Citations

Abstract Background Evaluation of middle ear prostheses requires high-resolution imaging to assess position and structural integrity. Purpose To assess the diagnostic performance of photon-counting-detector (PCD)-CT for middle ear prosthesis imaging in cadaveric specimens. Materials and Methods Nine different middle ear prostheses were implanted in five fresh-frozen whole-head specimens, both in correct anatomic position and displaced to mimic malposition. Specimens were scanned on PCD-CT (NAEOTOM Alpha, Siemens) and energy-integrating-detector (EID)-CT (SOMATOM Force, Siemens), reconstructed at 0.2mm and 0.4mm, respectively. Eighteen cases (9 prostheses, 2 positions) per scanner were evaluated by two neuroradiologists (36 readings), blinded to scanner and position, who scored prosthesis position, reader confidence, and overall image quality. Agreement with the reference standard and between readers was compared. Results PCD-CT showed higher diagnostic confidence compared with EID-CT, while accuracy and inter-reader agreement did not demonstrate significant differences between scanners. Correct readings, PCD-CT versus EID-CT: lateral contact, 31/36 (86.1%; 95% CI: 58.3%-94.4%) vs. 29/36 (80.6%; 55.6%-91.7%), p = 0.500; medial contact, 30/36 (83.3%; 55.6%-94.4%) vs. 26/36 (72.2%; 50.0%-83.3%), p = 0.250. PCD-CT identified all cases of complete contact loss (score 3), while EID-CT missed one reading per contact. Inter-reader agreement may be higher with PCD-CT vs EID-CT (lateral: κw: 0.804 [0.578-0.941] vs. 0.571 [0.302-0.778], p = 0.250; medial: 0.684 [0.191-0.934] vs. 0.481 [0.024-0.835], p = 0.250). Reader confidence was significantly higher with PCD-CT; mean paired differences for Readers 1 and 2 were 9.4 (1.8-17.1; Holm-adjusted p = 0.019) and 23.1 points (13.4-32.7; p < 0.001) for lateral contact, and 16.4 (10.0-22.8; p < 0.001) and 17.8 points (6.8-28.8; p = 0.007) for medial contact. Readers preferred PCD-CT image quality in 16/18 (88.9%; 65.3%-98.6%) and 17/18 cases (94.4%; 72.7%-99.9%), respectively. Conclusion PCD-CT was associated with significantly higher reader confidence and preferred image quality, without significant differences in diagnostic accuracy or inter-reader agreement. These findings suggest PCD-CT is a promising modality for postoperative middle ear evaluations that warrants further investigations.

Objective To assess the effect of Moses™ 2.0 (Lumenis Be Ltd., Yokneam Illit, Israel; Boston Scientific, Marlborough, MA, USA) for lithotripsy of renal stones of 8–20 mm in diameter on operative time, surgeon workload, and retropulsion. Subjects/Patients and Methods In our multicentre, randomised, double‐blind clinical trial, patients were randomised 1:1 to standard or Moses 2.0 laser lithotripsy and stratified by stone size. Patients and surgeons were blinded to laser modality. Primary outcomes were total operative time as well as surgeon workload assessed by the National Aeronautics and Space Administration‐Task Load Index (NASA‐TLX). Secondary outcomes were stone retropulsion evaluated by blinded video review and postoperative clinical outcomes. Linear regression modelling was used for analysis. Results A total of 153 patients (79 Standard, 74 Moses 2.0) with similar clinical, stone, and operative characteristics were evaluated. There was no significant difference in operative times between the Standard and Moses 2.0 groups ( P = 0.73). Moses 2.0 was associated with lower effort, frustration, mental, physical, and temporal workload, as well as higher rated overall performance compared to the standard laser. Video review demonstrated no difference in rates of retropulsion ( P = 0.13). Complication rates (Standard: 13%; Moses 2.0: 10%) and stone‐free rates (Standard: 51%; Moses: 2.0 55%) were comparable. Conclusion Our study evaluated the impact of Moses 2.0 technology on high‐powered renal stone dusting, constituting the largest double‐blind trial of its kind to date. There was insufficient evidence to suggest any difference in operative times or clinical outcomes when using Moses 2.0 compared to standard laser lithotripsy. Moses 2.0 was associated with reduced surgeon workload, which has implicit impact on surgeon wellness.

Abstract Background Glioblastoma (GBM) represents the most common and aggressive central nervous system malignancy where overall survival is a dismal 14.6 months despite an aggressive standard of care treatment regimen that includes maximally safe surgical resection, radiotherapy, and temozolomide. It has recently been established that GBM tumors have increased transferrin receptor expression and iron content which corresponds with worse patient prognosis. This has led to the hypothesis that iron metabolism is a viable therapeutic target. An emergent therapeutic strategy to target GBM iron metabolism is gallium maltolate (GaM), which is an orally bioavailable form of Ga3+ that functions as a redox inactive iron mimic to disrupt iron metabolism. As mitochondrial iron metabolism serves as a central connection point between iron and DNA metabolism, the goal of this study was to determine if GaM could disrupt this system. Methods The effects of GaM on GBM cells were interrogated using conventional techniques including colony formation assays to assess clonogenicity, alkaline comet assays to evaluate DNA damage induction, and MitoFerro Green analysis to evaluate mitochondrial iron content. The effects of GaM on tumor growth in vivo were evaluated using a subcutaneous flank xenograft model system to determine the induction of DNA damage and an orthtopic model system to evaluate the combinatorial effects of GaM, radiation, and temozolomide on murine survival. Results This study uncovered that maintenance of high mitochondrial iron content corresponds with increased proliferative capacity in GBM cells. This study also shows that GaM can deplete mitochondrial iron to induce DNA damage both in vitro and in a subcutaneous xenograft model. Furthermore, GaM enhances the efficacy of radiation and temozolomide when delivered concomitant and adjuvantly in an orthotopic GBM model system. Conclusion These results suggest that GaM warrants further consideration for use in combination with standard of care GBM therapy.

Abstract Skin and soft tissues infections (SSTIs) are common conditions, affecting millions worldwide. SSTIs range from uncomplicated cellulitis to necrotizing fasciitis and can be divided into non-purulent and purulent forms. Non-purulent SSTI is most commonly associated with beta-haemolytic streptococci, while purulent SSTI is typically associated with Staphylococcus aureus . Cellulitis most commonly presents with acute warmth, pain, tenderness to palpation, erythema, and oedema. Skin abscess typically presents with a fluctuant tender area with erythema. Laboratory testing is of limited use in most patients. Point-of-care ultrasound is useful for distinguishing cellulitis from abscess if the diagnosis is unclear. Management of SSTI includes antibiotics such as penicillin VK, dicloxacillin, or a cephalosporin, while treatment for skin abscess includes incision and drainage, with antibiotics recommended in select patients. Patients should elevate the affected extremity when possible, and non-steroidal anti-inflammatory drugs may reduce pain and inflammation. The effectiveness of decolonization for patients with recurrent cellulitis or skin abscess is controversial. While most patients with cellulitis or skin abscess are appropriate for discharge with follow-up, patients with sepsis and those with challenges adhering to therapy, immunosuppression, or failed outpatient therapy should be referred to the emergency department. Novel antibiotics such as tedizolid, delafloxacin, omadacycline, and ceftaroline may be considered in select cases.

Hyperglycemia in prediabetes is accompanied by increased amino acid (AA) concentrations and impaired suppression of glucagon secretion by glucose. It is unknown whether an abnormal response to AA contributes or hepatic steatosis exacerbates α-cell dysfunction. Therefore, lean participants and participants with obesity (with and without hepatic steatosis) were studied on two occasions in random order using a graded glucose infusion. Saline or an AA mixture was infused. The glucagon secretion rate (GSR) was derived from peripheral glucagon concentrations, and the change in glucose required to reduce GSR by 50% (G50) was calculated for each participant. AAs were measured during the experiment. On both occasions, experimental conditions produced a progressive rise in insulin secretion and an inverse exponential suppression of glucagon. G50 did not differ between groups in response to glucose alone. AA infusion did not change G50 in lean participants. G50 increased during AA infusion in participants with obesity with and without hepatic steatosis, leading us to report these participants as a single group. The relative change in AA concentrations across study days was generally similar between groups. We conclude that despite a normal response to glucose, obesity increases α-cell responses to AA in humans. Article Highlights The aim of this study was to understand the pathogenesis of α-cell dysfunction in prediabetes. The primary hypothesis was that α-cell responsivity to glucose (reduction of the glucagon secretion rate by 50%) is impaired by amino acid (AA) infusion. A secondary hypothesis was that this abnormal response is exacerbated by hepatic steatosis. AA infusion impaired α-cell suppression in response to rising glucose in participants with obesity, but not in lean participants, despite a normal response to glucose alone. This abnormal response was unaffected by the presence or absence of hepatic steatosis. It seems likely that an abnormal α-cell response to AAs precedes an abnormal response to glucose alone.

ABSTRACT Background Optimizing access to cost‐effective care in capacity‐constrained health systems is a contemporary imperative. We evaluated whether machine learning (ML) models using patient‐reported data could optimize access for patients requiring surgical care in rhinology clinics, without need for CT imaging. The outcome was defined as any rhinologic surgery within 90 days of initial evaluation. Methods A de‐identified electronic dataset from patients seen at five distinct sites within an integrated healthcare system between 2018 and 2025 was used to train models. Demographic data and 22‐item Sinonasal Outcome Test (SNOT‐22) responses were studied. Models were trained using stratified 5‐fold cross‐validation with an 80% development cohort and validated in a 20% held‐out validation cohort. Hyperparameters were optimized with Optuna. The primary outcome was performance of any rhinologic surgical intervention within 90 days of initial SNOT‐22. Results Data from 35,170 patients were evaluated. Item‐level responses outperformed use of total SNOT‐22 score in the models. Among models, XGBoost demonstrated best discrimination with AUC of 0.70 (95% CI, 0.69–0.71), outperforming logistic regression (0.66), random forest (0.63), and TabNet (0.66) (all p < 0.001). At optimal threshold, XGBoost achieved 66% sensitivity, 64% specificity, 28% PPV, and 90% NPV. Top predictors for surgery were age, nasal blockage, facial pain or pressure, and decreased sense of smell or taste. Validation on the held‐out cohort remained stable (AUC 0.70), with strong discrimination across sites despite surgical rates ranging from 11.5% to 27.4%. Conclusions Demographics and item‐level SNOT‐22 responses were successful in developing an ML model that demonstrated moderate discrimination and high NPV (90%) for performance of surgery within next 90 days. ML models balanced with human oversight may accelerate triage and optimize surgical yield for rhinology clinics.

Abstract Introduction Conversion of sleeve gastrectomy (SG) to Roux-en-Y gastric bypass (RYGB) is performed for gastroesophageal reflux disease (GERD), recurrent weight gain, and suboptimal clinical response. We compared early safety, weight loss, and healthcare utilization across indications. Methods We retrospectively analyzed adults undergoing SG-to-RYGB conversion in the 2023 MBSAQIP Participant Use File linked to the Long-Term Follow-Up file. Patients were grouped by indication as GERD, recurrent weight gain, suboptimal clinical response, or other. Baseline, operative, 30-day, and 6-month outcomes were compared using unadjusted analyses. Results Among 12,350 patients, indications were GERD in 59.2%, recurrent weight gain in 24.7%, suboptimal clinical response in 10.5%, and other in 5.6%. Patients with weight-related indications had higher baseline BMI. Major 30-day complications were uncommon and did not differ significantly across groups. Among 8,797 patients with 6-month weight data, mean percent total weight loss (%TWL) was 14.2% for recurrent weight gain, 13.3% for suboptimal clinical response, and 12.7% for both GERD and other indications (P < 0.001). The maximum absolute difference was 1.5 percentage points. Six-month intervention rates were 6.4% for GERD and 6.8% for other indications, compared with 4.2% for recurrent weight gain and 2.8% for suboptimal clinical response (P < 0.001); mortality remained uncommon. Conclusion SG-to-RYGB conversion was associated with low short-term complication rates across indications. Six-month weight loss and healthcare utilization differed in unadjusted comparisons, but weight-loss differences were modest and may reflect baseline case-mix differences.

Background/Objectives: Hospital-at-home (HaH) programs have emerged as an alternative model to brick-and-mortar (BaM) hospital management of acute conditions such as heart failure, pneumonia, pyelonephritis, and chronic obstructive pulmonary disease exacerbation among the others. However, the clinical management of acute pancreatitis in the HaH setting has never been described in the literature. The primary objective of this study was to describe the demographic and clinical characteristics of patients with acute pancreatitis managed in a Mayo Clinic Advanced Care at home (ACH) program. The secondary objective was to describe feasibility and short-term clinical outcomes. Methods: This multistate, multicenter, retrospective descriptive study included 40 unique patients with acute pancreatitis managed at ACH between 13 October 2020 and 1 June 2024. Repeat admissions were excluded from the primary analysis. Results: The most common etiologies were idiopathic (42.5%), gallstone-related (22.5%), and alcohol-related (12.5%). Peripancreatic fluid collections occurred in 17.5%, necrotizing pancreatitis in 10.0%, pleural effusion in 12.5%, and infected pancreatitis in 7.5%. Intravenous antiemetics were administered to 22.5%, intravenous fluids to 62.5%, and intravenous opioids to 7.5%. Median total hospital length of stay was 5.0 days (IQR, 3.0–8.25), including a median of 3.0 days (IQR, 2.0–4.0) in ACH. Four patients (10.0%; exact 95% CI, 2.8–23.7%) were transferred from ACH to BaM care. Seven-day and 30-day readmission rates were 10% (95% CI: 2.8%, 23.7%) and 5% (95%CI: 0.6%, 16.9%), respectively. The 30-day emergency department visit was 0%. Although 30-day mortality was 2.5% (95% CI: 0.0%, 13.2%), in-program mortality was 0%. Conclusions: Among a highly selected group of clinically stable patients meeting the program’s eligibility criteria, management of acute pancreatitis in ACH was feasible and was associated with low observed rates of unplanned escalations and short-term adverse outcomes.

ABSTRACT The cohesin complex, composed of SMC1, SMC3, RAD21, and STAG1/STAG2, is essential for chromosome cohesion, DNA repair, and transcriptional regulation. Pathogenic variants in cohesin components cause cohesinopathies. The classical characteristics of cohesinopathies include developmental delay (DD), intellectual disability (ID), feeding difficulties, hypotonia, short stature, hearing loss, and dysmorphic features. Here, we present a 5‐year‐old boy with classical cohesinopathy features, including DD/ID and feeding difficulties, along with non‐classical features such as hypoglycemia, recurrent fever, and immunodeficiency. Trio exome sequencing identified a novel de novo missense variant of uncertain significance (NM_005862.3:c.643G>A(p.Val215Ile)) in the STAG1 gene. The variant localizes to the RAD21 interaction interface, and molecular dynamics (MD) simulations revealed conformational changes comparable to other STAG1 variants reported as likely pathogenic in patients, supporting a deleterious effect which may disrupt the STAG1‐RAD21 interaction interface. This case expands the phenotypic and molecular spectrum of STAG1‐related cohesinopathy and advances our understanding of the disease mechanism.

Background Studies suggest that hypoperfusion from heart failure (HF) may contribute to cognitive decline. However, the relationship between the HF subtypes and cognition remains poorly described in real‐world populations. Methods We conducted a cross‐sectional study of patients aged ≥18 years seen at the Mayo Clinic in 2022 who underwent echocardiogram and cognitive assessment within 1 year. HF was classified per the 2022 American Heart Association as no HF, HF with preserved ejection fraction (EF), HF with mildly reduced EF, and HF with reduced EF. Cognitive impairment was categorized using the Montreal Cognitive Assessment score as normal (≥26), mild (18–25), and moderate to severe (<18). Linear regression assessed EF–Montreal Cognitive Assessment correlation and logistic regression the association between HF subtypes and cognitive dysfunction, adjusting for age, sex, race, and vascular risk factors. Results A total of 1592 patients met inclusion criteria (mean age, 75.7±13.8 years; 48.5% women). Lower EF was associated with worse cognitive performance (postadjustment β=0.033, P =0.013). Patients with HF with reduced EF and patients with HF with preserved EF had significantly lower Montreal Cognitive Assessment scores than those without HF (17.6±6.2 and 18.9±5.8 versus 19.9±6.0, P <0.001). The prevalence of moderate to severe cognitive impairment was highest in HF with reduced EF (43.3%), followed by HF with preserved EF (34.4%), no heart failure (28.6%), and HF with mildly reduced EF (23.4%) (adjusted trend P =0.032). Conclusions HF, independent of ejection fraction alone, is associated with cognitive impairment. Further studies should confirm these findings and evaluate the impact of interventions targeting EF and HF subtypes on cognitive outcomes.