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BACKGROUND/OBJECTIVES:Atherosclerotic plaque instability is driven by complex interactions among inflammatory, structural, and cellular remodeling programs. While bulk RNA sequencing provides insight into tissue-level transcriptional states and single-cell RNA sequencing (scRNA-seq) defines cellular heterogeneity, integration across these transcriptomic layers remains limited. We aimed to identify coordinated transcriptional programs associated with stable and unstable plaque phenotypes and map these programs to specific cellular compartments and regulatory networks. METHODS:Paired bulk RNA-seq data from stable and unstable human carotid plaques (GSE120521) and scRNA-seq data from human coronary atherosclerotic lesions (GSE131778) were analyzed. Differential expression and Hallmark gene set enrichment analyses were performed using limma and clusterProfiler. Bulk-derived inflammatory and structural signatures were projected onto single-cell data using Seurat module scoring. Compartment-level transcriptional scores, an inflammatory-structural endotype index, and transcription factor activity inference using decoupleR and DoRothEA were used to characterize plaque-associated transcriptional states. RESULTS:Unstable plaques demonstrated enrichment of inflammatory pathways, including interferon gamma response, inflammatory response, TNFα/NF-κB signaling, IL6/JAK/STAT3 signaling, complement activation, and reactive oxygen species pathways. In contrast, stable plaques demonstrated relative enrichment of myogenesis and structural remodeling programs. Projection of bulk-derived signatures onto single-cell data localized inflammatory programs predominantly to TREM2hi and inflammatory macrophage populations, whereas structural programs localized to smooth muscle cell and fibromyocyte-like compartments. Compartment-level analyses showed increased myeloid and adaptive immune signatures in unstable plaques and increased smooth muscle cell/fibro-remodeling signatures in stable plaques. Transcription factor activity analysis identified increased SPI1, NFKB1, RELA, and STAT1 activity in unstable plaques and higher SRF and TEAD1 activity in stable plaques. CONCLUSIONS:Integrative analysis of bulk and single-cell transcriptomic data identified distinct inflammatory and structural plaque transcriptional states associated with unstable and stable plaque phenotypes, respectively. These findings support a systems-level framework linking tissue-level plaque behavior to specific cellular and regulatory programs and provide evidence for inflammatory and structural plaque endotypes in human atherosclerosis.
Abstract Introduction Necrotizing fasciitis (NF) is an aggressive bacterial infection of the skin and subcutaneous tissues that requires urgent surgical intervention to excise necrotic and infected tissues. Patients are often left with large, open wounds, for which there is no standard of care treatment protocol. A fully synthetic electrospun fiber matrix (SEFM) may regeneration of viable tissue while remaining resistant to harsh cleaning solutions needed to ensure a clean wound bed. Case description A 39-year-old male presented with NF requiring surgical excision of affected tissues across the torso, flanks, groin, anterior thighs, genitalia, and right arm, resulting in a total body surface area of 32% with exposed structures. Meshed SEFM sheets were applied with abdominal pads during the initial operation. To maintain SEFM contact with the wound and limit fluid loss, SEFM reapplication with homograft overlay was performed in sections starting at Day 35. Vascularized tissue was observed at Day 21 and covered the left torso and bilateral thighs by Day 35. Split-thickness skin grafts were then applied in sections with meshed homograft overlay for all excised regions, resulting in 95% graft take. Discussion The success demonstrated here suggests use of SEFM for post-excision NF wounds warrants further investigation. Learning points
Objective To determine if extraneous presenting chief complaints or concomitant non-appendicitis ED diagnoses correlate with ED LOS in pediatric patients with appendicitis. Background Appendicitis is a common pediatric emergency encountered in United States Emergency Departments (ED). However, pediatric patients frequently present to the ED with extraneous complaints such as fever or headache. Such complaints have been demonstrated in previous literature to increase missed diagnosis of appendicitis1. Missed diagnosis in EDs is not uncommon and patients often undergo additional diagnostics to evaluate extraneous complaints2. Additional diagnostics and workup can increase time to definitive care and contribute to a longer ED length of stay (LOS). This study aims to further categorize if extraneous presenting chief complaints or concomitant non-appendicitis ED diagnoses correlate with ED LOS in pediatric patients with appendicitis. Methods The National Hospital Ambulatory Medical Care Survey (NHAMCS) was searched for patients less than 18 years of age who had an ED diagnosis of Appendicitis. Visits from 2007-2019 were included, excluding 2016 and 2017 as there was no ED LOS data documented. Patients that were included in the “Fever/URI” group had a chief complaint or additional ED diagnosis of a respiratory illness, SIRS/ sepsis, lab abnormality (i.e. leukocytosis), or other general complaint (i.e. fever, headache). Patients were included in the “Appendicitis alone” group if they did not have an associated extraneous chief complaint or diagnosis. The difference in ED length of stay was the outcome difference measured. Results/Conclusions There were 215 rows resulted, representing 1,128,000 total visits. Appendicitis alone was in 169 rows (905,000 visits), and Fever/URI in 46 rows (223,000 visits). 16 rows (83,000 visits had missing length of stay data and were excluded from analysis). For the Appendicitis alone group, median LOS (IQR) was 236 minutes (172-352). For Fever/URI group, median LOS (IQR) was 276 minutes (213-409).
Background Stress urinary incontinence (SUI) is a common pelvic floor disorder with significant physical and psychosocial impacts. Thyroid dysfunction may contribute to SUI by affecting skeletal muscle contractility, neuromuscular transmission, and connective tissue integrity. Limited research exists on this association among Saudi women. This study assessed the prevalence of hypothyroidism and its co-occurrence with clinical and demographic factors in women with clinically diagnosed SUI. Methods This retrospective cross-sectional study reviewed medical records of 288 women aged 20-50 years diagnosed with SUI at King Fahad Hospital, Al-Baha, Saudi Arabia (January 2020 to December 2025). Hypothyroidism was categorized as clinical (thyroid-stimulating hormone (TSH) >4.5 mIU/L with low free T4) or subclinical (TSH >4.5 mIU/L with normal free T4). Chi-square tests assessed associations with BMI, parity, diabetes, and hypertension. Age association was evaluated across three groups (20-29, 30-39, and 40-50 years) and by binary logistic regression. ORs with 95% CIs were calculated; p ≤ 0.05 was considered significant. Results The median age was 41 years (IQR: 12; range: 20-50 years); 54.2% of patients were aged 40-50 years. Hypothyroidism was identified in 136 patients (47.2%): 113 (39.2%) with clinical hypothyroidism and 23 (8.0%) with subclinical hypothyroidism. Significant associations were found with BMI (p = 0.003), parity (p = 0.005), and hypertension (p = 0.020); diabetes showed no significant association (p = 0.774). Hypothyroidism prevalence increased progressively with age: 33.3% (20-29 years), 43.8% (30-39 years), and 51.9% (40-50 years). Logistic regression confirmed a significant positive association between age and hypothyroidism (OR = 1.039 per year, 95% CI: 1.007-1.074, p = 0.019). Conclusions Hypothyroidism was highly prevalent among women with clinically diagnosed SUI and was frequently observed alongside higher BMI, multiparity, hypertension, and advancing age. These findings are hypothesis-generating; prospective interventional studies are needed before formal screening recommendations can be established.
Anemia is a common finding in pediatric practice and is most often attributed to nutritional deficiency; however, it may also represent the earliest manifestation of underlying systemic disease. We describe the case of a six-year-old girl who presented for a routine well-child visit and was found to have severe normocytic, normochromic anemia despite appearing clinically asymptomatic. Subsequent laboratory evaluation revealed profound renal dysfunction with metabolic acidosis and electrolyte abnormalities. Renal imaging demonstrated bilaterally small kidneys without hydronephrosis, consistent with advanced chronic kidney disease (CKD) likely due to congenital renal hypoplasia. The patient required emergent initiation of hemodialysis and was later transitioned to long-term renal replacement therapy. This case underscores the importance of maintaining a broad differential diagnosis when evaluating unexplained anemia in children and highlights that CKD may remain clinically silent until late stages, with anemia serving as a critical early diagnostic clue.
