Citations

Odontogenic myxoma (OM) is an uncommon, locally aggressive odontogenic neoplasm with characteristic histologic and clinico-radiographic features but with potential for histologic overlap with other odontogenic and non-odontogenic entities and a non-specific immunoprofile. Widespread loss of heterozygosity (LOH) has been recently described in rare cases of OM. The aim of this study was to determine whether widespread LOH represents a recurrent molecular signature that can be leveraged for clinical decision-making. Allele-specific copy number variation data from chromosomal microarray were generated from 7 OM, comprising a combined prospective and retrospective cohort. Four tumors arose in the mandible and 3 in the maxilla in patients ranging in age from 18 to 94 years (median: 44), with tumor size ranging from 2.2 to 13.0 cm. Variable amounts of fibrous stroma (odontogenic “fibromyxoma”) were present in 4/7 OM, and hypercellularity not typically appreciated in conventional OM was present in 3/7 cases. All OM (7/7) demonstrated widespread LOH, with 5 cases showing a near-haploid/low hypodiploid genomes (multiple monosomies) and 2 cases showing evidence of pseudo-hyperdiploidy due to probable endoreduplication. Both pseudo-hyperdiploid cases were ≥10 cm in size; 1 represented local recurrence. Chromosomes 1 to 3, 6, 9, 11, 13, 15, and 22 demonstrated LOH in ≥75% of cases (chromosomes 1 to 3, 6, and 9 in 100% of cases), while chromosomes 5, 12, 19, and 20 universally retained heterozygosity. Altogether, widespread LOH is a recurrent event in OM and a novel finding in odontogenic pathology, and allele-specific copy number variation analysis can serve as a diagnostic adjunct in challenging cases.

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 Staphylococcus aureus causes a multiplicity of human diseases acquired in community and healthcare settings alike around the globe. While most studies focus on coding changes to assess genome evolution and study genetic adaptation, interrogation of silent mutations in the form of synonymous codon usage bias is less well-studied. As such, understanding of patterns in codon bias at the gene and genome levels, and how codon bias impacts protein expression in S. aureus remains incomplete. Methods The codon bias of 2,565 protein encoding genes from NCTC 8325 was queried against all publicly available closed S. aureus genomes. Using public BioSample data, genomes were sorted by disease state, submitting institution, and collection site. Codon bias was assessed at the level of gene and genome using the codon adaptation index (CAI), calculated using 30S and 50S ribosomal genes. Gene set enrichment analysis was applied to determine associations between physiological functions, CAI gene scores, and interquartile ranges. CAI scores were also compared to an in vitro S. aureus proteomics database to correlate codon bias and protein expression. Results CAI scores varied within and between isolates at the gene and genome levels. Genes with ribosome-associated functions were most enriched among high CAI genes, and had low CAI interquartile ranges (IQR), suggesting selective pressure to maintain high expression of these genes across all S. aureus isolates. Genome sequences submitted by Aga Khan University Hospital, Nairobi, Kenya were most different from others. For the LAC USA 300 strain, CAI and protein expression were moderately positively correlated (cor = 0.534, p < 2.2e-16). Conclusions Codon bias in S. aureus was shown to vary between gene, and to be a source of genetic variation between isolates; CAI and in vitro protein expression were positively correlated.

Assessing balance is crucial in neurological rehabilitation, yet while wearable sensors enable real-world monitoring, identifying reliable digital biomarkers remains challenging. This study utilized a high-fidelity instrumented walkway to determine which gait parameters best predict balance impairment, providing robust targets for future wearable applications. We analyzed 49 steady-state gait metrics from 140 individuals with diverse neurological conditions. Using statistical analysis and machine learning, we evaluated these parameters against objective force plate sway scores and clinical fall-history labels. Group analysis identified 16 parameters significantly distinguishing fallers from non-fallers, and a neural network classified fallers with an area under the curve of 0.75. Across all analytical approaches, overall gait variability, e.g., Stride Width S.D. and the Gait Variability Index, emerged as a universal predictor of balance impairment and fall risk. Furthermore, while traditional linear models emphasized spatial postural control, machine learning classification uniquely identified inter-limb asymmetry as a premier driver of fall prediction. These findings indicate that instrumented gait analysis effectively identifies digital biomarkers for balance deficits. Isolating these specific metrics provides a clear blueprint for meaningful metrics required for continuous objective monitoring and future development of personalized, adaptive rehabilitation strategies.

Background: Pulse pressure variation (PPV) is widely used to guide fluid responsiveness in mechanically ventilated patients, but its accuracy in the prone position remains uncertain. Prone positioning alters respiratory mechanics and venous return, potentially diminishing the respiratory variation in stroke volume that PPV is designed to detect. We conducted a systematic review and meta-analysis to evaluate the diagnostic accuracy of PPV for predicting fluid responsiveness during prone spine surgery. Methods: We searched MEDLINE, Embase, Scopus, and Cochrane through July 2025 for prospective studies evaluating PPV in adults undergoing prone spine surgery. Two reviewers independently screened studies, extracted data, assessed risk of bias using QUADAS-2, and pooled diagnostic performance using a bivariate random-effects model. The protocol was registered with PROSPERO (CRD420251106134). Results: Of 599 records, 34 underwent full-text review, and 10 studies (433 patients) were included. PPV thresholds ranged from 7% to 15%. Most studies were at low risk of bias except for the index test because thresholds were determined post hoc. For predicting fluid responsiveness, PPV had a pooled sensitivity of 68% (95% CI: 61%-75%) and specificity of 76% (95% CI: 65%-84%), with a summary area under the receiver operating characteristic curve of 0.72 (95% CI: 0.64-0.80). Conclusions: PPV showed only moderate diagnostic performance for predicting fluid responsiveness during prone spine surgery. Its performance may have been influenced by threshold variability, heterogeneous reference standards, fluid-challenge protocols, ventilation strategies, and positioning systems. PPV should therefore be interpreted alongside complementary dynamic assessments rather than in isolation, particularly during lung-protective ventilation.

Background Transcatheter edge‐to‐edge repair (TEER) and replacement (TTVR) have emerged as new modalities to treat patients with symptomatic significant tricuspid regurgitation. This study aimed to compare invasive hemodynamic and right ventricular (RV) changes and symptom improvement over 1 year. Methods Patients who underwent TEER/TTVR at Mayo Clinic (Rochester, MN, 2017–2024) were included. Hemodynamic profiles were described before and immediately after intervention, in addition to RV enlargement/dysfunction ≥moderate at 30 days and change in symptoms over time. Results Of 100 patients included (50 per group, median age 81 versus 80 years and female 62% versus 42%, in TTVR and TEER, respectively), all had ≥ moderate–severe symptomatic tricuspid regurgitation. Post intervention, mean right atrial pressure decreased in TEER (16 to 14 mm Hg, P <0.001), V wave decreased in both groups (to 16 mm Hg, P <0.001). RV enlargement was less prevalent in both cohorts at 30 days (60%–40% in TEER, P =0.01, and 72 to 58% in TTVR, P =0.07), yet prevalence of RV dysfunction decreased only in TEER (26 to 15%, P =0.17) as opposed to TTVR (31 to 44%, P =0.13). TTVR resulted in a higher stroke volume index and more complete tricuspid regurgitation elimination at 30 days. Both groups resulted in similar improvements in New York Heart Association class, with overall similar survival. Conclusions TEER was associated with a greater reduction in right atrial pressure and more favorable RV remodeling at 30 days, as opposed to TTVR, which achieved more complete and sustained elimination of tricuspid regurgitation with higher forward stroke volume.

Abstract T-cell immune tolerance is established in part through the activity of the autoimmune regulator (AIRE) transcription factor in medullary thymic epithelial cells (mTEC) of the thymus. AIRE induces expression of peripheral tissue–specific self-antigens for presentation to naïve T cells to promote activation/deletion of autoreactive T cells. This traditional role of AIRE in mTECs is to prevent autoimmunity. Herein, we demonstrate that tumors mimic the role of AIRE in mTECs to evade immune rejection. We found that AIRE induced a profile of “selfness” at the RNA and protein levels which, when presented on major histocompatibility complexes (MHC), shielded the tumor from inherently self-tolerized T cells. Moreover, we describe an in vivo immunotherapy in which engineered changes in AIRE expression in tumor cells altered their profile of selfness, exposing both AIRE-modified and parental unmodified tumor cells to T-cell attack. Therefore, by resetting the immunologic selfness of cancer cells, this AIRE-mediated immunotherapy (i) converted a highly tolerized T-cell compartment into a tumor-reactive T-cell population; (ii) conferred upon nonimmunogenic tumors de novo sensitivity to immune checkpoint blockade; (iii) removed the need to identify potentially immunogenic tumor-associated antigens as targets for generation of T-cell responses; and (iv) lead to potent T cell–mediated rejection of aggressive, immunologically cold, nonimmunogenic tumors. Patient RNA sequencing data showed that the expression of AIRE predicted response to immune therapies with a strong correlation between AIRE expression and markers of T-cell receptor signaling, suggesting that our studies have therapeutic translational value.

OBJECTIVE Multisegmental pathological autofusion is a hallmark feature of ankylosing spondylitis (AS) and diffuse idiopathic skeletal hyperostosis (DISH), creating a rigid, brittle spine highly susceptible to three-column fractures and devastating neurological injury. This study aimed to evaluate survival outcomes in this patient population and identify clinical and demographic predictors of mortality. METHODS Adults with DISH or AS who sustained a fracture and were admitted to a single tertiary care center for spinal fracture were retrospectively identified using ICD-10 diagnostic codes. Data were extracted on demographics, clinical presentation, fracture characteristics, and details of treatment. RESULTS A total of 383 patients (median age 78 years, 75.2% male) were included. Over a median follow-up of 17.3 months, overall mortality was 38.1%, in-hospital mortality was 5.2%, 30-day mortality was 5.7%, and 1-year mortality was 18.0%. Initial treatment consisted of external orthosis in 220 (57.4%) and surgery in 144 (37.6%), while 19 (5.0%) were left untreated. Patients who died were older (median 83 vs 74 years, p < 0.001), had a lower BMI (29.4 vs 32.3 kg/m 2 , p < 0.001), had higher frailty on the 5-item modified frailty index (mFI-5), and more commonly had congestive heart failure (CHF), cancer, functional dependency, and chronic kidney disease (CKD) (all p < 0.01). Mortality was not associated with fracture location, mechanism of injury, fracture number, or the presence of neurological deficits. Univariable time-to-event analysis showed that decreased survival was predicted by older age (HR 1.08, p < 0.0001), lower BMI (HR per kg/m 2 0.93, p < 0.0001), functional dependency (HR 2.05, p < 0.001), cancer (HR 1.55 p = 0.01), CKD (HR 1.48, p = 0.019), CHF (HR 2.18, p < 0.001), and higher mFI-5 score (HR per point 1.34, p < 0.001). On multivariable analysis, older age (HR 1.06 per year, p < 0.001), lower BMI (HR per kg/m 2 0.95, p < 0.001), and mFI-5 score (HR per patient 1.37, p < 0.001) remained significant independent predictors of mortality. Treatment modality did not predict mortality. CONCLUSIONS AS- or DISH-associated spinal fractures have a high associated mortality, regardless of mechanism or severity. Treatment modality did not affect odds of survival, suggesting that nonoperative management with an external orthosis may be an appropriate option, particularly in older and medically complex patients.

ABSTRACT Introduction Operating room (OR) noise during holmium laser enucleation of the prostate (HoLEP), particularly from laser activation, may impair surgical workflow and staff performance. Methods 84 HoLEP procedures were recorded at three academic institutions between June 2024 and January 2026. Laser platforms included Lumenis Moses 2.0, Quanta Litho 150, Quanta Magneto, and Dornier Thulio. Sound measurements were obtained using a standardized smartphone‐based system during three phases: laser‐off (baseline), idle (not firing), and active lasing. Acoustic metrics included average sound level (LAeq), peak sound level (Lcpeak), and sound levels exceeded for 10%, 50%, and 90% of the recording time (L10, L50, and L90). Background noise correction was performed using baseline measurements to account for ambient noise and isolate laser‐related sound. OR staff completed a validated survey assessing perceived noise burden (0–10 scale). Results Background‐corrected noise during active lasing differed significantly by platform. Litho demonstrated lower mean noise levels compared to Thulio for LAeq (60.6 vs. 68.2 dB, p = 0.023) and L10 (61.5 vs. 70.6 dB, p = 0.023), while Moses had higher LAeq compared to Litho (63.1 vs. 60.6 dB, p = 0.043). Overall, Litho had the lowest noise levels, whereas Thulio had the highest. Survey responses paralleled these findings. Litho was associated with lower perceived overall effort (2.1 ± 0.9), while Moses demonstrated higher overall effort (3.6 ± 1.2) for communication and concentration (Figure 2). Significant pairwise differences were observed between Moses and Litho (all p < 0.05). Trends were consistent across sites. Conclusions Noise levels during HoLEP varied by laser technology and correlated with differences in perceived communication and cognitive effort. Litho demonstrated the lowest acoustic burden, while Moses and Thulio had higher noise exposure. These findings highlight the impact of laser selection on the OR environment and intraoperative team performance.