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The premise of research in human physiology is to explore a multifaceted system whilst identifying one or a few outcomes of interest. Therefore, the control of potentially confounding variables requires careful thought regarding the extent of control and complexity of standardisation. One common factor to control prior to testing is diet, as food and fluid provision may deviate from participants' habitual diets, yet a self-report and replication method can be flawed by under-reporting. Researchers may also need to consider standardisation of physical activity, whether it be through familiarisation trials, wash-out periods, or guidance on levels of physical activity to be achieved before trials. In terms of pharmacological agents, the ethical implications of standardisation require researchers to carefully consider how medications, caffeine consumption and oral contraceptive prescriptions may affect the study. For research in females, it should be considered whether standardisation between- or within-participants in regards to menstrual cycle phase is most relevant. The timing of measurements relative to various other daily events is relevant to all physiological research and so it can be important to standardise when measurements are made. This review summarises the areas of standardisation which we hope will be considered useful to anyone involved in human physiology research, including when and how one can apply standardisation to various contexts. [ABSTRACT FROM AUTHOR]

BACKGROUND: Persons who speak languages other than English are underrepresented in clinical trials, likely in part because of inadequate multilevel resources. We conducted a survey of institutions affiliated with the Childrens Oncology Group (COG) to characterize current research recruitment practices and resources regarding translation and interpretation services. METHODS: In October 2022, a 20-item survey was distributed electronically to institutions affiliated with COG to assess consent practices and resources for recruiting participants who speak languages other than English to COG trials. Descriptive statistics were used to summarize responses; responses were compared by institution size and type as well as respondent role. RESULTS: The survey was sent to 230 institutions, and the response rate was 60% (n = 139). In total, 60% (n = 83) of those respondents had access to short-form consent forms. Full consent form translation was required at 50% of institutions, and 12% of institutional review boards restricted use of centrally translated consent forms. Forty-six percent (n = 64) of institutions reported insufficient funding to support translation costs; 19% (n = 26) had access to no-cost translation services. Forty-four percent (n = 61) were required to use in-person interpreters for consent discussions; the most frequently cited barrier (56%) to obtaining consent was lack of available in-person interpreters. Forty-seven percent (n = 65) reported that recruiting persons who speak languages other than English to clinical trials was somewhat or very difficult. CONCLUSIONS: Institutions affiliated with COG face resource-specific challenges that impede recruitment of participants who speak languages other than English for clinical trials. These findings indicate an urgent need to identify strategies aimed at reducing recruitment barriers to ensure equitable access to clinical trials.

The articles in the June issue serve not only to inform senior care pharmacists on the importance of evidence-based approaches to reduce unnecessary aspirin use, but they also underscore the urgent need for the large and rapid increase in older adult representation in clinical trials and clinical research in general. A striking analysis performed in the United States that examined the trial populations used for Medicare coverage determinations found that while the average age of a Medicare enrollee was 70.8 years old (74.7 years old for older Medicare participants), the average age of the clinical trial population patients used in technology assessments for Medicare coverage determinations was 60.1 years. Hence, the US Medicare system, one of the largest national health care purchasers for older patients in the world, has relied on non-representative data to inform medical coverage decisions.

PurposeMany survivors of rectal cancer experience persistent bowel dysfunction. There are few evidence-based symptom management interventions to improve bowel control. The purpose of this study is to describe recruitment and pre-randomization baseline sociodemographic, health status, and clinical characteristics for SWOG S1820, a trial of the Altering Intake, Managing Symptoms in Rectal Cancer (AIMS-RC) intervention.MethodsSWOG S1820 aimed to determine the preliminary efficacy, feasibility, and acceptability of AIMS-RC, a symptom management intervention for bowel health, comparing intervention to attention control. Survivors with a history of cancers of the rectosigmoid colon or rectum, within 6-24 months of primary treatment completion, with a post-surgical permanent ostomy or anastomosis, and over 18 years of age were enrolled. Outcomes included total bowel function, low anterior resection syndrome, quality of life, motivation for managing bowel health, self-efficacy for managing symptoms, positive and negative affect, and study feasibility and acceptability.ResultsThe trial completed accrual over a 29-month period and enrolled 117 participants from 34 institutions across 17 states and one US Pacific territory. At baseline, most enrolled participants reported self-imposed diet adjustments after surgery, persistent dietary intolerances, and bowel discomfort post-treatment, with high levels of constipation and diarrhea (grades 1-4).ConclusionsSWOG S1820 was able to recruit, in a timely manner, a study cohort that is demographically representative of US survivors of rectal cancer. Baseline characteristics illustrate the connection between diet/eating and bowel symptoms post-treatment, with many participants reporting diet adjustments and persistent inability to be comfortable with dietary intake.ClinicaltrialsGov registration date12/19/2019.ClinicaltrialsGov identifierNCT#04205955.

Background: Children with inflammatory bowel disease (IBD) experience extraintestinal side effects including altered body composition, impaired muscle strength, and aerobic capacity. Exercise training may remedy these issues. Purpose: To assess the feasibility, safety, participant satisfaction, and efficacy of a training program for youth with IBD. Methods: Children with IBD completed 16 weeks of training (2 supervised + 1 home sessions per week). Feasibility was assessed by tracking recruitment, adherence, and compliance rates. Safety was assessed by tracking symptoms and adverse events. Posttraining interviews gauged satisfaction. Circulating inflammatory markers, body composition, muscle strength, aerobic fitness, and habitual physical activity were measured at baseline, midtraining (8 wk), and posttraining. Results: Eleven youth were recruited and 10 completed the study. Participants adhered to 28 (1) of 32 prescribed supervised sessions and 8 (4) of 16 prescribed home sessions. There were no adverse events, and overall feedback on training was positive. Posttraining, we observed an increase in lean mass (+2.4 [1.1] kg), bone density (+0.0124 [0.015] g·cm−2), aerobic fitness (+2.8 [5.7] mL·kg LM−1· min−1), and vigorous physical activity levels (+13.09 [8.95] min·h−1) but no change in inflammation or muscle strength. Conclusion: Supervised exercise training is feasible, safe, and effective for youth with IBD and should be encouraged. [ABSTRACT FROM AUTHOR]

IntroductionWe elicited Vietnamese Americans' perspectives on culturally appropriate recruitment into a new research registry: Collaborative Approach for Asian Americans, Native Hawaiians, and Pacific Islanders (AANHPIs) Research and Education (CARE).MethodsThree focus groups were conducted with 21 Vietnamese Americans. Topics included knowledge about and experiences with research, outreach and recruitment methods for research participation and registry enrollment, and views about research incentives. Focus group transcripts were analyzed thematically.ResultsMean age of participants was 41 years (range 18-73), 57% were male, 86% were non-US born, and 81% had never participated in a research study. Themes that emerged included (1) motivations to participate in research to gain knowledge: for oneself, for family's benefit, and for the Vietnamese American community as a whole; (2) necessity of trustworthy and credible individuals/spokespersons to promote the research initiative; (3) recruitment strategies that are age-specific and culturally appropriate, and (4) importance of monetary incentives.ConclusionFindings from this study will be used to guide recruitment into and engagement with CARE among Vietnamese Americans but are also relevant for other registries aiming to diversify their participants.

PURPOSE: Clinical trials are valuable evidence for managing urologic malignancies. Early termination of clinical trials is associated with a waste of resources and may substantially affect patient care. We sought to study the termination rate of urologic cancer clinical trials and identify factors associated with trial termination. METHODS: A cross-sectional search of ClinicalTrials.gov identified completed and terminated kidney, prostate, and bladder cancer clinical trials started. Trials were assessed for reasons for termination. Multivariable analyses were conducted to determine the significant factors associated with the termination. RESULTS: Between 2000 and 2020, 9,145 oncology clinical trials were conducted, of which 11.30% (n = 1,033) were urologic cancer clinical trials. Of the urologic cancer clinical trials, 25.38% (n = 265) were terminated, with low patient accrual being the most common reason for termination, 52.9% (n = 127). Multivariable analysis showed that only the university funding source odds ratio (OR) of 2.20 (95% CI, 1.45 to 3.32), single-center studies OR of 2.11 (95% CI, 1.59 to 2.81), and sample size of

Study Design. Meta-analysis. Objective. This meta-analysis investigates the outcomes of laminoplasty (LP) and laminectomy with fusion (LF) to guide effective patient selection for these 2 procedures. Background. Although LF traditionally offers the ability for excellent posterior decompression, it may alter cervical spine bio-mechanics and increase the risk of adjacent segment degeneration. LP aims to preserve the natural kinematics of the spine but has not been universally accepted, and may be associated with inadequate decompression, neck pain, and recurrent stenosis. Materials and Methods. PubMed, Cochrane, and Google Scholar (pages 1-20) were searched up until March 2024. The outcomes studied were surgery-related outcomes [operative time (OR) time, estimated blood loss (EBL), and length of stay], adverse events (overall complications, C5 palsy, and reoperations), radiographic outcomes (cervical lordosis, cervical sagittal vertical axis, and T1 slope angle), and patient-reported outcome measures (Neck Disability Index, Visual Analog Scale for neck pain, and Japanese Orthopaedic Association). Results. Twenty-two studies were included in this meta-analysis, of which 19 were retrospective studies, 2 were prospective non-randomized studies, and 1 was a randomized controlled trial. A total of 2128 patients were included, with 1025 undergoing LP and 1103 undergoing LF. Patients undergoing LP experienced significantly shorter operative time (P = 0.009), less EBL (P = 0.02), a lower rate of overall complications (P < 0.00001) and C5 palsy (P = 0.003), a lower T1 slope angle (P = 0.02), and a lower Neck Disability Index (P = 0.0004). No significant difference was observed in the remaining outcomes. Conclusion. This meta-analysis demonstrates that for cervical myelopathy, LP has the benefits of shorter operative time time, less EBL, and reduced incidence of C5 palsy as well as overall complication rate. Given these findings, LP remains an important surgical option with a favorable complication profile in patients with cervical myelopathy, although careful patient selection is still paramount in choosing the right procedure for individual patients. Level of Evidence. 4. [ABSTRACT FROM AUTHOR]

In the past year, notable advances were achieved toward improving oncological outcomes in patients with advanced and recurrent endometrial cancer because of reporting of high‐level results of several phase 3 clinical trial combining an immune checkpoint inhibitor with chemotherapy in the first‐line setting. For the first time, patients with recurrent or advanced endometrial cancer have options for treatment that are superior to traditional chemotherapy alone. What remains to be determined is population specificity of these recommendations. All four major studies were in agreement that patients with endometrial cancer with deficient mismatch repair markedly benefited from addition of an immune checkpoint inhibitor for progression‐free survival; some showed preliminary results demonstrating a potential overall survival. Molecular characterization details are needed to determine if and which patients with tumors that are mismatch proficient should receive this new combination approach. Plain Language Summary: Combining an immune checkpoint inhibitor with chemotherapy in the first‐line setting treatment of patients with advanced endometrial cancer improved progression‐free survival, especially in patients with mismatch repair deficiency.Improving patient selection with potential biomarkers of sensitivity and biomarkers of resistance is key in developing the next clinical trials and will assist in directing therapy to the correct patients and minimize toxicity. Significant advancements have been made in the treatment of advanced and recurrent endometrial cancer, with positive results from phase 3 clinical trials combining immune checkpoint inhibitors with chemotherapy in the first‐line setting. These findings offer patients previously limited by traditional chemotherapy alone new treatment options. [ABSTRACT FROM AUTHOR]

Percutaneous active mechanical circulatory support (MCS) devices are being increasingly used in the treatment of acute myocardial infarction-related cardiogenic shock (AMICS) despite conflicting evidence regarding their effect on mortality. We aimed to ascertain the effect of early routine active percutaneous MCS versus control treatment on 6-month all-cause mortality in patients with AMICS. In this individual patient data meta-analysis, randomised controlled trials of potential interest were identified, without language restriction, by querying the electronic databases MEDLINE via PubMed, Cochrane Central Register of Controlled Trials, and Embase, as well as ClinicalTrials.gov , up to Jan 26, 2024. All randomised trials with 6-month mortality data comparing early routine active MCS (directly in the catheterisation laboratory after randomisation) versus control in patients with AMICS were included. The primary outcome was 6-month all-cause mortality in patients with AMICS treated with early routine active percutaneous MCS versus control, with a focus on device type (loading, such as venoarterial extracorporeal membrane oxygenation [VA-ECMO] vs unloading) and patient selection. Hazard ratios (HRs) of the primary outcome measure were calculated using Cox regression models. This study is registered with PROSPERO, CRD42024504295. Nine reports of randomised controlled trials (n=1114 patients) were evaluated in detail. Overall, four randomised controlled trials (n=611 patients) compared VA-ECMO with a control treatment and five randomised controlled trials (n=503 patients) compared left ventricular unloading devices with a control treatment. Two randomised controlled trials also included patients who did not have AMICS, who were excluded (55 patients [44 who were treated with VA-ECMO and 11 who were treated with a left ventricular unloading device]). The median patient age was 65 years (IQR 57–73); 845 (79·9%) of 1058 patients with data were male and 213 (20·1%) were female. No significant benefit of early unselected MCS use on 6-month mortality was noted (HR 0·87 [95% CI 0·74–1·03]; p=0·10). No significant differences were observed for left ventricular unloading devices versus control (0·80 [0·62–1·02]; p=0·075), and loading devices also had no effect on mortality (0·93 [0·75–1·17]; p=0·55). Patients with ST-elevation cardiogenic shock without risk of hypoxic brain injury had a reduction in mortality with MCS use (0·77 [0·61–0·97]; p=0·024). Major bleeding (odds ratio 2·64 [95% CI 1·91–3·65]) and vascular complications (4·43 [2·37–8·26]) were more frequent with MCS use than with control. The use of active MCS devices in patients with AMICS did not reduce 6-month mortality (regardless of the device used) and increased major bleeding and vascular complications. However, patients with ST-elevation cardiogenic shock without risk of hypoxic brain injury had a reduction in mortality after MCS use. Therefore, the use of MCS should be restricted to certain patients only. The Heart Center Leipzig at Leipzig University and the Foundation Institut für Herzinfarktforschung. [ABSTRACT FROM AUTHOR]

Background: Recruitment for neonatal clinical trials can be particularly challenging. Low enrollment rates bias the research population and decrease generalizability of findings. We identified a critical need for an intervention to improve how researchers recruit for neonatal clinical trials. Working within the US neonatal research context, we developed the Better Research Interactions for Every Family (BRIEF) Intervention, which had two overarching goals: to improve the recruitment experience for all parents, focusing on minoritized populations, and to increase participation, focusing on decreasing disparities in research participation. Methods: We used intervention mapping (IM) to guide all steps of intervention development. IM is a planning framework that provides a systematic process and detailed protocol for step-by-step decision-making for intervention development, implementation, and evaluation. Results: We performed IM's six steps. In step 1, we convened two stakeholder groups, a parent panel and an expert panel, who provided guidance through development of all BRIEF components. Through a recent systematic review, empirical data collected by our team, and consultations with the panels, we identified key determinants (barriers and facilitators) of low enrollment rates and research team members as change agents. In step 2, we iteratively refined our list of key factors to include and linked determinants of behavior changes to these performance objectives. In step 3, we chose three theories (social cognitive theory, theory of information processing, and the trans-theoretical model), methods from identified practical applications suitable for the population (research team members) and the context (busy research NICU teams). In step 4, we developed and refined the intervention components, including self-guided pre-work and a single in-person session. In step 5, we identified the Darbepoetin plus slow-release intravenous iron trial as our partner study in which to pilot BRIEF. In step 6, we developed a multi-stage evaluation plan that included five distinct levels of outcomes. Conclusions: This manuscript shares our rationale and processes for the creation of a research team member-facing intervention aiming to improve recruitment processes for neonatal clinical trials. Our approach can inform those aiming to improve recruitment for neonatal clinical trials and those who may be considering use of IM within similar contexts. [ABSTRACT FROM AUTHOR]

Background: Risk stratification and treatment benefit prediction models are urgent to improve negative sentinel lymph node (SLN-) melanoma patient selection, thus avoiding costly and toxic treatments in patients at low risk of recurrence. To this end, the application of artificial intelligence (AI) could help clinicians to better calculate the recurrence risk and choose whether to perform adjuvant therapy. Methods: We made use of AI to predict recurrence-free status (RFS) within 2-years from diagnosis in 94 SLN- melanoma patients. In detail, we detected quantitative imaging information from H&E slides of a cohort of 71 SLN- melanoma patients, who registered at Istituto Tumori "Giovanni Paolo II" in Bari, Italy (investigational cohort, IC). For each slide, two expert pathologists firstly annotated two Regions of Interest (ROIs) containing tumor cells alone (TUMOR ROI) or with infiltrating cells (TUMOR + INF ROI). In correspondence of the two kinds of ROIs, two AI-based models were developed to extract information directly from the tiles in which each ROI was automatically divided. This information was then used to predict RFS. Performances of the models were computed according to a 5-fold cross validation scheme. We further validated the prediction power of the two models on an independent external validation cohort of 23 SLN- melanoma patients (validation cohort, VC). Results: The TUMOR ROIs have revealed more informative than the TUMOR + INF ROIs. An Area Under the Curve (AUC) value of 79.1% and 62.3%, a sensitivity value of 81.2% and 76.9%, a specificity value of 70.0% and 43.3%, an accuracy value of 73.2% and 53.4%, were achieved on the TUMOR and TUMOR + INF ROIs extracted for the IC cohort, respectively. An AUC value of 76.5% and 65.2%, a sensitivity value of 66.7% and 41.6%, a specificity value of 70.0% and 55.9%, an accuracy value of 70.0% and 56.5%, were achieved on the TUMOR and TUMOR + INF ROIs extracted for the VC cohort, respectively. Conclusions: Our approach represents a first effort to develop a non-invasive prognostic method to better define the recurrence risk and improve the management of SLN- melanoma patients. [ABSTRACT FROM AUTHOR]

Background: Dads and Daughters Exercising and Empowered (DADEE) is a program targeting fathers/father-figures to improve their daughters' physical activity and well-being. Previous randomised controlled efficacy and effectiveness trials of DADEE demonstrated meaningful improvements in a range of holistic outcomes for both fathers and daughters in the short-term. This study aims to assess the long-term impact (12-months) of the program when delivered in the community by trained facilitators. Methods: Fathers/father-figures and their primary school-aged daughters were recruited from Newcastle, Australia into a single-arm, non-randomised, pre-post study with assessments at baseline, 10-weeks (post-intervention) and 12-months. The 9-session program included weekly 90-min educational and practical sessions, plus home-based tasks. The primary outcome was fathers' and daughters' days per week meeting national physical activity recommendations (≥ 30 min/day of MVPA for fathers, ≥ 60 min/day MVPA for daughters). Secondary outcomes included physical activity, screen time, self-esteem, father-daughter relationship, social-emotional well-being, parenting measures, and process outcomes (including recruitment, attendance, retention and program acceptability). Results: Twelve programs were delivered with 257 fathers (40.0 ± 9.2 years) and 285 daughters (7.7 ± 1.9 years). Mixed effects regression models revealed significant intervention effects for the primary outcome, with fathers increasing the days/week meeting physical activity recommendations by 27% at 10-weeks (p < 0.001) and by 19% at 12-months (p < 0.001) compared with baseline. Likewise, for daughters there was a significant increase by 25% at 10-weeks (p < 0.001) and by 14% at 12-months (p = 0.02) when compared to baseline. After conducting a sensitivity analysis with participants unaffected by COVID-19 lockdowns (n = 175 fathers, n = 192 daughters), the primary outcome results strengthened at both time-points for fathers and at 12-months for daughters. Additionally, the sensitivity analysis revealed significant intervention effects at post-program and 12-months for all secondary outcomes in both fathers and daughters. Furthermore, the process outcomes for recruitment capability, attendance, retention and satisfaction levels were high. Conclusions: Findings provide support for a sustained effect of the DADEE program while delivered in a community setting by trained facilitators. Further investigation is required to identify optimised implementation processes and contextual factors to deliver the program at scale. Trial registration: ACTRN12617001450303. Date registered: 12/10/2017. [ABSTRACT FROM AUTHOR]

This document is a letter to the editor in response to an article comparing the quality-of-life outcomes of robotic-assisted partial nephrectomy (RAPN) and conventional open partial nephrectomy (OPN). The authors of the letter commend the study for its use of a randomized controlled trial design and multiple well-defined questionnaires to evaluate the outcomes. However, they point out some missing details that could enhance the study's quality, such as the inclusion of other scoring systems and clarification on the distribution of data. The authors also suggest that future research with larger cohorts and longer follow-up periods is needed to further understand the long-term outcomes and refine patient selection criteria for RAPN. [Extracted from the article]

Background: It is accepted that tumor stage and size can influence response to neoadjuvant therapy in locally advanced rectal cancer (LARC). Studies on organ preservation to date have included a wide variety of size and TNM stage tumors. The aim of this study was to report tumor response based on each relevant TNM stage and tumor size. Methods: Patients treated with LARC from 2014 to 2021 with cT2–3NxM0 tumors who received neoadjuvant chemoradiotherapy with or without induction chemotherapy were included. Tumors were staged and tumor size calculated on pelvic MRI at the time of diagnosis (cTNM). Tumor size was based on the largest dimension taken on the longest axis of each tumor. Clinical response was defined on the basis of post-treatment pelvic MRI and pathological response following surgery, when performed. Statistical analysis was performed using IBM SPSS Statistics™, version 20. Data from 432 patients were analyzed as follows: cT2N0 (n = 51), cT2N+ (n = 36), cT3N0 (n = 76), cT3N+ (n = 270). Results: The rate of complete or near-complete response (cCR or nCR) varied from 77% in cT2N0 ≤ 3 cm to 20% in cT3N+ > 4 cm. Organ preservation without recurrence at 2 years was achieved in 86% of patients with cT2N0, 50% in cT2N+, 39% in cT3N0, and 12% in cT3N+. Conclusion: There is significant variation in tumor response according to tumor stage and size. Tumor response appears inversely proportional to increasing TNM stage and tumor size. This data can support both refinement of selective patient recruitment to organ preservation programs and shared decision-making. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Ancillary immunohistochemistry testing for p16 loss has been proposed as a diagnostic tool for melanoma, but its accuracy remains uncertain.A systematic review and meta‐analysis were conducted on 26 studies involving 979 melanomas and 974 nevi.Through bivariate analysis of data across all cut‐off values, the sensitivity and specificity were calculated to be 0.55 (95% confidence interval [CI]: 0.38, 0.70) and 0.85 (95% CI: 0.70, 0.94), respectively. Summary estimates of diagnostic accuracy fell below recommended thresholds for effective tests, but subgroup analysis suggested that p16 loss could aid in diagnosing ambiguous lesions as melanoma in certain scenarios. However, the presence of p16 expression in these contexts does not definitively rule out melanoma. The findings were limited by underpowered exploratory study designs at risk for bias in patient selection and test interpretation.While the use of p16 immunohistochemistry for detecting melanoma is not universally reliable, it may serve as a confirmatory test in differential diagnoses involving common, congenital, acral, Spitz, and deep penetrating nevi. Nevertheless, further studies are needed to validate its utility. Until then, the application of p16 immunohistochemistry in melanoma diagnosis should be regarded as experimental. [ABSTRACT FROM AUTHOR]

Recruitment of non-canonical BCOR-PRC1.1 to non-methylated CpG islands via KDM2B plays a fundamental role in transcription control during developmental processes and cancer progression. However, the mechanism is still largely unknown on how this recruitment is regulated. Here, we unveiled the importance of the Poly-D/E regions within the linker of BCOR for its binding to KDM2B. Interestingly, we also demonstrated that these negatively charged Poly-D/E regions on BCOR play autoinhibitory roles in liquid-liquid phase separation (LLPS) of BCORANK-linker-PUFD/PCGF1RAWUL. Through neutralizing negative charges of these Poly-D/E regions, Ca2+ not only weakens the interaction between BCOR/PCGF1 and KDM2B, but also promotes co-condensation of the enzymatic core of BCOR-PRC1.1 with KDM2B into liquid-like droplet. Accordingly, we propose that Ca2+ could modulate the compartmentation and recruitment of the enzymatic core of BCOR-PRC1.1 on KDM2B target loci. Thus, our finding advances the mechanistic understanding on how the tethering of BCOR-PRC1.1 enzymatic core to KDM2B is regulated. Mechanistic studies on KDM2B interaction with BCOR/PCGF1 sheds light on the role of calcium and liquid-liquid phase separation in KDM2B recruiting BCOR-PRC1.1 on chromatin. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma (RCC) is the most common solid tumour of the kidney and accounts for 3% of all cancers. While immune checkpoint inhibitor (ICI)-based combination therapies have emerged as the first-line treatment for metastatic renal cell carcinoma (mRCC), the role of surgery has become more controversial. This review summarizes the evidence, current role and future directions for surgery in mRCC management. The survival benefits of cytoreductive nephrectomy (CN) shown in the interferon era have encountered increasing disputes in the tyrosine-kinase inhibitor (TKI) and ICI eras. Undoubtedly, several systematic reviews based on retrospective data have supported the survival benefits of CN. Nevertheless, 2 prospective trials, CARMENA and SURTIME, proved that sunitinib as the upfront therapy resulted in noninferior survival outcomes compared with immediate CN. The safety of CN does have solid ground in the current literature. Several studies suggested that preoperative systemic therapy did not seem to aggravate perioperative complications or mortality rates, in experienced centres. Meticulous patient selection is the rule of thumb in the modern management of mRCC patients. The limitations of the existing prognostication models, however, must be acknowledged. Clinicians should adopt a multidisciplinary and holistic approach and contemplate all patient, disease, surgeon and socio-economical factors, before deciding who should go for surgery. The advent of metastasis-directed therapy (MDT) and survival benefits of adjuvant pembrolizumab shown in the oligometastatic subgroup, where complete metastasectomy could be achieved (M1 NED), calls for more comparative studies against upfront ICI combinations. In summary, CN brings survival benefits to well-selected good-to-intermediate-risk mRCC patients. Individualized and multidisciplinary care is pivotal. [ABSTRACT FROM AUTHOR]

Objective: To assess the effectiveness of Internet-based self-help interventions in treating depression in adolescents and young adults. Methods: A systematic search was conducted across six databases, including PubMed, to identify randomized controlled trials (RCTs) that satisfied the specified inclusion and exclusion criteria. The intervention measure consisted of Internet-based self-help interventions. Results: A total of 23 randomized controlled trials (RCTs) were included in this analysis. Meta-analysis indicated that Internet-based self-help therapies significantly reduced depression scores in adolescents and young adults. (OR = -0.68, 95%CI [-0.88, -0.47], P < 0.001). We examined the effects of patient recruitment from various regions, medication usage, therapist involvement, weekly intervention time, and intervention duration. Patients selected from school, primary healthcare centers, clinics and local communities had better results. Intervention lasting 30 to 60 min and 60 to180 minutes per week were effective in the short term. Conclusion: The internet-based self-help intervention can be effective in treating depression in adolescents and young adults. However, factors such as patient recruitment locations, medication usage, Therapists' involvement, weekly intervention time, and intervention duration interacted with the outcome. Subgroup analysis on potential adverse effects and gender was impossible due to insufficient data from the included studies. [ABSTRACT FROM AUTHOR]

Importance: Understanding treatment expectations of patients and their clinicians is of great importance in improving personalized medical services and enhancing patient safety systems. Objective: To investigate treatment expectations of patients and their clinicians and compare differences between both, by using a pair of validated structured assessment tools covering three key aspects/dimensions of clinical interests. Design, setting, and participants: This single-center cross-sectional study was conducted at Peking Union Medical College Hospital in China. The study enrolled patients aged 16 years and older receiving inpatient care and their clinicians. Patient recruitment was conducted from March 2023 to November 2023. Assessments: In addition to demographic and clinical characteristics, this study employed two validated structured assessment tools to evaluate treatment expectations among patients and their clinicians: the Hospitalized Patients' Expectations for Treatment Scale-Patient version (HOPE-P) and its counterpart, the Hospitalized Patients' Expectations for Treatment Scale-Clinician version (HOPE-C). Results: A total of 233 patients (mean [SD] age, 52.3 [15.1] years; 108 [46.4%] female) along with their clinicians, who numbered 75 in total were enrolled in this study. The distribution of total scores for HOPE-P and HOPE-C displayed similar patterns, with most scores concentrated in the higher range (above 50% of the full score). The mean HOPE-P total score was higher than that of HOPE-C (mean [SD] score, 38.78 [4.86] vs 37.49 [4.32]; t = 3.12, P = 0.002). In Dimension 2, the HOPE-P score was higher than HOPE-C (23.67 [3.20] vs 21.72 [3.03]; t = 6.98, P < 0.001). However, in Dimensions 1 and 3, HOPE-P scored lower than HOPE-C (13.37 [2.44] vs 13.84 [1.73]; t = -2.384, P < 0.018; 1.74 [1.14] vs 1.94 [1.00]; t = -2.00, P = 0.047). Certain demographic and clinical characteristics led to variations in patients' treatment expectations, including marital status, monthly family income, and smoking history. [ABSTRACT FROM AUTHOR]

A study published in Translational Neurodegeneration introduces a new blood-based biomarker, the plasma p-tau181 assay, which accurately reflects tau pathology in Alzheimer's disease (AD). Unlike current assays, this new biomarker is not affected by amyloid accumulation and shows higher specificity for tau pathology. It has the potential to detect and stage AD tau pathologies in the brain, offering a more accessible and functional alternative to PET scans. The assay may also help predict therapeutic response to current treatments and identify suitable patients for anti-amyloid therapies. However, more research with larger sample sizes is needed to confirm these findings. [Extracted from the article]

Objectives: Pancreatic cancer with peritoneal metastasis presents a challenging prognosis, with limited effective treatment options available. This study aims to evaluate the efficacy and safety of combining cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) as a treatment strategy for this patient group. Methods: A retrospective analysis was conducted on patients with peritoneal metastasis of pancreatic cancer who underwent CRS + HIPEC treatment at Beijing Shijitan Hospital from March 2017 to December 2023. The study focused on assessing clinical features, the incidence of sever adverse events (SAEs), and overall survival (OS). Results: A total of 10 patients were enrolled in this study. The median OS was 24.2 months, suggesting an improvement over traditional therapies. While SAEs were noted, including two cases of severe complications necessitating additional surgical interventions, no perioperative fatalities were recorded. The overall survival time for patients with CC0/1 was not significantly different from that of patients with CC2/3, and no prognostic predictors were identified. Conclusions: The combination of CRS and HIPEC appears to be a viable and promising treatment modality for patients with peritoneal metastasis of pancreatic cancer, offering an improved survival rate with manageable safety concerns. Further research is needed to refine patient selection criteria and to explore the long-term benefits of this approach. [ABSTRACT FROM AUTHOR]

Total knee arthroplasty (TKA) is one of the most common procedures in orthopaedics, but there is still debate over the optimal fixation method for long-term durability: cement versus cementless bone ingrowth. Recent improvements in implant materials and technology have offered the possibility of cementless TKA to change clinical practice with durable, stable biological fixation of the implants, improved operative efficiency, and optimal long-term results, particularly in younger and more active patients. This symposium evaluated the history of cementless TKA, the recent resurgence, and appropriate patient selection, as well as the historical and modern-generation outcomes of each implant (tibia, femur, and patella). Additionally, surgical technique pearls to assist in reliable, reproducible outcomes were detailed. Historically, cemented fixation has been the gold standard for TKA. However, cementless fixation is increasing in prevalence in the United States and globally, with equivalent or improved results demonstrated in appropriately selected patients. Cementless TKA provides durable biologic fixation and successful long-term results with improved operating room efficiency. Cementless TKA may be broadly utilized in appropriately selected patients, with intraoperative care taken to perform meticulous bone cuts to promote appropriate bony contact and biologic fixation. [ABSTRACT FROM AUTHOR]

Simple Summary: Liver transplantation (LT) is one of the primary treatments for hepatocellular carcinoma (HCC) and significantly improves patient survival. However, the application of LT for HCC faces challenges owing to advancements in cancer-specific treatments and increased patient comorbidities. This review explores the current controversies and advancements in LT for HCC, focusing on managing comorbidities, the impact of frailty, selection criteria, the role of radiology, and the potential use of immunotherapy. We emphasize the importance of immunosuppression management and surveillance for HCC recurrence. A multidisciplinary approach is crucial to optimize the outcomes of patients with HCC undergoing LT, ensuring comprehensive care and improved survival rates. Liver transplantation (LT) remains one of the most effective treatments for hepatocellular carcinoma (HCC) and significantly enhances patient survival. However, the application of LT for HCC faces challenges owing to advancements in cancer-specific treatment modalities and the increased burden of patients' comorbidities. This narrative review explores current controversies and advancements in LT for HCC. Key areas of focus include the management of comorbidities and patient education by advanced practice nurses, impacts of frailty on waitlists and post-LT outcomes, selection criteria for LT in the era of new downstaging tools, role of radiology in patient selection, and implications of potential immunotherapy use both before and after LT. Additionally, the importance of immunosuppression management with strategies aimed at minimizing rejection while considering the risk of HCC recurrence and the role of surveillance for HCC recurrence is highlighted. This review also underscores the importance of a multidisciplinary approach for optimizing outcomes in patients with HCC undergoing LT. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast reconstruction is considered for any patient who is undergoing surgical treatment for breast cancer. Many factors must be considered when discussing reconstruction, including patient risk factors, the type of material used for breast restoration, and the timing of surgery relative to other adjuvant treatments, such as radiotherapy. Plans for post-mastectomy radiotherapy significantly impact whether a breast reconstruction may be performed at the same time as a mastectomy (immediate reconstruction) or delayed for a later time (delayed reconstruction). The risk of surgical complications from irradiating a reconstructed breast is often weighed against the benefits of fewer surgeries and the potential for an improved quality of life when discussing eligibility for immediate reconstruction. This narrative review covers the current trends and controversies regarding breast reconstruction and radiotherapy. We aim to provide the context and relevant evidence for general community-practice oncologists and oncology providers who counsel patients on the sequencing and modalities of radiotherapy and breast reconstruction. Immediate breast reconstruction (IBR) following a mastectomy, combined with radiotherapy, presents a multifaceted approach to breast cancer treatment, balancing oncological safety and aesthetic outcomes. IBR, typically involving the use of implants or autologous tissue, aims to restore breast morphology directly after a mastectomy, minimizing the psychological and physical impacts. However, integrating radiotherapy with IBR is complex due to the potential adverse effects on reconstructed tissues. Radiotherapy, essential for reducing local recurrence, can induce fibrosis, capsular contracture, and compromised aesthetic results. This narrative review covers the current trends in the sequencing of breast reconstruction and radiotherapy. We discuss patient selection, timing of radiotherapy, and reconstructive techniques, with special attention paid to quality-of-life outcomes that are increasingly reported in clinical trials. Emerging evidence supports the feasibility of IBR with careful patient selection and tailored therapeutic approaches, although ongoing research is necessary to refine protocols and enhance outcomes. Overall, IBR in the context of radiotherapy remains a promising but intricate treatment modality, requiring a nuanced balance between cancer control and aesthetic restoration. [ABSTRACT FROM AUTHOR]

Primary: aldosteronism is a frequent cause of secondary hypertension. With access to specialized care, an increasing number of patients with aldosteronism are being identified. Primary aldosteronism is treatable by adrenal surgery if aldosterone excess originates from one of the two, and not from both, adrenals. Bilateral hyperplasia requires lifelong mineralocorticoid receptor antagonist treatment. Up till now, adrenal venous sampling (AVS) has been widely used to distinguish between one-sided and two-sided aldosterone overproduction and patient selection for surgery. AVS is an invasive technique, and the unsuccessful sampling of the right adrenal vein during AVS often prevents side comparison, making the AVS procedure useless. Molecular imaging using [131I]6ß-iodomethyl-19-norcholesterol with SPECT CT imaging (SPECT/CT) may be a potential alternative. Methods: In 42 consecutive patients with confirmed primary aldosteronism, molecular imaging has been performed. After dexamethasone suppression of the non-affected adrenal tissue, 37 MBq [131I]6ß-iodomethyl-19-norcholesterol was injected i.v., and SPECT/CT images were taken 7 days later. Based on the visual evaluation of the images by two nuclear medicine specialists, patients with one-sided tracer accumulation underwent adrenalectomy. To identify a SPECT/CT parameter that best characterizes the side difference, the maximum counts and the mean counts of spherical VOIs were analyzed. Results: Of the 42 patients, 24 had one-sided aldosterone overproduction by SPECT/CT. After surgical removal of the involved adrenal, all 24 patients with SPECT/CT-identified unilateral aldosteronism achieved biochemical cure, defined as a normalized potassium level combined with an aldosterone-to-renin ratio ≤ 30. To identify the best measurable parameter of SPECT/CT side difference, the mean counts and maximum counts of a series of spherical VOIs of different diameters were analyzed. The ratio of the mean counts of 3 cm spherical VOIs of the right and left adrenal regions (lateralization index) was the best discriminator; a ratio of ≥1.29 was characteristic of one-sided disease, without overlap between the one-sided and two-sided patient groups. Conclusions: [131I]6ß-iodomethyl-19-norcholesterol SPECT/CT with a count-based image interpretation and side-ratio calculation may be an equipollent non-invasive substitute for adrenal venous sampling in the lateralization of mineralocorticoid overproduction. It reliably identifies unilateral disease and facilitates patients' selection for surgical intervention. If confirmed by others, this functional imaging may replace AVS when lateralization is required for management decisions in primary aldosteronism. [ABSTRACT FROM AUTHOR]

Aim: Extracorporeal membrane oxygenation (ECMO) is resource-intensive, is associated with significant morbidity and mortality, and requires careful patient selection. This study examined whether the model for end-stage liver disease (MELD) score is a suitable predictor of in-hospital mortality in patients with COVID-19. Materials and Methods: We retrospectively assessed patients with COVID-19 on ECMO at our institution from March 2020 to May 2021. MELD scoring was performed using laboratory values recorded prior to ECMO initiation. A multiple logistic regression model was established. Results: A total of 66 patients with COVID-19 on ECMO were included (median age of 58.5 years; 83.3% male). The in-hospital mortality was 74.2%. In relation to mortality, patients with MELD Na scores >13.8 showed 6.5-fold higher odds, patients aged >53.5 years showed 18.4-fold higher odds, and male patients showed 15.9-fold higher odds. The predictive power of a model combining the MELD Na with age and sex was significant (AUC = 0.883, p < 0.001). The findings in the COVID-19 patients were not generalizable to a group of non-COVID-19 patients on ECMO. Conclusions: A model combining the MELD Na, age, and sex has high predictive power for in-hospital mortality in patients with COVID-19 on ECMO, and it may be clinically useful for guiding patient selection in critically ill COVID-19 patients both now and in the future, should the virus widely re-emerge. [ABSTRACT FROM AUTHOR]

Since the early 2000s, minimally invasive forefoot surgery (MIS), particularly hallux valgus correction, has significantly advanced with the introduction of the Shannon burr. However, despite numerous relevant studies being published, no comprehensive review articles have summarized MIS for various forefoot conditions. Therefore, in this comprehensive review, we examined the relevant studies about the application of MIS (excluding arthroscopy and endoscopy) for various forefoot conditions. Additionally, we discuss the essential considerations for achieving favorable surgical outcomes and preventing complications associated with each technique. We analyzed the characteristics of each surgical procedure and identified areas for future focus. Effective surgical treatment not only requires MIS, but also the appropriate selection of patients based on suitable indications and executing procedures within the surgeon's capabilities. We hope that this review will help readers to enhance their expertise in this field. [ABSTRACT FROM AUTHOR]

Purpose: Office-based rhinologic procedures (OBRP) have become widely available in North America due to technological advances and appropriate patient selection. Nevertheless, the literature exploring the safety of these procedures remains limited. The objective of this study was to further evaluate the safety, tolerability and efficacy of these procedures with a more robust sample size to allow for capture of rare events. Methods: A retrospective chart review of all patients who underwent OBRP from May 2015 to March 2023. Information regarding patient demographics, the indication for surgery, wait time, tolerability, intra- and postoperative complications, need for revisions, and type of revision (if applicable) was recorded. Results: 1208 patients underwent OBRP during the study period. No patients were excluded. These included turbinoplasties (35%), endoscopic sinus surgeries (ESS) (26%), septoplasties (15%), nasal fracture reductions (7%), and a variety of other procedures. For ESS procedures, the anterior ethmoids and the maxillary sinuses were the most common sinuses treated. 1.1% of procedures were aborted prior to completion. The post-operative complication rate was 3.2%, with 2 major complications (significant bleeding and sepsis) encountered. The mean follow-up overall was 11 months and for ESS it was 15.8 months. Conclusion: Office-based rhinologic procedures are well tolerated and safe for the appropriate patient and associated with shorter wait-times as well as avoidance of general anesthesia. The complication rates are similar to or lower than previously reported rates for rhinologic surgeries done in the operating room. The low rates of revision surgery also demonstrate the efficacy of these procedures. [ABSTRACT FROM AUTHOR]

Local ablation for hepatocellular carcinoma, a non-surgical option that directly targets and destroys tumor cells, has advanced significantly since the 1990s. Therapies with different energy sources, such as radiofrequency ablation, microwave ablation, and cryoablation, employ different mechanisms to induce tumor necrosis. The precision, safety, and effectiveness of these therapies have increased with advances in guiding technologies and device improvements. Consequently, local ablation has become the first-line treatment for early-stage hepatocellular carcinoma. The lack of organized evidence and expert opinions regarding patient selection, pre-procedure preparation, procedural methods, swift post-treatment evaluation, and follow-up has resulted in clinicians following varied practices. Therefore, an expert consensus-based practical recommendation for local ablation was developed by a group of experts in radiology and hepatology from the Research Committee of the Korean Liver Cancer Association in collaboration with the Korean Society of Image-Guided Tumor Ablation to provide useful information and guidance for performing local ablation and for the pre- and post-treatment management of patients. [ABSTRACT FROM AUTHOR]

Why you should read this article: • UK care homes are an important example of a complex environment where research is essential but faces multiple challenges in terms of rigour and methodology • This paper offers a variety of important methodological strategies to identify and address challenges that could impact findings and the ability to carry out research • It highlights the importance of taking a critical stance with all elements of the research process and illustrates the need to identify and mitigate challenges when conducting research in complex environments. Background: The evidence base for hydration practice in care homes is underdeveloped. High-quality research is therefore needed to determine what practices support older people with dementia in drinking sufficient fluid. However, methodological developments are needed to be able to do this. Aim: To highlight the methodological issues researchers encountered during a feasibility cluster, randomised controlled trial of ThinkDrink, a hydration care guide for people with dementia living in UK care homes. Discussion: This is a challenging area because of the complexity of recruitment, participation and data collection in care homes. Researchers must pay extra attention to rigour and quality in the design of their studies. There may be multiple challenges, so various strategies may be required. Conclusion: It is important that researchers continue to reflect on rigorous approaches to develop evidence in a crucial area of care, despite these challenges. Implications for practice: Researchers working in complex environments face a variety of challenges to complete methodologically rigorous research. It is important for researchers to be critical of research processes and data, to mitigate and overcome these challenges. [ABSTRACT FROM AUTHOR]

Intracranial cavernous malformations (CMs) are benign vascular lesions associated with hemorrhage, seizures, and corresponding neurological deficits. Recent evidence shows that frailty predicts neurosurgical adverse outcomes with superior discrimination compared to greater patient age. Therefore, we utilized the Risk Analysis Index (RAI) to predict adverse outcomes following cavernous malformation resection (CMR). This retrospective study utilized the Nationwide Inpatient Sample to identify patients who underwent craniotomy for CMR (2019–2020). Multivariate analysis used RAI to assess the ability of frailty to predict nonhome discharge (NHD), extended length of stay (eLOS), and postoperative adverse outcomes. Receiver operating characteristic curve analysis evaluated the discriminatory accuracy of RAI for prediction of NHD. One thousand two hundred CMR patients were identified. Mean patient age was 38 ± 1.2 years, 53.3% (N = 640) were female, and 58.3% (N = 700) had private insurance. Patients were stratified into 4 frailty tiers based on RAI scores: "robust" (0–20, R), N = 905 (80.8%); "normal" (21–30, N), N = 110 (9.8%); "frail" (31–40, F), N = 25 (2.2%); and "very frail" (41+, VF), N = 80 (7.1%). Increasing frailty was associated with eLOS and higher rates of NHD (P < 0.05). The RAI demonstrated strong discriminatory accuracy (C-statistic = 0.722) for prediction of NHD following CMR in area under the receiver operating characteristics. Preoperative frailty independently predicts adverse outcomes, including eLOS and NHD in patients undergoing resection of cranial CMs. Integrating RAI into preoperative frailty risk assessment may optimize risk stratification and improve patient selection and reallocate perioperative management resources for better patient outcomes. [ABSTRACT FROM AUTHOR]

Idiopathic normal pressure hydrocephalus, secondary chronic hydrocephalus, and other cerebrospinal fluid (CSF) disorders are often challenging to diagnose. Since shunt surgery is usually the only therapeutic option and carries significant morbidity, optimal patient selection is crucial. The tap test is the most commonly used prognostic test to confirm the diagnosis but lacks sensitivity. The lumbar infusion study (LIS) appears to be a better option, offering additional information on brain dynamics without increasing morbidity. However, this technique remains underused. In this narrative review, supported by the extensive experience of several European expert centers, we detail the physiological basis, indications, and CSF dynamics parameters that can be measured. We also discuss technical modalities and variations, including one versus 2 needles, patient positioning, and the site of CSF measurement, as well as in vivo shunt testing. Finally, we discuss the limitations and morbidity associated with the LIS. This review aims to assist teams wishing to incorporate LIS into their screening tools for chronic hydrocephalus and other CSF disorders. [ABSTRACT FROM AUTHOR]

Background and Objective: Percutaneous Nephrolithotomy (PCNL) is recommended for large Kidney Stones. It is mostly done in prone position. However, PCNL in Supine position is another safe option. Only few centers in country are doing it and so it is challenging task to adopt supine PCNL approach in an institution initially. In this study our purpose was to assess initial experience of Supine PCNL in our center. Methods: It is a preliminary retrospective study of our first fifty-one supine PCNL procedures, performed by a single Surgeon, over Twelve months period, from April 2021 to April 2022. We managed a retrospective review of patients’ records. Analysis was completed by utilizing SPSS version 20. Implementation of Mean along with standard deviation values was utilized for continuous variables. While frequency/percentages represented categorical factors. Results: Patients mean age was 39 years, comprising of 62.74% male and 37.25% female patients. Thirty patients had their stones treated on the left side. Mean Stone burden was 3.2 cm. Most of the stones were GUYs score one and two (complexity wise). The mean procedure time 147minutes. Mean hospital stay of 2.17 days was observed in this study. Forty patients were stone free. Only seven patients (14%) had level I-II complications (Clavien-Dindo classification). Conclusion: Supine PCNL can be adopted safely in an institute if careful selection of patients is done before surgery. In our center it had acceptable success rates and few complications. [ABSTRACT FROM AUTHOR]

Purpose: Novel interventions for the prevention or treatment of acute kidney injury (AKI) are currently lacking. To facilitate the evaluation and adoption of new treatments, the use of the most appropriate design and endpoints for clinical trials in AKI is critical and yet there is little consensus regarding these issues. We aimed to develop recommendations on endpoints and trial design for studies of AKI prevention and treatment interventions based on existing data and expert consensus. Methods: At the 31st Acute Disease Quality Initiative (ADQI) meeting, international experts in critical care, nephrology, involving adults and pediatrics, biostatistics and people with lived experience (PWLE) were assembled. We focused on four main areas: (1) patient enrichment strategies, (2) prevention and attenuation studies, (3) treatment studies, and (4) innovative trial designs of studies other than traditional (parallel arm or cluster) randomized controlled trials. Using a modified Delphi process, recommendations and consensus statements were developed based on existing data, with > 90% agreement among panel members required for final adoption. Results: The panel developed 12 consensus statements for clinical trial endpoints, application of enrichment strategies where appropriate, and inclusion of PWLE to inform trial designs. Innovative trial designs were also considered. Conclusion: The current lack of specific therapy for prevention or treatment of AKI demands refinement of future clinical trial design. Here we report the consensus findings of the 31st ADQI group meeting which has attempted to address these issues including the use of predictive and prognostic enrichment strategies to enable appropriate patient selection. [ABSTRACT FROM AUTHOR]

Purpose: The Minimum Speech Test Battery (MSTB) for adults was introduced in 1996 (Nilsson et al., 1996) and subsequently updated in 2011 (Advanced-Bionics et al., 2011). The MSTB has been widely used by clinicians as a guide for cochlear implant (CI) candidacy evaluations and to document post-operative speech recognition performance. Due to changes in candidacy over the past 10 years, a revision to the MSTB was needed. Method: In 2022, the Institute for Cochlear Implant Training (ICIT) recruited a panel of expert CI audiologists to update and revise the MSTB. This panel utilized a modified Delphi consensus process to revise the test battery and to improve its applicability considering recent changes in CI care. Results: This resulted in the MTSB--Version 3 (MSTB-3), which includes test protocols for identifying not only traditional CI candidates but also possible candidates for electric--acoustic stimulation and patients with single-sided deafness and asymmetric hearing loss. The MSTB-3 provides information that supplements the earlier versions of the MSTB, such as recommendations of when to refer patients for a CI, recommended patient-reported outcome measures, considerations regarding the use of cognitive screeners, and sample report templates for clinical documentation of pre- and post-operative care. Electronic versions of test stimuli, along with all the materials described above, will be available to clinicians via the ICIT website (https://www.cochlearimplanttraining.com). Conclusion: The goal of the MSTB-3 is to be an evidence-based test battery that will facilitate a streamlined standard of care for adult CI candidates and recipients that will be widely used by CI clinicians. [ABSTRACT FROM AUTHOR]

Background: Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by autonomic failure and various motor symptoms. While MSA‐C (cerebellar type) predominates in East Asia, MSA‐P (parkinsonian type) predominates in Europe and North America. This nationwide patient registry aimed to (1) conduct a prospective natural history study of MSA in Japan, (2) facilitate patient recruitment for clinical trials, and (3) deposit bioresources and clinical information in a biobank. Methods: Thirteen institutions participated in this study. Clinical information was obtained by neurologists from the patients visiting the hospital every 12 months to assess the UMSARS Part 2 scores and by telephone interviews by nurses every 6 months to assess UMSARS Part 1 scores and to determine whether clinical events had occurred. Results: Demographic data from 329 MSA patients (216 MSA‐C and 113 MSA‐P) were analyzed. The mean age at symptom onset was 58.2 years (standard deviation, 8.9); the mean duration of symptoms at enrollment was 3.5 years (standard deviation, 2.2). The mean 12‐month changes in the UMSARS Part 1 and Part 2 scores were 7.9 (standard deviation, 5.6) and 6.4 (standard deviation, 5.9), respectively. The patient registry proved useful in recruiting participants for clinical trials, including those with gene variants. Clinical information and biospecimens were deposited in a biobank. Discussion: The study highlighted the importance of telephone interviews in minimizing drop‐out rates in natural history studies and demonstrated similar MSA progression rates across populations. The deposited bioresources are available to researchers upon request, aiming to contribute to future MSA researches. [ABSTRACT FROM AUTHOR]

The Principles of Humane Experimental Technique established what many know today as the "3 R's"--refinement, reduction, and replacement--when it was published in 1959. Since their formulation, these principles have guided decision-making for many about nonhuman animal subjects' uses in laboratory-based research. Discussion about how to amend or replace the 3 R's is ongoing, driven mainly by philosophical ethics approaches to nonhuman animal rights and by scientific advancement. This article explores merits and drawbacks of possible updates to and interpretations of the 3 R's. [ABSTRACT FROM AUTHOR]

Under‐representation of subgroups of the population in clinical trials has been and continues to be a problem despite goals of academia, industry, and government. Older adults are among the groups that are under‐represented in trials of medications that they are likely to receive once marketing approval has been received. Recent legislation that mandates that clinical trial participants be representative of patient population has been passed and creates hope that greater numbers of older adults will be enrolled in clinical trials and that they will be representative of "typical" geriatric patients. However, there is the need for collection of current data on disease prevalences with granularity as to age, gender, and race as well as geriatric co‐morbidities to assess the representativeness of clinical trial participants relative to patient populations. Consensus on definitions and collection of data relevant to geriatric patient populations are needed to evaluate effects of comorbidities, frailty, cognitive and physical function. There will also be a need for expansion of the geriatric research workforce, facilities for research both in academic centers but also in the community and long‐term care facilities, and for engagement with and involvement of communities that have been traditionally under‐represented to conduct clinical trials that enroll truly representative patient populations. [ABSTRACT FROM AUTHOR]

The article discusses the U.S. Food & Drug Administration's (FDA) guidelines and potential actions to enhance older adult drug evaluation as of September 2024. Topics covered include potential solutions to the underrepresentation of older adult patients in new drug therapy evaluation, and the possible safety deficiency due to lack of a subgroup's information that could disapprove a drug for market access. Also noted is the Consolidated Appropriations Act's support of patient representation.

The article discusses the European Geriatric Medicine Society's (EuGMS) view on improving drug evaluation in older patients as of September 2024. Topics covered include guidance on evaluating patients' frailty and morbidity status, the challenge of older subjects' heterogeneity in determining medication, and concerns on the choice of outcomes for them. Also noted is the need to consider outcomes that matter most to older people.

Older adults are persistently underrepresented in clinical drug trials worldwide, despite increasing multiple long‐term conditions and significant prescribing in this demographic. We discuss systemic challenges such as the exclusion of people with comorbid conditions and the lack of assessment for comorbidities as modifiers of treatment effects and highlight the rising trend of polypharmacy, especially among the oldest age groups, which is linked to a significant percentage of unplanned hospitalizations and medication errors. The consequences of these trends prompted the United Kingdom National Overprescribing review, culminating in a set of recommendations for drug development tailored to older adults. Building on this, two critical reports released in April 2023 by the International Longevity Centre (ILC) and the Nuffield Council on Bioethics (NCOB) are discussed. These reports emphasize the importance of diversity and inclusion in clinical trials, advocating for ethical frameworks and methodologies that cater to the complex needs of older adults. The development of inclusive criteria, innovative statistical methodologies, and the integration of patient‐reported outcomes are needed to address the persistent barriers to older adult participation in research, suggesting that pragmatic trials, exemplified by the UK's RECOVERY trial during the COVID‐19 pandemic, could pave the way for more inclusive research practices. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a widely utilized treatment for various hematological diseases. While selection criteria for unrelated donors are well established, there is a lack of consistency and standardization in the selection of related donors. This study investigated the current approach of hematologists to the selection of related donors at Turkish HSCT centers. The study employed a cross-sectional survey design, distributing a self-administered questionnaire to 95 adult and pediatric transplantation centers in Türkiye to investigate their approaches to related donor selection for allo-HSCT. The questionnaire collected data on various topics including the center's experience in performing allo-HSCT, patient groups treated, number of allo-HSCT procedures conducted between 2015 and 2021, preferences for related donors, considerations in related donor selection (such as sex and past pregnancies), guidelines utilized for related donor selection, upper age limit for related donors, and the use of specialized advanced analyses for elderly donors. The response rate to the survey was 38.9%. Variability was observed across centers in terms of sex consideration and the impact of past pregnancies on related female donor rejection. Different guidelines were employed for related donor selection, with the European Bone Marrow Transplantation guidelines being the most commonly used. Regarding the upper age limit for related donors, 8.1% of centers accepted an upper age limit of 55 years, 48.7% preferred an upper age limit of 65 years, and 43.2% selected related donors aged 65 and above. The lack of standardized guidelines for related donor selection in HSCT centers leads to variability in criteria and potential risks. Collaboration among centers is essential to establish consensus and develop standardized protocols. [ABSTRACT FROM AUTHOR]

Purpose: Subacromial balloon spacer implantation (SBSI) efficacy for massive rotator cuff tear treatment was evaluated based on perceived shoulder function, active shoulder mobility, pain, complications and research study methodological quality. The purpose was to better discern the efficacy of this device from both surgical and rehabilitative perspectives to improve patient outcomes. Methods: PubMed, EMBASE and Cochrane Library databases were searched (1 January 2010 to 1 June 2024) using 'balloon spacer', 'subacromial spacer', 'subacromial balloon spacer', 'shoulder spacer' and 'inspace' terms. Pre‐surgery (baseline), 12‐month (12‐m) and 24‐month (24‐m) post‐SBSI mean changes were compared using one‐way ANOVA and Scheffe post hoc tests, and comparative study effect sizes were calculated (p ≤ 0.05). Results: This review consists of 27 studies with 894 patients (67.8 ± 5 years of age) and 29.4 ± 17‐month follow‐up. Modified Coleman Methodology Scores (MCMS) revealed fair overall quality (mean = 61.4 ± 11). Constant–Murley scores improved from 34.8 ± 6 (baseline), to 64.2 ± 9 (12‐m) and 67.9 ± 8 (24‐m) (12‐m, 24‐m > baseline, p < 0.001). ASES scores improved from 35.1 ± 14 (baseline), to 83.3 ± 7 (12‐m) and 81.8 ± 5 (24‐m)(12‐m, 24‐m > baseline, p < 0.001). VAS pain scores improved from 6.6 ± 1 (baseline), to 2.6 ± 1 (12‐m) and 2.0 ± 1 (24‐m) (12‐m, 24‐m < baseline, p < 0.001). Flexion increased from 108.5 ± 25° (baseline), to 128.5 ± 30° (12‐m) and 151.2 ± 14° (24‐m) (24‐m > 12‐m, baseline, p = 0.01). Abduction increased from 97.7 ± 24° (baseline) to 116.3 ± 23° (12‐m) and 142.3 ± 15° (24‐m) (24‐m > 12‐m, baseline, p = 0.02). External rotation (ER) in adduction changed from 33.1 ± 7° (baseline) to 32.5 ± 4° (12‐m) and 53.9 ± 9° (24‐m)(24‐m > 12‐m, baseline, p = 0.01). ER at 90° abduction increased from 56.3 ± 3° (baseline) to 83.5 ± 5° (12‐m) and 77.1 ± 4° (24‐m) (24‐m, 12‐m > baseline, p = 0.01). Comparison studies, however, displayed insignificant results with small effect sizes. Conclusion: Despite overall fair MCMS scores, at 24‐m post‐SBSI, shoulder function improved and pain decreased. More rigorous comparative studies, however, revealed insignificant findings. Patients with the potential to re‐establish the essential glenohumeral joint force couple that depresses the humeral head on the glenoid fossa and who comply with physical therapy may be more likely to achieve success following SBSI. Level of Evidence: Level IV. [ABSTRACT FROM AUTHOR]

Background: People with coeliac disease (CD) are at increased risk of osteoporosis and fractures. Currently, baseline dual-energy X-ray absorptiometry (DXA) is recommended for all patients with newly diagnosed CD. We aimed to determine the prevalence of osteoporosis and the clinical utility of the Fracture Risk Assessment Tool (FRAX) in predicting major osteoporotic fractures (MOF) in patients with biopsy-proven CD. Methods: We retrospectively collected data for consecutive adult patients with biopsy-proven CD between 2001 and 2015 who underwent DXA scanning within 1 year of diagnosis and were followed up for a minimum of 7 years. Fracture risk was assessed using FRAX scores, and the incidence of major osteoporotic fractures during the follow-up period was analysed. Results: A total of 593 patients (median age 45.0 years, 68.5% female) were included. The prevalence of osteopenia and osteoporosis were 32.3% and 14.5%, respectively. Increasing age (OR 1.06, p <.0001), decreasing BMI (OR 0.90, p =.003), and higher baseline immunoglobulin A-tissue tissue transglutaminase titre (OR 1.04, p =.03) were significantly associated with increased risk of osteoporosis. The sensitivity, specificity, positive and negative predictive values of the FRAX tool to predict MOF were 21.2%, 91.3%, 16.3%, 93.5%, respectively. A higher risk of fractures was associated with ongoing gluten exposure (OR 1.86, p =.02), previous fractures (OR 2.69, p =.005), and older age (OR 1.03, p <.0001). Conclusion: Osteoporosis is a common finding in patients with CD. The FRAX tool showed high specificity in predicting osteoporotic fractures and could be used to aid with patient selection for DXA scanning in some cases. [ABSTRACT FROM AUTHOR]

An editorial is presented which expresses the views on the emerging role of clinical genetics in pediatric patients with chronic kidney disease (CKD). Topics include the significance of genetic testing for diagnosing various CKD forms, the advancements in sequencing technologies such as whole-exome sequencing and genome sequencing, and the importance of a multidisciplinary approach to improve diagnostic yields and treatment outcomes for pediatric CKD patients.

To develop an aggregate model that integrated clinical data, habitat characteristics, and intratumoral and peritumoral features to assess the risk categorization of thymomas. We retrospectively analyzed 140 thymoma patients (70 low-risk and 70 high-risk), including pathological data. The patients were randomly divided into training cohort (n = 114) and test cohort (n = 26). The k-means clustering was utilized to partition the primary tumor into habitats based on intratumoral radiomic features, 6 distinct habitats were identified. By expanding the region of interest (ROI) mask, 2 peritumoral regions were obtained. Finally, 7 clinical characteristics, 3 habitat values, 20 radiomic features were utilized to develop an aggregated model, to predict the risk of thymoma. Shapley additive explanations (SHAP) interpretation was used for features importance ranking. The accuracy and area under curve (AUC) were used to analyze the performance of the models. The aggregated model, which utilized the XGBoost classifier, demonstrated the best performance with an AUC of 0.811 and an accuracy of 0.769. In comparison, the radiomic model produced an AUC of 0.654 and an accuracy of 0.692. Additionally, the Intratumoral + peritumoral model exhibited an AUC of 0.728 and an accuracy of 0.769. Our study establishes a novel tool to predict the risk of thymoma with a good performance. If prospectively validated, the model may refine thymoma patient selection for risk-adaptative therapy and improve prognosis. • The first use of tumor habitat, peritumoral on thymomas opens new research avenues. • We designed a new method to describe the internal heterogeneity of tumor. • Our model has the potential to improve the accuracy of diagnosis assessment. [ABSTRACT FROM AUTHOR]

Much research has been conducted on young people as a population rather than with them. Traditionally, porn research has focused on effects – on the assumption that people, especially young people, are impacted by the sexual media they consume, which leads to negative outcomes such as violence and addiction. In this sense, porn is framed as risky and children and young people become especially 'at risk'. Sex, sexuality and sexual media are then portrayed as a threat from which young people should be protected. Nevertheless, for many young people watching porn is a normal activity and engaging with porn online is a part of everyday life for some teenagers. Scholars have indicated that many young people perceive porn as ubiquitous, as part of society, and difficult to avoid. In this reflexive article I will interrogate the need for such research, even if it is considered as a form of 'dirty work', within an alarmist and sensationalist media-driven culture. By examining my experiences of the ethics review process, access to participants, and the fieldwork itself, I hope to demonstrate moments of texture and detail throughout the process which future sex, sexuality and porn researchers can draw upon. [ABSTRACT FROM AUTHOR]

Lack of available organs poses a significant challenge in meeting the needs of patients with life‐threatening liver disease who could benefit from liver transplantation (LT). Psychosocial vulnerability markers have been linked to post‐transplant outcomes, raising questions about their use in patient selection. However, their incorporation into selection criteria raises concerns about health equity and potential discrimination. As a result, there is a pressing need to refine fair allocation systems that consider both clinical and psychosocial factors to ensure equitable access and optimize post‐transplant outcomes. The Equitable Benefit Approach (EBA) proposed in this paper by the multidisciplinary group of clinical experts in LT from the Italian Society for the Study of the Liver seeks to address these concerns. It presents four procedural principles, the two allocative principles usually applied in transplantation (urgency and utility) and introduces a new one, the principle of health equity. The EBA aims to prioritize patients with the highest transplant benefit while addressing health inequalities. It emphasizes evidence‐based decision‐making and standardized assessment tools to reliably evaluate psychosocial risk factors. Implementing the EBA involves a multi‐step process, including stakeholder engagement, prospective studies to validate its efficacy, development of institutional policies and algorithms, and ongoing monitoring and revision. By following these steps, health care providers can ensure that LT allocation decisions are transparent and responsive to evolving clinical and social contexts. Ultimately, the EBA should offer a comprehensive framework for fair patient selection in LT, considering both biomedical and psychosocial aspects. [ABSTRACT FROM AUTHOR]

Objectives: This study compares hearing outcomes of two prosthesis materials, bone and titanium, used in ossiculoplasty. Design: This retrospective nationwide registry‐based study uses data systematically collected by the Swedish Quality Registry for Ear Surgery (SwedEar). Setting: The data were obtained from clinics in Sweden that perform ossiculoplasty. Participants: Patients who underwent ossiculoplasty using either bone or titanium prostheses were registered in SwedEar between 2013 and 2019. Main Outcome Measures: Hearing outcome expressed as air–bone gap (ABG) gain. Results: The study found no differences between bone and titanium for ABG or air conduction (AC) for either partial ossicular replacement prostheses (PORP) or total ossicular replacement prostheses (TORP). In a comparison between PORP and TORP for ABG and AC outcomes, regardless of the material used, PORP showed a small advantage, with an additional improvement of 3.3 dB (95% CI [confidence interval], 0.1–4.4) in ABG and 2.2 dB (95% CI, 1.7–4.8) in AC. In secondary surgery using TORP, titanium produced slightly better results for high‐frequency pure tone average. The success rate, a postoperative ABG ≤20 dB, was achieved in 62% of the operations for the whole group. Conclusion: Both bone and titanium used to reconstruct the ossicular chain produce similar hearing outcomes for both PORP and TORP procedures. However, titanium may be a preferable option for secondary surgeries involving TORP. The success rate, a postoperative ABG ≤20 dB, is consistent with other studies, but there is room for improvement in patient selection criteria and surgical techniques. [ABSTRACT FROM AUTHOR]