Cell crowding activates pro-invasive mechanotransduction pathway in high-grade DCIS via TRPV4 inhibition and cell volume reduction

Cell crowding is a common microenvironmental factor influencing various disease processes, but its role in promoting cell invasiveness remains unclear. This study investigates the biomechanical changes induced by cell crowding, focusing on pro-invasive cell volume reduction in ductal carcinoma in situ (DCIS). Crowding specifically enhanced invasiveness in high-grade DCIS cells through significant volume reduction compared to hyperplasia-mimicking or normal cells. Mass spectrometry revealed that crowding selectively relocated ion channels, including TRPV4, to the plasma membrane in high-grade DCIS cells. TRPV4 inhibition triggered by crowding decreased intracellular calcium levels, reduced cell volume, and increased invasion and motility. During this process, TRPV4 membrane relocation primed the channel for later activation, compensating for calcium loss. Analyses of patient-derived breast cancer tissues confirmed that plasma membrane-associated TRPV4 is specific to high-grade DCIS and indicates the presence of a pro-invasive cell volume reduction mechanotransduction pathway. Hyperosmotic conditions and pharmacologic TRPV4 inhibition mimicked crowding-induced effects, while TRPV4 activation reversed them. Silencing TRPV4 diminished mechanotransduction in high-grade DCIS cells, reducing calcium depletion, volume reduction, and motility. This study uncovers a novel pro-invasive mechanotransduction pathway driven by cell crowding and identifies TRPV4 as a potential biomarker for predicting invasion risk in DCIS patients

ASRA pain medicine narrative review and expert practice recommendations for gastric point-of-care ultrasound to assess aspiration risk in medically complex patients undergoing regional anesthesia and pain procedures

Gastric point-of-care ultrasound (POCUS) may offer clinical value in assessing aspiration risk among medically complex patients undergoing regional anesthesia and pain procedures. While the American Society of Anesthesiologists (ASA) preoperative fasting guidelines primarily apply to healthy individuals, medically complex populations often present with differing gastric emptying and aspiration risk. This narrative review, conducted by the American Society of Regional Anesthesia and Pain Medicine (ASRA-PM), adhered to PRISMA guidelines and was registered with PROSPERO. It focused on seven medically complex patient groups: those who are pregnant, obese, diabetic, have gastroesophageal reflux disease (GERD), are receiving emergency care, are enterally fed, or are taking GLP-1 receptor agonists (GLP-1RA). Study quality was assessed using the Mixed Methods Appraisal Tool (MMAT). Practice recommendations were developed using an iterative expert consensus process, with final recommendations based on evidence strength, clinical relevance, and expert agreement. Findings support the use of gastric POCUS in patients in active labor, those undergoing urgent cesarean sections, and those with diabetes. Conditional support is given for obesity, emergency care, enteral feeding, and GLP-1RA use. Routine use is not recommended in non-laboring pregnancies, elective cesarean delivery, or GERD. While gastric POCUS may aid with aspiration risk evaluation, its use should complement clinical judgment. Implementation may be limited by practical and training constraints, requiring individualized decision-making. These recommendations serve as a foundation for future research and potential clinical guideline development. PROSPERO registration number: CRD42023445927

Defining Diastolic Dysfunction Post-Fontan: Threshold, Risk Factors, and Associations with Outcomes

BACKGROUND: Following the Fontan procedure, patients with single ventricle physiology are at high risk of diastolic dysfunction (DD) and elevated end-diastolic pressure (EDP). OBJECTIVE: This study aims to determine (1) the optimal EDP threshold correlated with adverse outcomes post-Fontan and (2) the clinical and imaging predictors of DD. METHODS: The study included patients from the Fontan Outcome Registry using CMR Examinations (FORCE) who underwent cardiac catheterization and cardiac magnetic resonance (CMR) within a two-year window. The composite outcome was defined as all-cause mortality, sustained atrial or ventricular arrhythmia, plastic bronchitis, protein-losing enteropathy, or listing for transplantation. The EDP cutoff was determined using the lowest Brier score from Cox proportional hazard models. RESULTS: The study included 861 patients (mean age 16.4 ± 9.3 years). Mean EDP was 9.0 ± 3.5 mm Hg, with DD defined at an optimal EDP threshold \u3e13 mm Hg. Patients were followed for a median of 3.6 years after catheterization. By univariable analysis patients with DD were more likely to have Fontan associated liver disease (40% vs 29%, p=0.03) and kidney disease (19% vs 6%, p\u3c0.001). In multivariable analyses, DD was associated with the composite outcome (HR 3.37, 95% CI: 2.03-5.59, p\u3c0.001). Ninety-seven patients (11.3%) had DD. Multivariable analysis demonstrated that older age at catheterization, greater body mass index (BMI), non-left ventricular morphology, and higher ventricular end-diastolic volume (EDV) were associated with DD. CONCLUSION: DD, defined as an EDP \u3e13 mm Hg, is linked to over threefold higher risk of adverse outcomes. Risk factors for DD include older age, higher BMI, non-left ventricular morphology, and larger EDV. The presence of risk factors may warrant screening catheterization to identify DD and modify care accordingly

Bias in vital signs? Machine learning models can learn patients\u27 race or ethnicity from the values of vital signs alone

OBJECTIVES: To investigate whether machine learning (ML) algorithms can learn racial or ethnic information from the vital signs alone. METHODS: A retrospective cohort study of critically ill patients between 2014 and 2015 from the multicentre eICU-CRD critical care database involving 335 intensive care units in 208 US hospitals, containing 200 859 admissions. We extracted 10 763 critical care admissions of patients aged 18 and over, alive during the first 24 hours after admission, with recorded race or ethnicity as well as at least two measurements of heart rate, oxygen saturation, respiratory rate and blood pressure. Pairs of subgroups were matched based on age, gender, admission diagnosis and disease severity. XGBoost, Random Forest and Logistic Regression algorithms were used to predict recorded race or ethnicity based on the values of vital signs. RESULTS: Models derived from only four vital signs can predict patients\u27 recorded race or ethnicity with an area under the curve (AUC) of 0.74 (±0.030) between White and Black patients, AUC of 0.74 (±0.030) between Hispanic and Black patients and AUC of 0.67 (±0.072) between Hispanic and White patients, even when controlling for known factors. There were very small, but statistically significant differences between heart rate, oxygen saturation and blood pressure, but not respiration rate and invasively measured oxygen saturation. DISCUSSION: ML algorithms can extract racial or ethnicity information from vital signs alone across diverse patient populations, even when controlling for known biases such as pulse oximetry variations and comorbidities. The model correctly classified the race or ethnicity in two out of three patients, indicating that this outcome is not random. CONCLUSION: Vital signs embed racial information that can be learnt by ML algorithms, posing a significant risk to equitable clinical decision-making. Mitigating measures might be challenging, considering the fundamental role of vital signs in clinical decision-making

Scoping Review of Trauma-Informed Yoga (TIY) for Survivors of Sexual, Domestic, and Interpersonal Violence and Development of the WELLNESS Mnemonic to Characterize TIY Outcomes

This scoping review provides an overview of the current evidence base for trauma-informed yoga (TIY) for survivors of sexual, domestic, and interpersonal violence to document the spectrum of study designs, population and intervention characteristics, and associated results of TIY for trauma survivors. Authors utilized the scoping review methodology outlined by Arksey and O\u27Malley (2005). Pubmed and Scopus were searched initially conducted on August 16, 2022, and updated to include any new studies on March 25, 2025. Data extracted included study design, population characteristics, intervention specifics, and results. Authors devexbvgloped an innovative mnemonic to inform discussion of results: WELLNESS: Well-being; Empathy; Longevity (durability of therapeutic effect); Lessen trauma symptoms; Nurturing (self-compassion), Ease stress, Security, and Self-awareness). The combined initial and updated literature searches yielded 4167 studies. Title and abstract screening netted 35 studies meeting review criteria. Full-text review netted 18 studies meeting criteria. Sexual, interpersonal, and domestic violence survivors who participated in TIY reported enhancement of physical and psychological function and well-being. Effects included increased sense of safety, self-compassion, personal growth, and self-regulation. Studies reported reduced depression, anxiety, negative thoughts, stress and trauma symptoms, and increased self-esteem; positive coping; improved relationships, better sleep and enhanced mindfulness; and sense of peace. TIY is beneficial to survivors of sexual, domestic, and interpersonal violence by promoting peaceful embodiment without retraumatization and enhancing affect regulation to decrease reactivity and agitation. The constellation of effects can improve the sequelae of trauma, and survivors may benefit from long-term TIY programming to ensure more robust improvement

Two Non-myeloablative HLA-Matched Related Donor Allogeneic Hematopoietic Cell Transplant Regimens in Patients with Severe Sickle Cell Disease

BACKGROUND: Non-myeloablative (NMA) conditioning is increasingly being used with success in matched related donor (MRD) and alternative donor allogeneic hematopoietic cell transplant (allo-HCT) in individuals with sickle cell disease (SCD). Advantages include decrease toxicity and applicability in patients otherwise unable to tolerate conditioning regimens due to end organ damage or age. OBJECTIVE(S): We aimed to add to published data outcomes of two similar NMA protocols Protocol 1 (clinicaltrials.gov ID: NCT00061568) and Protocol 2 (clinicaltrials.gov ID: NCT02105766)) in mainly adult patients with SCD to evaluate safety, toxicity, and success of these regimens in individuals at high-risk for poor transplant-related outcomes. We also evaluated the tolerability and outcomes of Protocol 2, which included pre-conditioning immuno-depletion, in patients at even higher risk of T-cell mediated rejection or plasma/B-cell mediated anti-donor erythrocyte antibody production-the latter due to ABO incompatibility or recipient red blood cell alloimmunization to a donor antigen. Lastly, we evaluated the incidence and trajectory of mixed donor myeloid chimerism over time following allo-HCT. STUDY DESIGN: In this retrospective analysis of the two prospective phase 2 NMA transplant protocols, 91 individuals with SCD or transfusion-dependent beta thalassemia underwent MRD allo-HCT at the National Heart, Lung, and Blood Institute; regimens contained alemtuzumab, low dose radiation, and sirolimus for graft-versus-host disease (GVHD) prophylaxis with or without preconditioning immuno-depletion with pentostatin and oral cyclophosphamide (Protocol 2). RESULTS: In the total cohort of 91 transplant recipients, outcomes were favorable with timely neutrophil and platelet engraftment (median: 21 days (range, 7-67) and 21 days (10-112), respectively), minimal high-grade acute and no chronic GVHD, overall survival of 90%, sickle-free survival of 85%, and mixed donor myeloid chimerism in 43% at a median follow up of 7.3 years (range, 0.8-20). Most patients with mixed myeloid chimerism at 2-years post-HCT remained stable in their values. In analyzing each protocol separately, outcomes were comparable except for higher cytomegalovirus reactivation requiring treatment in Protocol 2, without associated increase in graft failure. In the combined cohort, graft failure occurred in 11 patients and hematologic malignancy or abnormal cytogenetics on bone marrow evaluation developed in 7 recipients. On a sub-analysis of factors that may implicate transplant outcomes, the number of RBC units transfused post-HCT was significantly higher in recipients with pre-HCT history of alloimmunization to donor red blood cell antigens. There was no difference in RBC units transfused, duration of transfusion, or in red cell engraftment in those with major ABO incompatibility; pre-conditioning immune-depletion and pre-treatment with rituximab were likely helpful. CONCLUSION: Both NMA allo-HCT protocols were successful in achieving adequate engraftment and sickle-free survival with minimal toxicity, including in individuals with mixed donor myeloid chimerism. The addition of pre-conditioning immuno-depletion was well-tolerated and reduced graft failure rate in high-risk recipients

ACR Appropriateness Criteria® Cervical Pain or Cervical Radiculopathy: 2024 Update

Cervical spine pain is one of the most common reasons for seeking medical care as it ranks in the top 5 causes of global years lost to disability. The economic burden of cervical pain is also significant. Imaging is at the center of diagnosis of cervical pain and its causes. However, different symptoms and potential causes of cervical pain require different initial imaging to maximize the benefit of diagnostic usefulness of imaging. In this document we address different cervical pain variants with detailed assessment of the strengths and weaknesses of different modalities for addressing each specific variant. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation

A Proposed Framework for Ranking and Prioritizing Food Safety Risks in Low Resource Settings Using Foodborne Disease Burden Metrics: A Case Study in Ethiopia

Risk-based food safety systems are recognized as the best way to address food safety in an effective and efficient manner. Central to risk-based food safety systems is an assessment, ranking, and prioritization of risks associated with foodborne hazards that informs objective, evidence-based decisions on risk mitigation in a systematic and transparent manner. While the importance of such approaches is well recognized, many governments struggle with where to begin. We adapted and implemented a framework for risk-based decision-making in low resource settings using Ethiopia as an example, engaging Ethiopian stakeholders in a multi-phase process to identify food safety priorities. First, stakeholder representatives were engaged to define statements of concern and purpose; identify foodborne hazards of public health relevance in Ethiopia; and select appropriate risk metrics for risk ranking and prioritization. Second, estimates for each risk metric were calculated for selected foodborne hazards using World Health Organization (WHO) data and expert elicitation. Third, stakeholder representatives were engaged in ranking the hazards as High, Medium, or Low risk; notably, mortality was the preferred risk metric in decision-making. Fourth, attribution estimates to food groups were developed for hazards ranked as High risk using expert elicitation to supplement WHO data. Lastly, stakeholder representatives were engaged in a risk prioritization exercise that identified key control points in four food supply chains and quantified their impact on risk through mitigation of hazards or prevention of contamination. Our proposed framework provides a systematic, evidence-based and adaptable method for prioritizing allocation of public sector resources. The process can generate the evidence needed to strengthen regulatory systems and support efficient implementation of national-level food safety strategies that span from farm to fork to improve public health

Occupational Therapy Assessment Practice Patterns for Core Domains in Adult Populations

Practitioners need to demonstrate the value of occupational therapy services in achieving effective patient outcomes. To intervene effectively, we must have adequate assessment practices. This study examines variation in occupational therapy assessment practices by facility type, areas addressed, and types of instruments. The study characterizes commonly and frequently used assessment practices in core occupational domains and identifies potential practice gaps related to assessment. A cross-sectional online survey across six domains central to adult occupational therapy practice (activities of daily living [ADL], instrumental activities of daily living [IADL], fear of falling, functional cognition, psychosocial, and vision) was administered to practitioners in various settings. Surveys were obtained from 1,198 respondent. Survey responses identified differences in domains being assessed and assessment methods used by occupational therapy practitioners across hospital inpatient post-acute care facilities and community settings. There is variability in the methods used to assess domains critical to occupational therapy practice and the degree to which occupational therapists evaluate domains in practice settings