Pharmacogenomic knowledge and awareness among diverse patients treated with angiotensin converting enzyme inhibitors.

We developed novel electronic phenotyping algorithms for the BioMe biobank data, which accurately identified angiotensin converting enzyme inhibitor (ACEi)-induced angioedema cases and controls. A survey was mailed to all 1075 patients and 91 were returned. Over a third reported that prescribing physicians had not discussed with them the concepts of interindividual drug response variability or adverse event risk, and 73% of patients were previously unaware of pharmacogenomics; however, most patients were interested in having pharmacogenomic testing. Moreover, 67% of patients indicated that pharmacogenomic testing would positively influence their medication compliance. In addition to identifying an innovative approach to define biobank cohorts for pharmacogenomic studies, these results indicate that patients are interested in pharmacogenomic testing, which could translate to improved adherence.

Cervical spinal cord compression from subdural hematoma caused by traumatic nerve root avulsion: illustrative case.

BACKGROUND: Posttraumatic intradural hematomas of the cervical spine are rare findings that may yield significant neurological deficits if they compress the spinal cord. These compressive hematomas require prompt surgical evacuation. In certain instances, intradural hematomas may form from avulsion of cervical nerve roots. OBSERVATIONS: The authors present the case of a 29-year-old male who presented with right upper-extremity weakness in the setting of polytrauma after a motor vehicle accident. He had no cervical fractures but subsequently developed right lower-extremity weakness. Magnetic resonance imaging (MRI) demonstrated a compressive hematoma of the cervical spine that was initially read as an epidural hematoma. However, intraoperatively, it was found to be a subdural hematoma, eccentric to the right, stemming from an avulsion of the right C6 nerve root. LESSONS: Posttraumatic cervical subdural hematomas require rapid surgical evacuation if neurological deficits are present. The source of the hematoma may be an avulsed nerve root, and the associated deficits may be unilateral if the hematoma is eccentric to one side. Surgeons should be prepared for the possibility of an intradural hematoma even in instances in which MRI appears consistent with an epidural hematoma.

Progress towards triple elimination of mother-to-child transmission of HIV, hepatitis B and syphilis in Pacific Island Countries and Territories: a systematic review.

The diverse geographic, demographic, and societal factors in the Pacific Island Countries and Territories (PICTs) have contributed to unique epidemiological patterns of HIV, syphilis, and hepatitis B. Transmission can be during pregnancy, at the time of birth or via breastfeeding for HIV, and can have long-term adverse outcomes. Given the similarities in prevention of mother-to-child transmission of these infections, coordinated interventions for triple elimination are used. This systematic review has evaluated the peer-reviewed literature, grey literature, and global databases to assess the availability of data to report against elimination targets in the WHO Regional Framework for the Triple Elimination of Mother-to-Child Transmission of HIV, Hepatitis B and Syphilis in Asia and the Pacific 2018-2030. The secondary objective is to report on progress towards these targets. The findings show that none of the PICTs are on track to achieve triple elimination by 2030. Amongst the limited publicly available indicator data, there is suboptimal coverage for most indicators. It is important that there is an increase in availability of and access to antenatal care, testing, and treatment for pregnant women. Increased efforts are needed to collect data on key indicators and integrate reporting into existing systems to avoid extra burden. Funding: Leila Bell was supported by an Australian Government Research Training Program (RTP) Scholarship, Australia. Funding sources had no role in paper design, data collection, data analysis, interpretation, or writing of the paper.

Impact of the Thompson method on breastfeeding exclusivity and duration: Multi-method design.

BACKGROUND: How hospital clinicians facilitate breastfeeding in the first 48-72 h is critical to breastfeeding exclusivity and duration. Mothers who discharge hospital directly breastfeeding are more likely to continue exclusively breastfeeding at 3-months. OBJECTIVE: To assess the impact of facility-wide implementation of a physiological breastfeeding method (the Thompson method) on direct breastfeeding at hospital discharge and exclusive breastfeeding at 3-months of age. DESIGN: Multi-method design using interrupted time series analysis and surveys. SETTING(S): An Australian tertiary maternity hospital. PARTICIPANTS: 13,667 mother-baby pairs (interrupted time series analysis) and 495 postnatal mothers (surveys). METHODS: The Thompson method includes cradle position and hold, alignment of mouth-to-nipple, baby-led connection and seal, maternal fine-tuning for symmetry, and leisurely duration. We used a large pre-post implementation dataset and conducted interrupted time series analysis using a 24-month baseline period (January 2016 - December 2017); and a 15-month post-implementation period (April 2018 - June 2019). We recruited a sub-sample of women to complete surveys at hospital discharge and 3-months postpartum. Surveys were primarily used to measure impact of Thompson method on exclusive breastfeeding at 3-months, compared with a baseline survey conducted in same setting. RESULTS: Following implementation of the Thompson method, the declining trend in direct breastfeeding at hospital discharge was significantly averted by 0.39% each month relative to baseline (95% CI: 0.03% to 0.76%; p = 0.037). While the 3-month exclusive breastfeeding rate in the Thompson group was 3 percentage points higher than the baseline group; this result did not reach statistical significance. However, a subgroup analysis of women who discharged hospital exclusively breastfeeding revealed the relative odds of exclusive breastfeeding at 3-months in the Thompson group was 0.25 (95% CI: 0.17 to 0.38; p < 0.001), significantly better than the baseline group (Z = 3.23, p < 0.01) where the relative odds was only 0.07 (95% CI: 0.03 to 0.19; p < 0.001). CONCLUSIONS: Implementation of the Thompson method for well mother-baby pairs improved direct breastfeeding trends at hospital discharge. For women who discharged hospital exclusively breastfeeding, exposure to the Thompson method reduced the risk of exclusive breastfeeding discontinuation by 3-months. The positive impact of the method was potentially confounded by partial implementation and a parallel rise in birth interventions which undermine breastfeeding. We recommend strategies to strengthen clinician buy-in to the method, and future research using a cluster randomised trial design. TWEETABLE ABSTRACT: Facility-wide implementation of the Thompson method improves direct breastfeeding at hospital discharge and predicts breastfeeding exclusivity at 3-months.

Resection of an Intradural Extramedullary Capillary Hemangioma in the Lumbar Spine.

BACKGROUND AND IMPORTANCE: Capillary hemangiomas are space-occupying lesions that rarely affect the central nervous system. When they present within the spinal canal, they can cause insidious symptoms and threaten neurological function. In this study, we present a case of an intradural extramedullary capillary hemangioma of the lumbar spine, discuss our management strategy, and review the current literature. For the first time for this diagnosis, we also provide an operative video. CLINICAL PRESENTATION: The patient is a previously healthy 40-year-old man who presented with complaints of progressive low back and leg pain, numbness, and intermittent subjective urinary incontinence. MRI revealed a discrete, homogenously enhancing intradural extramedullary lesion at L4. This lesion was resected by performing an L4 laminoplasty, which entails en bloc removal of the L4 lamina and then securing it back into place once the intradural resection and dural closure are completed. Histological analysis revealed a diagnosis of capillary hemangioma. The patient had full resolution of his symptoms postoperatively. DISCUSSION: Definitive management of spinal capillary hemangiomas involves gross total resection and can be accomplished with laminoplasty. Because these benign tumors can be adherent to adjacent structures, intraoperative neuromonitoring is helpful adjunct to preserve neurological function for a good outcome. CONCLUSION: Capillary hemangiomas rarely affect the spine but should be considered on the list of differential diagnoses of intradural lesions.

BET Protein Inhibition Regulates Macrophage Chromatin Accessibility and Microbiota-Dependent Colitis.

Introduction: In colitis, macrophage functionality is altered compared to normal homeostatic conditions. Loss of IL-10 signaling results in an inappropriate chronic inflammatory response to bacterial stimulation. It remains unknown if inhibition of bromodomain and extra-terminal domain (BET) proteins alters usage of DNA regulatory elements responsible for driving inflammatory gene expression. We determined if the BET inhibitor, (+)-JQ1, could suppress inflammatory activation of macrophages in Il10-/- mice. Methods: We performed ATAC-seq and RNA-seq on Il10-/- bone marrow-derived macrophages (BMDMs) cultured in the presence and absence of lipopolysaccharide (LPS) with and without treatment with (+)-JQ1 and evaluated changes in chromatin accessibility and gene expression. Germ-free Il10-/- mice were treated with (+)-JQ1, colonized with fecal slurries and underwent histological and molecular evaluation 14-days post colonization. Results: Treatment with (+)-JQ1 suppressed LPS-induced changes in chromatin at distal regulatory elements associated with inflammatory genes, particularly in regions that contain motifs for AP-1 and IRF transcription factors. This resulted in attenuation of inflammatory gene expression. Treatment with (+)-JQ1 in vivo resulted in a mild reduction in colitis severity as compared with vehicle-treated mice. Conclusion: We identified the mechanism of action associated with a new class of compounds that may mitigate aberrant macrophage responses to bacteria in colitis.

Tobacco Use Is Associated With Increased 90-Day Readmission Among Patients Undergoing Surgery for Degenerative Spine Disease.

STUDY DESIGN: Retrospective database study. OBJECTIVE: Tobacco use is associated with complications after surgical procedures, including poor wound healing, surgical site infections, and cardiovascular events. We used the Nationwide Readmissions Database (NRD) to determine if tobacco use is associated with increased 30- and 90-day readmission among patients undergoing surgery for degenerative spine disorders. METHODS: Patients who underwent elective spine surgery were identified in the NRD from 2010 to 2014. The study population included patients with degenerative spine disorders treated with discectomy, fusion, or decompression. Descriptive and multivariate logistic regression analyses were performed to identify patient and hospital factors associated with 30- and 90-day readmission, with significance set at P value <.001. RESULTS: Within 30 days, 4.8% of patients were readmitted at a median time of 9 days. The most common reasons for 30-day readmission were postoperative infection (12.5%), septicemia (3.5%), and postoperative pain (3.0%). Within 90 days, 7.3% were readmitted at a median time of 18 days. The most common reasons for 90-day readmission were postoperative infection (9.6%), septicemia (3.5%), and pneumonia (2.3%). After adjustment for patient and hospital characteristics, tobacco use was independently associated with readmission at 90 days (odds ratio 1.05, 95% confidence interval 1.03-1.07, P < .0001) but not 30 days (odds ratio 1.02, 95% confidence interval 1.00-1.05, P = .045). CONCLUSIONS: Tobacco use is associated with readmission within 90 days after cervical and thoracolumbar spine surgery for degenerative disease. Tobacco use is a known risk factor for adverse health events and therefore should be considered when selecting patients for spine surgery.

'When they do that kind of bad things to me, I feel that they encourage me to be strong and be who I am': How transfeminine people in Samoa, Tonga and the Cook Islands experience discrimination, acceptance and a sense of place.

Data on transfeminine participants from a 2016 Pacific Multi-Country Mapping and Behavioural Study evidence high levels of verbal, physical and sexual abuse, as well as discrimination. In interviews from the same study, accounts of hardship were frequently countered with assertions of happiness and talk of acceptance. This paper analyses these accounts and, in particular, the ways in which interviewees viewed and managed their place in society. Data provide insights into the factors that support transfeminine occupation of a positive place in some contemporary Pacific settings, highlighting negotiation between modern and traditional, and local and global, cultures and values.

Air Pollution Particulate Matter Amplifies White Matter Vascular Pathology and Demyelination Caused by Hypoperfusion.

Cerebrovascular pathologies are commonly associated with dementia. Because air pollution increases arterial disease in humans and rodent models, we hypothesized that air pollution would also contribute to brain vascular dysfunction. We examined the effects of exposing mice to nanoparticulate matter (nPM; aerodynamic diameter ≤200 nm) from urban traffic and interactions with cerebral hypoperfusion. C57BL/6 mice were exposed to filtered air or nPM with and without bilateral carotid artery stenosis (BCAS) and analyzed by multiparametric MRI and histochemistry. Exposure to nPM alone did not alter regional cerebral blood flow (CBF) or blood brain barrier (BBB) integrity. However, nPM worsened the white matter hypoperfusion (decreased CBF on DSC-MRI) and exacerbated the BBB permeability (extravascular IgG deposits) resulting from BCAS. White matter MRI diffusion metrics were abnormal in mice subjected to cerebral hypoperfusion and worsened by combined nPM+BCAS. Axonal density was reduced equally in the BCAS cohorts regardless of nPM status, whereas nPM exposure caused demyelination in the white matter with or without cerebral hypoperfusion. In summary, air pollution nPM exacerbates cerebrovascular pathology and demyelination in the setting of cerebral hypoperfusion, suggesting that air pollution exposure can augment underlying cerebrovascular contributions to cognitive loss and dementia in susceptible elderly populations.

Air Pollution Particulate Matter Exposure and Chronic Cerebral Hypoperfusion and Measures of White Matter Injury in a Murine Model.

BACKGROUND: Exposure to ambient air pollution particulate matter (PM) is associated with increased risk of dementia and accelerated cognitive loss. Vascular contributions to cognitive impairment are well recognized. Chronic cerebral hypoperfusion (CCH) promotes neuroinflammation and blood-brain barrier weakening, which may augment neurotoxic effects of PM. OBJECTIVES: This study examined interactions of nanoscale particulate matter (nPM; fine particulate matter with aerodynamic diameter ≤200 nm) and CCH secondary to bilateral carotid artery stenosis (BCAS) in a murine model to produce white matter injury. Based on other air pollution interactions, we predicted synergies of nPM with BCAS. METHODS: nPM was collected using a particle sampler near a Los Angeles, California, freeway. Mice were exposed to 10 wk of reaerosolized nPM or filtered air (FA) for 150 h. CCH was induced by BCAS surgery. Mice (C57BL/6J males) were randomized to four exposure paradigms: a) FA, b) nPM, c) FA + BCAS, and d) nPM + BCAS. Behavioral outcomes, white matter injury, glial cell activation, inflammation, and oxidative stress were assessed. RESULTS: The joint nPM + BCAS group exhibited synergistic effects on white matter injury (2.3× the additive nPM and FA + BCAS scores) with greater loss of corpus callosum volume on T2 magnetic resonance imaging (MRI) (30% smaller than FA group). Histochemical analyses suggested potential microglial-specific inflammatory responses with synergistic effects on corpus callosum C5 immunofluorescent density and whole brain nitrate concentrations (2.1× and 3.9× the additive nPM and FA + BCAS effects, respectively) in the joint exposure group. Transcriptomic responses (RNA-Seq) showed greater impact of nPM + BCAS than individual additive effects, consistent with changes in proinflammatory pathways. Although nPM exposure alone did not alter working memory, the nPM + BCAS cohort demonstrated impaired working memory when compared to the FA + BCAS group. DISCUSSION: Our data suggest that nPM and CCH contribute to white matter injury in a synergistic manner in a mouse model. Adverse neurological effects may be aggravated in a susceptible population exposed to air pollution. https://doi.org/10.1289/EHP8792.

Nanoparticulate matter exposure results in white matter damage and an inflammatory microglial response in an experimental murine model.

Exposure to ambient air pollution has been associated with white matter damage and neurocognitive decline. However, the mechanisms of this injury are not well understood and remain largely uncharacterized in experimental models. Prior studies have shown that exposure to particulate matter (PM), a sub-fraction of air pollution, results in neuroinflammation, specifically the upregulation of inflammatory microglia. This study examines white matter and axonal injury, and characterizes microglial reactivity in the corpus callosum of mice exposed to 10 weeks (150 hours) of PM. Nanoscale particulate matter (nPM, aerodynamic diameter ≤200 nm) consisting primarily of traffic-related emissions was collected from an urban area in Los Angeles. Male C57BL/6J mice were exposed to either re-aerosolized nPM or filtered air for 5 hours/day, 3 days/week, for 10 weeks (150 hours; n = 18/group). Microglia were characterized by immunohistochemical double staining of ionized calcium-binding protein-1 (Iba-1) with inducible nitric oxide synthase (iNOS) to identify pro-inflammatory cells, and Iba-1 with arginase-1 (Arg) to identify anti-inflammatory/ homeostatic cells. Myelin injury was assessed by degraded myelin basic protein (dMBP). Oligodendrocyte cell counts were evaluated by oligodendrocyte transcription factor 2 (Olig2). Axonal injury was assessed by axonal neurofilament marker SMI-312. iNOS-expressing microglia were significantly increased in the corpus callosum of mice exposed to nPM when compared to those exposed to filtered air (2.2 fold increase; p<0.05). This was accompanied by an increase in dMBP (1.4 fold increase; p<0.05) immunofluorescent density, a decrease in oligodendrocyte cell counts (1.16 fold decrease; p<0.05), and a decrease in neurofilament SMI-312 (1.13 fold decrease; p<0.05) immunofluorescent density. Exposure to nPM results in increased inflammatory microglia, white matter injury, and axonal degradation in the corpus callosum of adult male mice. iNOS-expressing microglia release cytokines and reactive oxygen/ nitrogen species which may further contribute to the white matter damage observed in this model.

Serotonin 5-HT1B receptor-mediated behavior and binding in mice with the overactive and dysregulated serotonin transporter Ala56 variant.

RATIONALE: Elevated whole-blood serotonin (5-HT) is a robust biomarker in ~ 30% of patients with autism spectrum disorders, in which repetitive behavior is a core symptom. Furthermore, elevated whole-blood 5-HT has also been described in patients with pediatric obsessive-compulsive disorder. The 5-HT1B receptor is associated with repetitive behaviors seen in both disorders. Chronic blockade of serotonin transporter (SERT) reduces 5-HT1B receptor levels in the orbitofrontal cortex (OFC) and attenuates the sensorimotor deficits and hyperactivity seen with the 5-HT1B agonist RU24969. We hypothesized that enhanced SERT function would increase 5-HT1B receptor levels in OFC and enhance sensorimotor deficits and hyperactivity induced by RU24969. OBJECTIVES: We examined the impact of the SERT Ala56 mutation, which leads to enhanced SERT function, on 5-HT1B receptor binding and 5-HT1B-mediated sensorimotor deficits. METHODS: Specific binding to 5-HT1B receptors was measured in OFC and striatum of naïve SERT Ala56 or wild-type mice. The impact of the 5-HT1A/1B receptor agonist RU24969 on prepulse inhibition (PPI) of startle, hyperactivity, and expression of cFos was examined. RESULTS: While enhanced SERT function increased 5-HT1B receptor levels in OFC of Ala56 mice, RU24969-induced PPI deficits and hyperlocomotion were not different between genotypes. Baseline levels of cFos expression were not different between groups. RU24969 increased cFos expression in OFC of wild-types and decreased cFos in the striatum. CONCLUSIONS: While reducing 5-HT1B receptors may attenuate sensorimotor gating deficits, increased 5-HT1B levels in SERT Ala56 mice do not necessarily exacerbate these deficits, potentially due to compensations during neural circuit development in this model system.

Tobacco Use Is Associated with Readmission within 90 Days after Craniotomy.

OBJECTIVE: Tobacco use increases morbidity and mortality following craniotomy. Readmission is an important hospital metric of patient outcomes and has been used to inform reimbursement. This study aims to determine if tobacco use is associated with readmission within 90 days of hospital discharge among patients undergoing elective craniotomy. METHODS: The Nationwide Readmissions Database (NRD), a population-based, nationally representative database, was queried from 2010-2014. Patients undergoing craniotomy for benign or malignant tumors, vascular pathologies, and epilepsy were identified. Readmissions within 90 days of index hospitalization were characterized by admitting diagnoses. Tobacco use was defined by ICD-9 coding for active or prior use. Descriptive and multivariable regression analyses evaluated patient and hospital factors associated with readmission. RESULTS: The study population included 77,903 patients treated with craniotomy. Of these, 17,674 (22.6%) were readmitted within 90 days. The most common reasons for readmission were post-operative infection (5.8%), septicemia (4.2%), pulmonary embolism (3.9%), and pneumonia (2.9%). Tobacco use was associated with a 7% increased likelihood of 90-day readmission (OR 1.07, 95% CI 1.03-1.11, p = 0.0008) after accounting for other patient-, disease-, and hospital-level factors in multivariate analysis. CONCLUSIONS: Tobacco use was associated with increased 90-day readmission in patients undergoing craniotomy. Recognizing tobacco use as a modifiable risk factor of readmission presents an opportunity to identify susceptible patients.

Effects of ambient particulate matter on vascular tissue: a review.

Fine and ultra-fine particulate matter (PM) are major constituents of urban air pollution and recognized risk factors for cardiovascular diseases. This review examined the effects of PM exposure on vascular tissue. Specific mechanisms by which PM affects the vasculature include inflammation, oxidative stress, actions on vascular tone and vasomotor responses, as well as atherosclerotic plaque formation. Further, there appears to be a greater PM exposure effect on susceptible individuals with pre-existing cardiovascular conditions.

Comparison of Rates and Outcomes of Readmission to Index vs Non-index Hospitals After Intravenous Thrombolysis in Acute Stroke Patients.

National and regional systems of stroke care are designed to provide patients with widespread access to hospitals with thrombolytic capabilities. However, such triaging systems may contribute to fragmentation of care. This study aims to compare rates of readmission and outcomes between index and non-index hospitals for stroke patients following intravenous thrombolytic therapy (IVT). This study utilized a nationally representative sample of stroke patients with IVT from the Nationwide Readmissions Database from 2010 to 2014. Descriptive and regression analyses were performed for patient and hospital level factors that influenced 90-day readmissions and regression models were used to identify differences in mortality, complications, and repeat readmissions between patients readmitted to index (facility where IVT was administered) and non-index hospitals. In the study, 49415 stroke patients were treated with IVT, of whom 21.7% were readmitted within 90 days. Among readmissions, 79.4% of patients were readmitted to index hospitals and 20.6% to non-index hospitals. On multivariate logistic regression analysis, index hospital readmission was independently associated with lower frequency of second readmissions (non-index OR 1.09, 95%CI 1.07-1.11, p<0.0001) but not with increased mortality or major complications (p=ns). Approximately one-fifth of stroke patients treated with thrombolysis were readmitted within 90 days, one-fifth of whom were readmitted to non-index hospitals. Although readmission to index hospital was associated with lower frequency of subsequent readmissions, readmission to non-index hospital was not associated with increased mortality or major complications. This difference may be due to standardized algorithms, mature systems of care, and demanding metrics required of stroke centers.

Nisin M: a Bioengineered Nisin A Variant That Retains Full Induction Capacity but Has Significantly Reduced Antimicrobial Activity.

Nisin A is a potent antimicrobial with potential as an alternative to traditional antibiotics, and a number of genetically modified variants have been created that target clinically relevant pathogens. In addition to antimicrobial activity, nisin autoregulates its own production via a signal transduction pathway, a property that has been exploited in a protein expression system termed the nisin-controlled gene expression (NICE) system. Although NICE has become one of the most popular protein expression systems, one drawback is that the inducer peptide, nisin A, also has inhibitory activity. It has already been demonstrated that the N-terminal region of nisin A contributes to antimicrobial activity and signal transduction properties; therefore, we conducted bioengineering of nisin at positions Pro9 and Gly10 within ring B to produce a bank of variants that could potentially be used as alternative induction peptides. One variant, designated nisin M, has threonines at positions 9 and 10 and retains induction capacity comparable to that of wild-type nisin A, while most of the antimicrobial activity is abolished. Further analysis confirmed that nisin M produces a mix of peptides as a result of different degrees of dehydration of the two threonines. We show that nisin M exhibits potential as a more suitable alternative to nisin A for the expression of proteins that may be difficult to express or for production of proteins in strains that are sensitive to wild-type nisin. Moreover, it may address the increasing demand by industry for optimization of peptide fermentations to increase yields or production rates.IMPORTANCE This study describes the generation of a nisin variant with superior characteristics for use in the NICE protein expression system. The variant, termed nisin M, retains an induction capacity comparable to that of wild-type nisin A but exhibits significantly reduced antimicrobial activity and can therefore be used at concentrations that are normally toxic to the expression host.

Increased 30-day readmission rate after craniotomy for tumor resection at safety net hospitals in small metropolitan areas.

PURPOSE: Unplanned readmission of post-operative brain tumor patients is often attributed to hospital and patient characteristics and is associated with higher mortality and cost. Previous studies demonstrate multiple patient outcome disparities in safety net hospitals (SNHs) when compared to non-SNHs. This study uses the Nationwide Readmissions Database (NRD) to determine if initial brain tumor resection at SNHs is associated with increased 30-day non-elective readmission rates. METHODS: Patients with benign or malignant primary or metastatic brain tumor undergoing craniotomy for surgical resection were retrospectively identified in the NRD from 2010 to 2014. SNHs were defined as hospitals with Medicaid and uninsured patient burden in the top quartile. Descriptive and multivariate analyses employing survey-adjusted logistic regression evaluated patient and hospital level factors influencing 30-day readmissions. RESULTS: During the study period, 83,367 patients met inclusion criteria. 44.7% of patients had a benign tumor, and 55.3% had a malignant tumor. Secondary CNS neoplasm (5.99%), post-operative infection (5.96%), and septicemia (4.26%) caused most readmissions within 30 days. Patients had increased unplanned readmission rates if they underwent craniotomy for tumor resection at a SNH in a small metropolitan area (OR 1.11, 95% CI 1.02-1.21, p = 0.01), but not at a SNH in a large metropolitan area (OR 0.99, 95% CI 0.93-1.05, p = 0.73). CONCLUSION: This finding may reflect differences in access to care and disparities in neurosurgical resources between small and large metropolitan areas. Inequities in expertise and capacity are relevant as surgical volume was also related to readmission rates. Further studies may be warranted to address such disparities.

Frequency, predictors, and outcomes of readmission to index versus non-index hospitals after mechanical thrombectomy in patients with ischemic stroke.

BACKGROUND: Stroke systems of care employ a hub-and-spoke model, with fewer centers performing mechanical thrombectomy (MT) compared with stroke-receiving centers, where a higher number offer high-level, centralized treatment to a large number of patients. OBJECTIVE: To characterize rates and outcomes of readmission to index and non-index hospitals for patients with ischemic stroke who underwent MT. METHODS: This study leveraged a population-based, nationally representative sample of patients with stroke undergoing MT from the Nationwide Readmissions Database between 2010 and 2014. Descriptive, logistic regression analyses, and univariate and multivariate logistic regression models were carried out to determine patient- and hospital-level factors, mortality, complications, and subsequent readmissions associated with index and non-index hospitals' 90-day readmissions. RESULTS: In the study, 2111 patients with a stroke were treated with MT, of whom 534 were readmitted within 90 days. The most common reasons for readmission were: septicemia (5.9%), atrial fibrillation (4.8%), and cerebral artery occlusion with infarct (4.8%). Among readmitted patients, 387 (74%) were readmitted to index and 136 (26%) to non-index hospitals. On multivariable logistic regression analysis, non-index hospital readmission was not independently associated with major complications (p=0.09), mortality (p=0.34), neurological complications (p=0.47), or second readmission (p=0.92). CONCLUSION: One-quarter of patients with a stroke treated with MT were readmitted within 90 days, and one quarter of these patients were readmitted to non-index hospitals. Readmission to a non-index hospital was not associated with mortality or increased complication rates. In a hub-and-spoke model it is important that follow-up care for a specialized procedure can be performed effectively at a vast number of non-index hospitals covering a large geographic area.

Failure of Flow Diverter Therapy: Predictors and Management Strategies.

Flow diversion is a safe and effective treatment for many types of brain aneurysms. Even so, there remain some aneurysms that persist despite initial treatment. In studies with the longest follow-up (5 yr), at least 5% of aneurysms persist with this treatment modality. As the cumulative experience and clinical indications for flow diversion continue to expand, the anatomic and functional characteristics that are associated with aneurysm persistence are increasingly described. Identification of these factors preoperatively can help to guide initial treatment decisions, enhance monitoring protocols in the follow-up period, and establish best practices for re-treatment when necessary. Herein, we review published clinical series and provide examples to highlight variables implicated in aneurysm persistence after treatment with flow diversion.