Citations

Abstract BACKGROUND Cerebrospinal fluid (CSF) leak is a well-recognized complication after surgical resection of vestibular schwannomas and is associated with a number of secondary complications, including readmission and meningitis. OBJECTIVE To identify risk factors for and timing of 30-d readmission with CSF leak. METHODS Patients who had undergone surgical resection of a vestibular schwannoma from 1995 to 2010 were identified in the California Office of Statewide Health Planning and Development database. The most common admission diagnoses were identified by International Classification of Disease, ninth Revision, diagnosis codes, and predictors of readmission with CSF leak were determined using logistic regression. RESULTS A total of 6820 patients were identified. CSF leak, though a relatively uncommon cause of admission after discharge (3.52% of all patients), was implicated in nearly half of 490 readmissions (48.98%). Significant independent predictors of readmission with CSF leak were male sex (odds ratio [OR] 1.72, 95% confidence interval [CI] 1.32-2.25), first admission at a teaching hospital (OR 3.32, 95% CI 1.06-10.39), CSF leak during first admission (OR 1.84, 95% CI 1.33-2.55), obesity during first admission (OR 2.10, 95% CI 1.20-3.66), and case volume of first admission hospital (OR of log case volume 0.82, 95% CI 0.70-0.95). Median time to readmission was 6 d from hospital discharge. CONCLUSION This study has quantified CSF leak as an important contributor to nearly half of all readmissions following vestibular schwannoma surgery. We propose that surgeons should focus on technical factors that may reduce CSF leakage and take advantage of potential screening strategies for the detection of CSF leakage prior to first admission discharge.

BACKGROUNDThere is a glaring lack of published evidence‐based strategies to improve the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) patient experience scores on the physician domain. Strategies that have been used are resource intensive and difficult to sustain.OBJECTIVEWe hypothesized that prompting providers to assess their own etiquette‐based practices every 2 weeks over the course of 1 year would improve patient experience on the physician domain.DESIGNRandomized controlled trial.SETTING4 acute care hospitals.PARTICIPANTSHospitalists.INTERVENTIONHospitalists were randomized to the study or the control arm. The study arm was prompted every 2 weeks for 12 months to report how frequently they engaged in 7 best‐practice bedside etiquette behaviors. Control arm participants received similarly worded questions on quality improvement behaviors.MEASUREMENTProvider experience scores were calculated from the physician HCAHPS and Press Ganey survey provider items.RESULTSPhysicians reported high rates of etiquette‐based behavior at baseline, and this changed modestly over the study period. Self‐reported etiquette behaviors were not associated with experience scores. The difference in difference analysis of the baseline and postintervention physician experience scores between the intervention arm and the control arm was not statistically significant (P = 0.71).CONCLUSIONIn this 12‐month study, biweekly reflection and reporting of best‐practice bedside etiquette behaviors did not result in significant improvement on physician domain experience scores. It is likely that hospitalists' self‐assessment of their bedside etiquette may not reflect patient perception of these behaviors. Furthermore, hospitalists may be resistant to improvement in this area since they rate themselves highly at baseline.

Blood coagulation is essential for physiological hemostasis but simultaneously contributes to thrombotic disease. However, molecular and cellular events controlling initiation and propagation of coagulation are still incompletely understood. In this study, we demonstrate an unexpected role of eosinophils during plasmatic coagulation, hemostasis, and thrombosis. Using a large-scale epidemiological approach, we identified eosinophil cationic protein as an independent and predictive risk factor for thrombotic events in humans. Concurrent experiments showed that eosinophils contributed to intravascular thrombosis by exhibiting a strong endogenous thrombin-generation capacity that relied on the enzymatic generation and active provision of a procoagulant phospholipid surface enriched in 12/15-lipoxygenase–derived hydroxyeicosatetraenoic acid–phosphatidylethanolamines. Our findings reveal a previously unrecognized role of eosinophils and enzymatic lipid oxidation as regulatory elements that facilitate both hemostasis and thrombosis in response to vascular injury, thus identifying promising new targets for the treatment of thrombotic disease.

Abstract Follicular Th (Tfh) cells are a distinct subset of Th cells that help B cells produce class-switched antibodies. Studies have demonstrated that Tfh cells are highly prone to HIV infection and replication. However, the molecular mechanisms underlying this phenomenon are largely unclear. Here, we show that murine and human Tfh cells have diminished constitutive expression of IFN-stimulated genes (ISGs) inclusive of antiviral resistance factor MX dynamin-like GTPase 2 (MX2) and IFN-induced transmembrane 3 (IFITM3) compared with non-Tfh cells. A lower antiviral resistance in Tfh was consistent with a higher susceptibility to retroviral infections. Mechanistically, we found that BCL6, a master regulator of Tfh cell development, binds to ISG loci and inhibits the expression of MX2 and IFITM3 in Tfh cells. We demonstrate further that inhibition of the BCL6 BR-C, ttk, and bab (BTB) domain function increases the expression of ISGs and suppresses HIV infection and replication in Tfh cells. Our data reveal a regulatory role of BCL6 in inhibiting antiviral resistance factors in Tfh cells, thereby promoting the susceptibility Tfh cells to viral infections. Our results indicate that the modulation of BCL6 function in Tfh cells could be a potential strategy to enhance Tfh cell resistance to retroviral infections and potentially decrease cellular reservoirs of HIV infection.

Objective Limited data exist regarding the outcomes of non-cardiac procedures (NCPs) in adult patients after Fontan operations (Fontan patients). Methods To compare procedural outcomes after NCPs in Fontan patients with outcomes for two matched control groups: patients with repaired congenital heart disease and biventricular circulation (CHD-BiV) and patients with no heart disease (NHD). We defined cyanosis as oxygen saturation <90% and procedural hypoxia as saturation <80% or a decrease in saturation >10% from baseline. Results There were 538 NCPs in 154 Fontan patients (mean age, 30 years) performed in 1990–2015. Sedation and anaesthesia types were monitored anaesthesia care (256,48%), general anaesthesia (51,9%), minimal sedation (105,20%), local anaesthesia (75,14%) and regional anaesthesia (51,9%). Ninety-three complications occurred in 79 procedures (15%) and included arrhythmia requiring intervention (9), hypotension (14), bradycardia (8), hypoxia (38), heart failure requiring intravenous diuretics (2), acute kidney injury (3), bleeding requiring blood transfusion (1), unplanned procedures for dialysis catheter placement (2), readmission (2), unplanned hospitalisation for hypoxia (8) and unplanned transfer to intensive care unit (1). Baseline cyanosis was the only multivariable risk factor for complications (HR, 1.87 (95% CI 1.14 to 3.67), p=0.04). Procedural complications were more common in the Fontan group (18%) than in the CHD-BiV (5%) and NHD groups (1.4%) (p=0.001). Conclusions Complications after NCPs were more common in Fontan patients, and baseline cyanosis was a risk factor for complications. All-cause mortality was low and may be related to the multidisciplinary care approach used for Fontan patients at our centre.

ABSTRACTPSP is a pathologically defined neurodegenerative tauopathy with a variety of clinical presentations including typical Richardson's syndrome and other variant PSP syndromes. A large body of neuroimaging research has been conducted over the past two decades, with many studies proposing different structural MRI and molecular PET/SPECT biomarkers for PSP. These include measures of brainstem, cortical and striatal atrophy, diffusion weighted and diffusion tensor imaging abnormalities, [18F] fluorodeoxyglucose PET hypometabolism, reductions in striatal dopamine imaging and, most recently, PET imaging with ligands that bind to tau. Our aim was to critically evaluate the degree to which structural and molecular neuroimaging metrics fulfill criteria for diagnostic biomarkers of PSP. We queried the PubMed, Cochrane, Medline, and PSYCInfo databases for original research articles published in English over the past 20 years using postmortem diagnosis or the NINDS‐SPSP criteria as the diagnostic standard from 1996 to 2016. We define a five‐level theoretical construct for the utility of neuroimaging biomarkers in PSP, with level 1 representing group‐level findings, level 2 representing biomarkers with demonstrable individual‐level diagnostic utility, level 3 representing biomarkers for early disease, level 4 representing surrogate biomarkers of PSP pathology, and level 5 representing definitive PSP biomarkers of PSP pathology. We discuss the degree to which each of the currently available biomarkers fit into this theoretical construct, consider the role of biomarkers in the diagnosis of Richardson's syndrome, variant PSP syndromes and autopsy confirmed PSP, and emphasize current shortfalls in the field. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

ABSTRACTBackgroundProgressive supranuclear palsy (PSP) is a neuropathologically defined disease presenting with a broad spectrum of clinical phenotypes.ObjectiveTo identify clinical features and investigations that predict or exclude PSP pathology during life, aiming at an optimization of the clinical diagnostic criteria for PSP.MethodsWe performed a systematic review of the literature published since 1996 to identify clinical features and investigations that may predict or exclude PSP pathology. We then extracted standardized data from clinical charts of patients with pathologically diagnosed PSP and relevant disease controls and calculated the sensitivity, specificity, and positive predictive value of key clinical features for PSP in this cohort.ResultsOf 4166 articles identified by the database inquiry, 269 met predefined standards. The literature review identified clinical features predictive of PSP, including features of the following 4 functional domains: ocular motor dysfunction, postural instability, akinesia, and cognitive dysfunction. No biomarker or genetic feature was found reliably validated to predict definite PSP. High‐quality original natural history data were available from 206 patients with pathologically diagnosed PSP and from 231 pathologically diagnosed disease controls (54 corticobasal degeneration, 51 multiple system atrophy with predominant parkinsonism, 53 Parkinson's disease, 73 behavioral variant frontotemporal dementia). We identified clinical features that predicted PSP pathology, including phenotypes other than Richardson's syndrome, with varying sensitivity and specificity.ConclusionsOur results highlight the clinical variability of PSP and the high prevalence of phenotypes other than Richardson's syndrome. The features of variant phenotypes with high specificity and sensitivity should serve to optimize clinical diagnosis of PSP. © 2017 International Parkinson and Movement Disorder Society

The mononegaviral family Filoviridae has eight members assigned to three genera and seven species. Until now, genus and species demarcation were based on arbitrarily chosen filovirus genome sequence divergence values (≈50% for genera, ≈30% for species) and arbitrarily chosen phenotypic virus or virion characteristics. Here we report filovirus genome sequence-based taxon demarcation criteria using the publicly accessible PAirwise Sequencing Comparison (PASC) tool of the US National Center for Biotechnology Information (Bethesda, MD, USA). Comparison of all available filovirus genomes in GenBank using PASC revealed optimal genus demarcation at the 55–58% sequence diversity threshold range for genera and at the 23–36% sequence diversity threshold range for species. Because these thresholds do not change the current official filovirus classification, these values are now implemented as filovirus taxon demarcation criteria that may solely be used for filovirus classification in case additional data are absent. A near-complete, coding-complete, or complete filovirus genome sequence will now be required to allow official classification of any novel “filovirus.” Classification of filoviruses into existing taxa or determining the need for novel taxa is now straightforward and could even become automated using a presented algorithm/flowchart rooted in RefSeq (type) sequences.