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Influenza vaccine effectiveness against medically attended outpatients illness, United States, 2023-2024 season
No full textBACKGROUND: The 2023-2024 US influenza season was characterized by a predominance of A(H1N1)pdm09 virus circulation with cocirculation of A(H3N2) and B/Victoria viruses. We estimated vaccine effectiveness (VE) in the United States against mild-to-moderate medically attended influenza illness in the 2023-2024 season.
METHODS: We enrolled outpatients aged ≥8 months with acute respiratory illness in 7 states. Respiratory specimens were tested for influenza type/subtype by reverse-transcriptase polymerase chain reaction. Influenza VE was estimated with a test-negative design comparing odds of testing positive for influenza among vaccinated versus unvaccinated participants. We estimated VE by virus subtype/lineage and A(H1N1)pdm09 genetic subclades.
RESULTS: Among 6629 enrolled patients, 1780 (27%) tested positive for influenza, including 806 with A(H1N1)pdm09, 567 with B/Victoria, and 328 with A(H3N2). VE against any influenza illness was 44% (95% confidence interval, 36%-51%): 29% (15%-41%) against influenza A(H1N1)pdm09, 74% (65%-81%) against B/Victoria, and 30% (8%-47%) against A(H3N2). Statistically significant protection against any influenza was found for all age groups except adults aged 50-64 years. Lack of protection in this age group was specific to influenza A-associated illness. We observed differences in VE by birth cohort and A(H1N1)pdm09 virus genetic subclade.
CONCLUSIONS: Vaccination reduced outpatient medically attended influenza overall by 44% and provided protection overall against circulating influenza A and B viruses. Serologic studies would help inform differences observed by age groups
Thalamic and visual network dysfunction relates to tremor response in thalamic deep brain stimulation
No full textBACKGROUND: Essential tremor (ET) is the most common movement disorder in adults, but its pathogenesis is incompletely understood. Deep brain stimulation of the ventral intermediate thalamic nucleus (VIM DBS) provides effective treatment for medically-refractory cases. We aimed to determine how pre-surgical resting-state functional connectivity (FC) in medically-refractory ET relates to VIM DBS clinical response.
METHODS: We analyzed resting-state FC MRI in 21 participants with medically-refractory ET who subsequently underwent VIM DBS and 34 matched controls. We applied rigorous quality assurance to minimize motion artifact. Whole-brain correlation matrices were computed across 300 cortical, subcortical, and cerebellar regions and compared across groups using object-oriented data analysis, a powerful novel approach. We used multiple linear regression to determine whether network FC (calculated as mean cross-correlation between nodes) in defined networks predicts VIM DBS response. We assessed regional FC using a seed in motor thalamus.
RESULTS: Whole-brain correlation matrices and regional motor thalamus FC differed significantly between groups. Post-hoc network-level testing revealed decreased thalamus-somatomotor, thalamus-visual, and auditory-visual FC in ET versus controls. Regional FC showed increased primary motor cortex and decreased occipital-parietal and cerebellar FC with motor thalamus in ET relative to controls. Visual-lateral somatomotor network FC negatively predicted tremor improvement with VIM DBS.
DISCUSSION: Whole-brain, network, and regional FC results demonstrate cerebello-thalamo-motor pathway dysfunction in ET. Robust FC differences in motor and visual regions related to VIM DBS outcomes. These results, employing rigorous quality control, support the need for additional investigation into the role of visual cortical networks in ET and DBS response
Cortical spectral dynamics of vibrotactile frequency processing
No full textWhile scientific research has extensively explored how the brain integrates touch and pain signals, the cerebral processing of specific vibrotactile frequencies remains poorly understood. This gap is particularly significant given clinical evidence that vibrotactile stimulation can reduce pain in both chronic pain patients and experimental settings. Our study investigated the cortical electrophysiological correlates of peripheral vibrotactile stimulation across different frequencies in healthy volunteers, with a focus on frequency-dependent patterns of neuronal activation. While electroencephalogram (EEG) was recorded, healthy participants received vibrotactile stimulation (high-frequency burst stimulation with different inter-burst intervals) to the left index fingertip at frequencies corresponding to established neural rhythms: delta (2 Hz), theta (6 Hz), alpha (12 Hz), beta (20 Hz), and gamma (40 Hz). We compared the EEG bandwidth activity between vibrotactile stimulation conditions relative to resting baseline. Our findings demonstrated that vibrotactile stimulation produces distinct frequency-dependent patterns of cortical activation. A key finding was that 6 Hz stimulation selectively enhanced theta power in the left prefrontal cortex - an electrophysiological signature previously linked to successful pain relief. These findings advance the understanding of the spectrotopic nature of vibrotactile frequency processing in the cortex and provide a mechanistic foundation for developing novel vibration-based therapies in the future
A combined naturalistic driving, clinical, and neurobehavioral data set for investigating aging and dementia
No full textAlzheimer\u27s disease and related dementia (ADRD) are becoming increasingly prevalent and are predicted to affect up to 153 million globally by 2050. Outside of biomarkers that measure pathology, there is a lack of methods to quantify and study complex behaviors such as driving and managing finances that precede cognitive decline among older adults. The DRIVES Project at Washington University School of Medicine has developed a pipeline to measure naturalistic driving behavior of older adult drivers enrolled in longitudinal studies of aging and ADRD. This driving behavior is captured in the form of tabular data for each trip a participant takes and is processed in two formats: low-frequency driving data, comprising approximately 2.8 million trips (37 GB), and high-frequency driving data, with approximately 1.4 million trips (2.6 TB). This pipeline also captures common participant sociodemographic characteristics, clinical features, and environmental context across various weather conditions, as well as the Area Deprivation Index and the Social Vulnerability Index, to comprehensively characterize the multidimensional nature of neurodegenerative processes among older adults
FUSION: A web-based application for in-depth exploration of multi-omics data with brightfield histology
No full textSpatial technologies examining the cell and tissue microenvironment at near single-cell resolution are revealing important molecular insights. However, few tools enable integrated, interactive analysis of spatial-omics with tissue morphology in the same functional tissue unit. Here, we present FUSION (Functional Unit State Identification in Whole Slide Images), a web-based platform for visualizing and analyzing spatial-omics data with high-resolution histology. FUSION provides workflows for assessing cell compositions, quantitative morphometrics, and comparative tissue analyses. We demonstrate applicability across spatial assays, including 10x Visium, Visium HD, 10x Xenium, Cell DIVE, and PhenoCycler, applied to healthy and diseased tissues from kidney, small intestine, lung, and skin in the Human BioMolecular Atlas Program. FUSION is cloud-based, open-source, and accessible at https://fusion.hubmapconsortium.org/ , hosting over 50 paired datasets and tutorials. In a series of use cases, we show its capacity to distinguish renal glomeruli injury states, quantify morphometric changes, and characterize fibrosis with immune infiltration
Diagnostic efficacy and clinical impact of image-guided core needle biopsy of suspected adult nonvertebral osteomyelitis
No full textOBJECTIVES: The diagnostic yield and clinical impact of image-guided core needle biopsy (ICNB) of suspected nonvertebral osteomyelitis in adults is heterogenous in published studies because of small sample size, indicating the need for large cohort studies.
METHODS: A retrospective analysis of ICNBs was performed from 2010 to 2021 for patients with suspected nonvertebral osteomyelitis. For each biopsy, a series of factors were analyzed, as well as if histopathology was diagnostic of osteomyelitis and if microbiological cultures were positive. Additionally, it was recorded in what way biopsy influenced clinical management regarding antimicrobial treatment. Multivariate statistical analysis was performed to evaluate the factors associated with yield.
RESULTS: A total of 883 biopsies performed on 787 patients were included. A histopathologic diagnosis of osteomyelitis was made in 51.6% (381/738) of biopsies, and microbiological cultures were positive in 28.7% (253/883) of biopsies. Antimicrobial exposure before biopsy was negatively associated with positive cultures from bone core samples (odds ratio [OR] = 0.52; 95% confidence interval [CI], .33-.83;
CONCLUSIONS: In this large cohort, ICNB yielded approximately 30% positive cultures and changed clinical management in more than one fourth of patients.
SUMMARY STATEMENT: In a retrospective study of 883 image-guided biopsies of suspected nonvertebral osteomyelitis, microbiological cultures were positive in 28.7% (253/883) of biopsies, a histopathologic diagnosis of osteomyelitis was made in 51.6% (197/381), and 26.2% (231/883) of biopsies affected clinical management
Trajectories of Recovery after Intravenous propofol versus inhaled VolatilE anaesthesia (THRIVE) randomised controlled trial in the USA: A protocol
No full textINTRODUCTION: Millions of patients receive general anaesthesia every year with either propofol total intravenous anaesthesia (TIVA) or inhaled volatile anaesthesia (INVA). It is currently unknown which of these techniques is superior in relation to patient experience, safety and clinical outcomes. The primary aims of this trial are to determine (1) whether patients undergoing (a) major inpatient surgery, (b) minor inpatient surgery or (c) outpatient surgery have a superior quality of recovery after INVA or TIVA and (2) whether TIVA confers no more than a small (0.2%) increased risk of definite intraoperative awareness than INVA.
METHODS AND ANALYSIS: This protocol was co-created by a diverse team, including patient partners with personal experience of TIVA or INVA. The design is a 13 000-patient, multicentre, patient-blinded, randomised, comparative effectiveness trial. Patients 18 years of age or older, undergoing elective non-cardiac surgery requiring general anaesthesia with a tracheal tube or laryngeal mask airway will be eligible. Patients will be randomised 1:1 to one of two anaesthetic approaches, TIVA or INVA, using minimisation. The primary effectiveness endpoints are Quality of Recovery-15 (QOR-15) score on postoperative day (POD) 1 in patients undergoing (1) major inpatient surgery, (2) minor inpatient surgery or (3) outpatient surgery, and the primary safety endpoint is the incidence of unintended definite intraoperative awareness with recall in all patients, assessed on POD1 or POD30. Secondary endpoints include QOR-15 score on POD0, POD2 and POD7; incidence of delirium on POD0 and POD1; functional status on POD30 and POD90; health-related quality of life on POD30, POD90, POD180 and POD365; days alive and at home at POD30; patient satisfaction with anaesthesia at POD2; respiratory failure on POD0; kidney injury on POD7; all-cause mortality at POD30 and POD90; intraoperative hypotension; moderate-to-severe intraoperative movement; unplanned hospital admission after outpatient surgery in a free-standing ambulatory surgery centre setting; propofol-related infusion syndrome and malignant hyperthermia.
ETHICS AND DISSEMINATION: This study is approved by the ethics board at Washington University, serving as the single Institutional Review Board for all participating sites. Recruitment began in September 2023. Dissemination plans include presentations at scientific conferences, scientific publications, internet-based educational materials and mass media.
TRIAL REGISTRATION NUMBER: NCT05991453
Active DNA demethylation upstream of rod-photoreceptor fate determination is required for retinal development
No full textRetinal cell fate specification from multipotent retinal progenitors is governed by dynamic changes in chromatin structure and gene expression. Methylation at cytosines in DNA (5mC) is actively regulated for proper control of gene expression and chromatin architecture. Numerous genes display active DNA demethylation across retinal development; a process that requires oxidation of 5mC to 5-hydroxymethylcytosine (5hmC) and is controlled by the ten-eleven translocation (TET) methylcytosine dioxygenase enzymes. Using an allelic series of conditional TET enzyme mutants in mice, we determine that DNA demethylation is required upstream of NRL and NR2E3 expression for the establishment of rod-photoreceptor fate. Using histological, behavioral, transcriptomic, and base-pair resolution DNA methylation analyses, we establish that inhibition of active DNA demethylation results in global changes in gene expression and methylation patterns that prevent photoreceptor precursors from adopting a rod-photoreceptor fate, instead producing a retina in which all photoreceptors specify as cones. Our results establish the TET enzymes and DNA demethylation as critical regulators of retinal development and cell fate specification, elucidating a novel mechanism required for the specification of rod-photoreceptors
Exposure to household air pollution from biomass cooking and severe pneumonia in infants
No full textIMPORTANCE: Household air pollution from biomass cooking is considered an important risk factor for child pneumonia.
OBJECTIVE: To evaluate the longitudinal association between exposure to particulate matter with a diameter of less than or equal to 2.5 µm (PM2.5) or carbon monoxide (CO) and severe pneumonia in infants.
DESIGN, SETTING, AND PARTICIPANTS: This cohort study included infants (aged ≤12 months) whose mothers participated in a 4-country randomized clinical trial. Conducted from May 2018 to September 2021, the trial tested whether an 18-month liquefied petroleum gas stove and fuel distribution intervention reduced the incidence of severe pneumonia in offspring during infancy when compared with biomass cooking. The trial was conducted in communities where residents cooked primarily with biomass fuels in Guatemala, India, Peru, and Rwanda. Data analysis was conducted from December 2024 to July 2025.
EXPOSURES: Twenty-four hour personal exposure to PM2.5 and CO was measured 3 times during pregnancy and 3 times during infancy.
MAIN OUTCOME AND MEASURES: In this exposure-response analysis, severe pneumonia cases were identified using respiratory signs and symptoms with confirmation of consolidation by imaging and hypoxemia by pulse oximetry. The longitudinal association between severe pneumonia in infants and PM2.5 or CO exposures by infant-quarters, adjusted for confounders, was modeled.
RESULTS: Overall, 3061 infants (48.2% girls; mean [SD] gestational age at birth, 39.3 [1.7] weeks) contributed 11 996 infant-quarters and 13 910 measurements of personal PM2.5 exposures (range, 5.4-1182.0 µg/m3). A total of 175 episodes of severe pneumonia were identified in 160 infants. Those with at least 1 episode of severe pneumonia had similar mean (SD) prenatal (101 [100] µg/m3 vs 88 [80] µg/m3; P = .11) and postnatal (70 [78] µg/m3 vs 67 [93] µg/m3; P = .68) PM2.5 exposures when compared with infants without severe pneumonia. There were no associations between prenatal (adjusted risk ratio [RR], 1.03; 95% CI, 0.94-1.13) or postnatal (adjusted RR, 0.97; 95% CI, 0.87-1.09) PM2.5 exposures and severe pneumonia or between CO exposures and severe pneumonia.
CONCLUSIONS AND RELEVANCE: In this cohort study with exposure-response analysis, there was no evidence of an association between longitudinal PM2.5 or CO exposures and severe pneumonia in infants. Taken with the intention-to-treat analysis from the randomized clinical trial, these results challenge prior research suggesting that PM2.5 or CO exposures from biomass cooking are an important risk factor for severe pneumonia in infants
Availability of multidisciplinary treatment modalities and outcomes among patients with resected early-stage non-small cell lung cancer
No full textBACKGROUND: Comprehensive, multidisciplinary care is crucial for managing early-stage non-small cell lung cancer (NSCLC), typically treated via lung resection or stereotactic body radiation therapy (SBRT). We evaluated how variable access to on-site SBRT may be associated with clinical outcomes for patients with stage I NSCLC receiving surgical resection within an integrated health-care system.
METHODS: We performed a retrospective cohort study of patients with stage I NSCLC treated with lung resection at Veterans Health Administration (VHA) facilities between 2006 and 2016. The VHA provides thoracic surgery at approximately 100 facilities, whereas lung SBRT is currently available at approximately 20 facilities. We compared short- and long-term outcomes for patients treated at surgery-only facilities vs those at facilities offering surgery and SBRT.
RESULTS: We identified 6289 patients undergoing lung resection, with 4673 (74.3%) treated at surgery-only sites and 1616 (25.7%) at surgery + SBRT sites. Sociodemographic factors were similar between cohorts. Surgery + SBRT sites showed higher adherence to operative quality metrics and improved patient selection. Short-term outcomes were better at surgery + SBRT sites with lower rates of 30-day major complications, 30-day mortality, and 90-day mortality. With a median follow-up of 6.3 years, 5-year overall survival was higher at surgery + SBRT sites (59.4% vs 56.9%; adjusted hazard ratio 1.12, 95% CI = 1.02 to 1.23).
CONCLUSION: Short- and long-term outcomes were better for patients with stage I NSCLC who underwent lung resection at facilities delivering thoracic surgery and SBRT. These findings support recommendations to increase SBRT availability at medical centers offering lung resection to ensure comprehensive multidisciplinary care is provided