Citations

AbstractINTRODUCTIONStudies suggest distinct differences in the development, presentation, progression, and response to treatment of Alzheimer's disease (AD) between females and males. We investigated sex differences in cognition, neuroimaging, and fluid biomarkers in dominantly inherited AD (DIAD).METHODSThree hundred twenty‐five mutation carriers (55% female) and one hundred eighty‐six non‐carriers (58% female) of the Dominantly Inherited Alzheimer Network Observational Study were analyzed. Linear mixed models and Spearman's correlation explored cross‐sectional sex differences in cognition, cerebrospinal fluid (CSF) biomarkers, Pittsburgh compound B positron emission tomography (11C‐PiB PET) and structural magnetic resonance imaging (MRI).RESULTSFemale carriers performed better than males on delayed recall and processing speed despite similar hippocampal volumes. As the disease progressed, symptomatic females revealed higher increases in MRI markers of neurodegeneration and memory impairment. PiB PET and established CSF AD markers revealed no sex differences.DISCUSSIONOur findings suggest an initial cognitive reserve in female carriers followed by a pronounced increase in neurodegeneration coupled with worse performance on delayed recall at later stages of DIAD.

AbstractBackgroundSomali immigrants and refugees constitute one of the largest African ethnic groups immigrating to the United States over the past three decades with the majority resettling in the state of Minnesota. Previous studies have documented significant cancer screening disparities between the Somali population and the general population. However, little is known about cancer incidence among Somali groups living in the United States.MethodsWe determined the incidence of 18 types or sites of malignancy using ICD‐9 and ICD‐10 codes and compared them between Somali and non‐Somali populations in Olmsted County, Minnesota utilizing the Rochester Epidemiology Project medical records‐linkage infrastructure for the years 2000–2020. Poisson regression models were used to model the rates for each malignancy.ResultsThere was a higher incidence and relative risk of liver malignancies among the Somali population versus non‐Somali population, but lower relative risk and incidence of the following malignancies: breast, cervical, and melanoma. After direct age‐sex adjustment to the United States 2000 Census population, liver was the most common cancer in Somali men, while breast cancer was the most common malignancy in women.ConclusionMalignancies related to infectious agents such as viral hepatitis have a higher incidence in the Somali immigrant population of Olmsted County. There is a lower incidence of malignancies related to lifestyle factors in this Somali population. Findings of this study may help inform cancer prevention and screening strategies among Somali communities in the United States.

Abstract Sex and gender influence every aspect of human health; thus, sex- and gender-related topics should be incorporated in all aspects of health education curricula. Sex and gender health education (SGHE) is the rigorous, intersectional, data-driven integration of sex and gender into all elements of health education. A multisectoral group of thought leaders has collaborated to advance SGHE since 2012. This cross-sector collaboration to advance SGHE has been successful on several fronts, primarily developing robust interprofessional SGHE programs, hosting a series of international SGHE summits, developing sex- and gender-specific resources, and broadening the collaboration beyond medical education. However, other deeply entrenched challenges have proven more difficult to address, including accurate and consistent sex and gender reporting in research publications, broadening institutional support for SGHE, and the development and implementation of evaluation plans for assessing learner outcomes and the downstream effects of SGHE on patient care. This commentary reflects on progress made in SGHE over the first decade of the current collaboration (2012–2022), articulates a vision for next steps to advance SGHE, and proposes 4 benchmarks to guide the next decade of SGHE: (1) integrate sex, gender, and intersectionality across health curricula; (2) develop sex- and gender-specific resources for health professionals; (3) improve sex and gender reporting in research publications; and (4) develop evaluation plans to assess learner and patient outcomes.

Abstract Autoimmune gastritis is a relatively common but likely underdiagnosed form of chronic gastritis that is associated with iron-deficiency anemia as well as vitamin B12/cobalamin deficiency. This disease confers a 13-fold increased risk of gastric well-differentiated neuroendocrine tumors, due to persistently elevated gastrin levels, and a 3- to 7-fold increased risk of gastric adenocarcinoma. The case described here has a typical presentation of the disease, and the following review highlights key histologic features that aid in the identification of this inflammatory process. Additionally, background information on ancillary testing and mechanisms of disease are discussed with a focus on details most useful for the pathologist who is presented with the opportunity to make this often unexpected but medically significant diagnosis.

Abstract Eosinophilic esophagitis is an immune-mediated chronic disease of the esophagus. It is clinically characterized by symptoms related to esophageal dysfunction and histologically by eosinophil-rich inflammation with a peak intraepithelial eosinophil count of at least 15 eosinophils per high-power field. Both children and adults can be affected with a strong male predominance. Food appears to be the key trigger, although the exact mechanisms remain unclear. Treatment for eosinophilic esophagitis can be summarized as the 3 D's: dietary, drugs, and dilatation. The differential diagnosis includes gastroesophageal reflux disease, eosinophilic gastroenteritis, drug hypersensitivity, hypereosinophilic syndrome, infection, Crohn disease, connective tissue diseases, and vasculitis.

Objectives: Gain insights into the pathophysiology of idiopathic subglottic stenosis (iSGS) by investigating differences in transcriptome of subglottic mucosal tissue between patients with iSGS and controls, and between tracheal and subglottic tissue within patients. Methods: RNA sequencing was conducted on biopsied mucosal samples collected from subglottic and tracheal (in-patient control) regions in iSGS patients, and from subglottis in controls. The gene expression differences were validated on a protein level by (1) staining the tissue samples obtained from a second cohort of patients and controls; and (2) in vitro functional assays using primary subglottic epithelial cells from both iSGS patients and healthy donors. Results: We found 7 upregulated genes in the subglottic region of iSGS patients relative to both the tracheal mucosa and subglottic region of controls. A gene ontology enrichment analysis found that the epithelial cell differentiation and cornification pathways are significant, involving specifically 3 of the genes: involucrin ( IVL), small proline rich protein 1B ( SPRR1B), and keratin 16 ( KRT16). Involvement of these pathways suggests squamous metaplasia of the epithelium. Histological analyses of epithelium in subglottic mucosal biopsies revealed squamous metaplasia in 41% of the samples from iSGS patients and in 25% from controls. Immunohistochemical evaluation of the samples presented with squamous epithelium revealed increased expression of the protein encoded by SPRR1B, hyperproliferative basal cells, shedding of apical layers, and accompanying lesions in iSGS compared to CTRL. Cultured primary subglottic epithelial cells from iSGS patients had higher proliferation rates compared to healthy donors and squamous metaplastic differentiation formed thinner epithelia with increased expression proteins encoded by INV, SPRR1B, and KRT16, suggesting intrinsic dysfunction of basal cells in iSGS. Conclusions: Abnormal squamous differentiation of epithelial cells may contribute to the pathogenesis of iSGS. Patients having metaplastic epithelial phenotype may be sensitive to drugs that reverse it to a normal phenotype.

Abstract Erdheim-Chester disease (ECD) and Langerhans cell histiocytosis (LCH) are two rare diseases typically separated by clinical, radiologic, and histologic criteria. However, coexistence of both entities is rare, with fewer than 50 cases reported. Although there are reports of patients with LCH and ECD in the same organ, there have been no reported cases of the two diseases involving the lung. We report two cases of ECD-LCH “overlap syndrome” occurring in the lung. In both cases, the diagnoses were supported by typical immunohistochemical patterns, and in both cases, the BRAF V600E mutation was identified by next-generation sequencing and confirmed by droplet digital polymerase chain reaction. In neither case was either diagnosis suspected. The recognition of overlap histiocytoses is important. Although LCH and ECD may differ in treatment and prognosis, in some cases, such as the two patients reported here, they may have the same activating mutations and may be able to be treated with the same targeted therapy.

Introduction Hospitalizations, proton-pump inhibitors (PPI), and systemic antibiotics increase the risk of Clostridioides difficile infection (CDI) in cirrhosis. We compare the risk of CDI with hepatic encephalopathy (HE) medications, hypothesizing that rifaximin may decrease CDI risk. Materials and Methods A retrospective study of hospitalized HE patients treated with lactulose and/or rifaximin at Mayo Clinic Minnesota, Florida, and Arizona from 2008 to 2013 was conducted. Data on demographics, hospitalizations, antibiotics, and PPI use and CDI were gathered. Univariate and multivariable cox models were constructed. Results We found 1,112 hospitalizations in 1,055 unique patients (55 had 1 subsequent readmission, 1 patient had 2); 428 (40.6%) patients were women (median age: 58 years [interquartile range: 52–65]). CDI developed after 66/1,112 (5.9%) hospitalizations within 12 months post-discharge. Lactulose was administered in 21 (31.8%), rifaximin in 5 (7.6%), both in 40 (60.6%) hospitalizations. Systemic antibiotics were used in 28 (42.4%) patients and PPIs in 60 (90.9%) patients.Univariate analysis using medication (with lactulose alone as the reference group) showed rifaximin was not significantly associated with CDI compared with lactulose (hazard ratio [HR]: 1.57, 95% confidence interval [CI]: 0.57–4.33, p = 0.39). Use of both medications was not significant compared with lactulose (HR: 1.41, 95% CI: 0.84–2.38, p = 0.19). Results were similar after controlling for confounders. Multivariable analysis based on length of stay, age, and gender showed no differences between rifaximin versus lactulose and both versus lactulose. Conclusion There is no significant difference between lactulose and rifaximin on CDI development in HE patients. However, CDI should still be considered when managing diarrhea in HE patients.

Background Clostridioides difficile infection (CDI) is associated with frequent recurrences. The role of probiotics in preventing CDI remains unclear despite patients frequently using them. Methods We performed a systematic-review and meta-analysis to evaluate the role of Saccharomyces boulardii, a yeast probiotic, in preventing primary or recurrent CDI in patients on systemic antimicrobial therapy. We searched MEDLINE, Embase, and Web of Science up to December 2021 to identify studies (case-control, cohort, or clinical trial studies) reporting the use of systemic antimicrobials with or without S. boulardii and providing information on primary or recurrent CDI. Pooled odds ratios with 95% confidence intervals were calculated using a random effects model. Results Eight studies (six randomized control trials and two cohort studies) were included. Six studies with 9,712 patients evaluated primary prevention. The rate of CDI in patients who received S. boulardii was 0.73% (44/5977) compared to 1.09% (41/3735) in the control group. Meta-analysis showed no difference in the risk of CDI among the two groups (odds ratio [OR], 0.71; 95%CI, 0.46–1.10; p = 0.124) with no significant heterogeneity (I2 = 0%). In two studies with 292 patients evaluating secondary prevention, the rate of recurrent CDI was 36.73% (54/147) on S. boulardii compared to 46.20% (67/145) in controls, with no significant difference (p = 0.19). Subgroup analysis of studies using S. boulardii (250 mg twice daily) showed no difference in the CDI risk with or without S. boulardii. No serious adverse events from S. boulardii were noted. Conclusion The use of S. boulardii appears to have no benefit for preventing either primary or recurrent CDI in patients taking systemic antimicrobials.