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There have been no large comparisons of the clinical and laboratory features of familial neonatal hemophagocytosis (f-nHLH) and infectious neonatal hemophagocytosis (i-nHLH). The objectives of this study were the following: (1) Describe the demographic, diagnostic, and clinical features of patients with familial nHLH (F-nHLH) and infectious HLH (i-nHLH). (2) Compare key variables between f-nHLH and i-nHLH. (3) Compare the clinical outcomes of f-nHLH and i-nHLH. (4) Summarize literature on cytokine levels in patients with nHLH. Data from a previously published nHLH meta-analysis report were used to describe and compare features of infants with f-nHLH versus i-nHLH. Variables were tested with the χ 2 test or Fisher exact test, Cochran-Armitage test, independent 2-sample t test, or Wilcoxon rank-sum test as appropriate. Odds ratios were calculated for any comparison with a P -value of <0.05. Data extracted from 99 cases of f-nHLH and 54 cases of i-nHLH were included in this analysis. Infants with f-HLH met HLH criteria at the following rates: fever (84%); organomegaly (100%); pancytopenia (75%); hypofibrinogenemia (84%); hypertriglyceridemia (48%); hypofibrinogenemia or hypertriglyceridemia (82%); hemophagocytosis (81%); hyperferritinemia (99%); low or absent NK cell activity (91%); and elevated soluble CCD25 (91%). Infants with i-nHLH had higher median ferritin levels (22,537 ng/mL) than infants with f-nHLH (7587 ng/mL) ( P =0.072). Infants with f-nHLH had higher rates of symptoms in utero, preterm birth, family history of HLH, and family history of infant death. The overall survival among infants with familial nHLH was lower than infectious nHLH ( P =0.037). Management of nHLH requires rapid diagnosis and prompt treatment, as current literature suggests nHLH has high mortality rates. Distinguishing between familial and infectious causes of nHLH can aid in determining the correct treatment of choice.

Few pharmacologic options exist for patients with clozapine-resistant schizophrenia (CRS) or schizoaffective disorder. Xanomeline/trospium represents a new class of antipsychotic medication that has efficacy as monotherapy for schizophrenia. Despite distinct mechanistic differences from standard antipsychotics, phase III evidence suggest limited benefit of xanomeline/trospium in the augmentation of non-clozapine antipsychotics. Research on the use of xanomeline/trospium in patients with clozapine-resistant illness or with partial response to clozapine is even more limited. Two cases of this combination are described with a discussion on key considerations for the management of CRS. The first case is a 42-year-old patient whose clozapine dose was limited by supratherapeutic clozapine levels in response to minor infections. She was ultimately stabilized on a combination of clozapine and xanomeline/trospium, with yet further improvements from electroconvulsive therapy (ECT). The second case is a 31-year-old patient who elected to discontinue clozapine and ECT due to cognitive side effects, despite improvement in psychosis. The addition of xanomeline/trospium to clozapine caused sialorrhea and did not produce observable clinical benefits and was thus discontinued. These case reports describe clozapine-resistant patients who were trialed on xanomeline/trospium combined with clozapine and still required consideration of ECT for symptom control. Overall, future investigation into xanomeline/trospium effectiveness as an augmentation agent or as monotherapy for CRS is necessary to guide clinical decision-making.

ABSTRACT Purpose Malignant rhabdoid tumor of the kidney (MRTK) is a rare, aggressive tumor seen in young children. The optimal timing of resection for locally advanced tumors is not well‐defined. The purpose of this study is to evaluate modern oncologic outcomes and the impact of surgical timing. Methods A multicenter retrospective review was performed by institutions participating in the Pediatric Surgical Oncology Research Collaborative. Children younger than 21 years old with MRTK diagnosed between 2000 and 2022 were included. Results Sixty‐nine patients were identified with MRTK and met the inclusion criteria. Median age of diagnosis was 10.1 months. Overall survival (OS) at 1, 5, and 10 years was 49%, 32%, and 19%, respectively. Patients with local Stage III disease who underwent upfront resection ( n = 18) compared to those who had delayed resection after NAT ( n = 15) had a similar OS, median OS greater than 60 months versus 14.6 months, respectively; p = 0.396. The surgical timing groups were balanced in terms of the presence of metastasis, length of follow‐up, and tumor characteristics. There was one occurrence of primary intraoperative tumor spill and two occurrences of organ injury in the upfront resection group compared to none in the delayed resection group. Conclusion MRTK carries a poor prognosis despite multimodal treatment. Histologic diagnosis may not be confirmed at presentation, and MRTK cannot be reliably distinguished from Wilms tumor on imaging alone. As overall survival is similar, the decision regarding surgical timing in locally advanced tumors should be individualized based on perceived resectability, balancing the risk of intraoperative complications against the possibility of tumor progression during neoadjuvant therapy.

ABSTRACT Background The optimal long‐term antithrombotic strategy after apparently successful catheter ablation of atrial fibrillation (AF) remains uncertain, particularly in patients who meet conventional guideline thresholds for oral anticoagulation (OAC). Objectives To compare continuation versus cessation strategies of long‐term OAC after successful AF ablation and to quantify net clinical benefit (NCB) integrating thromboembolic and bleeding outcomes. Methods We searched PubMed, Cochrane CENTRAL, and Embase from inception through February 2026 for randomized and comparative observational studies evaluating long‐term OAC continuation versus cessation (no OAC and/or switch to aspirin) after successful AF ablation. Risk of bias was assessed using RoB2 for randomized trials and a modified Newcastle–Ottawa Scale (NOS) for observational studies. Random‐effects meta‐analyses used a restricted maximum likelihood estimator with Hartung–Knapp adjustment. NCB was calculated as: thromboembolic event rate − (1.5 × major bleeding rate). Results Six studies met the inclusion criteria (four randomized trials and two observational cohorts). Stroke/transient ischemic attack (TIA) events were reported in six studies and were not significantly different between OAC continuation and cessation strategies (OR 0.69; 95% CI 0.24–1.99; p = 0.49). Systemic embolism (three studies) did not differ between groups ( p = 0.12). Major bleeding (five studies) was numerically higher with continued OAC but not statistically significant (OR 2.07; 95% CI 0.88–4.86; p = 0.09). In NCB analysis, continued OAC yielded more negative or near‐neutral NCB values, whereas, the cessation strategies were less negative or marginally positive; the fixed‐effect risk difference in NCB (continued OAC vs cessation) was +0.00067 (95% CI −0.00279 to +0.00413). Conclusion This meta‐analysis suggests that after successful AF ablation, continuing OAC does not significantly reduce stroke risk compared to cessation or switching to aspirin, but it may increase major bleeding. While NCB trends favor cessation, the low absolute event rates and the risk of silent AF recurrence necessitate caution.

ABSTRACT The term “trichobezoar” refers to foreign and indigestible material in the gastrointestinal tract, and it can indicate several underlying mental illnesses. A 38‐year‐old woman reported experiencing sudden intensive abdominal pain, along with a two‐month history of vomiting, nausea, exhaustion, and abdominal discomfort. The diagnosis of gastrointestinal perforation was validated by investigations. During an emergency laparotomy, a perforated stomach ulcer with enormous trichobezoar occupying the entire gastric lumen was revealed. The giant trichobezoar was removed, along with the appendix. The pathology report revealed serositis, fibrosis, and active chronic Helicobacter pylori gastritis. Trichobezoar exhibits variation in locations and volumes. These frequently starts with minimal symptoms but over time can produce nausea, vomiting, peritonitis, hematemesis, abdominal pain, or even perforation, especially in patients who are at risk of developing ulcers and have a large trichobezoar.

Abstract The circadian clock imposes a critical yet incompletely understood layer of regulation on adaptive immunity. T helper 17 (Th17) antimicrobial immune responses including expression of IL-17A by lamina propria CD4⁺ T cells, exhibit diurnal variation and are sensitive to circadian disruption. While the core circadian regulators CLOCK and BMAL1 canonically function as a heterodimer to drive rhythmic gene expression, emerging evidence suggests they may have distinct regulatory roles. Here we integrated ChIP-seq, ATAC-seq, and RNA-seq analyses in naïve CD4⁺ T cells to reveal that the CLOCK-BMAL1 complex controls circadian and metabolic programs through promoter binding, whereas exclusive CLOCK binding at promoters, together with CLOCK-BMAL1 binding at enhancers, regulates immune-associated genes. Using the mutant CLOCKΔ19, which lacks the transactivation domain, we observed disrupted circadian transcription and globally reduced chromatin accessibility, alongside increased accessibility at Th17-associated loci that their altered temporal regulation. Functionally, ClockΔ19 produces β-catenin stabilization in T cells, pronounced expansion of RORγt⁺ CD4⁺ T cells and Treg cells, impaired Treg suppression of Th17 responses, heightened Th17 responses, and reduced IFN-γ production during viral infection. Collectively, these findings define BMAL1 dependent and independent CLOCK functions that program naïve CD4⁺ T cell fate, restrain Th17 differentiation, and preserve immune homeostasis.

ABSTRACT Background Unknown primary cancer in the head and neck presents a difficult surgical treatment dilemma. Patients with squamous cell carcinoma of unknown primary (SCCUP) typically present with an enlarging neck mass found on biopsy but with no indication of primary site on diagnostic exams such as flexible laryngoscopy, CT, MRI, and/or PET/CT. Failure to identify primary sites eliminates surgical treatment as an option, pushing patients toward definitive chemoradiation with associated side effects. Methods Indocyanine green (ICG) has been used to identify primary carcinoma in known oropharyngeal squamous cell carcinoma while using transoral robotic surgery (TORS). In this case, we injected ICG intraoperatively in a patient with SCCUP to help with the real‐time localization of ICG in the tumor. Results ICG fluorescence successfully identified a previously undetected primary lesion within the oropharynx during TORS, which enabled precise surgical excision of the tumor. Conclusions This case demonstrates the potential of ICG‐guided TORS to localize primary tumors in SCCUP patients, offering a pathway to surgical treatment and potentially reducing reliance on chemoradiation.

Study Design. Systematic review and meta-analysis. Objective. To assess how operative order affects clinical outcomes and complications in patients with concomitant lumbar spinal and hip pathologies. Summary of Background Data. Concomitant lumbar spinal and hip pathologies are becoming increasingly prevalent in the growing population. Determining the optimal operative order for surgical treatment remains challenging, particularly when comparing spine arthrodesis followed by hip arthroplasty (SAHA) with hip arthroplasty followed by spine arthrodesis (HASA). Prior studies report conflicting results regarding outcomes and complications. Methods. A comprehensive literature search was performed to identify studies reporting on postoperative outcomes and complications in patients with concomitant lumbar spinal and hip pathologies. Random-effects model meta-analysis of pooled outcomes was performed comparing operative order groups (SAHA and HASA), with postoperative complications and revisions being our primary endpoints. Results. A total of 22 studies, yielding 161,326 patients who received surgical treatment for concomitant lumbar spinal and hip pathologies, were included. The majority of patients underwent SAHA (pooled estimate: 88.4%, 95% CI: 76.9–96.3%, P =0.01). Females comprised 56.1% (95% CI: 49.2–62.8%) of the study population. The mean age was 70.6±6.4 years, and the mean follow-up duration was 2.6±2.1 years. The mean number of treated levels was 2.1±1.4. No significant differences were noted between the SAHA and HASA groups with respect to complications, including hip dislocation ( P =0.7), mechanical loosening ( P =0.8), periprosthetic fractures ( P =0.7), deep venous thrombosis (DVT) ( P =0.8), and infection ( P =0.9). Revisions were required in 3.6% of patients in the SAHA group (95% CI: 2.5–4.9%) and 2.6% of patients in the HASA group (95% CI: 0.5–6.2%, P =0.5). Conclusion. Among patients surgically treated for concomitant lumbar spinal and hip pathologies, SAHA was significantly more commonly performed than HASA. Our analysis shows that postoperative complications and revisions did not significantly differ depending on operative order.

Study Design. Finite element (FE) analysis of retrospective clinical cohort. Objective. To determine whether preoperative CT-derived FE model outputs can improve subsidence prediction compared with conventional clinical measurements alone in patients undergoing transforaminal lumbar interbody fusion (TLIF). Summary of Background Data. Cage subsidence occurs in ∼20% of spinal fusion patients and can lead to complications requiring reoperation. While individual risk factors are known, no validated tool integrates patient anatomy, bone quality, and implant characteristics to predict subsidence. Finite element models have been hypothesized to predict subsidence but lack clinical validation. Materials and Methods. Patient-specific FE models were created from preoperative CT scans of 42 TLIF patients: N=22 severe subsidence (≥4 mm); N=20 nonsevere subsidence (<4 mm). Vertebral geometries were segmented, and bone material properties were assigned based on Hounsfield units (HU). Cage positions from postoperative scans were registered to preoperative anatomy. Endplate and trabecular stresses and strains from FE models were compared with clinical measures using receiver operating characteristic analysis. Results. Fifteen principal stresses and strains of the FE simulations showed significantly higher values in severely subsided patients compared with the nonsevere group. Average trabecular intermediate strain achieved the highest area under the curve score (AUC=0.809), outperforming all clinical metrics. Peak endplate minimum principal stress (AUC=0.775) was the second-best FE classifier. Traditional clinical measures showed lower discriminative ability: cage length (AUC=0.797), cage width (AUC=0.750), and cage height (AUC=0.698). Conclusion. Patient-specific FE model outputs significantly correlate with clinical subsidence outcomes and outperform several traditional metrics in classifying severe subsidence. Both endplate and trabecular stresses and strains are important predictors, with average values showing comparable or superior performance to peak values. Integration of FE models into the clinical workflow could provide a comprehensive preoperative subsidence prediction tool.