Citations

Background Odontogenic sinusitis (ODS) is a common cause of unilateral infectious maxillary sinusitis but is frequently underdiagnosed due to nonspecific symptoms, subtle dental findings on imaging, and limitations of traditional bacterial cultures—particularly for anaerobic organisms. Next-generation DNA sequencing (NGS) may enhance detection of odontogenic bacteria. Objective This study compared bacterial detection between standard cultures versus NGS in patients with confirmed ODS. Methods Twenty consecutive adults with confirmed ODS were enrolled. Maxillary sinus purulence was collected endoscopically and submitted for routine aerobic and anaerobic bacterial cultures and for NGS-based microbial profiling using 16S rRNA gene sequencing. Detected organisms were categorized by aerotolerance and ODS relationship, and likely nasal colonizers were excluded from analyses. Alpha diversity, beta diversity, and compositional differences between methods were analyzed statistically. Results NGS detected significantly more bacterial species per specimen than culture (mean 4.9 vs 2.7; P = .0015). Compared to cultures, NGS identified more anaerobic bacteria (4.2 vs 0.9; P = .00004) and more ODS-related species (4.4 vs 1.0; P = .0001), while detection of aerobic species was similar between methods. Cultures also often yielded nonspeciated results, whereas NGS consistently revealed polymicrobial communities dominated by oral anaerobes. Microbial composition differed significantly between detection methods. Conclusion In confirmed ODS, NGS detected significantly more anaerobic and ODS-related species than culture from the same specimens. These findings suggest that culture alone may underestimate odontogenic contributions to purulent sinusitis. Future studies should explore he utility of NGS as an adjunctive tool to facilitate diagnosis and treatment in the setting of possible ODS.

Importance TMEM106B is a frontotemporal lobar degeneration (FTLD) genetic susceptibility factor, and TMEM106B protein aggregates are a feature of aging and neurodegeneration. Whether TMEM106B protein levels are associated with clinical features is unknown. Objective To investigate the clinical associations of cerebrospinal fluid (CSF) TMEM106B in FTLD. Design, Setting, and Participants This cross-sectional study was conducted in 2 independent frontotemporal dementia (FTD) cohorts (recruitment from April 2009 through July 2023, with analyses from January 2025 through April 2026), with a 2-year follow up. This multicenter clinical study integrated clinical, genetic, biomarker, and neuroimaging data. Individuals were recruited through the University of California, San Francisco (n = 3733), or ALLFTD (n = 2343). Participants with available CSF were included. A discovery cohort (n = 271) included participants with sporadic neuropathology-confirmed FTLD; presymptomatic or symptomatic carriers of pathogenic variants in C9orf72 , GRN , or MAPT ; or controls. An independent validation cohort (n = 383) included participants with clinically diagnosed sporadic FTD, Alzheimer disease (AD), and controls. Exposures CSF samples for TMEM106B quantification with aptamer proteomics (SomaScan version 3.0 [discovery cohort] and SomaScan version 4.1 [validation cohort]). Main Outcomes and Measures Parametric tests compared the primary outcome, CSF TMEM106B, by disease severity, TMEM106B rs1990622 genotype, sex, clinical syndrome, pathological diagnosis, and pathogenic variant and determined associations with brain volume. Results In the discovery (n = 271; 136 women [51%]; median [IQR] age, 59 [38-80] years) and validation (n = 383; 183 women [48%]; median [IQR] age, 64 [50-78] years) cohorts, lower CSF TMEM106B was associated with more severe disease (β, −0.15; 95% CI, −0.24 to −0.04; P = .003), lower frontotemporal brain volumes (β, 0.42; 95% CI, 0.24-0.61; P < .001), and faster clinical progression (β, −2.21; 95% CI, −3.70 to −0.72; P = .001). Associations of TMEM106B with clinical disease severity were independent of those with neurofilament light chain. TMEM106B levels were influenced by TMEM106B rs1990622 genotype, where individuals with the protective G/G genotype had lower levels than the risk A/A genotype. CSF TMEM106B levels did not differentiate between FTLD subtypes or between FTLD and AD. Conclusions and Relevance Per the results of this cross-sectional study, TMEM106B is detectable in CSF and levels reflect disease severity in sporadic and genetic FTLD and AD, but levels are also influenced by the TMEM106B rs1990622 genotype. CSF TMEM106B could support further studies to understand the mechanisms of disease and develop clinical tools in FTLD and other neurodegenerative diseases.

Background The diagnosis of periprosthetic joint infection (PJI) is facilitated by consensus identification of synovial biomarkers, which may be aided by targeted microbial next generation sequencing (NGS) of synovial fluid. The primary objective of the study was to evaluate NGS performance across 3 years to ICM 2018 minor criteria for PJI. Methods Synovial fluid specimens submitted from 2020–2022 by outpatient surgical clinics to MicroGenDX for matched synovial biomarker and NGS analysis were selected for retrospective analysis. Synovial biomarkers tested included C-reactive protein (CRP), white blood cell (WBC) count, and polymorphonuclear (PMN) leukocyte percentage. Synovial fluid analysis compared NGS microbial positivity with positive incidence of PJI determined by scoring of synovial biomarkers using ICM 2018 minor criteria for infection. Results The overall sensitivity, specificity, and accuracy of NGS to ICM diagnosed PJI across 2,011 specimens was 76.4% [95% CI, 0.723–0.801], 92.3% [0.91–0.94], and 88.7% [0.87–0.90], respectively. When comparing the diagnostic performance of NGS and individual biomarkers to infection, NGS was more specific to PJI than synovial CRP (specificity = 0.894, 95% CI: 0.88–0.91), but not PMN or WBC. NGS was positive in 7.7% of ICM negative samples. NGS positive: ICM negative samples were associated with significantly elevated synovial PMN ( p = 0.001) and WBC ( p < 0.0001) compared to NGS negative: ICM negative samples. Across all samples, NGS positivity was associated with significantly elevated results for all tested biomarkers ( p < 0.0001). Eight bacterial species dominated the composition in 68% of samples, whereas 46 different microbes were dominant in the remaining third. Conclusion Microbial targeted NGS positivity was concordant with ICM minor criteria for PJI and should be considered a useful tool for diagnosis. There is a low risk of false positive detections comparable to ICM biomarkers. Elevated biomarkers in NGS positive: ICM negative samples may indicate infection occurring that is poorly captured by the three measured synovial biomarkers. Uncommon species are collectively common to PJI and NGS is uniquely positioned to detect such species as they are frequently missed by conventional microbiological testing, including culture and quantitative PCR. These results suggest formal diagnostic schemes would benefit from the addition of NGS as a diagnostic criterion.

Objective To determine the clinical features that identify patients with suspected rapidly progressive dementia (RPD) who will develop RPD. Methods Patients with suspected RPD were enrolled and followed at Mayo Clinic (Jacksonville, FL; January 2020 to October 2023) and Washington University (Saint Louis, MO; June 2016 to December 2019). Two dementia specialists independently reviewed clinical data and assigned diagnoses. Patients were diagnosed with RPD if they developed dementia within 1 year or incapacitation within 2 years of symptom onset. The associations between clinical features and causes and outcomes were explored via univariate and multivariate comparisons. Results Of 248 patients with suspected RPD, 185 (74.6%) met criteria for RPD. Patients with RPD were older (62.6 ± 14.5 vs 55.2 ± 18.1 years; p < 0.001), and more frequently diagnosed with Alzheimer's disease or related dementias (OR 3.13, 95% CI 1.40, 7.31) or Creutzfeldt–Jakob disease (OR 4.67, 95% CI 1.38, 15.75). Visual agnosia (15/183; 8.2%), substantial brain atrophy (27/182; 14.8%), and periodic epileptiform discharges (11/151; 7.3%) were exclusively detected in patients with RPD. After controlling for age, intensive care unit admission (OR 4.77, 95% CI 1.61, 14.12), lack of seizures (OR 2.47, 95% CI 1.15, 5.31), abnormal brain magnetic resonance imaging (OR 2.01, 95% CI 0.997, 4.05), and cerebrospinal fluid white blood cell count ≤5 cells/mm 3 (OR 3.30, 95% CI 1.60, 6.82) were also independently associated with RPD. Patients with RPD were more likely to die or develop severe dementia (mean time to outcome, 36.1 months; 95% CI 31.2–41.0). Interpretation Selected clinical features may identify patients with suspected RPD who are likely to continue to decline. Early recognition of these features may improve diagnostic accuracy and inform prognosis. ANN NEUROL 2025;98:764–776