Publications by Year: 2026

PURPOSE: Retinal vascular occlusive disease (RVOD) may occur as a consequence of systemic vascular dysfunction. Although RVOD has been associated with coronary artery disease, its incidence after acute coronary syndrome (ACS) and the influence of lipid control remain unclear.

MATERIALS AND METHODS: Using data from the Korean National Health Information Database (2002-2022), we conducted a nationwide retrospective cohort study including 55040 patients with newly diagnosed ACS [unstable angina (UA) or myocardial infarction (MI)] and age- and sex-matched controls. RVOD outcomes included retinal artery occlusion (RAO) and retinal vein occlusion (RVO). Low-density lipoprotein-cholesterol (LDL-C) control was stratified into four categories (excellent, good, suboptimal, poor) based on guideline-recommended targets. Competing risk analysis was performed to estimate adjusted hazard ratios (aHRs).

RESULTS: The risk of RVOD was higher in both the UA group [aHR=1.67, 95% confidence interval (CI): 1.56-1.79] and MI group (aHR=1.34, 95% CI: 1.15-1.56) compared with controls. Stratified analysis showed elevated risk in older patients (≥65 years) and males. Among LDL-C groups, poor LDL-C control (≥100 mg/dL) was associated with the highest RVOD risk (aHR = 2.27), compared with both the ACS-free control group and the excellent control group (<55 mg/dL).

CONCLUSION: ACS is independently associated with increased RVOD risk, particularly among patients with UA, older age, and poor LDL-C control. Intensive lipid-lowering therapy and ophthalmologic follow-up may reduce vision-threatening vascular events in this high-risk population.

Cardiovascular diseases (CVD) remain the leading cause of mortality worldwide, with chronic kidney disease (CKD) constituting a significant risk factor. Despite the crucial role of amino acids as fundamental dietary components, their impact on the comorbidities of CKD and CVD has been insufficiently studied and warrants greater research attention. Therefore, this systematic review provides a comprehensive overview of the current knowledge regarding the effects of amino acid supplementation on the comorbidities associated with CVD and CKD, as the basis for novel prevention and treatment options. The databases 'PubMed' and 'Web of Science' were used to perform a literature search on the effects of amino acid supplementation on the comorbidities associated with CVD and CKD. Data synthesis was conducted based on 60 publications, comprising 13 clinical, 43 in vivo and four in vitro studies. The risk of bias was assessed using three appropriate tools. Studies were classified based on preventive or harmful effects. Altogether, 43 publications reported preventive, and 18 described adverse effects, of which three described both preventive and adverse effects of different amino acids. Only two publications showed no effects caused by amino acids. Arginine and methionine were attributed to the highest number of preventive and adverse effects, respectively. However, a limitation of most publications is the pending translation to humans. Overall, these findings suggest that amino acid supplementation as a potentially valuable addition to treatment options for CVD and CKD patients, although further clinical studies are needed for validation of these findings. This systematic review was funded by the German Research Foundation (DFG, SFB/TRR219) and was registered in the PROSPERO database (CRD42023493924).

OBJECTIVE: This longitudinal study aims to identify the key factors influencing the weight loss trajectory during a 24-week intervention and their relevance at different stages of the treatment.

METHODS: We studied 1252 participants (age 18-65 years) of a cognitive behavioral program to lose weight. Body weight was measured weekly, and a range of variables at baseline and throughout the treatment period were assessed. Linear regression analyses were conducted to understand the factors involved in the weight loss trajectory across three treatment periods (0-6, 7-12, 13-24 weeks).

RESULTS: The rate of weight loss progressively decreased from the 1st to the 3rd period (770-198 g/week). During the 1st period, the recent history of the individual, including baseline metabolic status, dietary habits, and motivation, was the highest-ranked determinant. In the 2nd period, the sole predictor was the long-term personal history of obesity, that is, the duration of the individual's lifetime spent with overweight/obesity. In the 3rd period, emotional eating behaviors and related barriers emerged as the two highest-ranked determinants of reduced rate of weight loss.

CONCLUSIONS: Findings suggest targeted interventions that address the specific challenges of each period of weight loss interventions. As treatment progresses, strategies focused on emotional-related behaviors may be crucial for sustaining weight loss.

TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02829619.

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.

BACKGROUND: The nasal cavity's natural bacterial flora poses a risk for postoperative infections, prompting surgeons to administer prophylactic antibiotics during septorhinoplasty. However, this practice's effectiveness is debated due to concerns about antibiotic resistance and variability in practice. This study leverages a large nationwide database to evaluate the impact of perioperative antibiotics on infection, cellulitis, and sepsis rates following septorhinoplasty.

METHODS: A retrospective cohort study was conducted to identify patients undergoing septorhinoplasty using the TriNetX network, querying 133 million US medical records over 20 years. Outcomes up to three months post-surgery were compared between those administered antibiotics within one day before or on the day of surgery and those that were not. Antibiotics included cefazolin, amoxicillin, clindamycin, azithromycin, clarithromycin, and cephalexin. Propensity score matching was performed on demographics, tobacco use, and other immune-related comorbidities (diabetes mellitus, human immunodeficiency virus, systemic lupus erythematosus, rheumatoid arthritis, liver cirrhosis, chronic kidney disease, chronic systemic steroids, and chemotherapy status). Infection, cellulitis, and sepsis risks were compared across cohorts.

RESULTS: 14,760 septorhinoplasty patients were identified who received perioperative antibiotics, and 4,640 patients that did not. After propensity score matching, 4,086 patients remained in each cohort. There was no significant difference in infection risk (RR 1.110, p = 0.812) or cellulitis (RR 1.180, p = 0.565). No cases of sepsis were reported in either cohort.

CONCLUSION: Prophylactic antibiotics did not significantly reduce the risk of infection, cellulitis, or sepsis in septorhinoplasty patients. Future research is required to optimize evidence-based guidelines on antibiotic use in elective nasal surgeries.

LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Spatial transcriptomics aims to elucidate how cells coordinate within tissues by connecting cellular states to their native microenvironments. Imaging-based assays are especially promising, capturing molecular and cellular features at subcellular resolution in three dimensions. Interpretation of such data, however, hinges on accurate cell segmentation. Assigning individual molecules to the correct cells remains challenging. Here we re-analyze data from multiple tissues and platforms to find that segmentation errors currently confound most downstream analysis of cellular state, including differential expression, neighbor influence and ligand-receptor interactions. The extent to which misassigned molecules impact the results can be striking, frequently dominating the results. Thus, we show that matrix factorization of local molecular neighborhoods can effectively identify and isolate such molecular admixtures, thereby reducing their impact on downstream analyses, in a manner analogous to doublet filtering in single-cell RNA sequencing. As the applications of spatial transcriptomics assays become more widespread, accounting for segmentation errors will be important for resolving molecular mechanisms of tissue biology.

Sperm aging impacts male fertility and offspring health, highlighting the need for reliable aging biomarkers to guide reproductive decisions. However, the molecular determinants of sperm fitness during aging remain ill-defined. Here, we profiled sperm small non-coding RNAs (sncRNAs) using PANDORA-seq, which overcomes RNA modification-induced detection bias to capture previously undetectable sncRNA species associated with mouse and human spermatozoa throughout the lifespan. We identified an "aging cliff" in mouse sperm RNA profiles-a sharp age-specific transition marked by significant shifts in genomic and mitochondrial tRNA-derived small RNAs (tsRNAs) and rRNA-derived small RNAs (rsRNAs). Notably, rsRNAs in mouse sperm heads exhibited a transformative length shift, with longer rsRNAs increasing and shorter ones decreasing with age, suggesting altered biogenesis or processing with age. Remarkably, this sperm head-specific shift in rsRNA length was consistently observed in two independent human aging cohorts. Moreover, transfecting a combination of tsRNAs and rsRNAs resembling the RNA species in aged sperm was able to induce transcriptomic changes in mouse embryonic stem cells, impacting metabolism and neurodegeneration pathways, mirroring the phenotypes observed in offspring fathered by aged sperm. These findings provide novel insights into longitudinal dynamics of sncRNAs during sperm aging, highlighting an rsRNA length shift conserved in mice and humans.

The innate immune system is known for its ability to recognize cytosolic DNA as evidence of infection, but detailed studies of this process have been mostly limited to mice and cell lines. To investigate inflammasome responses in human primary cells, we used engineered viruses encoding the inflammasome reporter caspase-1CARD-EGFP. We show that released genomes of vaccinia virus and monkeypox virus trigger robust inflammasome assembly in human primary cells. To determine the involved inflammasome sensors, we generated nanobodies against AIM2. Three of them inhibit AIM2 inflammasome assembly by blocking the polymerization of the AIM2 Pyrin domain, most potently as bivalent nanobodies. Utilizing an engineered vaccinia virus expressing bivalent AIM2 nanobodies, we demonstrate that inflammasomes in primary human macrophages and keratinocytes are nucleated by AIM2, while CD14+ monocytes assemble NLRP3 inflammasomes. This finding resolves the discrepancy between the previously reported activation of AIM2 inflammasomes in mice and NLRP3 inflammasomes in humans, and provides the first evidence for cell-type-specific regulation of DNA-triggered inflammasome activation. The newly developed AIM2-specific nanobodies offer a precise tool to dissect and potentially target AIM2 inflammasome assembly in other disease contexts.

OBJECTIVES: Implementing a new electronic health record (EHR) system in high-pressure, high-stakes environments, such as documenting during pediatric and neonatal cardiac and respiratory arrest scenarios, can be challenging for health care staff. Poorly designed tools or technology that don't align with existing workflows may lead to incomplete or inaccurate documentation. Lower adoption rates and continued reliance on paper forms for code documentation can result in gaps in patient data within the EHR, requiring the transcription of critical information after the event.

METHODS: This project utilized human factors usability testing and systems-focused simulation evaluation methods to assess code documentation tools with end-users from critical care areas (ED, ICU, NICU) during the EHR design phase.

RESULTS: A total of 202 recommendations to enhance the EHR's usability and functionality were made across the 3 testing cycles (2 rounds of usability testing and 1 cycle of systems simulation sessions). The majority of recommendations were focused on improvements to the software and technology of the code narrator tool directly. Post-launch assessment showed that nearly 2/3 of the usability recommendations were implemented within the first year of use.

CONCLUSIONS: Improving the design of these tools and ensuring seamless workflow integration is essential for increasing adoption and enhancing the accuracy of patient records.