Publications by Year: 2026

BACKGROUND AND PURPOSE: Unstable pelvic ring fractures are severe injuries with substantial mortality and a high burden of associated injuries. Advances in trauma care have improved outcomes. However, recent data from high-volume centers remain scarce. We aimed to evaluate mortality, associated injuries, and predictors of mortality in surgically treated unstable pelvic ring fractures.

METHODS: We retrospectively analyzed 451 consecutive patients with surgically treated Tile B or C pelvic ring fractures admitted to a Level 1 trauma center between 2008 and 2021. Patient demographics, injury characteristics, and associated injuries were recorded. Kaplan-Meier methods were used to estimate survival, and Cox regression for identifying independent predictors of mortality.

RESULTS: Overall mortality at 3-month was 4.2% (95% CI 2.3-6.0) and at 1-year at 6.0% (95% CI 3.8-8.2). Tile C fractures had a higher early mortality than Tile B (3-month: 6.5% vs. 2.1%; 1-year: 7.4% vs. 4.7%). Associated injuries were common: 78% of patients had at least one and 66% had two or more injured regions. Patients with injuries in ≥2 regions had markedly higher intensive care unit (ICU) admission, transfusion requirements, and early mortality. In multivariable Cox regression, age (HR 1.06 per year), Glascow Coma Scale (GCS) ≤8 (HR 4.9), and Tile C (HR 3.6) were independently associated with 90-day mortality.

CONCLUSION: Mortality after surgically treated unstable pelvic ring fractures at 3- month and 1 year was 4.2% and 6.0%, respectively. Age, low GCS, and Tile C fracture pattern were independent predictors of early death. Associated injuries and overall trauma burden were strongly associated with ICU admission, transfusion, and early mortality.

BACKGROUND: Healthy sleep is a multidimensional behavior critical for chronic disease prevention, yet its long-term impact on mortality and life expectancy-particularly among individuals with atherosclerotic cardiovascular disease (ASCVD)-remains unclear.

OBJECTIVES: The purpose of this study was to evaluate the associations between sleep patterns and mortality and life expectancy among adults with and without ASCVD.

METHODS: We analyzed data from 148,622 U.S. adults (mean age 48.4 years, 50.6% female) in the National Health Interview Survey (2013-2018), with mortality follow-up through December 31, 2019. A composite sleep score based on 5 self-reported behaviors was constructed to categorize participants as having poor, intermediate, or healthy sleep patterns. Multivariable Cox models estimated hazard ratios (HRs) for all-cause mortality, and life expectancy was calculated using a flexible parametric survival model.

RESULTS: Over a median 4.3 years of follow-up (IQR: 2.8-5.5), 5,643 deaths occurred. Compared with those with poor sleep patterns, participants with healthy sleep patterns had significantly lower all-cause mortality, both among individuals with ASCVD (HR 0.74, 95% CI: 0.62-0.89) and those without ASCVD (HR 0.82, 95% CI: 0.70-0.95; P for additive interaction = 0.03). At age 45, a healthy sleep pattern was associated with an estimated life expectancy gain of 3.0 years (95% CI: 1.1-4.8) among individuals with ASCVD, and 1.5 years (95% CI: 0.3-2.6) among those without.

CONCLUSIONS: Multidimensional healthy sleep patterns are associated with lower mortality and increased life expectancy in adults, with greater absolute benefits observed in individuals with ASCVD.

The mesothelium is a squamous monolayer that ensheathes internal organs and lines the body cavities. Aside from facilitating tissue sliding, its additional functions remain poorly understood. Here, we study the mesothelium through investigating myelin regulatory factor (Myrf), a transcription factor expressed in the mesothelium and a top mutated gene in congenital diaphragmatic hernia (CDH), a developmental disorder that affects the lung and diaphragm. In mice, inactivation of Myrf early in embryogenesis resulted in CDH and defective mesothelium specification, compromising its role as a signaling center for lung growth. Inactivation after mesothelium specification led to additional defects, including enhanced differentiation into various mesenchymal cell types, causing a striking accumulation of elastin-expressing smooth muscle/myofibroblasts encasing the lung, mimicking pleuroparenchymal fibroelastosis (PPFE), a rare adult lung condition. Compound mutants demonstrate that MYRF functions synergistically with YAP/TAZ in mesothelium differentiation. Together, these findings highlight the complex role of the mesothelium in development and disease.

Senescent cells (SCs) accumulate with aging and contribute to the development of age-related pathologies. These cells evade apoptosis through upregulation of senescent cell anti-apoptotic pathways (SCAPs), making their selective elimination, a strategy termed senolysis, a promising therapeutic avenue. Proteolysis-targeting chimeras (PROTACs) represent an emerging class of bifunctional molecules that exploit the ubiquitin-proteasome system to degrade specific target proteins. By concurrently binding to a protein of interest and an E3 ubiquitin ligase, PROTACs catalyze the degradation of SCAP components, offering a novel pharmacological approach to clear SCs. This review summarizes the principles and recent advances in PROTAC technology, with a focus on its application as a senolytic strategy. We highlight how PROTACs can overcome limitations of conventional inhibitors, such as targeting "undruggable" SCAP proteins, and provide a comparative analysis of major PROTAC classes targeting BCL-2 family members, p53, BRD4, SA-β-gal, and other emerging senescence regulators. Furthermore, we also discuss the aging-specific biological and translational challenges, including altered proteasomal activity, pharmacokinetics, tissue microenvironment, and immune clearance, which must be addressed to advance PROTAC senolytics toward clinical use in age-related diseases.

INTRODUCTION: Acute kidney injury (AKI) is a major health concern, disproportionately affecting children in low- and lower-middle-income countries (LLMICs). Diarrhoeal diseases, a leading cause of paediatric morbidity and mortality, are significant contributors to AKI.

METHODS: This study systematically reviewed literature published post-2000 on three groups of children: those hospitalised with diarrhoea who developed AKI (Diarrhoea/AKI), those hospitalised with AKI attributable to diarrhoea (AKI/Diarrhoea), and those with diarrhoea-associated haemolytic uraemic syndrome (D+-HUS).

RESULTS: After screening 1895 titles and abstracts, 92 studies were included. Most focused on D+-HUS (76%), with fewer addressing AKI/Diarrhoea (15%) and Diarrhoea/AKI (9%). Studies were predominantly retrospective and high-income country (HIC)-based. In children hospitalised with diarrhoea, mean AKI prevalence was higher in LLMICs than in HICs (43.2±30.5% vs 10.1±12.7%). Similarly in children hospitalized with AKI, diarrhoea was more frequent in LLMICs compared with HICs (23.8±12.3% vs . 16.1±5.9%). Among children with D+-HUS, 60% required dialysis, and mortality was substantially higher in LLMICs compared with HICs (28.5±17.43% vs . 3.7±3.6%).

CONCLUSION: Diarrhoea is a common yet underreported associated clinical finding among children with AKI, particularly in resource-limited settings. Enhanced monitoring of kidney outcomes in children with diarrhoea is essential to address the overlapping burden of these conditions and improve outcomes globally.

BACKGROUND: Current techniques for surgical correction of spinal deformities impart realigning the deviated vertebrae along a rigid rod. Solid rods are a major restricting factor to vertebral manipulation, leading to incomplete, imprecise, and less predictable 3-dimensional (3D) correction. Additionally, forceful manual nonquantifiable maneuvers may result in potential implant failures and increased incidence of complications. We are introducing a machine-operated device for digitized segmental 6 degrees of freedom (6 DOF) correction of individual vertebral deviations.

METHODS: We manufactured a 3D coupler incorporating multiple self-locking uniaxial joints. The device's precision was tested by comparing targeted vs delivered motions. For functionality testing, we used computed tomography-based 3D-printed vertebral models to verify the device's ability to manipulate the vertebra in each direction of motion.

RESULTS: In all tested motions, the coupler accurately and repeatedly delivered the predicted targeted motions. The device could mobilize 2 vertebral models relative to each other in 4 out of 6 DOF.

CONCLUSIONS: The novel 3D coupler can deliver machine-driven, precise, and predictable multiplanar motion; it could manipulate the vertebral model in rotation and translation.

CLINICAL RELEVANCE: The novel device addresses a crucial unmet need in spinal surgery by offering digital precision, true 6 DOF correction, and supporting robotic execution of surgical actions.

BACKGROUND AND OBJECTIVE: Real-world evidence on the effectiveness of first-line immuno-oncology (IO)-based combinations or cabozantinib (CABO) over traditional targeted therapies in metastatic non-clear cell renal cell carcinoma (nccRCC) is limited. This study aims to compare the outcomes of first-line therapies for metastatic nccRCC according to histologic subtypes, including papillary renal cell carcinoma (RCC), unclassified RCC, and chromophobe RCC with or without sarcomatoid dedifferentiation.

METHODS: Using the International Metastatic Renal Cell Carcinoma Database Consortium, patients with metastatic nccRCC who received (1) IO plus vascular endothelial growth factor (IOVE) combination therapy, (2) IOIO doublet therapy, (3) CABO monotherapy, (4) sunitinib or pazopanib (SUN/PAZ) monotherapy, or (5) mammalian target of rapamycin (mTOR) monotherapy were included. Baseline patient characteristics, clinician assessment of objective response rates (ORRs), and overall survival (OS) were compared across first-line therapy regimens.

KEY FINDINGS AND LIMITATIONS: The most common nccRCC histology was papillary found in 725 (47%), and sarcomatoid dedifferentiation was found in 236 (15%) of the 1551 patients included. Within the papillary RCC cohort, ORRs and median OS were, respectively, 31% and 33.2 mo for IOVE, 26% and 31.9 mo for IOIO, and 37% and 30.7 mo for CABO, as compared with 13% and 17.2 mo for SUN/PAZ and 3.4% and 13.1 mo for mTOR. Within the sarcomatoid dedifferentiation cohort, receipt of IOIO was associated with the highest ORR and the longest median OS (39.0% and 31.9 mo, respectively).

CONCLUSIONS AND CLINICAL IMPLICATIONS: Distinct patient outcomes were observed across histologic subtypes. More histology-specific strategies are required given the differential activity of first-line therapy regimens against each nccRCC histology.

Depression affects up to 40% of Veterans in Veterans Health Administration's nursing homes, known as Community Living Centers (CLCs). We adapted an evidence-based intervention (Behavioral Activities Intervention; BE-ACTIV) to create BE-ACTIV(VA): a manualized behavioral activation intervention for CLC short-stay Veterans with depression. While BE-ACTIV relied on intensive in-person staff training, we developed online, self-paced trainings to fit staff members' busy schedules. The goals of this article are to report on the creation and content of BE-ACTIV(VA) trainings and CLC staff perceptions of their efficacy, feasibility, and acceptability. We used data from post-training surveys (survey responses: All CLC Staff Training n = 13; Activity Facilitator Training n = 10; Mental Health Provider Training n = 18) and qualitative interviews (n = 16) with staff. Survey responses were summed and averaged to provide a mean score for each question. We conducted brief, semi-structured interviews with staff implementing BE-ACTIV(VA), coded transcripts, and employed a thematic analysis approach to identify salient themes from the coding output. Survey data showed that staff were satisfied with the trainings (100% were satisfied with the Mental Health Provider Training; 100% were satisfied with the Activity Facilitator Training; 85% were satisfied with the All CLC Staff Training) and found the content to be effective and useful for their practice. We identified four main themes related to staff perceptions of the efficacy of the training (staff were prepared to implement BE-ACTIV(VA) post trainings, and felt trainings were clear and useful), feasibility of the training (fit well into staff workflow), and suggestions for improvement (to add interactive components or knowledge checks). To our knowledge, this is the first study to show that behavioral activation intervention training can be successfully done in a brief, online format within a CLC setting among a range of staff. Findings suggest that this training approach can support the dissemination and scale-up of manualized behavioral activation interventions to reduce depression across long-term care settings.

PURPOSE: The purpose of this study is to determine the trends in use of magnetically controlled growing rods (MCGRs) over time for the treatment of scoliosis.

METHODS: All patients treated with MCGRs were identified through a multi-center pediatric spine database from 2014 to 2021. MCGR use over time was analyzed with respect to individual variables within the dataset including demographics, etiology, primary vs conversion surgeries, and major curve magnitude.

RESULTS: A total of 1,404 patients treated with MCGRs were identified. MCGR usage grew quickly until 2017 and then steadily declined through 2021. There was minimal variation over time with respect to patients' age and weight. MCGR as the index implant as opposed to revision surgery increased from 67% in 2014 to 99% in 2021. Initially, MCGR utilization was consistent across scoliosis etiologies; however, over time, it grew among neuromuscular patients while decreasing among other etiologies. MCGR use decreased over time for curves with magnitude < 60 degrees, with a corresponding rise in curves > 80 degrees.

CONCLUSION: Use of MCGRs expanded quickly after initial FDA approval in 2014 with broad indications. Over time, the indications for use of MCGRs have steadily evolved. In recent years, a higher proportion of them are used in neuromuscular scoliosis and larger curves in contrast to declining use in smaller curves.

LEVEL OF EVIDENCE: III.