Re-Purposing the Ordering of Routine Laboratory Tests in Hospitalized Medical Patients (RePORT): protocol for a multicenter stepped-wedge cluster randomised trial to evaluate the impact of a multicomponent intervention bundle to reduce laboratory test over-utilization.

BACKGROUND: Laboratory test overuse in hospitals is a form of healthcare waste that also harms patients. Developing and evaluating interventions to reduce this form of healthcare waste is critical. We detail the protocol for our study which aims to implement and evaluate the impact of an evidence-based, multicomponent intervention bundle on repetitive use of routine laboratory testing in hospitalized medical patients across adult hospitals in the province of British Columbia, Canada. METHODS: We have designed a stepped-wedge cluster randomized trial to assess the impact of a multicomponent intervention bundle across 16 hospitals in the province of British Columbia in Canada. We will use the Knowledge to Action cycle to guide implementation and the RE-AIM framework to guide evaluation of the intervention bundle. The primary outcome will be the number of routine laboratory tests ordered per patient-day in the intervention versus control periods. Secondary outcome measures will assess implementation fidelity, number of all common laboratory tests used, impact on healthcare costs, and safety outcomes. The study will include patients admitted to adult medical wards (internal medicine or family medicine) and healthcare providers working in these wards within the participating hospitals. After a baseline period of 24 weeks, we will conduct a 16-week pilot at one hospital site. A new cluster (containing approximately 2-3 hospitals) will receive the intervention every 12 weeks. We will evaluate the sustainability of implementation at 24 weeks post implementation of the final cluster. Using intention to treat, we will use generalized linear mixed models for analysis to evaluate the impact of the intervention on outcomes. DISCUSSION: The study builds upon a multicomponent intervention bundle that has previously demonstrated effectiveness. The elements of the intervention bundle are easily adaptable to other settings, facilitating future adoption in wider contexts. The study outputs are expected to have a positive impact as they will reduce usage of repetitive laboratory tests and provide empirically supported measures and tools for accomplishing this work. TRIAL REGISTRATION: This study was prospectively registered on April 8, 2024, via ClinicalTrials.gov Protocols Registration and Results System (NCT06359587). https://classic. CLINICALTRIALS: gov/ct2/show/NCT06359587?term=NCT06359587&recrs=ab&draw=2&rank=1.

Analysis of the resistance profile of real-world alectinib first-line therapy in patients with ALK rearrangement-positive advanced non-small cell lung cancer using organoid technology in one case of lung cancer.

Background: Alectinib has achieved excellent therapeutic efficacy in anaplastic lymphoma kinase (ALK) fusion gene-positive non-small cell lung cancer (NSCLC) patients, however, patients eventually develop resistance to it. Exploring the gene variant mapping after alectinib resistance provides a basis for the whole management of ALK-positive advanced NSCLC. This study aimed to characterize the mutation profiles of real-world ALK rearrangement-positive advanced NSCLC patients after first-line alectinib treatment resistance. The research also investigated the treatment options and coping strategies after resistance. Methods: Clinical data of patients with advanced NSCLC who received first-line alectinib treatment in the First Affiliated Hospital of Guangzhou Medical University between November 2018 and April 2022 were collected. Moreover, next-generation sequencing (NGS) data of the patient's baseline and post-resistance tissues were gathered. One patient underwent lung cancer organoid culture and drug sensitivity testing. Results: Out of 35 first-line alectinib-treated patients with advanced NSCLC, 31 are presently in progression-free survival (PFS; 4.3-35.0 months). Four patients experienced progressive disease, and all of them were sequentially treated with ceritinib. Tissue NGS results before sequential treatment in three patients indicated an echinoderm microtubule-associated protein-like 4-ALK fusion that remained at the original baseline, and the PFS for ceritinib treatment was 0.5-1.3 months. One patient developed acquired resistance mutations in the structural domain of ALK protein kinase (V1180L and E1161D), and the PFS for ceritinib treatment was 6.7 months. For one patient who maintained original baseline ALK rearrangement positive without acquired mutation after progression of ceritinib resistance, lung cancer-like organ culture with sequential brigatinib and lorlatinib led to a PFS of 3.2 and 1.9 months, respectively, which aligned with the corresponding drug susceptibility testing results for this patient. Conclusions: For ALK rearrangement-positive patients, blind sequencing of other second-generation tyrosine kinase inhibitors (TKIs) or third-generation lorlatinib may not guarantee satisfactory tumor suppression following first-line second-generation ALK-TKI alectinib administration for treatment progression. NGS testing of patients' blood or tissue samples after disease progression may provide insight into the etiology of alectinib resistance. Patient-sourced drug sensitivity testing of lung cancer-like organs selects drug-sensitive medications based on NGS results and provides a reference for subsequent drug therapy for patients after drug resistance, particularly those who remain ALK rearrangement-positive at baseline.

A 3D Pancreatic Cancer Model with Integrated Optical Sensors for Noninvasive Metabolism Monitoring and Drug Screening.

A distinct feature of pancreatic ductal adenocarcinoma (PDAC) is a prominent tumor microenvironment (TME) with remarkable cellular and spatial heterogeneity that meaningfully impacts disease biology and treatment resistance. The dynamic crosstalk between cancer cells and the dense stromal compartment leads to spatially and temporally heterogeneous metabolic alterations, such as acidic pH that contributes to drug resistance in PDAC. Thus, monitoring the extracellular pH metabolic fluctuations within the TME is crucial to predict and to quantify anticancer drug efficacy. Here, a simple and reliable alginate-based 3D PDAC model embedding ratiometric optical pH sensors and cocultures of tumor (AsPC-1) and stromal cells for simultaneously monitoring metabolic pH variations and quantify drug response is presented. By means of time-lapse confocal laser scanning microscopy (CLSM) coupled with a fully automated computational analysis, the extracellular pH metabolic variations are monitored and quantified over time during drug testing with gemcitabine, folfirinox, and paclitaxel, commonly used in PDAC therapy. In particular, the extracellular acidification is more pronounced after drugs treatment, resulting in increased antitumor effect correlated with apoptotic cell death. These findings highlight the importance of studying the influence of cellular metabolic mechanisms on tumor response to therapy in 3D tumor models, this being crucial for the development of personalized medicine approaches.

The evolving role of interventional cytopathology from thyroid FNA to NGS: Lessons learned at Federico II University of Naples.

Fine-needle aspiration (FNA) guided by ultrasound (US) has emerged as a highly precise diagnostic method for managing thyroid nodules, significantly diminishing unnecessary surgeries. The effectiveness of US-guided FNA is high when a single specialist performs the FNA procedure and the microscopy. This paradigm has paved the way for the evolution of interventional cytopathology, a specialist with a pivotal role in the preoperative diagnostic process, encompassing patient history review, clinical examination, FNA execution under US guidance, preparation, and microscopic interpretation of cytological samples. As the landscape of precision medicine unfolds, molecular testing assumes greater importance in thyroid cytopathology, particularly in refining the risk of malignancy for indeterminate nodules. The updated Bethesda classification system underscores the clinical significance of molecular tests, emphasizing their role in refining diagnostic accuracy. With this evolving landscape, interventional cytopathologists must adapt by acquiring expertise in molecular technologies and addressing ongoing challenges in workflow harmonization and optimization. This paper delves into our decade-long experience as interventional cytopathologists, focusing on recent endeavours to ensure adequate samples not only for microscopic diagnosis but also for molecular testing. Additionally, here we review the challenges of integrating next-generation sequencing (NGS) technology into clinical practice, highlighting the importance of integrating clinically meaningful molecular data into comprehensive molecular cytology reports.

Cannabis in combat sports: position statement of the Association of Ringside Physicians.

and ARP Position Statement: Based on the available body of scientific evidence and with the goals of promoting safety of combat sports athletes and striving for the advancement of clean sport, the Association of Ringside Physicians recommends the following regarding cannabis:• Use of marijuana or synthetic cannabinoids by combat sports athletes is discouraged due to unproven benefits and many known adverse effects. Acute use can impair cognition and complex motor function, which likely leads to reduced performance in combat sports. Chronic use can increase risk for heart and lung disease, several cancers, schizophrenia, and can reduce testosterone in men and impair fertility. Benefits from cannabis in most contexts, including athletic performance, have not been proven.• Use of topical purified CBD is neither encouraged nor discouraged.• Since acute cannabis intoxication can impair complex cognitive and motor function, any athlete suspected of acute intoxication at the time of competition - based on clinical judgment - should be banned from that competition.• Wide-scale regulation of cannabis based on quantitative testing has limited usefulness in combat sports, for the following reasons:∘ Cannabis is not ergogenic and is likely ergolytic.∘ Concentrations in body fluids correlate poorly with clinical effects and timing of use.∘ Access to testing resources varies widely across sporting organizations.

Barriers and facilitators to the implementation of rapid HIV testing in Canadian Emergency Departments: a mixed methods study.

OBJECTIVES: 1 in 7 Canadians with Human Immunodeficiency Virus (HIV) do not know their status. Patients at increased risk of HIV routinely access the emergency department (ED), yet few are tested, representing a missed opportunity for diagnosis and linkage-to-care. Rapid HIV testing provides reliable results within the same ED encounter but is not routinely implemented. The objective of this study was to identify barriers and facilitators to rapid HIV testing in Ontario EDs. METHODS: We employed a mixed-methods, convergent, parallel design study including online surveys and semi-structured interviews of physicians, nurses, and allied health across four hospitals in Toronto and Thunder Bay, Ontario. Data were analyzed in equal priority using descriptive statistics for quantitative data and thematic analysis for qualitative data guided by the Theoretical Domains framework and Capability, Opportunity, Motivation Behaviour change model. RESULTS: Among 187 survey respondents, 150 (80%) felt implementing rapid HIV testing would be helpful in the ED. Facilitators included availability of resources to link patients to care after testing (71%), testing early in patient encounters (41%), and having dedicated staff with lived experience support testing (34%). Motivation to offer testing included opportunities to support an underserved population (66%). Challenges to implementation included limited time during ED patient encounters (51%) and a lack of knowledge around HIV testing (42%) including stigma. Interview themes confirmed education, and integration of people with lived experience being essential to provide rapid HIV testing and linkage-to-care in the ED. CONCLUSIONS: Implementation of rapid HIV testing in the ED is perceived to be important irrespective of practice location or profession. Intrinsic motivations to support underserved populations and providing linkage-to-care are novel insights to facilitate testing in the ED. Streamlined implementation, including clear testing guidelines and improved access to follow-up care, is felt to be necessary for implementation.

ABSTRAIT: OBJECTIFS: 1 Canadien sur 7 atteint du virus de l'immunodéficience humaine (VIH) ne connaît pas son statut. Les patients présentant un risque accru de contracter le VIH ont régulièrement accès au service des urgences (SU), mais peu d'entre eux sont testés, ce qui représente une occasion manquée de diagnostic et de lien avec les soins. Le dépistage rapide du VIH fournit des résultats fiables dans la même situation d'urgence, mais n'est pas systématiquement mis en œuvre. L'objectif de cette étude était d'identifier les obstacles et les facilitateurs au dépistage rapide du VIH dans les urgences de l'Ontario. MéTHODES: Nous avons utilisé une étude de conception mixte, convergente et parallèle, y compris des sondages en ligne et des entrevues semi-structurées auprès de médecins, d'infirmières et d'auxiliaires de la santé dans quatre hôpitaux de Toronto et de Thunder Bay, en Ontario. Les données ont été analysées en priorité égale à l'aide de statistiques descriptives pour les données quantitatives et d'analyses thématiques pour les données qualitatives guidées par le cadre des domaines théoriques et le modèle de changement de capacité, d'opportunité et de motivation. RéSULTATS: Parmi 187 répondants au sondage, 150 (80 %) étaient d'avis que la mise en œuvre d'un dépistage rapide du VIH serait utile à l'urgence. Les facilitateurs comprenaient la disponibilité de ressources pour lier les patients aux soins après le test (71 %), le dépistage précoce lors des rencontres avec les patients (41 %) et la présence d'un personnel dévoué avec des tests de soutien de l'expérience vécue (34 %). La motivation à offrir des tests comprenait des occasions de soutenir une population mal desservie (66 %). Les difficultés de mise en œuvre comprenaient un temps limité pendant les rencontres avec les patients aux urgences (51 %) et un manque de connaissances sur le dépistage du VIH (42 %), y compris la stigmatisation. Les thèmes des entrevues ont confirmé que l'éducation et l'intégration des personnes ayant une expérience vécue sont essentielles pour fournir un dépistage rapide du VIH et un lien avec les soins aux urgences. CONCLUSIONS: La mise en œuvre du dépistage rapide du VIH aux urgences est perçue comme importante, quel que soit le lieu de pratique ou la profession. Les motivations intrinsèques à soutenir les populations mal desservies et à fournir un lien avec les soins sont de nouvelles idées pour faciliter les tests à l'urgence. Une mise en œuvre simplifiée, y compris des lignes directrices claires sur les tests et un meilleur accès aux soins de suivi, est jugée nécessaire pour la mise en œuvre.

Population-based germline breast cancer gene association studies and meta-analysis to inform wider mainstream testing.

BACKGROUND: Germline genetic testing, previously restricted to familial and young-onset breast cancer, is now offered increasingly broadly to 'population-type' breast cancer patients in mainstream oncology clinics, with wide variation in the genes included. METHODS: Weighted meta-analysis was performed for three population-based case-control studies (BRIDGES, CARRIERS and UK Biobank) comprising in total 101,397 women with breast cancer and 312,944 women without breast cancer, to quantify for 37 putative breast cancer susceptibility genes (BCSGs) the frequency of pathogenic variants (PVs) in unselected, 'population-type' breast cancer cases and their association with breast cancer and its subtypes. RESULTS: Meta-analysed odds ratios (ORs) and frequencies of PVs in population-type breast cancer cases were generated for BRCA1 (OR= 8.73 (95% CI 7.47-10.20), 1 in 101), BRCA2 (OR=5.68 (5.13-6.30), 1 in 68) and PALB2 (OR= 4.30 (95% CI 3.68-5.03), 1 in 187). For both CHEK2 (OR=2.40 (95% CI 2.21-2.62), 1 in 73) and ATM (OR=2.16 (95%CI 1.93-2.41), 1 in 132) subgroup analysis showed stronger association with ER-positive disease. Magnitude of association and frequency of PVs were low for RAD51C (OR=1.53 (95%CI 1.15-2.04), 1 in 913), RAD51D (OR=1.76, (95%CI 1.15-2.41, 1 in 1079) and BARD1 (OR=2.34 (1.85-2.97), 1 in 672); frequencies and associations were moderately higher restricting to triple-negative breast cancers The PV-frequency in 'population-type' breast cancer cases was very low for 'syndromic' BCSGs TP53 (1 in 1844), STK11 (1 in 11,525), CDH1 (1 in 2668), PTEN (1 in 3755) and NF1 (1 in 1470), with metrics of association also modest ranging from OR=3.62 (95%CI 1.98-6.61) for TP53 down to OR=1.60 (95%CI 0.48-5.30) for STK11. CONCLUSIONS: These metrics reflecting 'population-type' breast cancer will be informative to defining the appropriate gene set as we continue to expand to germline testing out to more unselected population-type breast cancer cases.

Self-reported awareness of genetic testing, the impact of family history, and access to clinical trials for people diagnosed with ovarian cancer in Australia.

Objectives: To assess the understanding of people diagnosed with ovarian cancer regarding genetic testing; to understand knowledge gaps among people diagnosed with ovarian cancer that may impact best practice care; and to monitor overall changes in understanding from 2015 to 2022. Design: Longitudinal 'opt-in' study using an online survey tool at three timepoints: 2015, 2018 and 2022. Participants: People in Australia (or their families / caregivers) diagnosed with ovarian cancer between 2010 and 2022). Main outcome measures: Self-reported awareness of heritable risk factors for ovarian cancer, genetic testing approaches and participation in clinical trials. Results: The study indicated that there have been improvements in the understanding and awareness of people diagnosed with ovarian cancer regarding familial risk (an increase from 43.6% (45 of 149) in 2015 to 62.9% (166 of 264) in 2022); but people were less likely to be aware of the difference between somatic (tumour) and germline testing (120 of 266, 45.1%). However, there were self-reported improvements to clinical trial access in non-metropolitan areas (12 of 64, 18.8% in 2022 compared to 22 of 145, 15.2% in 2018), bringing it on par with metropolitan areas (32 of 169, 18.9% in 2022). Conclusions: Despite improved awareness about genetic testing among people diagnosed with ovarian cancer, there remain knowledge gaps in understanding of genetic testing types (germline and somatic) and gene variant targeted therapies; and further work to improve clinical trial awareness and access is required.

Assessing interventions promoting the uptake of cancer-related genomic services within the Latino community: A scoping review using the RE-AIM framework.

Cancer genomic services (CGS) can support genetic risk-stratified cancer prevention and treatment. Racial/ethnic minority groups are less likely to access and utilize CGS compared with non-Hispanic Whites. Little research has described characteristics of interventions targeted at CGS among Latinos. This scoping review aimed to (1) describe interventions promoting uptake of CGS among Latinos in the United States and Latin America, (2) describe intervention adaptations for Latino participants, and (3) summarize intervention implementation factors suggested by reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) framework. We conducted a search in English and Spanish of literature published between 2005 and 2022 across PubMed and Latin American and Caribbean Health Sciences Literature databases. Sixteen of 2344 papers met the inclusion criteria of the analysis. Efforts to promote CGS among Latino communities were limited in the US and lower in Latin America. This review highlights the need for in-depth exploration of acculturation-informed interventions and better reporting on implementation factors to enhance their scalability across diverse settings.

Rare pathogenic structural variants show potential to enhance prostate cancer germline testing for African men.

Prostate cancer (PCa) is highly heritable, with men of African ancestry at greatest risk and associated lethality. Lack of representation in genomic data means germline testing guidelines exclude for African men. Established that structural variations (SVs) are major contributors to human disease and prostate tumourigenesis, their role is under-appreciated in familial and therapeutic testing. Utilising a clinico-methodologically matched African (n = 113) versus European (n = 57) deep-sequenced PCa resource, we interrogated 42,966 high-quality germline SVs using a best-fit pathogenicity prediction workflow. We identified 15 potentially pathogenic SVs representing 12.4% African and 7.0% European patients, of which 72% and 86% met germline testing standard-of-care recommendations, respectively. Notable African-specific loss-of-function gene candidates include DNA damage repair MLH1 and BARD1 and tumour suppressors FOXP1, WASF1 and RB1. Representing only a fraction of the vast African diaspora, this study raises considerations with respect to the contribution of kilo-to-mega-base rare variants to PCa pathogenicity and African associated disparity.

Clinical, histologic, and immunologic signatures of Small Fiber Neuropathy in Systemic Lupus Erythematosus.

BACKGROUND AND OBJECTIVES: Systemic Lupus Erythematosus (SLE) often causes damage to small nerve fibers, leading to distressing painful and autonomic symptoms. Despite this, Small Fiber Neuropathy (SFN) remains an underrecognized complication for SLE patients. In this cross-sectional study, we aimed to assess SFN in patients with SLE and to explore its correlations with immunologic disease features and clinical manifestations. METHODS: We recruited 50 SLE patients (1 male to 12.5 females, aged 20-80 years) reporting painful disturbances. We conducted a comprehensive clinical and neurophysiological evaluation, using Nerve Conduction Studies and Quantitative Sensory Testing. Additionally, we carried out an extensive laboratory assessment of disease-related serological parameters. We also performed a thorough skin biopsy analysis, investigating somatic and autonomic innervation while detecting complement and inflammatory cell infiltrates within the skin. RESULTS: Out of 50 patients, 19 were diagnosed with SFN, primarily characterized by a non-length-dependent distribution; 7 had a mixed neuropathy, with both large and small fiber involvement. Patients with SFN were younger than patients with a mixed neuropathy (p = .0143); furthermore, they were more likely to have a history of hypocomplementemia (p = .0058) and to be treated with cyclosporine A (p = .0053) compared to patients without neuropathy. However, there were no significant differences in painful and autonomic symptoms between patients with and without SFN. DISCUSSION: This study highlights the relevant frequency of SFN with a non-length-dependent distribution among SLE patients experiencing painful symptoms. Indeed, SFN emerges as an early manifestation of SLE-related neuropathy and is closely associated with hypocomplementemia, suggesting a potential pathogenic role of the complement system. Moreover, SFN may be influenced by disease-modifying therapies. However, the precise role of SFN in shaping painful and autonomic symptoms in patients with SLE remains to be fully elucidated.

Design, in silico Evaluation, and Determination of Antitumor Activity of Potential Inhibitors Against Protein Kinases: Application to BCR-ABL Tyrosine Kinase.

Despite significant progress made over the past two decades in the treatment of chronic myeloid leukemia (CML), there is still an unmet need for effective and safe agents to treat patients with resistance and intolerance to the drugs used in clinic. In this work, we designed 2-arylaminopyrimidine amides of isoxazole-3-carboxylic acid, assessed in silico their inhibitory potential against Bcr-Abl tyrosine kinase, and determined their antitumor activity in K562 (CML), HL-60 (acute promyelocytic leukemia), and HeLa (cervical cancer) cells. Based on the analysis of computational and experimental data, three compounds with the antitumor activity against K562 and HL-60 cells were identified. The lead compound efficiently suppressed the growth of these cells, as evidenced by the low IC50 values of 2.8 ± 0.8 µM (K562) and 3.5 ± 0.2 µM (HL-60). The obtained compounds represent promising basic structures for the design of novel, effective, and safe anticancer drugs able to inhibit the catalytic activity of Bcr-Abl kinase by blocking the ATP-binding site of the enzyme.

ERRATUM: Genetic testing for inherited cardiovascular diseases. A position statement of the Polish Cardiac Society endorsed by Polish Society of Human Genetics and Cardiovascular Patient Communities.

According to the latest guidelines of European and American medical societies, genetic testing (GT) is essential in cardiovascular diseases for establishing diagnosis, predicting prognosis, enabling initiation of disease-modifying therapy, and preventing sudden cardiac death. The GT result may be relevant for cascade GT in the patient's relatives, for planning his/her profession and physical activity, and for procreative counseling. This position statement has been prepared due to the scarcity of GT in cardiovascular diseases in Poland and the need to expand its availability. We give a concise description of the genetic background of cardiomyopathies, channelopathies, aortopathies, familial hypercholesterolemia, pheochromocytomas, and paragangliomas. The article discusses various aspects of GT in specific populations, such as children or athletes, and also presents prenatal genetic diagnostics. We propose recommendations for GT and counselling, which take into account Polish needs and capabilities. We give an outline of legal regulations, good clinical practice in GT with respect for patient rights, the role of cardiologists and clinical geneticists in GT planning and post-test counseling, and the requirements for laboratories performing genetic tests. The Polish Cardiac Society and Polish Society of Human Genetics experts speak with one voice with cardiovascular patient communities to underline the need for a law on GT and increasing the availability of GT for cardiovascular patients.

Cardiopulmonary exercise variables and their association with postoperative morbidity and mortality after major oesophagogastric cancer surgery-a multicentre observational study.

Background: Outcomes after oesophagogastric cancer surgery remain poor. Cardiopulmonary exercise testing (CPET) used for risk stratification before oesophagogastric cancer surgery is based on conflicting evidence. This study explores the relationship between CPET and postoperative outcomes, specifically for patients undergoing neoadjuvant treatment. Methods: Patients undergoing oesophagogastric cancer resection and CPET (pre- or post-neoadjuvant treatment, or both) were retrospectively enrolled into a multicentre pooled cohort study. Oxygen uptake at peak exercise (VO2 peak) was compared with 1-yr postoperative survival. Secondary analyses explored relationships between patient characteristics, tumour pathology characteristics, CPET variables (absolute, relative to weight, ideal body weight, and body surface area), and postoperative outcomes (morbidity, 1-yr and 3-yr survival) were assessed using logistic regression analyses. Results: Seven UK centres recruited 611 patients completing a 3-yr postoperative follow-up period. Oesophagectomy was undertaken in 475 patients (78%). Major complications occurred in 25%, with 18% 1-yr and 43% 3-yr mortality. No association between VO2 peak or other selected CPET variables and 1-yr survival was observed in the overall cohort. In the overall cohort, the anaerobic threshold relative to ideal body weight was associated with 3-yr survival (P=0.013). Tumour characteristics (ypT/ypN/tumour regression/lymphovascular invasion/resection margin; P<0.001) and Clavien-Dindo ≥3a (P<0.001) were associated with 1-yr and 3-yr survival. On subgroup analyses, pre-neoadjuvant treatment CPET; anaerobic threshold (absolute; P=0.024, relative to ideal body weight; P=0.001, body surface area; P=0.009) and VE/VCO2 at anaerobic threshold (P=0.026) were associated with 3-yr survival. No other CPET variables (pre- or post-neoadjuvant treatment) were associated with survival. Conclusions: VO2 peak was not associated with 1-yr survival after oesophagogastric cancer resection. Tumour characteristics and major complications were associated with survival; however, only some selected pre-neoadjuvant treatment CPET variables were associated with 3-yr survival. CPET in this cohort of patients demonstrates limited outcome predictive precision. Clinical trial registration: NCT03637647.

Evaluating the feasibility and acceptability of a co-designed physical activity intervention for rural middle schoolers: a pilot study.

BACKGROUND: Lack of physical activity is a concern for children across diverse backgrounds, particularly affecting those in rural areas who face distinct challenges compared to their urban counterparts. Community-derived interventions are needed that consider the unique context and additional physical activity barriers in under-resourced rural settings. Therefore, a prospective pre-post pilot/feasibility study of Hoosier Sport was conducted over 8-weeks with 6th and 7th grade children in a low-socioeconomic rural middle school setting. The primary objective of the present study was to assess trial- and intervention-related feasibility indicators; and the secondary objective was to collect preliminary assessment data for physical activity levels, fitness, psychological needs satisfaction, and knowledge of physical activity and nutrition among participating youth. METHODS: This prospective 8-week pilot/feasibility study took place in the rural Midwestern United States where twenty-four middle school students participated in a mixed-methods pre-post intervention during physical education classes. The intervention included elements like sport-based youth development, individualized goal setting, physical activity monitoring, pedometer usage, and health education. Data were collected at baseline (T1) and post-intervention (T3), with intermediate measures during the intervention (T2). Qualitative data were integrated through semi-structured interviews. Analytical methods encompassed descriptive statistics, correlations, repeated measures ANOVA, and thematic analysis. RESULTS: Key findings indicate robust feasibility, with intervention-related scores (FIM, AIM, and IAM) consistently surpassing the "good" threshold and 100% retention and recruitment success. Additionally, participants showed significant physical performance improvement, shifting from the 25th to the 50th percentile in the 6-minute walk test (p < 0.05). Autonomy and competence remained high, reflecting positive perceptions of program practicality. Nutrition knowledge, initially low, significantly improved at post-intervention (p < 0.01), highlighting the efficacy of targeted nutritional education in Hoosier Sport. CONCLUSIONS: This study pioneers a community-engaged model for physical activity intervention in under-resourced rural settings. Positive participant feedback, coupled with improvements in physical fitness and psychosocial factors, highlights the potential of the co-design approach. The findings offer valuable insights and a practical template for future community-based research, signaling the promising impact of such interventions on holistic well-being. This research lays the foundation for subsequent phases of the ORBIT model, emphasizing collaborative, community-driven approaches to address the complex issue of declining physical activity levels among adolescents.

Geese as reservoirs of human colon cancer-associated Streptococcus gallolyticus.

Recently, an increased number of reports have described pathogens of animal origin that cause a variety of infections and a rise in their transmission to humans. Streptococcus gallolyticus, a member of the Streptococcus bovis/Streptococcus equinus complex (SBSEC), is one of these pathogens and infects a wide range of hosts from mammals to poultry and has a broad functionality ranging from pathogenicity to food fermentation. As S. gallolyticus causes complications including bacteremia, infective endocarditis, and colorectal malignancy in humans, it is important to investigate its occurrence in various hosts, including geese, to prevent potential zoonotic transmissions. This study aimed to investigate the presence of S. gallolyticus in the droppings of clinically healthy and diarrheic geese, which were raised intensively and semi-intensively, by the in vitro culture method, characterize the isolates recovered by PCR and sequence-based molecular methods and determine their antibiotic susceptibility by the disk diffusion and gradient test methods. For this purpose, 150 samples of fresh goose droppings were used. Culture positivity for S. gallolyticus was determined as 8% (12/150). PCR analysis identified 54.55% (n = 6) of the isolates as S. gallolyticus subsp. gallolyticus and 45.45% (n = 5) as S. gallolyticus subsp. pasteurianus. Following the 16S rRNA sequence and ERIC-PCR analyses, S. gallolyticus subspecies exhibited identical cluster and band profiles that could be easily distinguished from each other and were clonally identified. High rates of susceptibility to florfenicol, penicillin, rifampicin, and vancomycin were detected among the isolates, regardless of the subspecies diversity. Both subspecies showed high levels of resistance to bacitracin, clindamycin, doxycycline, tetracycline, trimethoprim-sulfamethoxazole, and erythromycin and multiple MDR profiles, indicating their potential to become superbugs. This first report from Türkiye demonstrates the occurrence of the S. gallolyticus subspecies in geese. In view of the recent increase of geese production and the consumption of goose meat in Türkiye, the occurrence of S. gallolyticus in geese should not be ignored to prevent zoonotic transmission.

The use of hearing tests to assess otitis media with effusion in children with Down syndrome.

BACKGROUND: Down syndrome is associated with an increased risk for otitis media with effusion (OME), a childhood condition in which fluid accumulates in the middle ear, potentially leading to hearing loss. The American Academy of Pediatrics Down syndrome guidelines and the American Academy of Otolaryngology - Head and Neck Surgery OME guidelines recommend hearing testing to assess the hearing status of children with Down syndrome diagnosed with OME. METHODS: Through an Institutional Review Board approved retrospective chart review at Children's Mercy, this project assessed how clinical factors affect the frequency in which children with Down syndrome receive hearing testing after diagnosis of OME. The study included data from all children with Down syndrome between 1 and 8 years old diagnosed with OME in the Down syndrome, general pediatrics, and otolaryngology clinics between 2018 and 2020. Demographics and clinical factors, including clinic setting, were collected. RESULTS: Of the 124 patients identified, 91.1 % were diagnosed with OME in the otolaryngology clinic and 33.1 % received hearing testing. While most diagnoses occurred in the otolaryngology clinic, a higher proportion of hearing testing at the time of diagnosis occurred in the Down syndrome clinic. This could be explained by the fact that the Down syndrome clinic is a multidisciplinary clinic, where yearly visits include hearing screening. Bivariate analysis using chi-square or Fisher's tests showed that clinic setting had a significant association (p-value <0.001) with hearing testing. However, logistic regression depicted all clinical factors had an insignificant effect on hearing testing at 5 % significance. CONCLUSION: While results indicate hearing testing is largely not performed to assess OME early in otolaryngology clinics, they may be used to assess intervention efficacy post-diagnosis. Results point to the importance of Down syndrome clinics in early diagnosis of hearing loss leading to timely referrals to otolaryngology clinics which diagnose and manage OME in children with Down syndrome.

Is there a need for screening of cervical HPV infections and carcinoma?

Antenatal cervical screening aims to detect cervical intraepithelial neoplasms as precancerous lesions and invasive cervical cancer. Whether this screening is performed routinely during pregnancy varies depending on each country's screening participation rates, guidelines, and the risks to the pregnant woman. In some countries with the high rate of routinely implemented cervical screening among the target women, women are recommended to defer cervical screening intentionally to post-delivery, though having screening in consultation with physicians may be possible if routine screening overlaps. However, when cervical screening rate in fertile women is low and the incidence of cervical cancer is high, cervical screening during pregnancy may play an important role in the early detection of cervical cancer. Cervical screening using high-risk human papillomavirus (HPV) testing is accepted worldwide as a highly sensitive and objective test method, and it should replace traditional primary cervical cytology in the future. However, the benefits and disadvantages of using HPV testing in pregnant women is unclear because a false positive rate may be increased due to pregnant women being generally under an immunosuppressed condition.

Efficient risk-based collection of biospecimens in cohort studies: Designing a prospective study of diagnostic performance for multicancer detection tests.

In cohort studies, it can be infeasible to collect specimens on an entire cohort. For example, to estimate sensitivity of multiple Multi-Cancer Detection (MCD) assays, we desire an extra 80mL of cell-free DNA (cfDNA) blood, but this much extra blood is too expensive for us to collect on everyone. We propose a novel epidemiologic study design that efficiently oversamples those at highest baseline disease risk from whom to collect specimens, to increase the number of future cases with cfDNA blood collection. The variance reduction ratio from our risk-based subsample versus a simple random (sub)sample (SRS) depends primarily on the ratio of risk model sensitivity to the fraction of the cohort selected for specimen collection subject to constraining the risk model specificity. In a simulation where we chose 34% of Prostate, Lung, Colorectal, and Ovarian Screening Trial cohort at highest risk of lung cancer for cfDNA blood collection, we could enrich the number of lung cancers 2.42-fold and the standard deviation of lung-cancer MCD sensitivity was 31-33% reduced versus SRS. Risk-based collection of specimens on a subsample of the cohort could be a feasible and efficient approach to collecting extra specimens for molecular epidemiology.

Case report: successful response to bevacizumab combined with erlotinib for a novel FH gene mutation hereditary leiomyoma and renal cell carcinoma.

FH-deficient Renal Cell Carcinoma (FH-deficient RCC) are inherited tumors caused by mutations in the fumarate hydratase (FH) gene, which plays a role in the tricarboxylic acid cycle. These mutations often result in aggressive forms of renal cell carcinoma (RCC) and other tumors. Here, we present a case of FH-deficient RCC in a 43-year-old woman with a history of uterine fibroids. She exhibited a new heterozygous mutation in exon six of the FH gene (c.799_803del, c.781_796del). The patient had multiple bone metastases and small subcutaneous nodules in various areas such as the shoulders, back, and buttocks. Biopsy of a subcutaneous nodule on the right side revealed positive expression of 2-succinate-cysteine (2SC), and FH staining indicated FH expression deletion. The patient underwent treatment with a combination of erlotinib and bevacizumab, which resulted in significant efficacy with moderate side effects. This treatment combination may be recommended as a standard regimen. This case underscores the importance of genetic testing in patients with advanced renal cancer to enhance diagnostic accuracy. Furthermore, it provides insights into potential treatment approaches for FH-deficient RCC.