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Importance Rapid whole-genome sequencing (WGS) has advanced inpatient genetic diagnosis, although most evidence comes from neonatal and pediatric intensive care unit (ICU) populations. Its utility for pediatric neurology inpatients across broader acute settings remains insufficiently established. Objective To assess the diagnostic yield, clinical impact, and factors associated with phenotype-concordant rapid WGS diagnoses. Design, Setting, and Participants This was a retrospective cohort study conducted from June 1, 2022, through January 17, 2026, at a tertiary medical center. Pediatric inpatients in the neonatal ICU, pediatric ICU, or general floor with an unexplained neurologic presentation were included. Those with established nongenetic etiology were excluded from analyses. Exposures Trio (77.8%), duo (9.1%), or singleton (13.1%) rapid WGS. Main Outcomes and Measures The primary outcome was the initial phenotype-concordant diagnostic yield at the point of care. Secondary outcomes were reanalysis yield (new diagnoses from reinterpreting nondiagnostic cases prompted by a new unexplained phenotype or family request), cumulative yield, and management change. Associations were assessed by logistic regression (odds ratios [ORs] and 95% CIs). Results Among 175 children (median [IQR] age, 4 months [1 day-4 years]; 93 male [53.1%]) who met inclusion criteria (82 neonates, 93 nonneonates), initial rapid WGS established a phenotype-concordant diagnosis in 79 (45.1%), higher in nonneonates (49 of 93 [52.7%]) than neonates (30 of 82 [36.6%]). Preliminary results returned at mean (SD) 4.0 (1.6) days and final reports at 10.4 (4.5) days. Positive nonconcordant findings occurred in 33 children (18.9%). Reanalysis of 14 nondiagnostic cases yielded 3 additional diagnoses, for a cumulative yield of 82 of 175 children (46.9%). Most diagnoses were monogenic (63 [76.8%]). Management changed in 54 of 82 phenotype-concordant cases (65.9%; 53 at the point of care, 1 after reanalysis) and 8 of 33 (24.2%) positive nonconcordant cases. Family history was most strongly associated with diagnosis (adjusted OR [aOR], 6.46; 95% CI, 3.23-12.93; P < .001), followed by multisystem involvement (aOR, 2.85; 95% CI, 1.24-6.54; P = .01) and congenital anomaly or dysmorphism (aOR, 2.47; 95% CI, 1.07-5.68; P = .03). Hypotonia was most strongly associated in neonates (OR, 20.63; 95% CI, 5.46-77.87; P < .001); ICU admission (OR, 10.25; 95% CI, 2.79-37.67; P < .001) predominated in nonneonates. Conclusions and Relevance Results of this cohort study suggest that rapid WGS diagnosed nearly half of pediatric neurology inpatients and changed management in two-thirds of diagnosed cases, supporting its potential use as early diagnostic testing. Associated features may guide patient selection, and reanalysis extends yield longitudinally.

Abstract Objective Rituximab causes B‐cell depletion and hypogammaglobulinemia, increasing risk for infections. This study aims to determine the incidence of chronic rhinosinusitis (CRS) in patients following rituximab therapy. Study Design Retrospective cohort study using chart review of patients prescribed rituximab between January 2019 and January 2025. Setting Multisite study across Mayo Clinic Enterprise locations in Arizona, Florida, Minnesota, and Wisconsin. Methods Patients with documented rituximab use were included; those with pre‐existing CRS were excluded. Demographic and clinical data—including timing and duration of rituximab therapy, CRS diagnosis, comorbidities (asthma, allergic rhinitis, GERD), and need for sinus surgery—were collected. Descriptive statistics summarized patient characteristics. Group comparisons were performed using t ‐tests, Mann‐Whitney U , and chi‐square tests. Analyses were conducted using SPSS v28. Results Among 17,851 patients prescribed rituximab (median age 64.0 years, M:F ratio 1.1:1), 1105 (6.2%) developed CRS, with an annual incidence of 1.03% (1032 cases per 100,000 person‐years). The median duration of rituximab therapy for those diagnosed with CRS was 5.9 months (IQR, 0.5‐42.6). Most CRS cases occurred after rituximab discontinuation (62.7%, n = 693) compared to during active treatment (37.3%, n = 412). The median delay between rituximab discontinuation and CRS diagnosis was 17.0 months (IQR, 4.3‐41.7). Conclusions This study demonstrates an annual incidence of 1.03% for CRS diagnoses following rituximab. While prior studies report varying CRS incidences in the general population (0.25%‐0.73%), our findings suggest increased risk among rituximab users. Most CRS diagnoses occurred after rituximab discontinuation, emphasizing the need for a comprehensive medication history review during CRS evaluation.

ABSTRACT Background While vaccination is a key strategy to mitigate the severity of coronavirus disease 2019 (COVID‐19) in children, the risk factors for symptomatic, medically attended (hereon referred to as “symptomatic”) COVID‐19 and the impact of vaccination are not well defined among pediatric solid organ transplant recipients (PSOTR). Methods PSOTR aged six months through 21 years at 11 centers in the Pediatric Infectious Diseases Transplant Network (PIDTRAN) were analyzed retrospectively for symptomatic COVID‐19 between July 2021 and May 2023. Using a Cox proportional hazards model, risk factors associated with COVID‐19‐associated hospitalization, in‐hospital oxygen use, mechanical ventilation, and the impact of COVID‐19 vaccination were analyzed. Results Of 1370 PSOTR, 410 (29%) had symptomatic COVID‐19 infection. Among those with symptomatic infection, 115 (28%) were hospitalized, 35 required in‐hospital oxygen, and three required mechanical ventilation. In the study, 45% were unvaccinated against COVID‐19. Compared to unvaccinated PSOTR, incompletely vaccinated PSOTR had 56% lower hazard (95% CI 0.26, 0.72, p = 0.001) of COVID‐19‐associated hospitalization whereas completely vaccinated did not have a statistically significant difference in hazard of hospitalization. Receipt of at least one dose of the bivalent vaccine was also associated with 92.5% lower hazard (95% CI 0.010, 0.55, p = 0.011) of hospitalization. Risk factors for hospitalization included chronic kidney disease, underlying heart disease, neurodevelopmental delay, and lymphocytopenia. Conclusions Most PSOTR with symptomatic COVID‐19 did not require hospitalization or respiratory support. Several comorbidities and lymphocytopenia are associated with severe COVID‐19 in PSOTR. COVID‐19 vaccination, mostly, protected PSOTR against COVID‐19‐associated hospitalization, but vaccine uptake among PSOTR was low. image

ABSTRACT Biofilm‐associated staphylococcal infections remain exceptionally difficult to treat due to the presence of resilient staphylococcal biofilms and the limited effectiveness of currently available antibiotics. To combat persistent infections, providers are often forced to use prolonged courses of combination antimicrobial therapies that have significant toxicities with limited effectiveness, leading to increased hospital stays, substantial health care costs and a rise in patient morbidity and mortality. Staphylococcus aureus is a dominant cause of recalcitrant biofilms, for which novel non‐antibiotic therapeutics are critically needed. Lysins, a class of protein‐based antimicrobials, rapidly kill staphylococci, exhibit potent anti‐biofilm activity, have a low propensity of resistance development and synergy with antibiotics. To address this unmet need, we evaluate an extracellular vesicle (EV)‐based delivery platform for the engineered anti‐staphylococcal lysin LYSG101, designed to improve stability and localization at sites of infection. Initial proof‐of‐concept work is provided here, demonstrating that human serum‐derived EVs can be loaded with LYSG101 to exert a potent in vitro antimicrobial effect against both planktonic and biofilm forms of S. aureus . EV‐mediated delivery achieved activity equivalent to free lysin, with additional translational advantages including stability and the potential for sustained intra‐articular retention. This work supports further development of the EV‐mediated lysin delivery as a broadly applicable antimicrobial platform, with potential future applications in biofilm‐associated infections, including prosthetic joint infection (PJI).

ABSTRACT Introduction Composite indolent B‐cell lymphomas may remain unrecognized when one component dominates the clinical presentation. Apparent relapse after therapy may, therefore, represent the emergence of a biologically distinct lymphoma rather than the recurrence of the original disease. Case Presentation An 82‐year‐old woman presented with systemic low‐grade B‐cell lymphoma that was most consistent with marginal zone lymphoma (MZL). Staging demonstrated peripheral blood involvement and multifocal FDG‐avid disease. Treatment with the CD20×CD3‐bispecific antibody mosunetuzumab resulted in complete metabolic remission. During surveillance, a new, isolated cervical lymph node developed despite sustained systemic response. Biopsy revealed follicular lymphoma (Grade 1–2) with a germinal center phenotype and a BCL2 rearrangement, findings discordant with recurrence of MZL. Retrospective review of the original specimen identified in situ follicular neoplasia within the initial biopsy. The disease course was, therefore, reinterpreted as a synchronous composite lymphoma in which treatment of the dominant MZL unmasked a previously clinically silent B‐cell neoplasm with follicular lineage. Local radiotherapy achieved remission of the follicular component. Conclusions New disease following treatment of an indolent lymphoma should not automatically be interpreted as relapse. Discordant clinical behavior, particularly focal progression after systemic response, warrants repeat biopsy and integrated pathologic reassessment. This case illustrates how therapy may reveal preexisting clonal heterogeneity and emphasizes the importance of temporality in distinguishing relapse from composite lymphoma. Trial Registration The authors have confirmed clinical trial registration is not needed for this submission

Importance As the use of robotic cholecystectomy increases, its value remains poorly defined for complex elective cholecystectomy (CEC), where complex gallbladder pathology results in increased technical difficulty. Objective To determine whether a robotic approach is associated with improved clinical outcomes and altered total hospital cost as compared with a laparoscopic approach for patients undergoing CEC. Design, Setting, and Participants This cohort study analyzed data from an academic hepatobiliary referral center for patients who underwent cholecystectomy from August 2018 to August 2024. CEC was defined by preoperative criteria: prior aborted or partial cholecystectomy, presence of a cholecystostomy tube, and/or history of gallbladder perforation or fistula. Exposure Robotic-assisted vs laparoscopic cholecystectomy. Main Outcomes and Measures The primary outcome was a composite of an unplanned postoperative endoscopic retrograde cholangiopancreatography or interventional radiology procedure. Secondary outcomes included operative time, postoperative complications, and operative and total hospital costs. Results A total of 863 patients underwent cholecystectomy and met inclusion criteria; 525 (60.8%) were female and 338 (39.2%) were male, and their median (IQR) age was 61 (45-71) years. Among patients undergoing CEC, the laparoscopic approach was independently associated with an increased need for unplanned endoscopic or percutaneous intervention compared with the robotic group (odds ratio, 4.24; 95% CI, 1.24-14.52; P = .02). There were no significant differences in postoperative outcomes between the laparoscopic and robotic groups in patients undergoing non-CEC. Patients undergoing the laparoscopic approach had significantly reduced operating room costs when compared with patients undergoing a robotic approach in both the CEC ($7720 vs $8936, respectively) and non-CEC groups ($6368 vs $ 8351, respectively). However, there was no difference in the overall total cost of care between laparoscopic CEC and robotic CEC groups ($14 309 vs $14 476, respectively). The overall total cost of care was significantly higher for patients undergoing robotic non-CEC as compared with laparoscopic non-CEC ($11 416 vs $9925, respectively). Conclusions and Relevance This study found that for complex gallbladder disease, robotic cholecystectomy offers a clinical advantage, reducing complications and downstream interventions without increasing the overall costs of care. These findings suggest strategic application of the robotic platform may offer clinical advantages in high-complexity gallbladder surgery, maximizing patient benefit and resource efficiency.

ABSTRACT Background Strongyloides stercoralis is an intestinal parasitic nematode that can infect humans with a 2%–7% prevalence in the United States. Immunosuppression is a crucial risk factor for disseminated infection. Diagnosis is often delayed and targeted treatment is frequently initiated late. We therefore sought to review the prevalence of positive Strongyloides antibody results and undertook a descriptive analysis of such patients. Methods We retrospectively reviewed patients with positive Strongyloides IgG serology from August 2012 to April 2023 across geographically distinct academic medical centers. Study period pre‐dated universal donor and recipient Strongyloides screening recommendation by the Organ Procurement and transplantation network (OPTN). Clinical presentation was classified into three categories: chronic infection (positive Strongyloides IgG serology without additional clinical manifestations), hyperinfection syndrome (positive serology with involvement of the skin, gastrointestinal tract, or lungs), and disseminated infection (positive serology with involvement beyond those typically involved in hyperinfection). Results A total of 412 patients were identified; median age was 59 years and 66% (272) were male. The primary indication for testing was pretransplant evaluation in 230 (56%), eosinophilia workup in 84 (20%), suspicion of symptomatic infection in 74 (18%), testing based on travel history in 27 (7%), and pre‐immunosuppression screening in 27 (7%). Furthermore, 401 patients (97.3%) were categorized as having chronic infection, 10 patients (2.42%) had hyperinfection, and one patient (0.24%) had disseminated infection, presenting with Escherichia coli bacteremia and meningitis. Symptomatic infection was more common at the Mayo Clinic in Rochester and Mayo Clinic Health Sciences than at the Arizona and Florida Mayo Clinic sites (6% vs. 2%, p = 0.079). Treatment was administered to 366/412 (89%) patients. Conclusion Most patients with positive Strongyloides serology were asymptomatic, and treatment regimens were not uniform. Patients who tested positive should be treated prior to immunosuppression initiation, though this was not systematically assessed in this cohort. The observed variability in treatment regimens highlights the need for standardized protocols.

Abstract Background Minimally invasive surgery (MIS) improved outcomes in hepatopancreatobiliary (HPB) cases, yet adoption is slowed by technical complexity and steep learning curves. This retrospective review sought to characterize MIS training variations across three fellowship pathways: HPB, complex general surgical oncology (CGSO), and transplant (TXP). Methods We analyzed anonymized Fellowship Council case logs (2014-2023) for 146 HPB, 55 CGSO, and 51 TXP fellows seeking AHPBA certification. Procedures were categorized by platform and type. Results HPB fellows logged significantly more total robotic cases (HPB: 12.5, CGSO: 8.5, TXP: 1.0, p <0.01), including robotic pancreaticoduodenectomies (HPB 4.4, CGSO 3.0, TXP 0.2, p <0.01) and robotic distal pancreatectomies (HPB 3.8, CGSO 3.2, TXP 0.6, p <0.01). Although TXP fellows performed more open major liver resections (HPB 24.0, CGSO 24.7, TXP 35.2, p <0.01), robotic anatomic (HPB 2.1, CGSO 1.5, TXP 0.03, p 0.01) and non-anatomic liver resections (HPB 1.8, CGSO 1.4, TXP 0.2, p <0.01) were highest among HPB fellows. Discussion Meaningful differences in MIS operative exposure exist across training pathways, with TXP fellows trailing significantly in robotic experience. These findings highlight a critical need for standardized MIS curricula to ensure technical proficiency across all HPB surgery pipelines.

ABSTRACT Introduction Chronic gastroduodenal disorders remain challenging to manage, and new diagnostic approaches are needed to better delineate underlying causes and guide therapeutic decisions. Body Surface Gastric Mapping (BSGM) technologies combine high‐resolution gastric myoelectrical activity measurements with symptom and psychological profiling to provide mechanistic insights into gastric motor and sensory dysfunction. An International Working Group convened to derive the first consensus classification of BSGM phenotypes (the “Auckland Classification”). Methods A Technical Group conducted a systematic literature and clinical database review to identify objective test biomarkers and candidate disease mechanisms. Evidence was synthesized across 50 studies (primarily in gastroparesis, chronic nausea and vomiting, and functional dyspepsia), and BSGM phenotypes were mapped to existing treatment guidelines. Subsequently, iterative review and development of consensus was performed by a Consensus Group composed of international clinical experts familiar with BSGM. Eleven statements underlying the classification were then derived and circulated as a final survey to establish agreement. Results Six BSGM phenotypes were endorsed: three defined by myoelectrical abnormalities (Dysrhythmic, High Frequency, and Low Meal Response) and three by characteristic symptom associations (Sensorimotor, Continuous, and Delayed Onset Symptoms). Published studies plausibly linked these phenotypes to mechanisms including interstitial cell of Cajal depletion, vagal impairment, hypomotility, visceral hypersensitivity, gut‐brain dysregulation, and small bowel dysfunction. Phenotypes were also mapped to existing mechanism‐based treatment guidelines. Ten out of the eleven statements had > 80% agreement. Conclusions The Auckland Classification, derived by international consensus, presents a structured framework for BSGM‐defined patient phenotypes. Evidence and mechanism‐based treatment options are suggested for each phenotype to provide a foundation for research, further validation, and a pathway for integrating BSGM into clinical care.