Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Characterization of a major protein of the mouse perinuclear Theca

The perinuclear theca (PT) is a cytoskeletal structure that covers the nucleus of mammalian spermatozoa and is believed to have a membrane binding role. The objectives of this study were to analyze the protein composition of the mouse PT, to identify its major protein component, and to characterize this protein's transcriptional and translational origins during spermatogenesis. The PT was extracted from demembranated and acrosome-depleted mouse sperm heads by alkaline treatment. The protein profile of the PT extract was composed of several polypeptides of which a 15 kDa subacrosomal protein predominated and was found to be immunocross-reactive with a previously cloned 15 kDa PT protein of the rat (PERF 15) that belongs to a family of lipid binding proteins. A primer pair designed from rat PERF 15 cDNA was then used to screen a mouse testicular cDNA library by polymerase chain reaction (PCR). The deduced amino acid sequence obtained from the PCR product was almost identical to the testicular-specific rat PERF 15. Developmental Northern blots and in situ hybridization studies performed with riboprobes encoding the mouse PERF 15 cDNA revealed that mRNA levels were highest in round and early elongating mouse spermatids. Immunohistochemistry indicated that PERF 15 began to be expressed in the cytoplasm of mid-pachytene spermatocytes and appeared to reach maximum expression in the distal cytoplasm of late elongating mouse spermatids, long after transcriptional arrest. During the development of round and early elongating spermatids, the immunolabel became progressively concentrated over the anterior half of the spermatid nucleus suggesting a subacrosomal deposition of PERF 15 during this phase of mouse spermatogenesis

Derivation of a Three Biomarker Panel to Improve Diagnosis in Patients with Mild Traumatic Brain Injury

BackgroundNearly 5 million emergency department (ED) visits for head injury occur each year in the United States, of which <10% of patients show abnormal computed tomography (CT) findings. CT negative patients frequently suffer protracted somatic, behavioral, and neurocognitive dysfunction. Our goal was to evaluate biomarkers to identify mild TBI (mTBI) in patients with suspected head injury.MethodsAn observational ED study of head-injured and control patients was conducted at Johns Hopkins University (HeadSMART). Head CT was obtained (ACEP criteria) in patients with Glasgow Coma Scale scores of 13–15 and aged 18–80. Three candidate biomarker proteins, neurogranin (NRGN), neuron-specific enolase (NSE), and metallothionein 3 (MT3), were evaluated by immunoassay (samples <24 h from injury). American Congress of Rehabilitation Medicine (ACRM) criteria were used for diagnosis of mTBI patients for model building. Univariate analysis, logistic regression, and random forest (RF) algorithms were used for data analysis in R. Overall, 662 patients were studied. Statistical models were built using 328 healthy controls and 179 mTBI patients.ResultsMedian time from injury was 5.9 h (IQR, 4.0; range 0.8–24 h). mTBI patients had elevated NSE, but decreased MT3 versus controls (p < 0.01 for each). NRGN was also elevated but within 2–6 h after injury. In the derivation set, the best model to distinguish mTBI from healthy controls used three markers, age, and sex as covariates (C-statistic = 0.91, sensitivity 98%, specificity 72%). Panel test accuracy was validated with the 155 remaining ACRM+ mTBI patients. Applying the RF model to the ACRM+ mTBI validation set resulted in 78% correctly classified as mTBI (119/153). CT positive and CT negative validation subsets were 91% and 75% correctly classified. In samples taken <2 h from injury, 100% (10/10) samples classified correctly, indicating that hyperacute testing is possible with these biomarker assays. The model accuracy varied from 72–100% overall, and had greater accuracy with increasing severity, as shown by comparing CT+ with CT− (91% versus 75%), and Injury Severity Score ≥16 versus <16 (88% versus 72%, respectively). Objective blood tests, detecting NRGN, NSE, and MT3, can be used to identify mTBI, irrespective of neuroimaging findings

COVID-19 convalescent plasma boosts early antibody titer and does not influence the adaptive immune response

Multiple randomized, controlled clinical trials have yielded discordant results regarding the efficacy of convalescent plasma in outpatients, with some showing an approximately 2-fold reduction in risk and others showing no effect. We quantified binding and neutralizing antibody levels in 492 of the 511 participants from the Clinical Trial of COVID-19 Convalescent Plasma in Outpatients (C3PO) of a single unit of COVID-19 convalescent plasma (CCP) versus saline infusion. In a subset of 70 participants, peripheral blood mononuclear cells were obtained to define the evolution of B and T cell responses through day 30. Binding and neutralizing antibody responses were approximately 2-fold higher 1 hour after infusion in recipients of CCP compared with saline plus multivitamin, but levels achieved by the native immune system by day 15 were almost 10-fold higher than those seen immediately after CCP administration. Infusion of CCP did not block generation of the host antibody response or skew B or T cell phenotype or maturation. Activated CD4+ and CD8+ T cells were associated with more severe disease outcome. These data show that CCP leads to a measurable boost in anti-SARS-CoV-2 antibodies but that the boost is modest and may not be sufficient to alter disease course

Head injury serum markers for assessing response to trauma: Design of the HeadSMART study.

BACKGROUND: Accurate diagnosis and risk stratification of traumatic brain injury (TBI) at time of presentation remains a clinical challenge. The Head Injury Serum Markers for Assessing Response to Trauma study (HeadSMART) aims to examine blood-based biomarkers for diagnosing and determining prognosis in TBI. METHODS: HeadSMART is a 6-month prospective cohort study comparing emergency department patients evaluated for TBI (exposure group) to (1) emergency department patients evaluated for traumatic injury without head trauma and (2) healthy persons. Study methods and characteristics of the first 300 exposure participants are discussed. RESULTS: Of the first 300 participants in the exposure arm, 70% met the American Congress of Rehabilitation Medicine criteria for TBI, with the majority (80.1%) classified as mild TBI. The majority of subjects in the exposure arm had Glasgow Coma Scale scores of 13-15 (98.0%), normal head computed tomography (81.3%) and no prior history of concussion (71.7%). CONCLUSION: With systematic phenotyping, HeadSMART will facilitate diagnosis and risk-stratification of the heterogeneous group of individuals currently diagnosed with TBI