Citations

Abstract INTRODUCTION Plasma biomarkers’ utility for predicting incident mild cognitive impairment (MCI) remains unclear. We evaluated associations of plasma Alzheimer's disease (AD) biomarkers and amyloid positron emission tomography (PET) with transitions from cognitively unimpaired (CU) to MCI in the Mayo Clinic Study of Aging (MCSA) and BioFINDER‐2 studies. METHODS Associations of continuous baseline plasma biomarker levels and amyloid PET Centiloid with progression to MCI, adjusting for age, sex, and education, were evaluated with Cox proportional hazards models. RESULTS The study included 381 MCSA and 584 BioFINDER‐2 participants. Amyloid PET and percent phosphorylated to non‐phosphorylated tau217 (%p‐tau217) were strong predictors of progression to MCI in both cohorts: hazard ratios of 1.49 and 1.23 in the MCSA and 1.72 and 1.65 in BioFINDER, respectively. Amyloid beta 42/40 was a significant predictor in BioFINDER‐2 only (hazard ratio 2.20). DISCUSSION Plasma %p‐tau217 was associated with progression from CU to MCI in both cohorts, although differences in biomarker associations may be related to differences in the two cohorts. Highlights Mass‐spectrometry‐based plasma phosphorylated tau217 was associated with cognitively unimpaired to mild cognitive impairment (MCI) progression. Plasma amyloid beta 42/40 was a significant predictor in BioFINDER but not the Mayo Clinic Study of Aging (MCSA). Amyloid positron emission tomography (PET) was the strongest predictor of progression to MCI in the MCSA. Plasma had added value to amyloid PET in BioFINDER but not the MCSA. Biomarker performance may vary with cohort and biomarker measurement differences.

Abstract Objective The aim of this study was to evaluate a large cohort of gallbladder amyloid cases to determine clinical and morphologic features. Methods Cholecystectomy specimens (N = 118) typed using proteomics-based techniques between 2008 and 2023 were identified. Clinical and morphologic features were reviewed. Results Six amyloid types were identified: ATTR (n = 63, 53.4%), AL (n = 46, 39.0%), AA (n = 4, 3.4%), AApoA1 (n = 2, 1.7%), ALECT2 (n = 2, 1.7%), and AEFEMP1 (n = 1, 0.8%). Amyloidogenic mutations were detected in 3 ATTR cases and 2 AApoA1 cases. Morphologic review (n = 26) revealed perimuscular vessel involvement in all cases. Amyloidosis was an unexpected diagnosis first made on the cholecystectomy specimen in half of the patients with clinical information (n = 10). All 9 patients with follow-up had evidence of systemic disease. In 2 patients, cholecystic involvement was initially missed and only retrospectively identified after the diagnosis of cardiac amyloidosis. Conclusions In patients with clinical data, amyloidosis was often unexpected, the gallbladder was commonly the first tissue sampled with amyloidosis, and all patients had systemic disease. Thorough review of cholecystectomy specimens with careful inspection of perimuscular vessels, coupled with a low threshold for ordering Congo red stain in elderly individuals and amyloid typing using a robust method such as proteomics, can prevent a delay in amyloid diagnosis and management.

Abstract Erdheim-Chester disease (ECD) is a rare systemic histiocytic neoplasm, with cardiac morbidities, including cardiovascular (CV) risk factors and cardiac conditions, playing a significant yet poorly understood role in the disease burden. This study evaluated the prevalence, characteristics, and prognosis of ECD in patients with (ECD-C) and without cardiac involvement (ECD-noC) and compared the burden of cardiac morbidities with matched controls. Patients diagnosed with ECD between 1990 and 2021 at a tertiary center were included, with cardiac involvement centrally assessed using radiographic studies. Cardiac morbidities were compared with a control group without ECD, matched for age, sex, body mass index, and smoking history. Among 104 patients with ECD, 39 (37%) had cardiac involvement. Patients with ECD-C had higher rates of hypertension (67% vs 46%), hyperlipidemia (67% vs 40%), heart failure (36% vs 8%), and pericardial effusion (28% vs 2%) than those with ECD-noC. Compared with the matched non-ECD cohort, patients with ECD had higher prevalence of coronary artery disease (20% vs 7%), heart failure (18% vs 4%), and antihypertensive drug use (55% vs 40%). Notably, patients with ECD-C had inferior progression-free survival (PFS) from frontline therapy compared with patients with ECD-noC (5-year PFS, 28.3% vs 70.5%). These findings highlight the burden of CV risk factors and cardiac conditions in ECD, even without a clinical diagnosis of ECD-C. Importantly, this cardiac morbidity burden is substantial for patients with ECD-C compared with ECD-noC. Our findings highlight the need for comprehensive cardiac risk assessment and management strategies to improve patient outcomes.

ABSTRACT Background Idiopathic subglottic stenosis (iSGS) occasionally affects women of childbearing age. Surgical intervention is the primary treatment, yet limited research exists on factors influencing disease severity. This study explores the impact of hormonal contraception on iSGS recurrence rates and surgery‐free intervals. Methods This retrospective study was conducted at a tertiary academic care center. Patients using hormonal birth control (e.g., estrogen‐progesterone pills, progesterone implants) during their first procedure were classified in “Birth Control (BC)” group, while those not using contraceptives were placed in “No Birth Control (NBC)” group. Poisson regression evaluated recurrence rates, and Mann–Whitney tests assessed surgery‐free intervals. Kaplan–Meier analysis estimated time to first recurrence, adjusting for age and follow‐up duration. Results Twenty‐six patients were in the NBC group and 12 in the BC group (average ages 37 and 34, respectively). Patients in the NBC group were 2.6 times more likely to experience recurrence compared to those in the BC group ( p = 0.001). The expected number of recurrences for the BC group was 0.4 times that of the NBC group (95% CI: 0.2–0.7; p = 0.001). Furthermore, patients taking birth control were significantly less likely to have a first recurrence (HR: 0.4; 95% CI: 0.2–0.9; p = 0.025) and had longer times to first recurrence (Figure 1; p = 0.031). Conclusions Birth control appears to protect against iSGS severity, potentially through hormonal mechanisms. Hormonal contraception may serve as a non‐surgical alternative for managing iSGS. Future prospective studies may evaluate outcomes in newly diagnosed iSGS patients started on birth control compared to those not using hormonal contraceptives. Level of Evidence 3.

Abstract Oral commensals such as Parvimonas micra are increasingly implicated in sporadic colorectal cancer (CRC). Several findings support an emerging notion that alterations in host DNA methylation constitute a mechanism by which P. micra adapts to the host microenvironment and contributes to pathogenic processes. However, multiple limitations hinder definitive conclusions, including the correlative nature of the human studies and the absence of human microbiota in mouse models. Here, we investigated how a complex human microbiome influences the adaptation and oncogenic potential of P. micra in a spontaneous mouse model of polyposis. Adult mice, following antibiotic conditioning, received fecal microbiota transplants (FMT) from a healthy human donor, with or without supplementation of P. micra. P. micra caused significant reshaping of the gut microbial community and altered co-occurrence network structures, which however largely recovered within 21 days post FMT. Despite the transient nature of these changes, P. micra caused a marked increase in both the number and invasive potential of intestinal polyps. Epigenomic profiling of polyp crypts revealed global DNA hypomethylation alongside gene-specific hypermethylation, accompanied by transcriptional changes in key oncogenic pathways. Affected pathways included Wnt signaling, epithelial-to-mesenchymal transition, circadian rhythm regulation, and host–microbe interactions. These findings demonstrate that P. micra exerts a profound influence on microbial ecology, host epigenetic programming, and tumorigenesis in a genetically predisposed host, highlighting its role as a microbial driver of intestinal carcinogenesis.

ABSTRACT Background Prompt detection and intervention are crucial for improving outcomes in acute invasive fungal rhinosinusitis (AIFS). Diagnostic prediction models assist in risk‐stratification, but their accuracy requires testing through external validation. This study aims to validate a previously published diagnostic prediction model for AIFS in an independent cohort. Methods A retrospective chart review was conducted at a tertiary care center (2008–2023) to identify patients with an otolaryngology consult for suspected AIFS. Of 65 patients identified, 11 (16.9%) were diagnosed with AIFS based on histopathology. Risk was calculated using Yin et al.’s predictive model. Predictive performance was assessed by calibration and discrimination. Results Patients had significantly higher rates of diabetes (46.2% vs. 26.1%, p = 0.002), long‐term steroid use (60% vs. 28.2%, p < 0.0001), and solid organ transplantation (38.5% vs. 8.5%, p < 0.001), compared with the development cohort, with conversely lower rates of hematologic malignancy (29.2% vs. 58.7, p < 0.001) and neutropenia (19.4% vs. 41%, p = 0.001). Despite these differences, both the three‐variable (C‐index: 0.844; 95% CI, 0.736–0.952) and four‐variable models (C‐index: 0.963; 95% CI, 0.919–1) showed adequate discrimination. Both models exhibited slight overprediction of risk, with a calibration‐in‐the‐large predicted risk of 24.1% (95% CI, 13.68–34.46) for the three‐variable model and 24.2% (95% CI, 13.76–34.57) for the four‐variable model. Calibration plots confirmed overprediction. Conclusion The AIFS diagnostic model demonstrates acceptable discrimination and calibration on external validation, with generalizability to patients with different comorbidities. Larger studies are recommended to further test the model's predictive performance and clinical applicability.