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Objectives Damaged articular cartilage cannot regenerate spontaneously. Chondrocyte therapy, the current treatment of choice, requires laboratory expansion, necessitating two surgical procedures. Adding a second cell type to intraoperatively isolated chondrocytes enables single-stage chondrocyte-based repair strategies and has shown promise in vitro . The benefit of this strategy in vivo and in the clinic has not yet been comprehensively assessed. This systematic review assesses the efficacy of cartilage repair by co-implantations of chondrocytes with other cell types over all available in vivo studies. Design Medline, Embase and Cochrane databases were searched for studies on co-implantations of chondrocytes with other cell types for hyaline cartilage repair. For each study, extracted data were tabulated and reporting quality and risk of bias were assessed. Studies were categorized based on their control groups for qualitative synthesis. Results The search yielded 48 studies across 46 publications: 44 animal studies (26 ectopic and 18 orthotopic) and four clinical trials. Ectopic studies scored poorly on reporting quality and bias, while orthotopic studies were only moderately better. Twenty-seven of 27 experiments with chondrocyte-only controls demonstrated synergistic cartilage formation through co-implantation. Cartilage formation by co-implantations was also found in 15 of 17 experiments without such control and in four clinical trials. Conclusion Cartilage repair by articular chondrocytes is improved by adding a second cell type, like mesenchymal stromal cells. This is likely caused by the second cell types’ stimulatory support. Other second cell types and chondrocyte sources have shown promising results too. This is encouraging for further clinical exploration of single-stage co-implantation strategies.

Background Rapid stroke type identification is essential for time‐sensitive interventions, yet timely neuroimaging remains limited, especially in pre‐hospital and resource‐constrained settings. The EMVision emu™ Brain Scanner is a portable neurodiagnostic device using non‐ionizing electromagnetic signals to distinguish stroke subtypes. In an Australian prevalidation study enrolling 277 suspected stroke patients, it demonstrated diagnostic accuracy with sensitivity and specificity of 92% and 85% for hemorrhagic and 95% and 80% for ischemic strokes, respectively. Case studies and image reconstructions provided (figures 1 and 2). This follow‐up study aims to validate the diagnostic performance of emu™ for detecting intracranial hemorrhage in an international cohort, targeting ≥80% sensitivity and specificity. Methods A prospective, multi‐center, international, paired diagnostic accuracy study, with 4 US sites and 2 Australian sites. It will enroll 300 patients presenting within 12 hours of stroke onset. Patients will be stratified into two arms: intracranial hemorrhage, and ischemic stroke, TIA, or stroke mimic. Participants will undergo standard imaging, followed by non‐invasive scan by the emu™ device. Ground‐truth diagnoses will be adjudicated by a blinded expert panel. The primary endpoints are the sensitivity and specificity of the emu™ device for detecting hemorrhage, calculated against the reference standard. Statistical inference will rely on whether the lower bound of the 95% confidence interval for sensitivity and specificity exceeds 80%. Results First Australian and US enrollments occurred on June 11, 2025, and July 3, 2025, respectively. Latest progress in the study will be presented at the time of conference. Conclusion This is the first international validation study of a portable electromagnetic brain scanner for intracranial hemorrhage detection; a novel, non‐ionizing, diagnostic tool that can revolutionize acute stroke triage, enabling earlier treatment decisions, improved workflows, and equitable access to neuroimaging. image image

Background Patients with single-ventricle physiology are often palliated with the Fontan operation, which may involve the creation of a fenestration. We aimed to evaluate differences in cardiopulmonary exercise test (CPET) performance between patients with fenestrated and non-fenestrated Fontan circulation. Methods Patients with a Fontan circulation referred to CPET between 2006 and 2024 were included and were categorised based on their fenestration status at the time of CPET. Logistic regression analyses were performed to assess the impact of fenestration on peak oxygen consumption (VO 2 ), and Cox proportional hazard to evaluate the impact of fenestration on cardiovascular outcomes (death, heart transplant and Fontan-related hospitalisation). Results Of the 184 patients, 141 were classified as non-fenestrated and 43 as fenestrated. The minute ventilation-carbon dioxide production (V E /VCO 2 slope) was higher in the fenestrated (36.9±7.9) versus (33.2±6.2; p=0.009) in the non-fenestrated group. There was no significant difference in predicted VO 2 between groups (non-fenestrated 51.9%±14.4 vs 51.3%±15.6; p=0.7). Resting oxygen saturation was higher in the non-fenestrated group (93%±4.7 compared with fenestrated group 90.1%±5; p<0.001). Fontan fenestration was not significantly associated with the composite outcome; older patient age at the time of the CPET, cirrhosis and ventricular ejection fraction <40% were significantly associated with higher risk, while higher resting systolic blood pressure, left ventricular morphology and higher predicted peak VO 2 were protective. Conclusions The increased hypoxia and reduced ventilatory efficiency associated with Fontan fenestration offset any potential benefits, resulting in similar exercise performance between the groups. Fontan fenestration was not significantly associated with cardiovascular outcomes.

ABSTRACT The American College of Clinical Pharmacy (ACCP) first described the role and history of the pharmacist as principal investigator (PI) in 2000. An update was published in 2010, citing evidence from NIH and the ClinicalTrials.gov registry that showed an increase in the number of individuals with a Pharm.D. degree engaging in pharmacist‐directed research. The 2025 ACCP Publications Committee was charged with providing an update to the 2010 paper. Key findings include a substantial increase in the total amount of federal funding awarded to schools of pharmacy (SoP) between 2011 and 2023, a modest increase in the number of pharmacists receiving federal grants when comparing 2010 with 2024, and evidence of pharmacist leadership and engagement in Clinical and Translational Science Award networks and service on national grant review panels. It remains challenging, however, to ascertain accurate and reliable data on pharmacists serving in PI roles because of the limitations of currently available data sources. This is especially true for pharmacist PIs who receive non‐federal funding. Future opportunities include a continued emphasis on training programs to prepare pharmacists for PI roles, greater institutional support (e.g., research infrastructure, mentoring programs) for pharmacists serving in PI roles, better promotion of research career tracks to Pharm.D. students and trainees, enhanced efforts at SoP to pursue institutional training grants, and more collaborative efforts across professional organizations to advocate for pharmacist‐scientists. An urgent call to action is necessary to ensure the future growth and success of pharmacist‐directed research.

Positive inotropic agents have an important role in the management of acute decompensated heart failure patients with reduced cardiac output and poor end-organ perfusion. However, despite their acute hemodynamic benefits, the role of inotropes in the management of chronic advanced heart failure remains limited to palliative therapy or as a bridging strategy to mechanical support or heart transplantation. Milrinone is one of the most common inotropic agents used in advanced heart failure to provide symptomatic relief and improved hemodynamics. This review discusses the current evidence of milrinone’s efficacy, indications, outcomes in advanced heart failure, evidence gap, and future directions.

Purpose: Lifestyle and social frailty factors are a new focus in the multidimensional concept of frailty, as recent reports have found strong associations with negative health outcomes. We searched for specific social and lifestyle frailty factors independently associated with 5-year survival and the risk of hospitalization in patients with severe chronic obstructive pulmonary disease (COPD). Methods: We retrospectively analyzed questionnaire data from the National Emphysema Treatment Trial (NETT) and identified items related to the published definition of social frailty. Classification and Regression Tree, a machine learning method, was used to select variables most strongly associated with survival time or hospitalizations beyond 12 months of NETT study enrollment. Kaplan-Meier curves, log-rank tests, and Cox proportional hazards models were used to determine relationships between social/lifestyle variables and hospitalization and survival. Results: Four social and lifestyle frailty factors were significantly related to survival (impaired lifting, bathing and dressing, in-store shopping, and loneliness). Two social and lifestyle frailty factors were significantly related to risk of hospitalization (emotional distress and difficulty performing work or activities). A combination of 6 questions provided clinical phenotypes that were robustly and independently associated with mortality risk and hospitalization with hazard ratios that ranged from 2.4 to 11.2 and 2.2 to 3.5 for survival and hospitalization, respectively, after adjustment for age, sex, disease severity, and physical frailty. Conclusion: Lifestyle and social frailty factors that could be easily identified in practice may represent a novel approach to a multidimensional frailty assessment to predict survival and hospitalization in patients with severe COPD.

In 2023, the American Congress of Rehabilitation Medicine Brain Injury Interdisciplinary Special Interest Group (ACRM BI-ISIG) Mild Traumatic Brain Injury (TBI) Task Force published updated diagnostic criteria for mild TBI. These criteria were developed in collaboration with a panel of 32 subject matter experts in mild TBI using the Delphi method. The 2023 ACRM diagnostic criteria marked the first update since 1993, incorporating three decades of research advancements in our understanding of mild TBI. To facilitate the consistent use of the new diagnostic criteria, the ACRM BI-ISIG Mild TBI Task Force initiated a special project in September 2023 to develop a structured interview to apply the ACRM diagnostic criteria for mild TBI in clinical and research settings. The purpose of this article is to describe the development of the ACRM Structured TBI Interview and the accompanying documents. The ACRM Structured TBI Interview was developed in four phases: (1) initial development of a draft interview by two project leads, (2) review and revision over three rounds by 17 members of the ACRM BI-ISIG Mild TBI Task Force, (3) external review by 19 subject matter experts in mild TBI, and (4) field testing of the ACRM Structured TBI Interview by 11 interviewers who completed 25 diagnostic interviews. In addition to the ACRM Structured TBI Interview, three other documents were developed to help facilitate the administration of the interview (Administration Guide) and to apply the diagnostic criteria (Diagnostic Coding Form and Diagnostic Flow Diagram). A Short Form was also developed for use in contexts where administering the full structured interview is not feasible due to time constraints.

ABSTRACT Introduction Cardiac resynchronization therapy (CRT) improves clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF). However, data on its efficacy in patients with sarcoidosis and HFrEF are limited. Methods Using the TriNetX network, we identified patients with sarcoidosis, heart failure with a left ventricular ejection fraction (LVEF) below 35%, and either left bundle branch block (LBBB) or prolonged QRS duration ( > 150 ms) between 2014 and 2019. Patients were categorized into two cohorts: (1) those who received CRT and (2) those who received an ICD‐only implant. Five‐year outcomes included all‐cause mortality, all‐cause hospitalization, heart failure exacerbation, and the proportion of patients with improvement in LVEF to greater than 40% and greater than 50%. Results Out of 245 eligible patients, we identified a cohort of 87 patients (mean age 62.6 ± 9.5 years) who received CRT and 87 patients (mean age 62.1 ± 11.1 years) who received ICD‐only implant, with similar propensity scores, and included them in a comparative analysis. At 5‐year follow‐up, the CRT group demonstrated outcomes comparable to the ICD‐only implant group for all‐cause mortality (14.9% vs. 20.7%; HR 0.63; 95% CI 0.31–1.28; p = 0.19), all‐cause hospitalization (83.9% vs. 77.0%; HR 1.24; 95% CI 0.89–1.73; p = 0.19), and heart failure exacerbation (28.7% vs. 28.7%; HR 0.90; 95% CI 0.52–1.57; p = 0.72). The proportion of patients with improvement in LVEF to greater than 40% and greater than 50% was also similar in both groups (LVEF > 40%, 43.7% vs. 33.3%; HR 1.30; 95% CI 0.80–2.10; p = 0.29; LVEF > 50%, 31.0% vs. 17.2%; HR 1.72; 95% CI 0.92–3.24; p = 0.09). Conclusion CRT implantation had similar long‐term outcomes compared to ICD‐only implantation in patients with sarcoidosis and HFrEF, particularly all‐cause mortality, all‐cause hospitalization, heart failure exacerbation, and the proportion of patients with improvement in LVEF to greater than 40% and greater than 50%.

Abstract Despite concerns about the toxicity of allogeneic hematopoietic cell transplantation (alloHCT) in older patients, prospective data characterizing prevalence or risk stratification for geriatric morbidity such as disability or frailty are limited. We prospectively assessed the prognostic impact of the novel composite health assessment risk model (CHARM), a score established to predict 1-year nonrelapse mortality (NRM), among 1105 patients aged ≥60 years enrolled on the Bone Marrow Transplant Clinical Trials Network Study 1704. Secondary end points were assessed post-alloHCT at day 100 (D100), D180, and D365 in multivariable models adjusted with predetermined clinical variables. Among alloHCT survivors, the prevalence of disability by instrumental activities of daily living (IADL), frailty by the Physical Frailty Phenotype, and physical function impairment by Patient Reported Measurement Information System (PROMIS) was highest at D100 and lower on D180 and D365. Higher CHARM scores were independently associated with greater disability (coefficient, −0.64; 95% confidence interval [CI], −0.85 to −0.43; P&lt; .001), increased frailty (coefficient, 0.19; CI, 0.081-0.31; P&lt; .001), worse PROMIS physical function, greater PROMIS depression, increased serious organ toxicity by D100, more cognitive decline at D100, and higher mortality after acute graft-versus-host disease (GVHD) but not significantly associated with PROMIS anxiety or acute GVHD. Higher CHARM scores predicted worse disability-free survival (odds ratio [OR], 2.03; CI, 1.66-2.48; P&lt; .001) and lower frailty-free survival (OR, 2.00; CI, 1.61-2.49). In summary, CHARM is an independent prognostic scoring system not only for NRM but also for geriatric morbidity and functional limitation–free survival through 1 year after alloHCT. Pre-alloHCT CHARM is a novel tool to aid shared decision-making for older patients. This trial was registered at www.clinicaltrials.gov as #NCT03992352.

Objective We examined the weight management practices of successful high school wrestlers to contribute meaningful data to the conversations that weight-certifying clinicians and athletic trainers have with athletes at the start of the wrestling season. Understanding how elite athletes navigate weight management can inform safer and more individualized guidance during preseason assessments. Specifically, we sought to determine the proportion of state-qualifying wrestlers who competed at or above their certified minimum weight class. We also quantified the magnitude of weight change from certification to state competition and analyzed seasonal trends in both body weight and body fat percentage over a 20-year period. Design Longitudinal retrospective review. Setting Four Minnesota high schools. Patients or Other Participants State-qualifying wrestlers from 2003 to 2023. Independent Variable State-qualifying weight class. Main Outcome Measure(s) Dependent variables are certification weight, measured body fat percent, and calculated minimum weight class. Results Only 48 wrestlers (52.7%; CI = 42.5%, 63.0%) competed at state in their minimum weight class, while the other 43 competed 1 to 2 weight classes above. Thirty-six wrestlers (39.6%) gained weight over the season. Conclusions Nearly half the successful wrestlers competed in weight classes above their minimum weight, while 5% lost 9% to 18% of their body mass over the wrestling season. This suggests factors other than maximizing individual athletic potential, such as team needs to fill a weight class, influence weight management decisions. Over the 20-year span of the study, trends toward lower measured body fat percentage and lower weight fluctuations suggest influences from sports specialization and year-round training and less emphasis on extreme leanness for competitive advantage. Athletes, in consultation with their coaches and clinicians, should select a competition weight class where they can adequately fuel, train, and recover. This may not be their minimum certified weight class.