Publications by Year: 2026

[This corrects the article DOI: 10.1016/j.eclinm.2025.103682.].

BACKGROUND: Bronchial stenosis is a known complication after lung transplantation, but risk factors remain incompletely understood. We identified predictors of bronchial stenosis requiring bronchoscopic intervention, with a focus on post-transplant bacterial infections, and its impact on clinical outcomes.

METHODS: We conducted a retrospective cohort study of 342 adult lung transplant recipients at a single center between 2017 and 2023. Bronchial stenosis was defined as localized airway narrowing requiring intervention. Clinical, perioperative, and infectious variables-censored to precede the onset of stenosis-were analyzed using univariate and multivariable logistic regression. Outcomes included survival, acute cellular and antibody-mediated rejection, and chronic lung allograft dysfunction (CLAD).

RESULTS: Thirty-four patients (9.9%) developed bronchial stenosis requiring intervention. Multivariable analysis identified male sex (OR: 2.77, 95% CI: 1.13-6.79, p = 0.0261), pulmonary graft dysfunction (PGD) (OR: 3.45, 95% CI: 1.23-9.69, p = 0.0190), length of index hospitalization (OR: 1.01, 95% CI: 1.00-1.02, p = 0.0479), and any positive post-transplant bacterial respiratory culture-prior to onset of stenosis-(OR: 3.97, 95% CI: 1.67-9.48, p = 0.0019) as independent risk factors. Pneumonia and colonization with Pseudomonas aeruginosa or other gram-negatives were strongly associated with stenosis, while Staphylococcus aureus infections and colonization were not. Bronchial stenosis did not significantly impact survival, rejection, or CLAD incidence.

CONCLUSIONS: Bronchial stenosis following lung transplantation is associated with PGD and bacterial airway infections, particularly Pseudomonas species or other gram negatives. These findings support an association between early gram-negative bacterial airway infections and bronchial stenosis and highlight the need for infection prevention and further prospective studies to clarify causal mechanisms and guide targeted interventions.

INTRODUCTION: In the emergency department (ED), commonly used analgesics for pain management are nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol, and opioids. The aim of this clinical trial was to evaluate the effectiveness of intravenous (IV) or oral (PO) paracetamol, combined with intramuscular (IM) diclofenac, in patients with acute limb injuries.

METHODS: This study utilized a double-blind, randomized controlled design to evaluate three different treatment groups. The trial included healthy adult males aged 18-65 years, who arrived at the ED with acute limb injuries, and an initial pain score of at least 5 on the Numerical Rating Scale (NRS). Participants were randomly assigned in equal numbers to one of three groups: one group received IM diclofenac (75 mg/3 mL), along with oral paracetamol (1000 mg); the second group was given IM diclofenac plus IV paracetamol (1000 mg in 100 mL); and the third group received IM diclofenac (75 mg/3 mL), accompanied by a placebo. The main goal of the study was to compare the average pain reduction among the three groups at 30 min after treatment (t30).

RESULTS: A total of 162 participants were recruited between October 2022 and February 2023. Pain levels were assessed at baseline (t0) and continued to be monitored up to 90 min after medication was administered (t90). The average reduction in pain scores for each group was as follows: diclofenac plus oral paracetamol resulted in a mean decrease of 2.5 ± 0.03, diclofenac plus IV paracetamol had a mean reduction of 2.6 ± 0.03, and diclofenac with placebo showed a mean decrease of 2.2 ± 0.04. These results indicate there was no statistically significant difference in pain relief among the three groups. Additionally, none of the groups required rescue pain medication, and no adverse events were reported in any group.

CONCLUSION: The results demonstrate that the three treatment groups achieved similar levels of pain relief within the observed timeframe, offering no significant advantage in terms of speed or extent of pain reduction. Nonetheless, additional studies are warranted to explore the potential synergistic effects of combining paracetamol with NSAIDs via various administration routes, as well as to assess possible adverse events, and the necessity for supplemental analgesia. Trial Registration: ClinicalTrials.gov identifier: NCT04199572.

BACKGROUND: CTP has increasingly been incorporated into the evaluation of all patients with suspected acute ischemic stroke (AIS), including those with minor symptoms. We aimed to assess the frequency with which CTP is performed in patients with possible AIS based on NIHSS as well as the role of CTP in acute treatment decision-making among patients with low NIHSS.

METHODS: We performed a retrospective cohort study of all patients who underwent CTP upon presentation to the ED at 3 academic, urban hospitals in Philadelphia, PA between January 1, 2022 and December 31, 2022. We collected data on initial NIHSS score, AIS treatment decisions, subsequent neuroimaging, and final diagnosis. The study was deemed exempt by the Hospital of the University of Pennsylvania IRB.

RESULTS: There were 530 patients with a median age of 65 years (IQR 54-73) and 56% were women. The frequency of CTP by NIHSS is displayed in the figure. A total of 89 CTP studies (16.8%) were performed in patients with very low NIHSS (defined as NIHSS ≤ 2). Of these, just 2 (2.2%) received thrombolysis and 0 (0%) received thrombectomy. CTP did not influence the treatment decision in either case.

CONCLUSIONS: CTP is frequently performed in patients with low NIHSS. It had limited impact on acute treatment decisions, notably none among those with NIHSS ≤ 2, suggesting that CTP may be over-utilized in this subset of patients with AIS.

Cell therapy has achieved a critical breakthrough through single-cell microgel technology. This miniaturized encapsulation platform enables precise microenvironment recapitulation, efficient targeted delivery, and tunable pericellular matrix control. Nevertheless, prevailing microfluidic and surface chemical engineering methodologies confront fundamental challenges in preserving cell viability and functionality. Here, we establish a simple and bioenzymatic strategy for fabricating single-cell microgels, using microbial transglutaminase adsorption. This surfactant- and oil-free approach, without surface modification, permits universal, high-viability encapsulation of diverse cell types and biomaterials. We achieve 100 % encapsulation efficiency and robust mechanical protection. Therapeutic efficacy was assessed in myocardial infarction (MI) and pulmonary fibrosis (PF) models. In MI, microgel-encapsulated MSCs (MSC SCMs) significantly improved in vivo retention and survival, exhibiting superior tissue regeneration and cardiac function. In bleomycin-induced PF, TNF-α-loaded MSC SCMs potentiated MMP-13 secretion, achieving enhanced respiratory function and attenuated fibrotic lesions. This robust and universally applicable platform thus for advanced cell therapies, overcomes limitations in encapsulation while demonstrating potent therapeutic efficacy across disease models.

Large and persistent sociodemographic disparities in rates of mental health treatment in the United States have been reported, but whether these differences reflect institutional mistrust or limited social support remains unclear. This study described current treatment use among American adults with moderate-to-severe depressive or anxiety symptoms and examined whether trust in health care institutions and availability of emotional support were associated with lack of treatment. A cross-sectional analysis was conducted using data from a nationally distributed, web-based opinion survey of 9733 American adults with moderate-to-severe depressive or anxiety symptoms (Patient Health Questionnaire-9 score ≥10 and/or Generalized Anxiety Disorder-2 score ≥3). The survey was fielded April 10th-28th, 2025, using quota sampling for age, gender, race, ethnicity, education, U.S. census region, and urbanicity; post-stratification weights approximated the U.S. adult population. The primary outcome was no current mental health treatment (neither antidepressant nor psychotherapy use). Weighted logistic regression estimated odds ratios for treatment absence by sociodemographic characteristics, trust in physicians and hospitals, scientists and researchers, the Centers for Disease Control and Prevention, pharmaceutical companies, and emotional support. Among 9733 adults with elevated symptoms, 66.3 % reported no current treatment. Racial and ethnic minority groups, men, and those born outside the United States had higher odds of being untreated, while public insurance predicted lower odds. Lower trust in doctors and hospitals, lower trust in science, and lack of emotional support each independently predicted treatment absence, but inclusion of these variables did not meaningfully attenuate sociodemographic disparities.

BACKGROUND: It is frequently reported that access to gender affirming medical care (GAMC) is burdened with many barriers, such as lack of parental support, geographic distance, absence of social support, and medical professionals' lack of knowledge. While the current knowledge shows that trans and nonbinary youth (TNBY) experience many challenges when accessing GAMC, there is still limited information available regarding how they navigate GAMC decisions as youth approach puberty.

METHODS: To fulfill that gap, a team of researchers conducted semi-structured interviews in six countries (Australia, Canada, India, Switzerland, the UK, and the US) with TNBY ages 8-14 years and their families.

RESULTS: Thematic analysis was conducted on baseline interview data from an international longitudinal study, yielding three themes, and subthemes, relevant to making GAMC decisions: (1) Participants' decisions guided by expectations, (2) conditions for reaching an informed decision, and (3) the role of time in GAMC decision-making. Of these themes, several subthemes allowed researchers to understand how families navigate whether to seek GAMC, and if so, deciding on specific care trajectories.

CONCLUSION: Results indicated that making decisions regarding GAMC is a process that moves beyond medical impacts and side-effects, as many family dynamics, access to information and time also played into TNBY's decisions to seek GAMC.

A roundtable discussion, held on 10 December, 2024, addressed requirements for protein quality assessment in United States and Canadian food labeling regulations, focusing on concerns with the protein digestibility-corrected amino acid score (PDCAAS), which includes an in vivo rat assay to determine true fecal protein digestibility. Because animal proteins tend to score higher, the PDCAAS disadvantages nonanimal foods in substantiating protein content claims despite dietary guidelines recommending increased intake of plant proteins. In addition, the use of animal testing raises ethical concerns for some consumers. Roundtable participants weighed the benefits and costs of requiring the PDCAAS and discussed alternative regulatory approaches to better promote human health, prevent chronic disease, replace animal testing, and support sustainable food production. Options included relying solely on the amount of protein per serving, correcting only for the amino acid score, using fixed coefficients of digestibility or in vitro assays to determine digestibility, and incorporating measures that reflect human health outcomes and environmental impact. Several in vitro methods, such as the pH-drop and pH-stat methods, were identified as promising candidates for regulatory acceptance. The consensus was that for foods that do not address special needs, relying solely on the amount of protein to substantiate content claims is appropriate for populations who already consume protein in excess of reference values from varied sources. This approach, already used in other high-income jurisdictions, allows more plant-based foods to qualify for protein claims while avoiding animal testing. Moving away from the in vivo derived PDCAAS would reduce existing regulatory barriers, better align with current dietary guidelines, and promote increased intake of plant-based foods, thereby improving public health and sustainability.

INTRODUCTION: Cardiovascular disease is the leading cause of death globally. Understanding the association between lifestyle habits, risk factors, and structural heart abnormalities is crucial for developing preventive strategies, especially among understudied populations.

METHODS: The HUDDLE trial was a cross-sectional study of National Football League alumni and their family members aged ≥50 years who self-reported health histories and underwent noninvasive cardiovascular disease screening, including transthoracic echocardiography. Cardiovascular disease risk factors were evaluated using a modified American Heart Association Life's Simple 7 (physical activity, tobacco use, obesity, hypertension, diabetes, alcohol intake, and hyperlipidemia) and assessed as ideal, intermediate, or poor.

RESULTS: Of 498 participants, 92.4% had at least 1 poor health metric, with 15.9% having ≥3. Former National Football League players aged <65 years had a higher prevalence of ≥3 poor metrics compared with other participants. Non-White former National Football League players exhibited nearly double the prevalence of having 3 or more poor health metrics as their White counterparts (23.9% vs 12.0%). Compared with those with no poor metrics, participants with 3-7 poor metrics had the highest odds of having structural heart abnormality (OR=2.40; 95% CI=1.08, 5.32), followed by those with 2 (OR=2.39; 95% CI=1.16, 4.92) and 1 (OR=1.79; 95% CI=0.87, 3.66) poor metric.

CONCLUSIONS: This subanalysis of the HUDDLE study identified a high prevalence of poor health metrics among former National Football League players and their families. Younger, non-White participants were more likely to have worse lifestyle habits than their counterparts. Increasing number of poor health metrics was associated with structural heart abnormalities.Trial registration: This study is registered at http://www.clinicaltrials.gov (NCT0500958).