salvador who received a wheelchair following the WHO 8-step process as well as maintenance reminders. Outcome measurements were performed via structured questionnaires and dataloggers at the initial assessment, at wheelchair delivery, and at 3- and 6-month follow-up. RESULTS: Significant improvements in wheelchair-related health indicators (all with p < 0.004) and quality of life (p = 0.001), and a significant reduction in national and "extreme" poverty probability (p = 0.004 and p = 0.012) were observed by six months. Wheelchair use significantly decreased (p = 0.011 and p = 0.035) and wheelchair skills increased (p = 0.009). Caregiver burden did not change (p = 0.226) but the number of activities of daily living (ADLs) that required no assistance significantly increased (p = 0.001) by three months and those who required complete assistance decreased (p = 0.001). No changes were observed in wheelchair repairs (p = 0.967) and breakdowns over time with new wheelchairs. CONCLUSIONS: Wheelchair service delivery using the WHO 8-step process on manual wheelchair users in El Salvador has positive effects on health and quality of life, wheelchair skills, caregiver assistance levels, and poverty. Further research is needed to determine the relative contributions of the intervention components.Implications for RehabilitationProviding manual wheelchairs using the 8-step process of the WHO has benefits on health and quality of life, wheelchair skills, caregiver assistance levels, and poverty.The WHO 8-steps service delivery process for manual wheelchairs can be used in less-resourced settings.

Creating a sustainable rural general surgery workforce: what enables fellows to return as rural general surgeons?

INTRODUCTION: In the context of shortfalls in rural general surgeon supply, this research aims to explore why rural general surgical Fellows returned and remained after fellowship at a single rural centre in Victoria, Australia. Fellowship positions post achievement of Fellowship of the Australasian College of Surgeons are traditionally not funded by government because they currently fall outside the accredited rural training post funding provided by the federal government. This article aims to explore if fellowship positions can be an important part in sustaining the rural general surgery workforce. METHODS: Semi-structured interviews were conducted with nine former general surgery Fellows from a single rural Australian institution. Interviews were recorded, transcribed, coded and themed to undertake analysis according to thematic analysis. RESULTS: This research demonstrates that consultant rural general surgeons can be recruited from a fellowship year when emphasis is placed on: (1) creating a positive workplace culture with safe working hours, (2) ensuring diversification of the general surgical case mix, (3) facilitating opportunities for schooling and work for the surgeon's family, and (4) preferentially selecting for those who identify as rural general surgeons. Rural towns can effectively recruit general surgeons when families are supported with career and school opportunities, and the newly qualified surgeon can initially commit to a 12-month position so that opportunities can be assessed by the entire family unit. Fellowship positions (post completion of general surgical training) allow young surgeons to 'try before they buy' prior to moving to a rural area. CONCLUSION: Ensuring a sustainable general surgical workforce in a rural community requires employee and surgical leadership to ensure a collaborative and progressive culture, which offers work diversity, supports the family lifestyle and petitions for selecting those who embody the rural general surgeon identity. Post-fellowship positions can enable young general surgeons to have exposure to the realities of a rural lifestyle, which is likely to have a positive effect on recruitment. Due to the return investment of the fellowship program, we propose that the federal government should look at funding post-fellowship positions to improve rural recruitment.

Wheelchair Skills Test in simulated versus community settings: a mixed-methods crossover study of experienced motorized mobility scooter users.

PURPOSE: The Wheelchair Skills Test (WST) is commonly conducted in a simulated setting. Although the WST can be done in the community setting, its usefulness in this setting has not been systematically evaluated. The purpose of this study was to compare the WST in the simulated versus community settings, and to explore participants' perceptions of performing in each environment. METHODS: For this mixed-methods study, we studied 20 motorized mobility scooter users who had used their devices for ≥ 3 months. Each participant completed the WST Version 4.3 twice in random order - once in a simulated setting and once in their community within a two-week period. Semi-structured interviews were conducted after completion of the WST in both environments. A self-report version of the WST (WST-Q) was also completed that measured perceived capacity, frequency of skill performance, and confidence. RESULTS: The mean (SD) total WST score in the simulated setting was 88.9% (8.6) and 92.7% (7.8) in the community setting. The two WST scores were moderately correlated (r = 0.306, p = 0.190). Community-setting WST scores were moderately correlated with WST-Q confidence scores. Simulated-setting scores were moderately correlated with WST-Q frequency scores. Although most participants preferred performing the WST in their communities due to convenience and familiarity, they perceived the simulated setting to be reflective of their community settings. CONCLUSION: Despite challenges, community-based testing may provide a better reflection of everyday performance for scooter users than testing in a simulated environment.

IMPLICATIONS FOR REHABILITATIONWheelchair Skills Test (WST) scores obtained from conducting the assessment in the community may be different from those obtained from conducting the assessment in a simulated setting.Since the WST conducted in the community likely provides different information from the WST conducted in the lab, clinicians should carefully consider which environment to access wheelchair skills in.In an urban, community setting, all WST skills were able to be found within a one block radius of participants' homes.

Rural general surgeon confidence with managing vascular emergencies: A national survey.

OBJECTIVE(S): Life and limb threatening vascular emergencies often present to rural hospitals where only general surgery services are available. It is known that Australian rural general surgical centres encounter 10-20 emergency vascular surgery procedures annually. This study aimed to assess rural general surgeons' confidence managing emergent vascular procedures. SETTING, PARTICIPANTS AND DESIGN: A survey was distributed to Australian rural general surgeons to determine their confidence (Yes/No) in performing emergent vascular procedures including limb revascularisation, revising arterio-venous (AV) fistulas, open repair of ruptured abdominal aortic aneurysm (AAA), superior mesenteric artery (SMA)/coeliac embolectomy, limb embolectomy, vascular access catheter insertion and limb amputation (digit, forefoot, below knee and above knee). Confidence level was compared with surgeon demographics and training. Variables were compared using univariate logistic regression. RESULTS: Sixteen per cent (67/410) of all Australian rural general surgeons responded to the survey. Increased age, years since fellowship and training prior to 1995 (when separation of Australian vascular and general surgery occurred) were associated with greater confidence in limb revascularisation, revising AV fistulas, open repair of ruptured AAA, SMA/coeliac embolectomy, and limb embolectomy (p < 0.05). Surgeons who completed >6 months of vascular surgery training were more comfortable with SMA/coeliac embolectomy (49% vs. 17%, p = 0.01) and limb embolectomy (59% vs. 28%, p = 0.02). Confidence in performing limb amputation was similar across surgeon demographics and training (p > 0.05). CONCLUSION: Recently graduated rural general surgeons do not feel confident in managing vascular emergencies. Additional vascular surgery training should be considered as part of general surgical training and rural general surgical fellowships.

Demographic and applicant-specific predictors of medical school research productivity in a national cohort of dermatology residents.

Research is a crucial aspect of medical advancement, and applicants applying to dermatology often have high research outputs. With United States Medical Licensing Examination (USMLE) Step 1 becoming pass/fail, research productivity may be more emphasized. We primarily sought to assess predictors of medical school research productivity. Class of 2023 dermatology residents publicly listed on Accreditation Council for Graduate Medical Education-accredited programs were included. Their medical school bibliography and demographics were assessed using PubMed and other platforms (eg, Doximity, LinkedIn). By multivariable analysis, students who attended a top 25 medical school (ranked by US News and World Report) or were PhD graduates had significantly higher H-indices, average impact factors, and total years of research activity (P < .01). Top 25 medical school graduates also had significantly higher total peer-reviewed publications, first authorships, and clinical research papers (P < .01). PhD graduates had significantly more clinical research and fewer dermatology-related papers (P < .03). Graduates of osteopathic medical schools had significantly fewer review papers (P = .02). Gender and graduation from an international medical school had no relationship with research productivity. Our study demonstrates a correlation between applicant-specific factors and research productivity. Because the emphasis on research productivity may increase, understanding the mechanisms behind these relationships may guide future dermatology applicants or their mentors.

A Remote-Learning Course can improve the subjective wheelchair-skills performance and confidence of wheelchair service providers: an observational cohort study.

PURPOSE: To test the hypothesis that a Remote-Learning Course improves the subjective wheelchair-skills performance and confidence of wheelchair service providers, and to determine the participants' views on the Course. METHODS: This was an observational cohort study, with pre-post comparisons. To meet the objectives of the six-week Course, the curriculum included self-study and weekly one-hour remote meetings. Participants submitted their Wheelchair Skills Test Questionnaire (WST-Q) (Version 5.3.1) "performance" and "confidence" scores before and after the Course. Participants also completed a Course Evaluation Form after the Course. RESULTS: The 121 participants were almost all from the rehabilitation professions, with a median of 6 years of experience. The mean (SD) WST-Q performance scores rose from 53.4% (17.8) pre-Course to 69.2% (13.8) post-Course, a 29.6% relative improvement (p < 0.0001). The mean (SD) WST-Q confidence scores rose from 53.5% (17.9) to 69.5% (14.3), a 29.9% relative improvement (p < 0.0001). Correlations between performance and confidence were highly significant (p < 0.0001). The Course Evaluation indicated that most participants found the Course useful, relevant, understandable, enjoyable, "just right" in duration, and most stated that they would recommend the Course to others. CONCLUSIONS: Although there is room for improvement, a Remote-Learning Course improves the subjective wheelchair-skills performance and confidence scores of wheelchair service providers by almost 30%, and participants were generally positive about the Course.

A Remote-Learning Course improves the subjective wheelchair-skills performance and confidence scores of wheelchair service providers by almost 30%.Participants were generally positive about the Course.

Evolution of cisplatin resistance through coordinated metabolic reprogramming of the cellular reductive state.

BACKGROUND: Cisplatin (CDDP) is a mainstay treatment for advanced head and neck squamous cell carcinomas (HNSCC) despite a high frequency of innate and acquired resistance. We hypothesised that tumours acquire CDDP resistance through an enhanced reductive state dependent on metabolic rewiring. METHODS: To validate this model and understand how an adaptive metabolic programme might be imprinted, we performed an integrated analysis of CDDP-resistant HNSCC clones from multiple genomic backgrounds by whole-exome sequencing, RNA-seq, mass spectrometry, steady state and flux metabolomics. RESULTS: Inactivating KEAP1 mutations or reductions in KEAP1 RNA correlated with Nrf2 activation in CDDP-resistant cells, which functionally contributed to resistance. Proteomics identified elevation of downstream Nrf2 targets and the enrichment of enzymes involved in generation of biomass and reducing equivalents, metabolism of glucose, glutathione, NAD(P), and oxoacids. This was accompanied by biochemical and metabolic evidence of an enhanced reductive state dependent on coordinated glucose and glutamine catabolism, associated with reduced energy production and proliferation, despite normal mitochondrial structure and function. CONCLUSIONS: Our analysis identified coordinated metabolic changes associated with CDDP resistance that may provide new therapeutic avenues through targeting of these convergent pathways.

Local anaesthetic infiltration in rubber band ligation of rectal haemorrhoids: study protocol for a three-arm, double-blind randomised controlled trial (PLATIPUS trial).

INTRODUCTION: Rubber band ligation ('banding') is a common approach for the management of symptomatic haemorrhoids. However, up to 90% of patients experience postprocedural pain, and there is no consensus regarding the optimal analgesic strategy. In practice, patients may receive submucosal local anaesthetic, pudendal nerve block or routine periprocedural analgesia. The aim of this study is to compare the efficacy of submucosal local anaesthetic, pudendal nerve block and routine analgesia for postprocedural pain in patients undergoing haemorrhoid banding. METHODS AND ANALYSIS: This is a multicentre, prospective, three-arm, double-blind randomised controlled trial of adults booked for haemorrhoid banding. Participants will be randomised to one of three groups in a 1:1:1 ratio: (1)submucosal bupivacaine injection; (2) pudendal nerve ropivacaine injection and (3) no local anaesthetic. The primary outcome is patient reported postprocedural pain (scored 0-10) from 30 min to 2 weeks. Secondary outcomes include postprocedural analgesia use, time to discharge, patient satisfaction, time to return to work and complications. A sample size of 120 patients is required to achieve statistical significance. ETHICS AND DISSEMINATION: This study received Human Research Ethics Approval from the Austin Health Human Research Ethics Committee (March 2022). Trial results will be submitted to a peer-reviewed journal, and presented at academic meetings. A summary of the trial results will be made available to study participants on request. TRIAL REGISTRATION NUMBER: ACTRN12622000006741p.