Citations

AbstractBackgroundInfants born via Cesarean section (C‐section) often have a distinct gut microbiome and higher risks of atopic and immune‐related conditions than vaginally delivered infants. We evaluated whether a microbiome‐based program could shift gut microbiome composition and improve microbiome‐associated health outcomes in C‐section born infants.MethodsThis open‐label, randomized, controlled trial included full‐term C‐section‐born infants aged 0–3 months, randomized to an intervention (n = 25) or control arm (n = 29). Over 6 months, the intervention arm received two microbiome reports, personalized recommendations based on their microbiome, educational materials, and coaching calls focused on microbiome health. Parents reported health conditions via surveys. Primary outcome: Difference between study arms in relative abundance of key gut microbiome taxa and functional genes. Other outcomes: Changes in a C‐section index—a taxonomy‐based metric comparing C‐section‐associated taxa to vaginally‐associated taxa—and prevalence of atopic conditions.ResultsCompared to controls, the intervention arm had higher Bifidobacterium (p = .025, q = .121) and higher abundance of genes associated with human milk oligosaccharide degradation (e.g., α‐L‐fucosidase, p = .019, q = .046) at timepoint 2. In the intervention arm, the C‐section index decreased to a level similar to vaginally born infants (p = .807, q = .807). At the end of the intervention, atopic dermatitis prevalence was lower in the intervention arm than in controls (odds ratio, 0.17 [95% CI, 0.023–0.723], p = .031).ConclusionA personalized microbiome‐based program can modulate the gut microbiome of C‐section‐born infants and may reduce the risk of atopic conditions (ClinicalTrials.gov: NCT06424691).

Background: In the emergency setting, many diagnostic pathways incorporate change in high-sensitivity cardiac troponin (hs-cTn) concentrations (i.e., the delta) to classify patients as low-risk (rule-out) or high-risk (rule-in) for possible myocardial infarction (MI). However, the impact of analytical variation on the delta for correct classification is unknown, especially at concentrations below and around the 99th percentile. Our objective was to assess the impact of delta variation for correct risk classification across the European Society of Cardiology (ESC 0/1 h and 0/2 h), the High-STEACS, and the common change criteria (3C) pathways. Methods: A yearlong accuracy study for hs-cTnT was performed where laboratories across Canada tested three patient-based samples (level 1 target value = 6 ng/L, level 2 target value = 9 ng/L, level 3 target value = 12 ng/L) monthly across 41 different analyzers. The assigned low-delta between levels 1 and 2 was 3 ng/L (i.e., 9 − 6 = 3 ng/L) and the assigned high-delta between levels 1 and 3 was 6 ng/L (i.e., 12 − 6 = 6 ng/L). The low- and high-deltas for each analyzer were determined monthly from the measured values, with the difference calculated from the assigned deltas. The obtained deltas were then assessed via the different pathways on correct classification (i.e., percent correct with 95% confidence intervals, CI) and using non-parametric analyses. Results: The median (interquartile range) difference between the measured versus assigned low-delta (n = 436) and high-delta (n = 439) was −1 ng/L (−1 to 0). The correct classification differed among the pathways. The ESC 0/1 h pathway yielded the lowest percentage of correct classification at 35.3% (95% CI: 30.8 to 40.0) for the low-delta and 90.0% (95% CI: 86.8 to 92.6) for the high-delta. The 3C and ESC 0/2 h pathways yielded higher and equivalent estimates on correct classification: 95.2% (95% CI: 92.7 to 97.0) for the low-delta and 98.2% (95% CI: 96.4 to 99.2) for the high-delta. The High-STEACS pathway yielded 99.5% (95% CI: 98.4 to 99.9) of correct classifications for the high-delta but only 36.2% (95% CI: 31.7 to 40.9) for the low-delta. Conclusions: Analytical variation will impact risk classification for MI when using hs-cTn deltas alone per the pathways. The 3C and ESC 0/2 h pathways have <5% misclassification when using deltas for hs-cTnT in this dataset. Additional studies with different hs-cTnI assays at concentrations below and near the 99th percentile are warranted to confirm these findings.

Introduction: Robot-assisted radical prostatectomy (RARP) with extended pelvic lymph node dissection (PLND) represents the gold standard surgical treatment for high-risk localized prostate cancer. PLND carries the risk of lymphocele formation, which can lead to complications such as deep vein thrombosis (DVT), infection, and voiding dysfunction. Many techniques have been described to minimize lymphocele formation, yet no method has seen widespread use or been described as sutureless. The objective of this study is to describe the novel, sutureless peritoneal window (PWIN) technique and assess its efficacy in lymphocele prophylaxis for extended PLND. Methods: This was a retrospective review of patients with high-risk prostate cancer undergoing RARP with extended PLND by a single surgeon from 2018 to 2024. PLND was carried out in the usual manner with bipolar cautery. PWIN technique is performed by excising a 3 × 5 cm PWIN over the lymphadenectomy bed to maintain lymphatic communication with the abdominal cavity. The primary outcome was a comparison between the incidence of symptomatic lymphoceles (SLs) with PWIN vs standard technique. SLs were defined as lymphoceles presenting with pain, DVT, voiding dysfunction, or infectious symptoms. Patients with asymptomatic lymphoceles were excluded. Results: Our study included 199 patients who underwent RARP with extended PLND. There were 46 patients (23.1%) in the standard approach group and 153 patients (76.9%) in the PWIN group. We identified 5/46 (10.9%) SLs in the standard technique, which were significantly higher than the 3/153 (2.0%) observed in the PWIN group (p = 0.017). There was no difference between the standard and PWIN cohorts regarding symptomology or treatment of their lymphocele. Conclusion: This study describes a novel, sutureless PWIN technique that significantly decreases SL after extended PLND. This technique offers a practical, time-efficient, and cost-effective alternative for lymphocele prevention. Future prospective studies are warranted to validate these findings.

Abstract Introduction Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disorder with a pathogenic mutation identified in approximately 50% of cases. The MYH7 and MYBPC3 genes account for over half of these cases, while dozens of other genes can be pathogenic(1). Genetic test results are not independently used to determine which people with HCM benefit from implanted cardiac defibrillators (ICDs)(2, 3). Little is known about the additive role of genetic testing results to existing indications for ICD insertion. Purpose This study aims to examine the interaction between genetic testing results and existing ICD indications and imaging results on defibrillator discharge rates in HCM. Methods Patients who underwent an ICD for HCM, who underwent a cardiac magnetic resonance (CMR) study and who underwent genetic testing were included across 3 sites. The outcome was the incidence rate of appropriate ICD discharges, calculated using cox regression controlling for current age and primary vs secondary prevention. Interaction analysis between genetic risk factors and existing ICD indications, and with CMR quantification of LGE and septal thickness, was performed, and stratum specific estimates calculated using linear computation. Results 177 patients were included in the study, of whom 70 (39.55%) had a pathogenic mutation, 5 (2.82%) had a variant likely pathogenic (VLP), 44 (24.86%) had a variant of undetermined significance (VUS) and 58 (39.55%) had no identifiable mutation. The event rate was 3.32 {2.28 to 4.84) per 100 person years. There was no association between genetic variables and ICD discharge rate. There was an 80% reduction in ICD discharge rate in people who underwent ICD insertion exclusively for family history of sudden cardiac death or for syncope who had no pathogenic or likely pathogenic mutation, however this change was not statistically significant (table 2). Conclusion There is no strong association between genetic characteristics and ICD discharge rates among people with hypertrophic cardiomyopathy with an existing ICD indication. There is a nonsignificant trend towards fewer ICD discharges among people who underwent ICD insertion for family history alone or for a history of syncope and did not have a pathologic variant.Table 1 Table 2

AbstractEnterocutaneous fistulas (ECFs) profoundly impact patients’ quality of life, contributing to high morbidity rates and increased mortality due to ineffective treatment options. To address this challenge, ECFGel, a multifunctional, tissue adhesive injectable hydrogel, designed to occlude, sterilize, and promote healing of ECF tracts, is developed. ECFGel is formulated using gelatin and oxidized dextran (O‐Dex) as base components, which form chemical crosslinks within the hydrogel and with surrounding biological tissues, ensuring tissue adhesiveness. A choline and geranate‐based ionic liquid (IL) is incorporated to provide dual functionality, potent antimicrobial activity, and mechanical enhancement. By optimizing IL concentration, ECFGel achieves rapid gelation, enhanced mechanical strength, and improved elastic recoverability. Additionally, iohexol (IOH) is added for radiopacity, enabling real‐time imaging and further strengthening the hydrogel's mechanical properties. ECFGel demonstrates antiswelling properties, biodegradability, and effective tract occlusion in porcine soft tissues. It shows strong antimicrobial activity against highly resistant, patient‐derived pathogens isolated from clinical ECF cases. In a porcine perianal fistula model, ECFGel enables rapid occlusion and complete healing, promoting tissue maturation, reducing bacterial load, and increasing markers of cell proliferation and vascularization compared to untreated controls. These promising results highlight ECFGel's potential as a new therapeutic option for treating infected ECFs.

Abstract Introduction: Endobronchial optical coherence tomography (EB-OCT) imaging has unique potential to diagnose and quantify early, microscopic disease changes and assess therapeutic responsivity in interstitial lung disease (ILD). However, training and time requirements for interpretation and quantitative evaluation of large volumetric EB-OCT datasets need to be optimized to facilitate clinical adoption. We develop and validate a computationally-efficient, rapid EB-OCT quantitative image analysis framework using artificial intelligence (AI) with deep learning architecture for 2D feature segmentation, 3D feature burden and spatial distribution mapping, and computer-aided diagnosis in early ILD subjects. Methods: Volumetric EB-OCT datasets, consisting of 2D cross-sectional images, were acquired from multiple locations in the bilateral lungs of ILD and healthy control subjects. EB-OCT features were manually segmented from cross-sectional images by an expert EB-OCT reader, including fibrosis, microscopic honeycombing, traction bronchiolectasis, normal parenchyma, and emphysema. EB-OCT images with corresponding feature segmentations were used to train and validate a multiclass convolutional neural network. The 2D AI-based segmentation model was subsequently evaluated against manual ‘ground truth’ segmentations for each feature in a de novo ‘test’ dataset of independent subjects using dice similarity score, precision, recall/sensitivity, specificity, and balanced accuracy. To generate 3D AI-based quantitative feature burden and spatial distribution maps, AI-based feature segmentation was performed on each EB-OCT 2D cross-sectional image within a volumetric imaging site. Three external pathologist readers independently interpreted 3D AI-based features maps for each EB-OCT imaging site acquired for a subject (without access to EB-OCT images) and provided a single diagnosis of usual interstitial pneumonia (UIP) or non-UIP ILD. Performance of computer-aided ILD diagnosis was compared against independently evaluated histopathology, clinical diagnosis, and prior EB-OCT image interpretation. Results: EB-OCT was acquired in 51 subjects: 30 in vivo early ILD, 5 in vivo non-ILD controls, and 16 ex vivo end-stage ILD. Overall pixel similarity between 2D manual and AI-based segmentation demonstrated high accuracy for each ILD feature (mean balanced accuracy 0.9). 3D quantitative AI-based feature maps demonstrated strong agreement (Spearman ρ0.87, p&lt;0.001) between manual and AI-based segmentation. AI-based computer-aided diagnosis demonstrated 100% sensitivity/specificity for histologic UIP and clinical IPF for all pathologist readers, with improved diagnostic accuracy and significantly reduced training (45-minute training, 75% reduction) and interpretation time (&lt;1 minute per subject for computer-aided diagnosis, 88% reduction) compared to EB-OCT image interpretation. Conclusion: The AI-based EB-OCT image analysis framework could expedite computer-aided diagnosis of early ILD and robust, quantitative assessment of microscopic disease burden, progression, and therapeutic responsivity.

Abstract Rationale: Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a pulmonary condition characterised by neuroendocrine cell proliferation along respiratory bronchioles resulting in tumourlet formation which may progress to pulmonary carcinoid. DIPNECH is a rare and under-recognised condition that predominantly affects females, with an estimated worldwide incidence of 5-6 people per million population. Given it's rarity and the poor understanding around the pathogenesis and treatment of this condition, we undertook the largest international case series to date of DIPNECH patients. We aim to further characterise this patient cohort to better understand the clinical features, identify common pulmonary function test (PFT) patterns and radiographic findings and describe current treatment practices. Methods: We collated data from 17 centres across 8 different countries comprising a total of 258 patients. Data collected included patient demographics, smoking history, symptoms, co-morbidities, pathological diagnosis, imaging findings, PFT pattern and therapies. Results: In total 258 patients were identified. The median age was 65 (SD+/- 10.6). 241 (93%) were female. 39% (n= 94/243) were ex-smokers. 79% (n=186/234) of patients reported pulmonary symptoms with cough being the most common symptom reported in 81% (n=151/186) of patients. Many patients were polysymptomatic, with cough and dyspnoea being the most common combination of symptoms described. (50.54%; n=94/186). Complete spirometry pattern was documented for 180 patients (69.78%) with an obstructive pattern being the most commonly observed (n=76/180; 42%). 27.5% (n=41/139) had clinically significant FEV1 reversibility post bronchodilator administration. Pathology specimens were available in 219 cases. Most common pathological features were neuroendocrine hyperplasia which was observed in 75% (n=165/219) and tumourlets in 74% (n=162/219) of cases. Carcinoid, either typical or atypical, was observed in 64% (n=141/219) of samples. 252 patients had computed tomography (CT) imaging performed. Pulmonary nodules were the most common feature identified in 99.60% of cases (248/250). Mosaic attenuation (69.30%; n=50/173) and airway dilatation (28.90%; n=50/173) were also frequently reported. There was no significant correlation between symptoms (cough, dyspnoea, wheeze) and airway dilatation (p=0.496), mosaic attenuation (p=0.496) and PFT pattern (p=0.837). There was a significant association between presence of symptoms and mosaic attenuation on CT (p=0.003). Conclusions: DIPNECH, while a rare disorder, is understudied. This international case series is the largest performed to date and highlights the complexity in management of these patients.

Abstract Aims Sodium-glucose cotransporter 2 inhibitors (SGLT2-Is) improve heart failure (HF) outcomes but their effects on acute myocardial infarction (AMI) remain poorly characterized. This study aimed to evaluate the 1-year cardiovascular outcomes of SGLT2-Is among patients with AMI. Methods and results We conducted an observational, retrospective cohort study using TriNetX data, including patients aged ≥18 with AMI identified via ICD-10 codes regardless of left ventricular ejection fraction (LVEF), categorized by SGLT2-Is use. Propensity score matching (PSM) was performed to balance baseline demographics, comorbidities, and medication use. Adjusted odds ratios (aORs) were estimated for the primary outcome (recurrent AMI) and the secondary outcomes (acute HF hospitalizations, stroke, all-cause hospitalizations, all-cause mortality, new-onset atrial fibrillation, and cardiac arrest). After PSM, 89 554 patients were analysed (44 777 SGLT2-Is users; 44 777 non-users). The mean age was ∼68 years in both cohorts with a similarly high burden of cardiovascular comorbidities. Mean follow-up duration was 290.854 days for SGLT2-Is users and 284.465 days for non-users. SGLT2-Is use was linked to lower rates of recurrent AMI [aOR: 0.459; 95% confidence interval (CI): 0.367–0.551], all-cause hospitalizations (aOR: 0.782; 95% CI: 0.762–0.803), all-cause mortality (aOR: 0.640; 95% CI: 0.612–0.670), and cardiac arrest (aOR: 0.834; 95% CI: 0.773–0.900). No differences were observed in acute HF hospitalizations, new-onset atrial fibrillation, or stroke. Conclusion SGLT2-Is are associated with improved cardiovascular outcomes in patients with AMI, including reductions in recurrent AMI, all-cause hospitalizations and mortality, and cardiac arrest. These findings emphasize the need for prospective clinical trials involving patients with AMI and other cardiovascular comorbidities, regardless of LVEF, to confirm these results.