Citations

Background Chlorhexidine is commonly used in prevention bundles for ventilator-associated pneumonia. Results for use of chlorhexidine in critically ill patients requiring mechanical ventilation via an endotracheal tube are mixed, and data for patients using a tracheostomy are lacking. Objectives To assess the risk for ventilator-associated pneumonia according to chlorhexidine exposure in patients requiring a new tracheostomy for mechanical ventilation. Methods This single-center, retrospective cohort study compared the development of ventilator-associated pneumonia according to chlorhexidine exposure in adult intensive care unit patients requiring new tracheostomy at a large academic medical center. Adults who received a new tracheostomy and required ventilator support for at least 48 hours were included. Patients treated for pneumonia at the time of tracheostomy or who met additional exclusion criteria were excluded. Results Of 235 patients who met the inclusion criteria, 203 received chlorhexidine and 32 did not. The cohort was predominantly White, male, and admitted to a surgical intensive care unit. Incidence of ventilator-associated pneumonia did not differ significantly between patients exposed or not to chlorhexidine (by 30 days, 32.5% vs 35.7%, P = .87). Time to development of ventilator-associated pneumonia also did not differ significantly between patients exposed or not (9 vs 12 days, respectively, P = .34). Conclusions Chlorhexidine exposure was not associated with a difference in the incidence of or time to ventilator-associated pneumonia after new tracheostomy. Further study is needed on the role of chlorhexidine in preventing ventilator-associated pneumonia after a new tracheostomy.

ABSTRACT Collection of hematopoietic progenitor cells and mononuclear cells by leukocytapheresis is a critical step of procuring cellular starting materials for future therapeutic use. Leukocytapheresis requires use of anticoagulant to prevent blood clotting in the extracorporeal circuit during collection. A commonly used anticoagulant is Acid Citrate Dextrose Solution A (ACD‐A). ACD‐A primarily prevents blood clotting by reversibly chelating free ionized calcium, which is essential for the clotting cascade. Electrolytes frequently affected by ACD‐A include calcium, magnesium, potassium, phosphate, and bicarbonate. Risks for development of electrolyte derangements include procedure‐related parameters as well as patient comorbidities. Symptoms range from mild paresthesias to life‐threatening cardiac arrhythmias. Recognition of related signs and symptoms is important for prompt intervention with procedure modification and electrolyte replacement to optimize patient safety. This paper will provide an enhanced understanding of the underlying pathophysiology and assist in timely identification and management of electrolyte abnormalities associated with cellular therapy collections.

Abstract Objective Current clinical risk models were developed for longer-term breast cancer risk stratification and therefore have limited utility for predicting short-term (1-year) breast cancer risk. This study evaluates the performance of a mammogram-based artificial intelligence (MB-AI) risk model for predicting breast cancer diagnosis within 1 year in high-risk women. Methods This retrospective case-control study included 340 women who underwent supplemental MRI screening within 1 year following a negative mammogram, of whom 101 (29.7%) developed breast cancer and 239 (70.3%) remained cancer-free during the same interval. Artificial-intelligence–assigned absolute 1-year risk scores, Tyrer–Cuzick (TC) lifetime and 10-year scores, and Gail lifetime and 5-year scores were analyzed. Model discrimination was evaluated using receiver operating characteristic (ROC) curves. Sensitivity, specificity, and predictive values were estimated at optimal cutoffs. Subgroup analyses examined model performance across genetic, menopausal, reproductive, and tumor-based strata. Results The MB-AI model demonstrated the highest overall discriminative ability (area under the curve [AUC] = 0.812), with strong performance in extremely dense breasts (AUC = 0.976). By comparison, TC lifetime (AUC = 0.625) and Gail lifetime (AUC = 0.668) models showed modest discrimination, while TC 10-year and Gail 5-year models did not discriminate (AUCs ≤0.49). Subgroup analyses showed consistent performance across clinical and pathological categories. The MB-AI model also showed an AUC comparable to that of previously developed AI models. Conclusions A mammogram-based AI model demonstrated improved performance compared with traditional clinical risk models for predicting breast cancer diagnosis within 1 year in women undergoing supplemental screening. These findings support that AI-based approaches may reflect both short-term risk and early imaging features of occult disease and suggest further investigation of AI as a complement to existing risk stratification strategies.

Objectives: Elevated intracranial pressure (ICP) remains a challenge and immediate danger in patients with acute brain injury. Current literature supports the use of a single hyperosmolar agent to reduce ICP. However, the efficacy and safety of overlapping hyperosmolar agents have not been evaluated. The objectives of this study are to analyze the ICP lowering effects and evaluate the safety profile of overlapping hyperosmolar therapy. Materials and Methods: This single-center, retrospective study included adults (≥18 y) admitted to the Neurosciences Intensive Care Unit between May 2018 and September 2024 with acute brain injury leading to intracranial hypertension refractory to a single hyperosmolar agent and an ICP monitor. They received overlapping doses of mannitol and hypertonic sodium approximately every 3 hours. We evaluated the impact of overlapping hyperosmolar therapy on ICP. Safety outcomes included acute kidney injury incidence, electrolyte disturbances, and volume status changes. Results: Forty-six patients were included in this study with a median (IQR) age of 46.5 (35.9, 62.4) years. Median (IQR) dose of mannitol was 40.1 (34.6, 50.0) g, while median (IQR) dose of hypertonic sodium was 120 (90, 125) mEq. About 86% of patients experienced a decrease in ICP after initiation of overlapping hyperosmolar therapy. Six acute kidney injuries occurred, and 7 patients experienced pulmonary edema. Median (IQR) peak sodium, chloride, and osmolar gap values were 149 (144, 155) mEq/L, 115 (111, 119) mEq/L, and 5.7 (0.7, 9.0) mOsm/kg. Conclusions: Overlapping hyperosmolar therapy may provide a transient ICP reduction without excessive adverse effects in patients with refractory ICP to a single hyperosmolar agent.

Importance Anhydramnios from fetal kidney failure causes lethal pulmonary hypoplasia. Serial amnioinfusions have shown promise in mitigating pulmonary disease from bilateral renal agenesis, but efficacy and safety for other causes of fetal kidney failure are unproven. Objective To assess the efficacy of serial amnioinfusions initiated before 26 weeks’ gestation to mitigate lethal pulmonary hypoplasia in cases of anhydramnios due to fetal kidney failure. Design, Setting, and Participants Prospective, nonrandomized clinical trial conducted at 13 US fetal therapy centers from December 2018 to February 2025. Outcomes for maternal-fetal pairs with anhydramnios before 22 weeks’ gestation due to fetal kidney failure without bilateral renal agenesis are reported; data collection for surviving infants continued until February 13, 2026. Exposure Thirty-two participants underwent serial amnioinfusions with isotonic fluid beginning before 26 weeks’ gestation. Main Outcomes and Measures The primary end point was neonatal survival for 14 days or longer with dialysis access placement. Secondary outcome measures of survival to discharge home and kidney transplant are reported. Results Twenty-nine of 32 participants (91%) had a live birth, with a median (IQR) gestational age at delivery of 34 weeks 1 day (31 weeks 5 days to 34 weeks 6 days). All participants delivered before 37 weeks’ gestation. No unexpected serious maternal adverse events occurred, and the most common maternal complications were preterm prelabor rupture of membranes in 19 participants (56%) and chorioamniotic separation in 10 (29%). The primary outcome occurred in 19 (65.5%) of 29 live-born neonates (95% CI, 45.7%-82.1%). Factors associated with survival to the primary outcome included receiving more amnioinfusions (median [IQR], 14 [9-18] in survivors vs 7 [4-11] in nonsurvivors; P = .01), longer time interval from first amnioinfusion to preterm prelabor rupture of membranes (63.5 [60.5-74.5] days in survivors vs 29.0 [22.0-56.0] days in nonsurvivors; P = .01), gestational age greater than 32 weeks (79% of survivors vs 38% of nonsurvivors; P = .03), and higher birth weight (2029 [1770-2250] g in survivors vs 1635 [1185-1915] g in nonsurvivors; P = .01). Fourteen live-born infants (48%) survived to hospital discharge at a median (IQR) age of 4.7 (3.4-5.7) months. Of the 11 infants surviving to date, 7 (64%) have undergone kidney transplant between ages 2 years to 5 years. Conclusions and Relevance Serial amnioinfusions mitigated lethal pulmonary hypoplasia in neonates with anhydramnios due to fetal kidney failure. Significant neonatal morbidity and mortality independent of early lung function was noted. Factors associated with survival were consistent with the Renal Anhydramnios Fetal Therapy trial’s bilateral renal agenesis cohort, suggesting common mechanistic pathways for mitigating pulmonary hypoplasia. Trial Registration ClinicalTrials.gov Identifier: NCT03101891

Abstract Objective: Antibiotics are frequently prescribed for acute sinusitis despite national guidelines recommending antibiotics only if specific symptom criteria are met. We aimed to define the proportion of acute sinusitis encounters meeting criteria for antibiotic prescribing, characterize prescribing practices, and identify factors associated with guideline-discordant prescribing. Design: This retrospective cohort study included 1,000 randomly selected adult ambulatory encounters with a primary diagnosis of acute sinusitis between January 1, 2024 and March 31, 2024. Encounter notes were reviewed for appropriate antibiotic prescribing criteria as per national guidelines. Encounters were evaluated for drug selection and duration concordance based on local guidelines. A multivariable logistic regression analysis was performed to identify predictors of inappropriate antibiotic prescribing. Setting: Emergency departments, urgent care centers, and primary care clinics. Results: Antibiotic prescribing criteria were met for 67.6% of included encounters. Antibiotics were prescribed in 93.5% of encounters that met prescribing criteria, and 80.2% of encounters that did not. Both drug selection and duration were guideline-concordant in 49.2% of total encounters. On multivariable analysis, predictors of inappropriate antibiotic prescribing included cough (OR 2.15, 95% CI 1.08–4.29; P = 0.03) and symptom duration between 7 and 9 days (compared to <6 days; OR 7.70, 95% CI 3.24–18.31; P < 0.001). Electronic encounters were associated with lower odds of prescribing compared to in-person encounters (OR 0.03, 95% CI 0.01–0.09; P < 0.001). Conclusions: Most encounters for acute sinusitis result in an antibiotic prescription, despite prescribing criteria not being met. These findings may aid antimicrobial stewardship programs in benchmarking and optimizing antibiotic prescribing for acute sinusitis.

Ex vivo liver perfusion (EVLP) sustains human or large animal livers outside the body under near-physiological conditions, enabling functional monitoring for lactate clearance, bile production, and oxygen consumption and allowing targeted therapeutic interventions. Originally developed to optimize donor grafts for transplantation, EVLP has evolved into a powerful translational research platform bridging preclinical discovery and early clinical translation. This review discusses EVLP as a platform for gene therapy, immunotherapy, pharmacology, and personalized medicine, with particular emphasis on gene- and immune-based interventions as mechanistically mature exemplars. We consolidate advances in pharmacological testing and toxicity modeling, viral and non-viral gene delivery, genome engineering, and immunomodulation using perfused livers. We further describe emerging applications, including autologous EVLP pathways for organ-confined therapy, ex vivo liver surgery, and bioengineering strategies such as biliary organoid repair, RNA interference, and mitochondrial transfer. We highlight how these applications align with a paradigm shift in biomedical research, including the NIH’s recent initiative to prioritize human-based experimental models over animal-only studies. By leveraging transplant-declined or surgically resected organs that would otherwise be unused, ex vivo perfusion bridges the gap between pre-clinical testing and clinical practice, enabling real-time evaluation of interventions in functional human tissue. We discuss both the scientific opportunities afforded by EVLP and the technical, biosafety, and ethical challenges that must be addressed to enable responsible clinical translation.

Abstract Background/Purpose Diagnosing wrist ligament injuries is challenging; early detection and treatment are important to prevent osteoarthritis progression. Interosseous proximity maps, a proxy measure for joint space, can be generated from volumetric imaging data and may provide important information about wrist health. Artificial intelligence (AI) could enhance accuracy of noninvasive diagnosis based on imaging-derived metrics. This work demonstrates feasibility of AI training using synthetic proximity map data generated from finite element models (FEMs). Methods Personalized wrist FEMs for two asymptomatic participants were created from four-dimensional computed tomography-derived anatomic and kinematic data. Monte Carlo sampling varied 22 ligament material properties and simulated 7,500 unique injury scenarios generating 9,000,000 labeled red, green, and blue (RGB) images of interosseous proximity vector fields from FEM-derived motions. Images were associated with 17 descriptive metrics, including gross wrist angles and bone surface pairs, and used to develop mixed-input convolutional neural networks (CNNs). Model performance was evaluated for identifying specific ligament injuries. Results Average area under receiver operating characteristic curve (AUROC) for CNNs was 0.757 across all injury types and kinematics. In a subset with clinically-relevant functional angles, the average AUROC was 0.824. Best-performing individual ligament AUROCs ranged from 0.807 to 0.999. Sensitivities and specificities exceeded 0.99 for some ligament injury simulations under specific wrist angles and bone surface pairs. Conclusion This study demonstrates the feasibility of using synthetic data from FEMs to train AI models for classifying wrist ligament injuries. Proximity-based RGB images may be a relevant biomarker of ligamentous injury.

Abstract The Tau Global Conference 2025, hosted by the Alzheimer's Association, CurePSP, and the Rainwater Charitable Foundation, convened international experts from academia, industry, government, and philanthropy to explore advances and challenges in tauopathy research. The meeting highlighted progress across tau biology, including emerging models of tau regulation, degradation, and propagation; advances in biomarker development for the diagnosis and staging of tauopathies; and evolving therapeutic strategies targeting diverse aspects of tau pathophysiology. Discussions also emphasized the importance of cross‐sector collaboration, and global initiatives to address disparities in tau research. This report synthesizes key insights from the conference and underscores the critical role of interdisciplinary, biomarker‐driven, and globally inclusive approaches in accelerating the translation of tau research into effective clinical applications.