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Background Eosinophilic oesophagitis (EoE) is a food allergen-induced inflammatory disorder characterised by interleukin (IL)-13-mediated oesophageal inflammation and epithelial basal cell hyperplasia (BCH). The role of mitochondria in EoE pathogenesis remains elusive. Design Prompted by single cell transcriptomics data, we interrogated the role of mitochondria in EoE pathobiology using patient biopsies, EoE-mouse models and oesophageal epithelial cells grown in monolayer and three-dimensional (3D) organoid cultures treated with EoE-relevant cytokines. 3D organoids and EoE-bearing mice were treated with omeprazole—a proton-pump inhibitor used as first-line EoE therapy. We performed CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) interference in mouse organoids to identify the key mitochondrial regulatory genes whose depletion may lead to BCH. We analysed mitochondrial membrane potential, mass and superoxide production by flow cytometry, cellular oxygen consumption by respirometry, mitochondrial structures and perturbation of cellular energy homeostasis by immunoblotting. Results Mitochondrial dysfunction appeared to be a hallmark of EoE-related BCH where mitochondrial structural damage was associated with impaired oxidative respiratory capacity, elevation of mitochondrial superoxide and decreased adenosine triphosphate (ATP) production, as corroborated by activation of the adenosine monophosphate (AMP) -activated protein kinase and suppression of mammalian target-of-rapamycin signalling. Depletion of PGC1A, the master regulator of mitochondria biogenesis, recapitulated EoE-related BCH, suggesting that mitochondrial dysfunction drives BCH. Further, omeprazole alleviated mitochondrial damage and dysfunction in EoE-related BCH modelled in mice and patient-derived organoids. Conclusion Mitochondrial dysfunction is tightly linked to perturbation of redox homeostasis in EoE-related BCH, which is promoted by IL-13 and reversible with omeprazole treatment.

Importance Pectus arcuatum is a rare anterior chest wall deformity that is often confused with excavatum, carinatum, or a mixed deformity. A complete understanding of its clinical and physiological basis will improve diagnostic accuracy and allow for standardized management. Objectives To gain a comprehensive understanding of pectus arcuatum, focusing on its nomenclatures, epidemiology, classification, pathophysiology, preoperative presentation and assessments, management options, and surgical outcomes. Evidence Review PubMed, Google Scholar, and subsequent reference searches were used to extract original studies addressing pectus arcuatum fully or partially. The searches were performed on February 2, 2025. Two independent reviewers screened articles based on preestablished inclusion and exclusion criteria. Quality assessment was performed, but given the rarity of arcuatum and the limited, heterogeneous nature of available literature, none of the studies were excluded based on the level of evidence or quality assessments. Using a standardized data extraction form, results were synthesized and presented as a review with recommendations to guide clinical decision-making. Findings A total of 65 studies were included in the final review. Of those, 37 (56.9%) were cohort studies, 18 (27.7%) were case reports, 8 (12.3%) were case series, and 2 (3.1%) were technical reports. A total of 455 cases of pectus arcuatum were represented. Heterogeneity was found in nomenclature, epidemiology, associated conditions, assessments, management, and outcomes. An open surgical approach and, more recently, hybrid open and minimally invasive technique are reported for surgical repair. Postoperative outcomes were good in most surgical series, with no significant difference when compared with the repair of other pectus deformities. Conclusions and Relevance Results of this systematic review reveal that pectus arcuatum is a rare variant of pectus deformities that is distinct from carinatum and excavatum. Unified terminology and standardized diagnostic criteria are important to facilitate proper management. Minimally invasive hybrid approaches continue to refine outcomes, balancing invasiveness with efficacy.

Importance Women diagnosed with breast cancer at a young age are felt to have a higher risk for locoregional recurrence (LRR) regardless of type of local therapy. Objective To assess the long-term incidence of isolated LRR by molecular subtype in a modern multicenter cohort of young women. Design, Setting, and Participants This cohort study, a multicenter prospective study named the Young Women’s Breast Cancer Study, enrolled 1302 women diagnosed with breast cancer at 40 years or younger from 2006 to 2016. Treatment information and incident LRR (ipsilateral breast/chest or lymph node recurrence) were self-reported on study surveys and confirmed with medical record review; molecular subtype was determined by record review. Analysis was reported from February 2023 to May 2025. Main Outcomes and Measures Cumulative incidence of isolated LRR was calculated using the Kaplan-Meier method; hazard ratios were estimated by Cox proportional hazards regression. Results The cohort included 1135 women with stage I through III breast cancer who had a median follow-up of 10.1 years (range, 0.4-16.3 years). The age at diagnosis was younger than 30 years for 145 patients (12.8%), 31 to 35 years for 318 patients (28.0%), and 36 to 40 years for 672 patients (59.2%). There were 59 isolated local recurrences (5.2%) and 4 isolated regional recurrences (0.4%). Among patients with local therapy and subtype data available (n = 1128), 366 (32%) had luminal A–like tumors; 240 (21%), luminal B–like tumors; 231 (20%) luminal ERBB2 positive (+)–like (formerly HER2 positive); 90 (8%) ERBB2 +-like; and 201 (18%) triple negative. A total of 346 women (30%) had breast-conserving therapy (BCT) (98% of whom had radiation), 296 (26%) unilateral mastectomy, and 487 (43%) bilateral mastectomy. Of women who had mastectomy, 425 (54%) had radiation. The cumulative incidence of LRR at 10.1 years by subtype was as follows: luminal A, 4.4% (range, 1.0%-6.9%); luminal B, 4.7% (range 1.8%-7.7%); luminal ERBB2 +, 6.1% (range, 3.1%-8.3%); ERBB2 +, 2.2% (range, 0%-6.3%); and triple negative, 6.5% (range, 4.2%-10.1%). The cumulative incidence of LRR by locoregional treatment type at 10.1 years was 6.7% after BCT (range, 4.3%-10.1%), 6.5% after mastectomy without radiation (range, 0%-7.7%), and 2.4% after mastectomy with radiation (range, 1%-4.2%). Although mastectomy with radiation was associated with the lowest risk of LRR on multivariable analysis, when examined within molecular subtype, there were no differences seen. Conclusions and Relevance In this contemporary cohort of women diagnosed with breast cancer at age 40 years or younger, risk of isolated LRR was relatively low (5.6%) at a median follow-up of 10.1 years, and significant differences were not seen by tumor subtype. Concerns for long-term risk of LRR should not influence surgical decision-making with young women, irrespective of molecular subtype.

Abstract Purpose It remains unclear whether increasing the frequency of administration of 0.01% atropine improves its effectiveness in slowing axial elongation or refractive progression. This study compared twice‐daily 0.01% atropine administration and traditional once‐nightly administration. Methods A hybrid design was adopted incorporating both retrospective and prospective elements, with participants observed for 1 year. The control group (received saline eye drops) and once‐daily 0.01% atropine group (Atropine‐1 group) were derived from two previous trials, while the twice‐daily 0.01% atropine group (Atropine‐2 group) was enrolled prospectively. A total of 163 participants were included in the intention‐to‐treat set, with 51, 70 and 42 participants in the control, Atropine‐1 and Atropine‐2 groups, respectively. The primary outcome was the change in axial length (AL), and the secondary outcome was the change in cycloplegic spherical equivalent refraction (SER). Results Compared with the control group (0.48 ± 0.22 mm), both Atropine‐1 (0.26 ± 0.17 mm) and Atropine‐2 (0.15 ± 0.18 mm) groups showed significantly reduced AL elongation ( p < 0.001). Notably, Atropine‐2 significantly improved slowing of AL elongation compared with Atropine‐1 ( p = 0.008). The result of the secondary outcome (adjusted SER change) was consistent. Atropine‐2 was significantly more effective in slowing SER progression (−0.15 ± 0.37 D) than Atropine‐1 (−0.41 ± 0.50 D) ( p = 0.02). Based on a multivariable model, age was identified as the key covariate to perform subgroup analyses. In the younger subgroup (8–10 years), AL elongation was significantly reduced in the Atropine‐2 group (0.16 ± 0.17 mm) compared with the Atropine‐1 group (0.36 ± 0.22 mm; p = 0.002). In the older subgroup (10–12 years), there was no significant difference in progression. Consistent results were observed in the sensitivity analyses based on the per‐protocol set. Conclusion Twice‐daily administration of 0.01% atropine was more effective than once daily in slowing AL elongation and SER progression in children 8 to 10 years of age. Further investigation with extended follow‐up is warranted to substantiate this finding.

BACKGROUND: Emergency colorectal surgery traditionally uses open approaches, with limited minimally invasive adoption. Although robotic surgery demonstrates benefits in elective procedures, its role in emergency settings remains unclear. This retrospective study evaluated outcomes of robotic vs laparoscopic and open approaches in emergency colorectal procedures and predicted future adoption trends. STUDY DESIGN: We analyzed 83,483 patients from the American College of Surgeons NSQIP database (2012 to 2021) who underwent emergency colorectal surgery: 53,731 open, 26,649 laparoscopic, and 3,103 robotic procedures. Outcomes were analyzed using multivariable regression, propensity score matching, and g-computation analysis. Classification and Regression Trees were used to analyze surgical approaches to selection factors, whereas vector autoregressive models projected future usage trends. RESULTS: Robotic surgery demonstrated significantly lower conversion rates to open surgery compared with laparoscopy (7.8% vs 24.2%; adjusted odds ratio 0.32, 95% CI 0.28 to 0.36), shorter length of stay (incidence rate ratio 0.67, 95% CI 0.65 to 0.69), and fewer surgical complications (odds ratio 0.65, 95% CI 0.60 to 0.72). Robotic usage increased from 0% to 6.6% (2012 to 2021), with trends suggesting substantial growth toward 20.2% by 2025. Patient selection favored robotics for stable patients with diverticulitis (68.4%) and cancer without sepsis, whereas open surgery remained predominant in patients with perforation, severe sepsis, or significant comorbidities. CONCLUSIONS: In selected emergency colorectal procedures, robotic surgery demonstrates superior outcomes vs conventional approaches. These outcomes may be partially influenced by patient selection factors because robotic cases involved more clinically stable patients. These findings support expanded robotic platform availability for emergency procedures, although careful patient selection remains essential. The projected increase in robotic usage reflects a growing acceptance of this technology, suggesting that its technical advantages can extend to more complex emergency cases than previously considered.

Objective: To determine if a Super Learner (SL) machine learning approach could improve the predictive accuracy of the American College of Surgeons Risk Calculator (ACS-RC) for postoperative complications in patients undergoing colorectal surgery. Summary of Background Data: Machine learning (ML) has shown significant potential to advance medical fields, including surgical risk prediction. Current tools, like the ACS-RC which uses logistic regression and extreme gradient boosting, are standard but may be enhanced by more advanced ML ensembles. Methods: This retrospective study analyzed colorectal surgery cases from the 2018-2022 ACS National Surgical Quality Improvement Program (NSQIP) database. An SL model, which combines multiple ML algorithms, was developed to predict fourteen postoperative outcomes. Its performance was compared against traditional logistic regression (LOG) and extreme gradient boosting (XGB) models. Key performance metrics included discrimination (AUROC, AUPRC) and calibration (Brier score, Hosmer-Lemeshow test). Results: The SL model demonstrated superior performance across all predicted complications when compared to both LOG and XGB. It showed superior discrimination for severe outcomes, achieving an AUROC greater than 0.94 for predicting mortality. The SL model was also more accurate in predicting infectious complications and length of stay, and its calibration metrics indicated a better overall fit and accuracy. Conclusions: The Super Learner model enhances the accuracy of postoperative risk prediction in colorectal surgery. Its superior performance suggests it is a promising tool for improving personalized patient counseling, aiding clinical decision-making, and optimizing resource allocation.

Background : The COVID-19 pandemic profoundly impacted healthcare, emphasizing the need to strengthen future pandemic responses and optimize resource allocation planning and deployment during times of disruption and crisis. Methods : This retrospective, single-center, cross-sectional study included participants ≤17 years-old admitted to the Children’s Hospital (CH) between 01/01/2017 and 12/31/2021. Clinical data was abstracted using Vizient ® Clinical Data Base and the internal data warehouse. Using the International Classification of Disease, 10 th Revision, Clinical Modification (ICD-10-CM) admit diagnosis, frequency and pattern of total admissions during the pre-pandemic phase (2017 Q1-2019 Q4) and intra-pandemic phase (2020 Q1-2021 Q4) were compared. Results : The study included 33,158 admissions. CH SARS-CoV-2 prevalence rate was 0.1% in 2020 and 0.5% in 2021. There was a decrease in overall admissions to the CH (p <0.01) and PICU (p <0.01) at the start of the pandemic. There were significant and variable differences in admission patterns for certain infectious, mental health, and seizure related diagnoses. Seasonality was noted for viral bronchiolitis during the pre-pandemic phase but was disrupted during the intra-pandemic phase with significantly lower admission rates for viral bronchiolitis in 2020 Q4 (p <0.05) and 2021 Q1 (p <0.01), followed by a significant early increase in viral bronchiolitis admissions in 2021 Q3 (p <0.01). Conclusion : The COVID-19 pandemic significantly impacted the number and pattern of admissions despite low SARS-CoV-2 prevalence in our hospital. These changes may be secondary to COVID-19 mitigation strategies implemented in the community. Results can inform anticipated patterns during future pandemics.

Abstract Background Protein biomarkers are routinely measured for disease diagnosis and prognosis in clinical laboratories. Since most assays focus on protein quantity, information about proteoforms is often not acquired. Proteoforms of a protein represent the complex integration of genetic polymorphism, alternative splicing of RNA transcripts, and post-translational modifications (PTMs) on the amino-acid backbone. A detailed analysis of the post-translationally modified proteoforms (PTMPs), which are influenced by pathophysiological conditions, may lead to more precise diagnosis and prognosis. Content This article first discusses the methodologies used to accurately detect and characterize PTMPs, i.e., immunoassays, electrophoresis, chromatography, and intact and proteolysis-aided mass spectrometry techniques. Then it reviews specific examples of PTMP biomarkers that have been successfully translated from biomarker discovery to clinical use. The examples include β2–transferrin for cerebrospinal fluid leak diagnosis, phosphorylated tau proteoforms for Alzheimer disease diagnosis, and fucosylated alpha-fetoprotein for hepatocellular carcinoma prognosis. In addition, the article provides prospective views of novel analytical technologies and promising new PTMP biomarkers entering clinical practice. Summary In summary, PTMs are controlled by biochemical processes to modulate the functions of proteins by expanding their chemical diversity. PTM alterations in proteins can be indicators for pathophysiological conditions. Advances in analytical technologies are deepening our understanding of PTMPs and paving the way for their translation to clinical use. As research continues to discover the clinical meaning of PTMP biomarkers, they are poised to become valuable additions to the clinical testing menu for precision medicine.

Introduction: Periaortitis is a rare inflammatory condition with both infectious and non-infectious aetiologies, often presenting a diagnostic challenge. A comprehensive evaluation—including history, physical examination, imaging, and a broad infectious work-up—is essential, as negative blood cultures do not rule out infection, and premature use of glucocorticoids may be harmful in cases of infectious periaortitis. Case description: We report the case of a 70-year-old man presenting with flank pain and periaortitis, in whom positron emission tomography/computed tomography (PET/CT) scan revealed moderate-to-severe 18F-fluorodeoxyglucose (FDG) uptake. Despite negative cultures, a Karius test and urine antigen confirmed Streptococcus pneumoniae as the causative agent. The patient underwent successful open surgical repair of a mycotic pararenal abdominal aortic aneurysm, followed by targeted antibiotic therapy. Discussion: Pneumococcal periaortitis is a rare condition with few reported cases, though S. pneumoniae has been implicated in various vascular infections including mycotic aneurysms, and diagnostic challenges persist, especially when blood cultures are negative. The Karius SpectrumTM, despite its cost and limited guidance for use, and FDG-PET/CT imaging have emerged as helpful tools in identifying infectious aetiologies, with high maximum standardized uptake value values favouring infection over autoimmune causes, as seen in this case. Conclusion: Infectious periaortitis should be suspected when there is a high uptake of FDG on PET/CT prompting an infectious disease work-up which may include a Karius test.