Osteoarthritis (OA) is the most common joint disorder in the United States, and the gut microbiome has recently emerged as a potential etiologic factor in OA development. Recent studies have shown that a microbiome is present at joint synovia. Therefore, we aimed to characterize the intra-articular microbiome within osteoarthritic synovia and to illustrate its role in OA disease progression. RNA-sequencing data from OA patient synovial tissue was aligned to a library of microbial reference genomes to identify microbial reads indicative of microbial abundance. Microbial abundance data of OA and normal samples was compared to identify differentially abundant microbes. We computationally explored the correlation of differentially abundant microbes to immunological gene signatures, immune signaling pathways, and immune cell infiltration. We found that microbes correlated to OA are related to dysregulation of two main functional pathways: increased inflammation-induced extracellular matrix remodeling and decreased cell signaling pathways crucial for joint and immune function. We also confirmed that the differentially abundant and biologically relevant microbes we had identified were not contaminants. Collectively, our findings contribute to the understanding of the human microbiome, well-known OA risk factors, and the role microbes play in OA pathogenesis. In conclusion, we present previously undiscovered microbes implicated in the OA disease progression that may be useful for future treatment purposes.

Head and neck squamous cell carcinoma (HNSCC) tumor phenotypes and clinical outcomes are significantly influenced by etiological agents, such as HPV infection, smoking, and alcohol consumption. Accordingly, the intratumor microbiome has been increasingly implicated in cancer progression and metastasis. However, few studies characterize the intratumor microbial landscape of HNSCC with respect to these etiological agents. In this study, we aimed to investigate the bacterial and fungal landscape of HNSCC in association with HPV infection, smoking, and alcohol consumption. RNA-sequencing data were extracted from The Cancer Genome Atlas (TCGA) regarding 449 tissue samples and 44 normal samples. Pathoscope 2.0 was used to extract the microbial reads. Microbe abundance was compared to clinical variables, oncogenic signatures, and immune-associated pathways. Our results demonstrated that a similar number of dysregulated microbes was overabundant in smokers and nonsmokers, while heavy drinkers were characterized by an underabundance of dysregulated microbes. Conversely, the majority of dysregulated microbes were overabundant in HPV+ tumor samples when compared to HPV- tumor samples. Moreover, we observed that many dysregulated microbes were associated with oncogenic and metastatic pathways, suggesting their roles in influencing carcinogenesis. These microbes provide insights regarding potential mechanisms for tumor pathogenesis and progression with respect to the three etiological agents.

The implications of the microbiome on Coronavirus disease 2019 (COVID-19) prognosis has not been thoroughly studied. In this study we aimed to characterize the lung and blood microbiome and their implication on COVID-19 prognosis through analysis of peripheral blood mononuclear cell (PBMC) samples, lung biopsy samples, and bronchoalveolar lavage fluid (BALF) samples. In all three tissue types, we found panels of microbes differentially abundant between COVID-19 and normal samples correlated to immune dysregulation and upregulation of inflammatory pathways, including key cytokine pathways such as interleukin (IL)-2, 3, 5-10 and 23 signaling pathways and downregulation of anti-inflammatory pathways including IL-4 signaling. In the PBMC samples, six microbes were correlated with worse COVID-19 severity, and one microbe was correlated with improved COVID-19 severity. Collectively, our findings contribute to the understanding of the human microbiome and suggest interplay between our identified microbes and key inflammatory pathways which may be leveraged in the development of immune therapies for treating COVID-19 patients.

Introduction: Pseudobulbar affect (PBA) is a disorder of emotional expression associated with neurological diseases, including stroke and Alzheimer disease. Depression and anxiety frequently co-occur, but whether psychiatric outcomes differ by neurological etiology remains unclear. Objective: To compare the risk and timing of depressive episodes and anxiety disorders in stroke-associated versus Alzheimer disease-associated PBA. Methods: We conducted a retrospective cohort study using the TriNetX Global Health Research Network (2020 to 2025). Two mutually exclusive cohorts were identified: PBA with stroke and PBA with Alzheimer disease. Outcomes were depressive episode (ICD-10-CM F32) and anxiety disorder, unspecified (ICD-10-CM F41.9), occurring after PBA diagnosis. One-to-one propensity score matching was performed for age, sex, race, and ethnicity. Kaplan-Meier analyses and Cox proportional hazards models assessed risk and timing. Results: After matching, 1074 patients per cohort were included for depression analysis. Depression occurred in 68.7% of Alzheimer disease-PBA versus 34.7% of stroke-PBA (absolute risk difference 34.0%, P <0.001; HR=2.52, 95% CI: 2.22-2.86). For anxiety (n=946 per cohort), rates were 48.8% versus 24.9% (absolute risk difference 23.9%, P <0.001; HR=1.98, 95% CI: 1.70-2.30). Conclusion: Alzheimer disease-associated PBA confers a higher and earlier risk of depression and anxiety, supporting enhanced psychiatric screening in neurodegenerative disease.

Aims: Epstein-Barr virus (EBV) infection, or infectious mononucleosis, is usually a self-limited illness in young adults characterized by pharyngitis, fever, and lymphadenopathy. Atypical presentations may involve hepatic dysfunction, hematologic abnormalities, or rarely, splenic infarction. We report a case of EBV mononucleosis with multiple atypical features and a prolonged course. Presentation of Case: A 33-year-old immunocompetent patient developed intermittent fever lasting 45 days at presentation, cholestatic hepatitis, hyperferritinemia, cytomegalovirus (CMV) IgM positivity, transient elevated smooth muscle and actin autoantibodies, and initially negative EBV serologies following recent travel to Japan. He was ultimately diagnosed with EBV mononucleosis. He improved with supportive management. Two weeks after discharge, he returned with left upper quadrant pain and was found to have splenomegaly and a splenic infarction. He was managed supportively and had stable recovery after discharge. Discussion: This case illustrates several uncommon features of EBV infection, including cholestatic hepatitis, marked hyperferritinemia, transient autoimmune marker elevations, CMV IgM cross-reactivity, and delayed splenic infarction. The patient’s prolonged febrile course (>60 days) highlights the potential for EBV to mimic autoimmune, malignant, or hyperinflammatory syndromes. Conclusion: EBV infection may rarely present with prolonged systemic illness, hepatic dysfunction, and splenic complications. Clinicians should consider EBV in the differential diagnosis of prolonged fever and cholestatic hepatitis, even when initial serologies are inconclusive.