Management Outcomes after Image-Guided Percutaneous Biopsy for Suspected Vertebral Osteomyelitis-Discitis.

BACKGROUND AND PURPOSE: Studies show a modest yield for image-guided biopsy of suspected vertebral osteomyelitis-discitis. Many studies evaluate factors to improve diagnostic yield, and few studies assess how biopsy results impact clinical management. We aim to evaluate the impact of biopsy results on clinical management in suspected vertebral osteomyelitis-discitis. MATERIALS AND METHODS: We performed a retrospective study of patients who underwent image-guided biopsy for suspected vertebral osteomyelitis-discitis. Data collected included risk factors, imaging findings, laboratory values, antibiotics, biopsy procedure details, microbiology and pathology results, and clinical course. Factors assessed for management change included whether biopsy results affected antibiotic type or course, decision to start or stop antibiotics, surgical decisions, or if an alternate diagnosis was determined. RESULTS: Three hundred ten biopsies were included. Biopsy yield with true-positive culture results was 34% (104/310) and similar for patients on antibiotics (36%, 34/94) and off antibiotics (32%, 66/204). Yield was greater when disc was sampled (36%, 82/228) versus bone only (8%, 2/24) and with aspiration of disc and/or bone (42%, 39/92) versus core only (29%, 56/193). With positive blood cultures before biopsy, biopsy yield was 50% (22/44) with concordance and discordance rates of 75% (18/24) and 17% (4/24), respectively, and 8% (2/24) of positive biopsy results deemed contaminants. Management was affected in 36% (113/310) of all biopsies and in 78% (81/104) of biopsies with a positive culture result. No management change occurred in 57% (177/310) of biopsies. Management change was unclear in 6% (20/310). Biopsy results changed antibiotics in 27% (85/310). Management change occurred in 23% (10/44) of cases with prior positive blood culture compared with 41% (93/233) without a prior culture source ( CONCLUSIONS: Image-guided biopsy for vertebral osteomyelitis-discitis has a meaningful impact on management despite modest yield. Greatest management impact is seen with positive culture results, no prior culture source, and patients not on antibiotics at the time of biopsy. Biopsy culture yield is not affected by preceding antibiotics, and yield is greater with disc sampling and aspiration

Ventral Midline Hysterectomy, Ovariectomy, and Ovariohysterectomy in Mus Musculus: A Surgical Protocol.

Mice (Mus musculus) are one of the most commonly used animal species in basic science and translational research worldwide. Ovariectomy and hysterectomy are frequently employed to explore the systemic effects of the sex-hormone axis and other pathological conditions. While several surgical protocols exist for dorsal ovariectomy in rodents, very few address a ventral midline technique, and none are specific to the mouse model. Historically, ventral midline approaches have been considered technically challenging due to unique anatomical features, including long, thin uterine horns, fragile salpinges, short ovarian suspensory ligaments, and small animal size. This protocol provides a detailed guide for performing ovariectomy, hysterectomy, or ovariohysterectomy in mice, including the microsurgical steps required. All procedures were performed using an operative stereomicroscope under 3-5x magnification. The mean weight of the mice was 24 g (SD = 2 g), with ages ranging from 19 to 21 weeks. Of the 255 surgeries performed, 3 post-operative deaths occurred, resulting in an attrition rate of 1.18%. Post-operatively, all mice were housed in groups with fresh, paddy husk bedding, and no infections or wound breakdown were observed. Despite their small size and the manipulation of several vital anatomical structures, this procedure is easily reproducible and well-tolerated in mice

Visual-Guided Transillumination Method for Accurate Percutaneous Tracheal Tube Placement

BACKGROUND: Percutaneous tracheostomy (PT) is generally considered a safe procedure, but complications such as malpositioning, bleeding, and tracheal ring rupture remain concerns, particularly during initial needle insertion. This study investigates the feasibility, ease of use, and safety of a novel device and technique for bedside PT, named the Illuminated Tracheal Alignment Guide (iTAG). METHODS: An interventional pilot study evaluated the feasibility and safety of the iTAG device and method. The study was approved by our local institutional review board and a Food and Drug Administration waiver was granted for use of our device. Patients in a neurocritical care unit requiring tracheostomy were screened and consented for inclusion. Exclusion criteria included significant vascular overlap and specific ventilator settings. The iTAG method involves a laser light source and a needle guide with a hard stop, used in conjunction with standard PT equipment. Data on demographics, procedure details, and early complications were collected and compared with historical control data from patients who underwent standard tracheostomy (ST). RESULTS: From January 2023 to July 2024, 30 patients underwent PT using the iTAG device. The mean time from intubation to tracheostomy was 15.53 days, with a mean ICU length of stay of 31.14 days. The iTAG group experienced significantly fewer early complications compared with the historical ST control group, including reduced hemorrhage, and there were no instances of tracheal ring fracture, posterior wall injury, or pneumothorax. The iTAG method allowed for safe PT in all patients. CONCLUSIONS: The iTAG device enhances the safety and efficacy of PT by providing precise visualization and limiting needle penetration, reducing early complications. Its use expands patient candidacy for PT and offers a valuable tool for training less-experienced practitioners. Further research with larger cohorts and randomized controlled trials is needed to confirm these findings and establish the iTAG method as a standard of care for PT

Histopathological analysis of duragen collagen matrix over time in humans.

DuraGen is a widely used type I collagen matrix derived from bovine Achilles tendon that promotes fibroblast ingrowth and neovascularization. However, it remains unknown the time required for dura regeneration and reabsorption of the graft. We evaluate the histopathological characteristics of implanted DuraGen in humans across multiple time points. Patients who underwent a decompressive craniectomy and duraplasty with DuraGen at our institution between January 2020 and September 2021 were prospectively enrolled. At the time of the subsequent surgery, including cranioplasty, DuraGen and associated tissues removed from patients were sent for histopathological analysis. For each patient, time from index surgery to subsequent surgery was categorized into three groups: early (0-20 days), intermediate (21-30 days), and late (\u3e 30 days). Baseline characteristics, primary disease, operative time, complication rate, and histopathological findings were compared between groups. A total of 28 patients were enrolled in the study. Seven specimens (25.0%) were collected within 20 days after craniectomy, 9 specimens (35.7%) between 21 and 30 days, and 12 specimens (39.3%) over 31 days. Histopathologically, implanted collagen matrix, erythrocyte infiltration, and fibrin layer decreased over time, whereas fibroblasts and endogenous collagen increased. Receiver operating characteristic analysis showed that the cut-off time post-implantation for presence of endogenous collagen was 34 days after DuraGen implantation (area under the curve = 0.810). We found that DuraGen was replaced by fibroblast-derived endogenous collagen as early as 34 days post-implantation. Although certain findings remain to be further validated, the present study substantiates DuraGen as a reliable substitute, with findings derived from clinical outcomes and histopathological changes

hiPSC-neurons recapitulate the subtype-specific cell intrinsic nature of susceptibility to neurodegenerative disease-relevant aggregation.

Alzheimer\u27s disease (AD) is characterized by the accumulation and spread of Tau intraneuronal inclusions throughout most of the telencephalon, leaving hindbrain regions like the cerebellum and spinal cord largely spared. These neuropathological observations, along with the identification of specific vulnerable sub-populations from AD brain-derived single nuclei transcriptomics, suggest that a subset of brain regions and neuronal subtypes possess a selective vulnerability to Tau pathology. Given the inability to culture neurons from patient brains, a disease-relevant in vitro model which recapitulates these features would serve as a critical tool to validate modulators of vulnerability and resilience. Using our recently established platform for inducing endogenous Tau aggregation in human induced pluripotent stem cell (hiPSC)-derived cortical excitatory neurons via application of AD brain-derived exogenous Tau aggregates, we explored whether Tau aggregates preferentially induce aggregation in specific neuronal subtypes. We compared Tau seeding in hiPSC-derived neuron subtypes representing regional identities across the forebrain, midbrain, and hindbrain. Higher susceptibility (i.e. more Tau aggregation) was consistently observed among cortical neuron subtypes, with CTIP2-positive, somatostatin (SST)-positive cortical inhibitory neurons showing the greatest aggregation levels across hiPSC lines from multiple donors. hiPSC-neurons also delineated between the disease-specific vulnerabilities of different protein aggregates, as α-synuclein preformed fibrils showed an increased propensity to induce aggregates in midbrain dopaminergic (mDA)-like neurons, mimicking Parkinson\u27s disease (PD)-specific susceptibility. Aggregate uptake and degradation rates were insufficient to explain differential susceptibility. The absence of a consistent transcriptional response following aggregate seeding further indicated that intrinsic neuronal subtype-specific properties could drive susceptibility. The present data provides evidence that hiPSC-neurons exhibit features of selective neuronal vulnerability which manifest in a cell autonomous manner, suggesting that mining intrinsic (or basal) transcriptomic signatures of more vulnerable compared to more resilient hiPSC-neurons could uncover the molecular underpinnings of differential susceptibility to protein aggregation found in a variety of neurodegenerative diseases

Sex Differences in Long COVID.

IMPORTANCE: A substantial number of individuals worldwide experience long COVID, or post-COVID condition. Other postviral and autoimmune conditions have a female predominance, but whether the same is true for long COVID, especially within different subgroups, is uncertain. OBJECTIVE: To evaluate sex differences in the risk of developing long COVID among adults with SARS-CoV-2 infection. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from the National Institutes of Health (NIH) Researching COVID to Enhance Recovery (RECOVER)-Adult cohort, which consists of individuals enrolled in and prospectively followed up at 83 sites in 33 US states plus Washington, DC, and Puerto Rico. Data were examined from all participants enrolled between October 29, 2021, and July 5, 2024, who had a qualifying study visit 6 months or more after their initial SARS-CoV-2 infection. EXPOSURE: Self-reported sex (male, female) assigned at birth. MAIN OUTCOMES AND MEASURES: Development of long COVID, measured using a self-reported symptom-based questionnaire and scoring guideline at the first study visit that occurred at least 6 months after infection. Propensity score matching was used to estimate risk ratios (RRs) and risk differences (95% CIs). The full model included demographic and clinical characteristics and social determinants of health, and the reduced model included only age, race, and ethnicity. RESULTS: Among 12 276 participants who had experienced SARS-CoV-2 infection (8969 [73%] female; mean [SD] age at infection, 46 [15] years), female sex was associated with higher risk of long COVID in the primary full (RR, 1.31; 95% CI, 1.06-1.62) and reduced (RR, 1.44; 95% CI, 1.17-1.77) models. This finding was observed across all age groups except 18 to 39 years (RR, 1.04; 95% CI, 0.72-1.49). Female sex was associated with significantly higher overall long COVID risk when the analysis was restricted to nonpregnant participants (RR, 1.50; 95%: CI, 1.27-1.77). Among participants aged 40 to 54 years, the risk ratio was 1.42 (95% CI, 0.99-2.03) in menopausal female participants and 1.45 (95% CI, 1.15-1.83) in nonmenopausal female participants compared with male participants. CONCLUSIONS AND RELEVANCE: In this prospective cohort study of the NIH RECOVER-Adult cohort, female sex was associated with an increased risk of long COVID compared with male sex, and this association was age, pregnancy, and menopausal status dependent. These findings highlight the need to identify biological mechanisms contributing to sex specificity to facilitate risk stratification, targeted drug development, and improved management of long COVID

Predicting Post-Mortem α-Synuclein Pathology by the Combined Presence of Probable REM sleep behavior disorder and Hyposmia.

BACKGROUND: Idiopathic rapid eye movement sleep behavior disorder (RBD) is a strong known predictor of a final clinicopathological diagnosis of a Lewy type α-synucleinopathy (LTS). Olfactory dysfunction is an early symptom of synucleinopathies and has been repeatedly associated with the presence of post-mortem LTS. OBJECTIVE: To assess the combined value of a clinician diagnosis of probable RBD (PRBD) and hyposmia in predicting the post-mortem presence of LTS in a broader, less-selected, volunteer elderly population. METHODS: We studied 652 autopsied subjects from the Arizona Study of Aging and Neurodegenerative Disorders, which were evaluated for PRBD, had completed annual movement and cognitive assessments, and had at least one the University of Pennsylvania Smell Identification Test (UPSIT) olfactory test. RESULTS: Histological evidence of LTS was significantly more frequent in those who had PRBD (112/152: 73.7%) than those without (177/494: 35.8%) (P \u3c 0.001). LTS was more frequent in cases with PRBD and a low UPSIT score (90.8%) compared to cases with PRBD only (73.7%) (P \u3c 0.001) or cases with a low UPSIT score only (69.4%) (P \u3c 0.001). Sensitivity of PRBD diagnosis for predicting LTS was 38.8% and specificity 88.8%, whereas sensitivity of a low UPSIT score was 74.4% and specificity 73.4% (Youden\u27s index = 0.276 for PRBD, 0.478 for UPSIT). When combining both measures, sensitivity was 34.3% and specificity increased to 97.2%. CONCLUSION: PRBD, diagnosed without sleep study confirmation, combined with a reduced olfactory performance is highly specific for predicting post-mortem presence of LTS. The combination of both measures may provide a cost-effective means of predicting LTS in a broader community

2024 Update of the RECOVER-Adult Long COVID Research Index.

IMPORTANCE: Classification of persons with long COVID (LC) or post-COVID-19 condition must encompass the complexity and heterogeneity of the condition. Iterative refinement of the classification index for research is needed to incorporate newly available data as the field rapidly evolves. OBJECTIVE: To update the 2023 research index for adults with LC using additional participant data from the Researching COVID to Enhance Recovery (RECOVER-Adult) study and an expanded symptom list based on input from patient communities. DESIGN, SETTING, AND PARTICIPANTS: Prospective, observational cohort study including adults 18 years or older with or without known prior SARS-CoV-2 infection who were enrolled at 83 sites in the US and Puerto Rico. Included participants had at least 1 study visit taking place 4.5 months after first SARS-CoV-2 infection or later, and not within 30 days of a reinfection. The study visits took place between October 2021 and March 2024. EXPOSURE: SARS-CoV-2 infection. MAIN OUTCOMES AND MEASURES: Presence of LC and participant-reported symptoms. RESULTS: A total of 13 647 participants (11 743 with known SARS-CoV-2 infection and 1904 without known prior SARS-CoV-2 infection; median age, 45 years [IQR, 34-69 years]; and 73% were female) were included. Using the least absolute shrinkage and selection operator analysis regression approach from the 2023 model, symptoms contributing to the updated 2024 index included postexertional malaise, fatigue, brain fog, dizziness, palpitations, change in smell or taste, thirst, chronic cough, chest pain, shortness of breath, and sleep apnea. For the 2024 LC research index, the optimal threshold to identify participants with highly symptomatic LC was a score of 11 or greater. The 2024 index classified 20% of participants with known prior SARS-CoV-2 infection and 4% of those without known prior SARS-CoV-2 infection as having likely LC (vs 21% and 5%, respectively, using the 2023 index) and 39% of participants with known prior SARS-CoV-2 infection as having possible LC, which is a new category for the 2024 model. Cluster analysis identified 5 LC subtypes that tracked quality-of-life measures. CONCLUSIONS AND RELEVANCE: The 2024 LC research index for adults builds on the 2023 index with additional data and symptoms to help researchers classify symptomatic LC and its symptom subtypes. Continued future refinement of the index will be needed as the understanding of LC evolves