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Astrocytes are critical for the development and function of synapses. There are notable species differences between human astrocytes and commonly used animal models. Yet, it is unclear whether astrocytic genes involved in synaptic function are stable or exhibit dynamic changes associated with disease states and age in humans, which is a barrier in understanding human astrocyte biology and its potential involvement in neurologic diseases. To better understand the properties of human astrocytes, we acutely purified astrocytes from the cerebral cortices of over 40 humans across various ages, sexes, and disease states. We performed RNA sequencing to generate transcriptomic profiles of these astrocytes and identified genes associated with these biological variables. We found that human astrocytes in tumor-surrounding regions downregulate genes involved in synaptic function and sensing of signals in the microenvironment, suggesting involvement of peritumor astrocytes in tumor-associated neural circuit dysfunction. In aging, we also found downregulation of synaptic regulators and upregulation of markers of cytokine signaling, while in maturation we identified changes in ionic transport with implications for calcium signaling. In addition, we identified subtle sexual dimorphism in human cortical astrocytes, which has implications for observed sex differences across many neurologic disorders. Overall, genes involved in synaptic function exhibit dynamic changes in the peritumor microenvironment and aging. These data provide powerful new insights into human astrocyte biology in several biologically relevant states that will aid in generating novel testable hypotheses about homeostatic and reactive astrocytes in humans.SIGNIFICANCE STATEMENTAstrocytes are an abundant class of cells playing integral roles at synapses. Astrocyte dysfunction is implicated in a variety of human neurologic diseases. Yet our knowledge of astrocytes is largely based on mouse studies. Direct knowledge of human astrocyte biology remains limited. Here, we present transcriptomic profiles of human cortical astrocytes, and we identified molecular differences associated with age, sex, and disease state. We found that peritumor and aging astrocytes downregulate genes involved in astrocyte–synapse interactions. These data provide necessary insight into human astrocyte biology that will improve our understanding of human disease.

Meningiomas are the most common intracranial neoplasms. Although genomic analysis has helped elucidate differences in survival, there is evidence that racial disparities may influence outcomes. African Americans have a higher incidence of meningiomas and poorer survival outcomes. The etiology of these disparities remains unclear, but may include a combination of pathophysiology and other factors. OBJECTIVE: To determine factors that contribute to different clinical outcomes in racial populations. METHODS: We retrospectively reviewed 305 patients who underwent resection for meningiomas at a single tertiary care facility. We used descriptive statistics and univariate, multivariable, and Kaplan-Meier analyses to study clinical, radiographical, and histopathological differences. RESULTS: Minority patients were more likely to present through the emergency department than an outpatient clinic (P < .0001). They were more likely to present with more advanced clinical symptoms with lower Karnofsky Performance scores, more frequently had peritumoral edema (P = .0031), and experienced longer postoperative stays in the hospital (P = .0053), and African-American patients had higher hospitalization costs (P = .046) and were more likely to be publicly insured. Extent of resection was an independent predictor of recurrence freedom (P = .039). Presentation in clinic setting trended toward an association with recurrence-free survival (P = .055). We observed no significant difference in gross total resection rates, postoperative recurrence, or recurrence-free survival. CONCLUSION: Minority patients are more likely to present with severe symptoms, require longer perioperative hospitalization, and generate higher hospitalization costs. This may be due to socioeconomic factors that affect access to health care. Targeting barriers to access, especially to subspecialty care, may facilitate more appropriate and timely diagnosis, thereby improving patient care and outcomes.

BACKGROUND CONTEXT Improving value is an established point of emphasis to reduce the rapidly rising health care costs in the United States. Back pain is a major driver of costs with a substantial fraction caused by lumbar radiculopathy. The most common surgical treatment for lumbar radiculopathy is microdiscectomy. Research is sparse regarding variables driving cost in microdiscectomies and often limited by cost data derived from payer-based Medicare data. PURPOSE To identify targets for cost reduction by determining variables associated with significant cost variation in microdiscectomies, using cost data derived from the Value Driven Outcomes tool and actual system costs. STUDY DESIGN Single-center, retrospective study of prospectively collected registry data. PATIENT SAMPLE Six hundred twenty-two patients identified by CPT code and manually screened for initial, unilateral, single-level lumbar discectomy performed between 2014 and 2018 at a single institution. OUTCOME MEASURES Primary outcome measures include total direct cost, clinical length of stay, and OR minutes. Total Direct Cost was further differentiated into facility and nonfacility costs. METHODS Univariate and multivariate generalized linear models (GLM) were used to identify variables associated with variation in primary outcome measures. Costs were normalized by mean cost for patients with normal body mass index (BMI) and a healthy American Society of Anesthesiologists (ASA) classification. Average marginal effects were reported as percentage of normalized costs. RESULTS Advanced age, male gender, Hispanic, black, unemployment, obesity, higher ASA class, insurance status, and being retired were positively associated with costs in univariate analysis. Asian, Native American, outpatient procedures, and being a student were associated with decreases in costs. In multivariate analysis, we found that obesity led to higher average marginal total direct (9%), total facility (15%), and facility OR costs (22%), as well as 24 more OR minutes per surgery. While being overweight was not associated with greater total direct costs, it was associated with higher total facility (8%), and facility OR costs (12%), with 11 more OR minutes per surgery. Age was associated with a longer LOS but not with OR costs. As expected, outpatient surgical costs, LOS, and OR time were significantly lower than inpatient procedures. Severe systematic disease was associated with greater total and nonfacility costs. In addition, Medicare patients had higher facility costs (14%) compared to privately insured patients. CONCLUSIONS Significant drivers of total direct cost in multivariate GLM analysis were obesity, severe systemic disease and inpatient surgery. Average LOS was increased due to age and inpatient status, conversely it was decreased by unemployment and retirement. Significant variables in OR time were male sex, Hispanic race and both obese and overweight BMIs.

This work presents automated apnea event de-tection using blood oxygen saturation (SpO2) and pulse rate (PR), conveniently recorded with a pulse oximeter. A large, diverse cohort of patients (n=8068, age≥40 years) from the sleep heart health study dataset with annotated sleep events have been employed in this study. A deep-learning model is trained to detect apnea in successive 30 s epochs and performances are assessed on two independent sub-cohorts of test data. The proposed algorithm showcases the highest test performance of 90.4 % area under the receiver operating characteristic curve and 58.9% area under the precision-recall curve for epoch-based apnea detection. Additionally, the model consistently performs well across various apnea subtypes, with the highest sensitivity of 93.4 % for obstructive apnea detection followed by 90.5 % for central apnea and 89.1 % for desaturation associated hypopnea. Overall, the proposed algorithm provides a robust and sensitive approach for sleep apnea event detection using a noninvasive pulse oximeter sensor. Clinical Relevance - The study establishes high sensitivity for automated epoch-based apnea detection across a diverse study cohort with various comorbidities using simply a pulse oximeter. This highly cost-effective approach could also enable convenient sleep and health monitoring over long-term.

ObjectivesTo inform national planning, six indicators posed by the Lancet Commission on Global Surgery were collected for the Mongolian surgical system. This situational analysis shows one lower middle-income country’s ability to collect the indicators aided by a well-developed health information system.DesignAn 11-year retrospective analysis of the Mongolian surgical system using data from the Health Development Center, National Statistics Office and Household Socio-Economic Survey. Access estimates were based on travel time to capable hospitals. Provider density, surgical volume and postoperative mortality were calculated at national and regional levels. Protection against impoverishing and catastrophic expenditures was assessed against standard out-of-pocket expenditure at government hospitals for individual operations.SettingMongolia’s 81 public hospitals with surgical capability, including tertiary, secondary and primary/secondary facilities.ParticipantsAll operative patients in Mongolia’s public hospitals, 2006–2016.Primary and secondary outcome measuresPrimary outcomes were national-level results of the indicators. Secondary outcomes include regional access; surgeons, anaesthesiologists and obstetricians (SAO) density; surgical volume; and perioperative mortality.ResultsIn 2016, 80.1% of the population had 2-hour access to essential surgery, including 60% of those outside the capital. SAO density was 47.4/100 000 population. A coding change increased surgical volume to 5784/100 000 population, and in-hospital mortality decreased from 0.27% to 0.14%. All households were financially protected from caesarean section. Appendectomy carried 99.4% and 98.4% protection, external femur fixation carried 75.4% and 50.7% protection from impoverishing and catastrophic expenditures, respectively. Laparoscopic cholecystectomy carried 42.9% protection from both.ConclusionsMongolia meets national benchmarks for access, provider density, surgical volume and postoperative mortality with notable limitations. Significant disparities exist between regions. Unequal access may be efficiently addressed by strengthening or building key district hospitals in population-dense areas. Increased financial protections are needed for operations involving hardware or technology. Ongoing monitoring and evaluation will support the development of context-specific interventions to improve surgical care in Mongolia.

BACKGROUND AND AIMS: In a United States randomized-effectiveness trial comparing extended-release naltrexone (XR-NTX) with buprenorphine-naloxone (BUP-NX) for the prevention of opioid relapse among participants recruited during inpatient detoxification (CTN-0051), the requirement to complete opioid detoxification prior to initiating XR-NTX resulted in lower rates of initiation of XR-NTX (72%-XR-NTX vs. 94%-BUP-NX). This led to higher relapse rates and average healthcare costs among XR-NTX participants. This study estimated the extent to which a more efficient model of XR-NTX induction would improve the economic value of XR-NTX relative to BUP-NX. DESIGN: This was a retrospective secondary analysis of CTN-0051 trial data, including follow up data over 24–36 weeks. SETTING: Eight community-based, inpatient-detoxification and follow-up outpatient treatment facilities in the USA. PARTICIPANTS: 283 participants randomized to receive XR-NTX. MEASUREMENTS: Efficiency was estimated using a multivariable generalized-structural-equation model to explore simultaneous determinants of XR-NTX induction and induction duration (detoxification + residential days). Cost-effectiveness was estimated from the healthcare sector perspective and included expected costs and quality-adjusted life-years (QALYs). FINDINGS: Treatment site was the only modifiable factor that simultaneously increased the likelihood of XR-NTX induction and decreased induction duration. Incorporating the higher predicted probability of XR-NTX induction, and fewer predicted days of detoxification and subsequent residential treatment into the cost-effectiveness framework, reduced the incremental average 24-week total cost of XR-NTX treatment from $5,317 more than that of BUP-NX (p=0.01) to a non-statistically-significant difference of $1,016 (p=0.63). QALYs gained remained similar across arms. CONCLUSION: Adopting an efficient model of extended-release naltrexone initiation could result in extended-release naltrexone and buprenorphine-naloxone being of comparable economic value from the healthcare sector perspective over 24–36 weeks for patients seeking treatment for opioid use disorder at an inpatient detoxification facility.

Patients with glioblastoma (GBM) need bold new approaches to their treatment, yet progress has been hindered by a relative inability to dynamically track treatment response, mechanisms of resistance, evolution of targetable mutations, and changes in mutational burden. We are writing on behalf of a multidisciplinary group of academic neuro-oncology professionals who met at the collaborative Christopher Davidson Forum at Washington University in St Louis in the fall of 2019. We propose a dramatic but necessary change to the routine management of patients with GBM to advance the field: to routinely biopsy recurrent GBM at the time of presumed recurrence. Data derived from these samples will identify true recurrence vs treatment effect, avoid treatments with little chance of success, enable clinical trial access, and aid in the scientific advancement of our understanding of GBM.

Evaluating the effect of convalescent plasma (CP) on some cytokine storm indices in severe COVID-19 patients. Totally, 62 patients were randomly assigned into two groups for this clinical trial. Patients in the intervention group received one unit (500 mL) plasma on the admission day plus standard drugs while the controls merely received standard treatments. Eventually, primary and secondary outcomes were evaluated. In the CP group, compared with controls, the mean levels of lymphocytes and IL-10 significantly increased while the levels of IL-6, TNF-α, and IFN-γ decreased (p 0.05) while WHO severity scores remarkably improved (p = 0.01), despite the higher frequency of underlying diseases among the CP group (66.7%) vs. controls (33.3%). Although CP has a remarkable immunomodulatory and antiviral potential to improve the cytokine storm and disease severity in COVID-19 patients, it did not considerably affect the mortality rate. Supplementary Information The online version contains supplementary material available at 10.1007/s11739-021-02734-8.

reSET-O is a Food and Drug Administration-cleared prescription digital therapeutic (PDT) indicated to improve outpatient-treatment retention of patients with opioid use disorder (OUD). This study examined the cost-effectiveness and budget impact of reSET-O in conjunction with treatment as usual (reSET-O + TAU) relative to TAU.Adult patients with ≥1 OUD diagnosis, treated with buprenorphine from 1 January 2015 to 30 March 2018, were identified from Truven Health MarketScan Commercial and Medicare Supplemental Research Databases. Twelve-week healthcare resource utilization (HCRU) costs for patients categorized as adherent and nonadherent to buprenorphine treatment were estimated. Total 12-week costs included OUD treatment and other HCRU costs. The cost-effectiveness of reSET-O + TAU was modeled in accordance with prior clinical trial outcomes. The 12-week budget impact of reSET-O was modeled for a 1 million-member healthcare plan.Higher buprenorphine adherence was associated with lower HCRU costs in claims data. Twelve-week per-patient total costs were $305 more for those receiving reSET-O + TAU than those receiving TAU. The incremental cost-effectiveness ratio was $18.70 per 1 percentage-point increase in the treatment retention rate. The probability that reSET-O + TAU would be considered cost-effective was over 92% for willingness-to-pay thresholds of $6,000 or more. The 12-week budget impact of reSET-O was $8,908, translating to $0.003 per member per month.The findings of the cost-effectiveness and budget impact modeling are limited by the assumptions of the models due to uncertainty around some inputs. While no model is free of bias, the inputs for this model were carefully selected to reflect contemporary treatment patterns.Depending on the payer's willingness to pay, reSET-O may be cost-effective in increasing buprenorphine treatment retention rates. reSET-O results in an approximate budget impact of $0.003 per member per month, depending on market share and the prevalence of the population receiving treatment for OUD.

Background Metastasis is the primary cause of cancer mortality accounting for 90% of cancer deaths. Our understanding of the molecular mechanisms driving metastasis is rudimentary. Results We perform whole exome sequencing (WES), RNA sequencing, methylation microarray, and immunohistochemistry (IHC) on 8 pairs of non-small cell lung cancer (NSCLC) primary tumors and matched distant metastases. Furthermore, we analyze published WES data from 35 primary NSCLC and metastasis pairs, and transcriptomic data from 4 autopsy cases with metastatic NSCLC and one metastatic lung cancer mouse model. The majority of somatic mutations are shared between primary tumors and paired distant metastases although mutational signatures suggest different mutagenesis processes in play before and after metastatic spread. Subclonal analysis reveals evidence of monoclonal seeding in 41 of 42 patients. Pathway analysis of transcriptomic data reveals that downregulated pathways in metastases are mainly immune-related. Further deconvolution analysis reveals significantly lower infiltration of various immune cell types in metastases with the exception of CD4+ T cells and M2 macrophages. These results are in line with lower densities of immune cells and higher CD4/CD8 ratios in metastases shown by IHC. Analysis of transcriptomic data from autopsy cases and animal models confirms that immunosuppression is also present in extracranial metastases. Significantly higher somatic copy number aberration and allelic imbalance burdens are identified in metastases. Conclusions Metastasis is a molecularly late event, and immunosuppression driven by different molecular events, including somatic copy number aberration, may be a common characteristic of tumors with metastatic plasticity.

Background Craniosynostosis is the premature fusion of ≥1 cranial sutures and often requires surgical intervention. Surgery may involve extensive osteotomies, which can lead to substantial blood loss. Currently, there are no consensus recommendations for guiding blood conservation or transfusion in this patient population. The aim of this study is to develop a machine-learning model to predict blood product transfusion requirements for individual pediatric patients undergoing craniofacial surgery. Methods Using data from 2143 patients in the Pediatric Craniofacial Surgery Perioperative Registry, we assessed 6 machine-learning classification and regression models based on random forest, adaptive boosting (AdaBoost), neural network, gradient boosting machine (GBM), support vector machine, and elastic net methods with inputs from 22 demographic and preoperative features. We developed classification models to predict an individual's overall need for transfusion and regression models to predict the number of blood product units to be ordered preoperatively. The study is reported according to the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) checklist for prediction model development. Results The GBM performed best in both domains, with an area under receiver operating characteristic curve of 0.87 ± 0.03 (95% confidence interval) and F-score of 0.91 ± 0.04 for classification, and a mean squared error of 1.15 ± 0.12, R-squared (R) of 0.73 ± 0.02, and root mean squared error of 1.05 ± 0.06 for regression. GBM feature ranking determined that the following variables held the most information for prediction: platelet count, weight, preoperative hematocrit, surgical volume per institution, age, and preoperative hemoglobin. We then produced a calculator to show the number of units of blood that should be ordered preoperatively for an individual patient. Conclusions Anesthesiologists and surgeons can use this continually evolving predictive model to improve clinical care of patients presenting for craniosynostosis surgery.

Opioid use disorder (OUD) is highly prevalent among incarcerated populations, and the risk of fatal overdose following release from prison is substantial. Despite efficacy, few correctional facilities provide evidence-based addiction treatment. Extended-release injectable naltrexone (XR-NTX) administered prior to release from incarceration may improve health and economic outcomes.We conducted an economic evaluation alongside a randomized controlled trial testing the effectiveness of XR-NTX before release from prison (n = 38) vs. XR-NTX referral after release (n = 48) of incarcerated participants with OUD, both groups continuing treatment at a community addiction treatment center. The incremental cost-effectiveness ratio (ICER) assessed the cost-effectiveness of XR-NTX before release compared to referral after release for three stakeholder perspectives at 12- and 24-week periods: state policymaker, health care sector, and societal. Effectiveness measures included quality-adjusted life-years (QALYs) and abstinent years from opioids. In addition, we categorized resources as OUD-related and non-OUD-related medical care, state transfer payments, and other societal costs (productivity, criminal justice resources, etc.).Results showed an association between XR-NTX and greater OUD-related costs and total costs from the state policymaker perspective. QALYs gained were positive but statistically insignificant between arms; however, results showed XR-NTX had an estimated 15.5 more days of opioid abstinence over 24 weeks and statistically significant at a 95 % confidence level based on the distribution of bootstrapped samples. We found that estimated ICERs to begt; $500,000 per QALY for all stakeholder perspectives. For the abstinent-year effectiveness measure, we found XR-NTX before release to be cost-effective at a 95 % confidence level for willingness-to-pay valuesgt;$49,000 per abstinent-year, across all perspectives.XR-NTX administered to persons who are incarcerated with OUD before release may provide value for stakeholders and bridge a well-known treatment gap for this vulnerable population. Lower than expected participant engagement and missing data limit our results, and study outcomes may be sensitive to methods that address missing data if replicated.

Cough is one of the most common symptoms of COVID-19. It is easily recorded using a smartphone for further analysis. This makes it a great way to track and possibly identify patients with COVID. In this paper, we present a deep learning-based algorithm to identify whether a patient's audio recording contains a cough for subsequent COVID screening. More generally, cough identification is valuable for the remote monitoring and tracking of infections and chronic conditions. Our algorithm is validated on our novel dataset in which COVID-19 patients were instructed to volunteer natural coughs. The validation dataset consists of real patient cough and no cough audio. It was supplemented by files without cough from publicly available datasets that had cough-like sounds including: throat clearing, snoring, etc. Our algorithm had an area under receiver operating characteristic curve statistic of 0.977 on a validation set when making a cough/no cough determination. The specificity and sensitivity of the model on a reserved test set, at a threshold set by the validation set, was 0.845 and 0.976. This algorithm serves as a fundamental step in a larger cascading process to monitor, extract, and analyze COVID-19 patient coughs to detect the patient's health status, symptoms, and potential for deterioration.

Since the COVID-19 pandemic began, research has shown promises in building COVID-19 screening tools using cough recordings as a convenient and inexpensive alternative to current testing techniques. In this paper, we present a novel and fully automated algorithm framework for cough extraction and COVID-19 detection using a combination of signal processing and machine learning techniques. It involves extracting cough episodes from audios of a diverse real-world noisy conditions and then screening for the COVID-19 infection based on the cough characteristics. The proposed algorithm was developed and evaluated using self-recorded cough audios collected from COVID-19 patients monitored by Biovitals

States' approaches to addressing prenatal substance use are widely heterogeneous, ranging from supportive policies that enhance access to substance use disorder (SUD) treatment to punitive policies that criminalize prenatal substance use. We studied the effect of these prenatal substance use policies (PSUPs) on medications for opioid use disorder (OUD) treatment, including buprenorphine, naltrexone, and methadone, psychosocial services for SUD treatment, opioid prescriptions, and opioid overdoses among commercially insured pregnant females with OUD. We evaluated: (1) punitive PSUPs criminalizing prenatal substance use or defining it as child maltreatment; (2) supportive PSUPs granting pregnant females priority access to SUD treatment; and (3) supportive PSUPs funding targeted SUD treatment programs for pregnant females.We analyzed 2006-2019 MarketScan Commercial Claims and Encounters data. The longitudinal sample comprised females aged 15-45 with an OUD diagnosis at least once during the study period. We estimated fixed effects models that compared changes in outcomes between pregnant and nonpregnant females, in states with and without a PSUP, before and after PSUP implementation.Our analytical sample comprised 2,438,875 person-quarters from 164,538 unique females, of which 13% were pregnant at least once during the study period. We found that following the implementation of PSUPs funding targeted SUD treatment programs, the proportion of opioid overdoses decreased 45% and of any OUD medication increased 11%, with buprenorphine driving this increase (13%). The implementation of SUD treatment priority PSUPs was not associated with significant changes in outcomes. Following punitive PSUP implementation, the proportion receiving psychosocial services for SUD (12%) and methadone (30%) services decreased. In specifications that estimated the impact of criminalizing policies only, the strongest type of punitive PSUP, opioid overdoses increased 45%.Our findings suggest that supportive approaches that enhance access to SUD treatment may effectively reduce adverse maternal outcomes associated with prenatal opioid use. In contrast, punitive approaches may have harmful effects. These findings support leading medical organizations' stance on PSUPs, which advocate for supportive policies that are centered on increased access to SUD treatment and safeguard against discrimination and stigmatization. Our findings also oppose punitive policies, as they may intensify marginalization of pregnant females with OUD seeking treatment.

Determining when a patient can be discharged from a care setting is critical to optimize the utilization and delivery of timely care. Furthermore, timely discharge can lead to better clinical outcomes by effectively mitigating the prolonged length of stay in a care environment. This paper presents a novel algorithm for the prediction of likelihood of patient discharge within the next 24 or 48 hours from acute or critical care environments on a daily basis. Continuous patient monitoring and health data obtained from acute hospital at home environment (n=303 patients) and a critical care unit environment (n=9,520 patients) are retrospectively used to train, validate and test numerous machine learning models for dynamic daily predictions of patients discharge. In the acute hospital at home environment, the area under the receiver operating characteristic (AUROC) curve performance of a top XGBoost model was 0.816 ± 0.025 and 0.758 ± 0.029 for daily discharge prediction within 24 hours and 48 hours respectively. Similar independent prediction models from the critical care environment resulted in relatively a lower AUROC for likewise predicting daily patient discharge. Overall, the results demonstrate the efficacy and utility of our novel algorithm for dynamic predictions of daily patient discharge in both acute- and critical care healthcare settings.

PURPOSE: Voiding dysfunction (VD) leading to urinary retention is a common neurogenic lower urinary tract symptom in patients with multiple sclerosis (MS). Currently, the only effective management for patients with MS with VD is catheterization. Transcranial Rotating Permanent Magnet Stimulator (TRPMS) is a noninvasive, portable, multifocal neuromodulator that simultaneously modulates multiple cortical regions and the strength of their functional connections. In this pilot trial (ClinicalTrials.gov Identifier: NCT03574610), we investigated the safety and therapeutic effects of TRPMS in modulating brain regions of interest (ROIs) engaged with voiding initiation to improve VD in MS women. MATERIALS AND METHODS: Ten MS women with VD (having % post-void residual/bladder capacity [%PVR/BC] ≥40% or being in the lower 10th percentile of the Liverpool nomogram) underwent concurrent functional magnetic resonance imaging/urodynamic study (fMRI/UDS) with 3 cycles of bladder filling/emptying, at baseline and post-treatment. Predetermined ROIs and their activations at voiding initiation were identified on patients’ baseline fMRI/UDS scans, corresponding to microstimulator placement. Patients received 10 consecutive 40-minute treatment sessions. Brain activation group analysis, noninstrumented uroflow, and validated questionnaires were compared at baseline and post-treatment. RESULTS: No treatment-related adverse effects were reported. Post-treatment, patients showed significantly increased activation in regions known to be involved at voiding initiation in healthy subjects. %PVR/BC significantly decreased. Significant improvement of bladder emptying symptoms were reported by patients via validated questionnaires. CONCLUSIONS: Both neuroimaging and clinical data suggested TRPMS effectively and safely modulated brain regions that are involved in the voiding phase of the micturition cycle, leading to clinical improvements in bladder emptying in patients with MS.

Targeted therapies for driver gene fusions in cancers have yielded substantial improvements in care. Here, the authors outline a case series of 6 patients with FGFR3-TACC3 fusion in primary brain tumors ranging from polymorphous low-grade neuroepithelial tumor of the young to papillary glioneuronal tumors and glioblastoma (GBM). Previous studies indicated the FGFR3-TACC3 fusion provides survival benefit to GBM patients. Consistent with this, 2 patients with GBM had unexpectedly good outcomes and survived for 5 and 7 years, respectively. In contrast, 2 patients with initially lower graded tumors survived only 3 years and 1 year, respectively. One patient received erdafitinib, a targeted FGFR inhibitor, for 3 months at late disease recurrence and no response was seen. There were varied histomorphological features, including many cases that lacked the characteristic FGFR3-TACC3 pathology. The findings of this cohort suggest that molecular testing is justified, even for glioma cases lacking classic histopathological signatures. Currently, FGFR3-TACC3 fusion gliomas are often classified on the basis of histopathological features. However, further research is needed to examine whether IDH1/2–wild-type tumors with FGFR3-TACC3 fusion should be classified as a subtype on the basis of this molecular fusion. Because patients with IDH1/2–wild-type GBM with FGFR3-TACC3 fusion have improved survival, routine molecular testing for this mutation in patients enrolled in clinical trials and subsequent stratification may be warranted.

To evaluate the efficacy of single low dose (75 mg) preoperative pregabalin in reducing post-operative pain of septorhinoplasty. A double blind single center Randomized controlled trial based on block randomization. In the pregabalin group (PG) 34 participants received 75 mg pregabalin orally one hour before anesthesia induction while in control group (CG) 34 participants received a placebo. Pain and sedation were repeatedly measured with Visual Analouge Scale (VAS) and Riker Sedation-Agitation Scale (RSAS) respectively, 0.5, 1, 2, 6, 24 hours postextubation. Cumulative doses of fentanyl and ibuprofen received in both groups were compared. Thirty-two of the participants in PG and 33 of the participants in CG completed the study. The Mean VAS pain score was less in PG versus CG 30 min postoperatively (2.30 ± 1.30 vs. 4.85 ± 1.17), one hour (2.28 ± 0.92 vs. 4.27 ± 0.78), two hours (2.11 ± 0.88 vs. 3.60 ± 0.61) and six hours (1.47 0.62 vs. 2.76 ± 0.91) but not 24-hours postoperatively (0.84 ± 0.62 vs. 1.09 ± 0.92). Participants in the PG were less agitated during early post-extubation period (at 10 min: RSAS 3.93 ± 0.43 vs. 4.42 ± 0.50) and more alert during the first hour post-extubation (at 60 min: RSAS 3.90 ± 0.29 vs. 3.36 ± 0.69). The total dose of rescue fentanyl and ibuprofen was lower in the PG compared to the CG. A single dose of 75 mg pregabalin is very effective for pain control after septorhinoplasty procedure when administered one hour before anesthesia induction. Side effects are rare and opioid sparing was noted. Clinical trial number: IRCT2017043033706N1

Background Discrepancies in controlled substance documentation are common and can lead to legal and regulatory repercussions. We introduced a visual analytics dashboard to assist in a quality improvement project to reduce the discrepancies in controlled substance documentation in the operating room (OR) of our free-standing pediatric hospital. Methods Visual analytics were applied to collected documentation discrepancy audit data and were used to track progress of the project, to motivate the OR team, and in analyzing where further improvements could be made. This was part of a seven-step improvement plan based on the Theory of Change with a logic model framework approach. Results The introduction of the visual analytics dashboard contributed a 24% improvement in controlled substance documentation discrepancy. The project overall reduced documentation errors by 71% over the studied period. Conclusion We used visual analytics to simultaneously analyze, monitor, and interpret vast amounts of data and present them in an appealing format. In conjunction with quality-improvement principles, this led to a significant improvement in controlled substance documentation discrepancies.

Background Venous thromboembolism (VTE) is a very common adverse event for astrocytoma patients, but validation of proposed risk biomarkers has been elusive. We examine whether the status of the isocitrate dehydrogenase (IDH) gene is a risk factor for the development of venous thromboembolism (VTE) in astrocytoma patients. Methods We conducted a retrospective chart review of 282 astrocytoma patients enrolled in the PROACTIVE (Prospective Assessment of Correlative Biomarker) study at MD Anderson Cancer Center (MDACC) from 9/1/2000 until 12/31/2013. Results We identified 282 astrocytoma patients consisting of 49 IDH mutant astrocytomas and 233 IDH wildtype astrocytomas. Glioblastoma was the initial histopathologic diagnosis in 30 (61.2%) of the IDH mutated astrocytomas compared to 227(97.4%) of the IDH wild type astrocytomas. VTE was identified in 52 (18.4%) of patients. VTE was diagnosed in 7 (14.3%) of the IDH mutated astrocytomas compared to 45(19.3%) of the IDH wild type astrocytoma s (p = 0.4094). Median time to VTE from diagnosis was 2.71 months. Median time to VTE from diagnosis was 2.6 months for IDH mutated astrocytomas compared to 3.06 months for the IDH wild type astrocytomas (p = 0.8663). Conclusions IDH gene status did not appear as a significant risk factor for the development of venous thromboembolism (VTE) in our cohort of astrocytoma patients. Further research into potential biomarkers for VTE may be warranted.

Introduction The alloimmunization following blood transfusion can be life‐threatening. The Rh alloantibodies are one of the most common causes contributing to alloimmunization. This study aimed to evaluate the rate and causes of alloimmunization and to determine the Rh phenotypes and genotypes among sickle cell disease (SCD) and sickle thalassemia (Sβ). Materials and Methods Our study included 104 SCD and Sβ patients referring to Baghaei 2 Hospital of Ahvaz in 2019 using a non‐random simple sampling method. The blood samples were collected for Rh phenotypes, alloantibody screening and identification, and molecular tests. The SSP‐PCR and RFLP methods with the Pst 1 enzyme were used. Results The alloimmunization rate was 9.6% and 13.2% based on immunohematological tests and medical records, respectively. The main alloantibodies (90%) were anti‐Rh, and 40% of the patients had multiple alloantibodies. A significant correlation was found between gender and alloimmunization. The phenotypes of DCce (37.5%), DCcEe (24%), Dce (20.2%), and dce (5.8%) and genotypes of R1r (25%), R1R2 (20.2%), R1R1 (18.3%), and R1R0 (10.6%) were the most prevalent. The R1R2 was a frequent genotype in Sβ. Conclusion R0r′ and R1R0 genotypes were limited to our population in Iran. Due to the differences in RH genotypes between our population and others, the blood transfusion from other ethnicities increased our total alloimmunization rate., The alloimmunization is the problem in 9.6% of sickle cell disease (SCD) and sickle thalassemia patients.The increase in the rate of alloimmunization was due to Rh alloantibodies.The Rh genotypes were different among sickle cell disease and sickle thalassemia patients than other populations and R1r′ and R0R1 genotypes were limited to our population.

Riassunto. L'ischemia miocardica silente (SMI) è un aspetto dello spettro della cardiopatia ischemica che varia dalla malattia coronarica asintomatica all'angina grave. Considerando il progressivo aumento della prevalenza di SMI e l'inaffidabilità di test diagnostici comuni, l'identificazione di biomarcatori SMI benefici è molto critica per una diagnosi rapida e un trattamento efficace della malattia. La presente revisione ha lo scopo di analizzare l'efficienza clinica di biomarcatori ben applicati e nuovi per la diagnosi e la previsione dei risultati dei pazienti con SMI. Questi biomarcatori includono cTnT, cTnI, hs-cTnT, hs-cTnI, hsCRP, NT-proBNP, sST2, GDF-15, Lp-PLA2, recettori della superficie cellulare, citochine antinfiammatorie, OPG, leptina, colesterolo totale, HDL, LDL, lipoproteine (a), omocisteina, albuminuria, microalbuminuria e miRNA circolanti. Nel database PubMed sono stati cercati rapporti scientifici (articoli originali) usando i termini "biomarcatori", "ischemia miocardica silenziosa", "biomarcatori cardiaci", "infiammatori", "marcatori", "stress ossidativo". Una migliore comprensione di vari biomarcatori SMI fornisce una migliore comprensione della sua varia patofisiologia e aspetto asintomatico, nonché dell'uso clinico di routine di questi biomarcatori.

INTRODUCTION: Meningiomas are the most common primary intracranial tumor. Recent next generation sequencing analyses have elaborated the molecular drivers of this disease. We aimed to identify and characterize novel fusion genes in meningiomas. METHODS: We performed a secondary analysis of our RNA sequencing data of 145 primary meningioma from 140 patients to detect fusion genes. Semi-quantitative rt-PCR was performed to confirm transcription of the fusion genes in the original tumors. Whole exome sequencing was performed to identify copy number variations within each tumor sample. Comparative RNA seq analysis was performed to assess the clonality of the fusion constructs within the tumor. RESULTS: We detected six fusion events (NOTCH3-SETBP1, NF2-SPATA13, SLC6A3-AGBL3, PHF19-FOXP2 in two patients, and ITPK1-FBP2) in five out of 145 tumor samples. All but one event (NF2-SPATA13) led to extremely short reading frames, making these events de facto null alleles. Three of the five patients had a history of childhood radiation. Four out of six fusion events were detected in expression type C tumors, which represent the most aggressive meningioma. We validated the presence of the RNA transcripts in the tumor tissue by semi-quantitative RT PCR. All but the two PHF19-FOXP2 fusions demonstrated high degrees of clonality. CONCLUSIONS: Fusion genes occur infrequently in meningiomas and are more likely to be found in tumors with greater degree of genomic instability (expression type C) or in patients with history of cranial irradiation.

Background Persons with an opioid use disorder (OUD) who were incarcerated face many challenges to remaining abstinent; concomitantly, opioid-overdose is the leading cause of death among this population, with the initial weeks following release proving especially fatal. Extended-release naltrexone (XR-NTX) is the most widely-accepted, evidence-based OUD pharmacotherapy in criminal justice settings, and ensures approximately 30 days of protection from opioid overdose. The high cost of XR-NTX serves as a barrier to uptake by many prison/jail systems; however, the cost of the medication should not be viewed in isolation. Prison/jail healthcare budgets are ultimately determined by policymakers, and the benefits/cost-offsets associated with effective OUD treatment will directly and indirectly affect their overall budgets, and society as a whole. Methods This protocol describes a study funded by the National Institute of Drug Abuse (NIDA) to: evaluate changes in healthcare utilization, health-related quality-of-life, and other resources associated with different strategies of XR-NTX delivery to persons with OUD being released from incarceration; and estimate the relative “value” of each strategy. Data from two ongoing, publicly-funded, randomized-controlled trials will be used to evaluate these questions. In Study A, (XR-NTX Before vs. After Reentry), participants are randomized to receive their first XR-NTX dose before release, or at a nearby program post-release. In Study B, (enhanced XR-NTX vs. XR-NTX), both arms receive XR-NTX prior to release; the enhanced arm receives mobile medical (place of residence) XR-NTX treatment post-release, and the XR-NTX arm receives referral to a community treatment program post-release. The economic data collection instruments required to evaluate outcomes of interest were incorporated into both studies from baseline. Moreover, because the same instruments are being used in both trials on comparable populations, we have the opportunity to not only assess differences in outcomes between study arms within each trial, but also to merge the data sets and test for differences across trials. Discussion Initiating XR-NTX for OUD prior to release from incarceration may improve patient health and well-being, while also producing downstream cost-offsets. This study offers the unique opportunity to assess the effectiveness and cost-effectiveness of multiple strategies, according to different stakeholder perspectives.

ObjectivesConferences are designed for knowledge translation, but traditional conference evaluations are inadequate. We lack studies that explore alternative metrics to traditional evaluation metrics. We sought to determine how traditional evaluation metrics and Twitter metrics performed using data from a conference of the Canadian Association of Emergency Physicians (CAEP).MethodsThis study used a retrospective design to compare social media posts and tradition evaluations related to an annual specialty conference. A post (“tweet”) on the social media platform Twitter was included if it associated with a session. We differentiated original and discussion tweets from retweets. We weighted the numbers of tweets and retweets to comprise a novel Twitter Discussion Index. We extracted the speaker score from the conference evaluation. We performed descriptive statistics and correlation analyses.ResultsOf a total of 3,804 tweets, 2,218 (58.3%) were session-specific. Forty-eight percent (48%) of all sessions received tweets (mean = 11.7 tweets; 95% CI of 0 to 57.5; range, 0–401), with a median Twitter Discussion Index score of 8 (interquartile range, 0 to 27). In the 111 standard presentations, 85 had traditional evaluation metrics and 71 received tweets (p > 0.05), while 57 received both. Twenty (20 of 71; 28%) moderated posters and 44% (40 of 92) posters or oral abstracts received tweets without traditional evaluation metrics. We found no significant correlation between Twitter Discussion Index and traditional evaluation metrics (R = 0.087).ConclusionsWe found no correlation between traditional evaluation metrics and Twitter metrics. However, in many sessions with and without traditional evaluation metrics, audience created real-time tweets to disseminate knowledge. Future conference organizers could use Twitter metrics as a complement to traditional evaluation metrics to evaluate knowledge translation and dissemination.

Objective Triplicate A2 segment of the anterior cerebral artery is a rare anatomical variant (1%–3% prevalence) that which is thought to result mainly from persistence of the embryonic median artery of the corpus callosum. We sought to determine whether the triple-A2 variant is specifically associated with anterior communicating artery (ACoA) aneurysm. Methods We reviewed 2-dimensional digital-subtraction angiography (2D-DSA) as well as 3-dimensional rotational angiography (3D-RA) images of 55 patients with ACoA aneurysms who presented for evaluation and treatment between 2009 and 2014 at our institution. The criteria for definitively obtaining an accurate accounting of all A2 segments was presence of adequate cross-filling across the ACoA on 2D-DSA or 3D-RA imaging, or ability to fuse left and right 3D-RA images. Patients whose imaging did not meet these criteria were excluded from further analysis. Results We obtained a definitive count of all A2 segments in 36 patients. Among these, 19 patients (5 with the triple-A2 variant) were treated surgically, and 17 patients (2 with the triple-A2 variant) were treated endovascularly. The triple-A2 variant was seen in 7 patients. The prevalence of triple-A2 variant among patients with ACoA aneurysm was 19.4%. Patients with ACoA aneurysms had a significantly higher prevalence of the triple-A2 variant compared with the general population (P Conclusions Compared with the normal population, patients with ACoA aneurysms deemed to require treatment have a significantly higher likelihood of having triplicate A2 segment. Knowledge of this anatomical variation is of critical importance in planning and executing endovascular and microsurgical treatment of ACoA aneurysms.

Objective To evaluate the cost-effectiveness of nusinersen with and without universal newborn screening for infantile-onset spinal muscular atrophy (SMA). Study design A Markov model using data from clinical trials with US epidemiologic and cost data was developed. The primary interventions studied were nusinersen treatment in a screening setting, nusinersen treatment in a nonscreening setting, and standard care. Analysis was conducted from a societal perspective. Results Compared with no screening and no treatment, the incremental cost-effectiveness ratio (ICER) for nusinersen with screening was $330 558 per event-free life year (LY) saved, whereas the ICER for nusinersen treatment without screening was $508 481 per event-free LY saved. For nusinersen with screening to be cost-effective at a willingness-to-pay (WTP) threshold of $50 000 per event-free LY saved, the price would need to be $23 361 per dose, less than one-fifth its current price of $125 000. Preliminary data from the NURTURE trial indicated an 85.7% improvement in expected LYs saved compared with our base results. In probabilistic sensitivity analysis, nusinersen and screening was a preferred strategy 93% of the time at a $500 000 WTP threshold. Conclusion Universal newborn screening for SMA provides improved economic value for payers and patients when nusinersen is available.

Improving access to surgical services and understanding the barriers to receiving timely care are necessary to save lives. The aim of this study was to assess barriers to timely presentation to an appropriate medical facility using the Three-Delay model, for patients presenting to Tamale Teaching Hospital, in northern Ghana. In 2013, patients with delays in seeking surgical care were prospectively identified. Pairwise correlation coefficients between delay in presentation and factors associated with delay were conducted and served as a foundation for a multivariate log-linear regression model. A total of 718 patients presented with an average delay of 22.1 months. Delays in receiving care were most common (56.4%), while delays in seeking care were seen in 52.3% of patients. “Initially seeking treatment at the nearest facility, but appropriate care was unavailable” was reported by 56.4% and predicted longer delays (p

Immune Thrombocytopenic Purpura (ITP) is a common autoimmune bleeding disorder characterized by a reduction in peripheral blood platelet counts. In this disease, autoantibodies (Auto-Abs) are produced against platelet GPIIb/GPIIIa by B cells, which require interaction with T cells. In this review, the importance of B and T lymphocytes in ITP prognosis has been studied. Relevant literature was identified by a PubMed search (1990-2016) of English-language papers using the terms B and T lymphocyte, platelet, CD markers and immune thrombocytopenic purpura. T and B lymphocytes are the main immune cells in the body. Defective function causes disrupted balance of different subgroups of lymphocytes, and abnormal expression of surface markers of these cells results in self-tolerance dysfunction, as well as induction of Auto-Abs against platelet glycoproteins (PG). Given the role of B and T cells in production of autoantibodies against PG, it can be stated that the detection of changes in CD markers' expression in these cells can be a good approach for assessing prognosis in ITP patients.

Background Intracranial metastasis of Gastrointestinal Stromal Tumors (GISTs) is rare but presents unique treatment challenges. We present a case of intracranial metastasis of GIST with a systematic review of the literature. A literature search using key terms “‘gastrointestinal stromal tumor’ AND brain AND metastasis”” was conducted through May 2019 via Embase and Pubmed according to PRISMA guidelines. Only cases describing intradural metastases rather than calvarial or intraorbital metastases were included. Case presentation A 57-year-old woman with history of GIST metastatic to the liver presented with a six-week history of left facial weakness, left hearing loss, and left facial numbness, and a one-week history of headaches, gait disturbance, and dizziness. MRI revealed a contrast-enhancing dural-based left middle cranial fossa mass measuring 2.9 cm × 3.1 cm × 3.4 cm with extension into the internal auditory canal and cerebral edema. A left temporal craniotomy was performed to excise the lesion, and the patient was discharged to a rehabilitation facility at her preoperative baseline. Intraoperative pathology revealed a spindle cell neoplasm, postoperative MRI demonstrated gross total resection of the lesion, and microscopic analysis demonstrated sheets of spindled tumor cells with short ovoid, irregular, hyperchromatic nuclei and scattered large atypical nuclei without extensive necrosis. Immunohistochemical staining was positive for KIT proto-oncogene (CD117, c-KIT), and the patient was put on imatinib (400 mg/day). Conclusions Of the 18 cases analyzed and our present case, metastasis typically involved the cerebrum with only one in infratentorial elements. The tumors in seven of the cases involved the dura, and one case metastasized to the pituitary. Eight patients died following treatment. Surgery remains the mainstay of intracranial metastatic GIST, however there are many reports of good responses to radiation or chemotherapy alone. More investigation is required to determine the best treatment course for these patients.

Economic evaluations provide evidence that informs stakeholders on how to efficiently allocate real and financial healthcare resources. The purpose of this study was to review and discuss the integration of economic evaluations into the National Drug Abuse Treatment Clinical Trials Network (CTN) since its inception, as well as expectations for the future of this relationship. A systematic review was performed on published and planned CTN economic evaluations in the CTN dissemination library and PubMed. The well-established Drummond checklist was used to evaluate the comprehensiveness and methodological rigor of published articles. One hundred thirty-eight ancillary, follow-up, or original protocols were reviewed, and 78 potentially relevant published articles were identified. A total number of 14 protocols included an economic evaluation. Of these, 6 protocols were completed, 2 were reported as active, and 6 were reported as in-development at the time of this review. Of the 78 published articles, 9 met the inclusion criteria. As gauged by the Drummond checklist, the quality of CTN published economic evaluations were found to improve over time, and recent published articles were identified as guides to cutting-edge economic research. As the CTN continues to grow and mature, it is imperative that high-quality economic evaluations are incorporated alongside trials in order to maximize the public health impact of the CTN.

The Norwood surgical procedure restores functional systemic circulation in neonatal patients with single ventricle congenital heart defects, but this complex procedure carries a high mortality rate. In this study we address the need to provide an accurate patient specific risk prediction for one-year postoperative mortality or cardiac transplantation and prolonged length of hospital stay with the purpose of assisting clinicians and patients’ families in the preoperative decision making process. Currently available risk prediction models either do not provide patient specific risk factors or only predict in-hospital mortality rates. We apply machine learning models to predict and calculate individual patient risk for mortality and prolonged length of stay using the Pediatric Heart Network Single Ventricle Reconstruction trial dataset. We applied a Markov Chain Monte-Carlo simulation method to impute missing data and then fed the selected variables to multiple machine learning models. The individual risk of mortality or cardiac transplantation calculation produced by our deep neural network model demonstrated 89 ± 4% accuracy and 0.95 ± 0.02 area under the receiver operating characteristic curve (AUROC). The C-statistics results for prediction of prolonged length of stay were 85 ± 3% accuracy and AUROC 0.94 ± 0.04. These predictive models and calculator may help to inform clinical and organizational decision making.

Optimal care for elderly patients with glioblastoma (GBM) remains in question due to their exclusion from and underrepresentation in many clinical trials (including EORTC 22,981) as well as their historically poor overall survival. A retrospective chart review was conducted at a single high-volume cancer center for newly diagnosed elderly (65 years old or older) GBM patients diagnosed from 2011 through 2017. A total of 158 newly diagnosed GBM patients aged 65 years and older were identified. One hundred forty-four patients (91.1%) received radiotherapy (RT) and 130 patients (90.3%) received concurrent temozolomide with RT. Sixty-one patients (38.6%) completed concurrent chemoradiation and 6 cycles of adjuvant temozolomide. 23% of patients discontinued temozolomide during concurrent or adjuvant treatment due to side effects or complications of chemotherapy. With a median follow-up time of 35.0 months, median overall survival (OS) time for the full cohort was 18.6 months, with estimated OS rates of 74.8%, 35.9%, and 9.5% at 1, 2, and 5 years, respectively. On multivariable analysis, higher KPS (p = 0.002, HR 0.46; 95% CI 0.63–0.82), completing planned RT course (p = 0.01, HR 0.29; 95% CI 0.11–0.75), and completing 6 cycles of adjuvant temozolomide (p = 0.01, HR 2.62; 95% CI 1.67–4.12) were independently associated with improved OS. Our cohort of elderly GBM patients was predominantly treated with standard of care therapy based on EORTC 22,981. Despite their age, these patients generally tolerated treatment well and had favorable outcomes compared to those reported for patients treated on EORTC 22,981. Based on these findings, using advanced age as the basis for treatment de-escalation or as an exclusionary criterion in clinical trials should be discouraged.

Informed consent is fundamental to the ethical practice of medicine and carries important legal implications. Of particular relevance to pediatric anesthesia is the Food and Drug Administration's Drug Safety Communication (DSC), which highlights potential yet theoretical adverse effects on brain development of repeated or prolonged anesthesia administration to children younger than 3 years of age.

Immunotherapy targeting T cells is increasingly utilized to treat solid tumors including non-small cell lung cancer (NSCLC). This requires a better understanding of the T cells in the lungs of patients with NSCLC. Here, we report T cell repertoire analysis in a cohort of 236 early-stage NSCLC patients. T cell repertoire attributes are associated with clinicopathologic features, mutational and immune landscape. A considerable proportion of the most prevalent T cells in tumors are also prevalent in the uninvolved tumor-adjacent lungs and appear specific to shared background mutations or viral infections. Patients with higher T cell repertoire homology between the tumor and uninvolved tumor-adjacent lung, suggesting a less tumor-focused T cell response, exhibit inferior survival. These findings indicate that a concise understanding of antigens and T cells in NSCLC is needed to improve therapeutic efficacy and reduce toxicity with immunotherapy, particularly adoptive T cell therapy., Relevant features of T cell repertoire in human cancer remain to be delineated. Here the authors show, by TCR sequencing in a large cohort of lung cancer patients, that while a majority of T cell clones are shared between tumor and adjacent lung tissue, less frequent tumor-unique T cell clones correlate with worse prognosis.

Background Papillary glioneuronal tumors (PGNTs) are rare World Health Organization grade I neoplasms that are characterized by a benign course and excellent response to surgical resection. A few reports exist of tumors with more aggressive clinical and histologic features. In this report we detail the case of an unusually aggressive PGNT in a 67-year-old woman. Case Description The patient had a 3-year history of seizures and was diagnosed with a frontoparietal mass on imaging. She underwent subtotal resection with a histologic diagnosis of PGNT. Less than a year after surgery, the patient experienced recurrence of disease and underwent reresection and adjuvant radiation treatment. The patient's disease continued to progress despite radiation treatment, so adjuvant temozolomide was initiated. Molecular testing was performed and revealed a TERT promotor mutation, an FGFR3-TACC3 oncogenic fusion, and a copy number loss in CDKN2A/CDKN2B. Conclusions PGNTs, while typically benign, can rarely recur after surgery. Molecular testing should be performed on all PGNTs to help possibly identify more aggressive tumors and potentially reveal novel treatment options.

The societal cost of preterm birth indicates potential economic gains from interventions that reduce the incidence of preterm birth. Changes in the epidemiology of preterm birth and healthcare costs require periodic updates to cost estimates. Previously reported incremental cost estimates for the United States in 2004 were updated. The discounted present value of the excess cost associated with prematurity for the 2016 US birth cohort was estimated to be $25.2 billion: $17.1 billion for medical care of persons born preterm, $2.0 billion for delivery care, $1.3 billion for early intervention and special education, and $4.8 billion in lost productivity due to associated disabilities in adults. The nominal and inflation-adjusted incremental costs per preterm birth increased by 26% and 4%, respectively, during 2004-2016. The aggregate cost decreased by 4%, associated with declines in overall births and the preterm birth rate and changes in the distribution by gestational age.

In this article, we aim to describe the presentation and management of a case of spontaneous intracranial hypotension caused by a dural tear from a ventral thoracic osteophyte at the T12 level that was refractory to non-surgical treatment modalities. A review of the literature has been performed. Also a proposal of diagnostic and treatment algorithm is presented. Intracranial hypotension and CSF leak as a result of dural tear is a common phenomenon. However, the detection of the source of CSF leak from a thoracic spinal osteophyte has rarely been reported. Diagnostic workup including MRI and CT Myelogram as well as application of epidural blood patches and surgical technique of hemilaminectomy and osteophytectomy by transpedicular approach have been described. Literature review was conducted using relevant search terms in PubMed. The patient’s spontaneous intracranial hypotension symptoms resolved and this persisted on follow up visits. Review our experience as well as similar cases in the literature pointed us towards a diagnostic and treatment algorithm. Spontaneous resolution is the norm for intracranial hypotension of most etiologies and management of all such cases begins with fluid resuscitation coupled with bed rest. On failure of conservative therapy, autologous epidural blood patches into the spinal epidural space should be tried, which often produce an immediate relief of symptoms. Osteophyte-induced dural tear and consequent intracranial hypotension may require surgical intervention if the symptoms are refractory to conservative treatment. Under all circumstances a careful step-wise approach for diagnosis and treatment of spontaneous intracranial hypotension needs to be followed, as we have proposed in our article.

Objective To examine the health-related quality-of-life (HRQoL) of persons with opioid use disorder (OUD) seeking treatment in an inpatient detoxification or short-term residential setting; continuing treatment as outpatients. Methods We conducted a secondary analysis of data from a clinical trial (N = 508) where participants were randomized to extended-release naltrexone or buprenorphine-naloxone for the prevention of opioid relapse. We used a generalized structural equation regression mixture model to identify associations of HRQoL (EQ-5D) trajectories, including latent characteristics, over the 24-week trial and 36-week follow-up period, among participants who reported HRQoL beyond baseline. This novel framework accounted for baseline and time-varying characteristics, while simultaneously identifying latent classes. Results We identified two subpopulations: HRQoL "pharmacotherapy responsive" (82.3 %) and HRQoL "characteristic sensitive" (17.7 %). The pharmacotherapy responsive subpopulation was characterized by a shortterm HRQoL improvement and then stable HRQoL over time, and by a positive association between HRQoL and receiving pharmacotherapy in the past 30 days. The characteristic sensitive subpopulation was characterized by an initial improvement in HRQoL with a gradual decline over time, and no significant HRQoL response to pharmacotherapy. HRQoL changes over time in this subpopulation were more influenced by baseline demographic, socioeconomic, and psychosocial characteristics. Conclusion Our findings suggest that while HRQoL may be improved and sustained through targeted efforts to promote use of pharmacotherapy for many persons with OUD, an identifiable subpopulation may require additional services that address socioeconomic and psychosocial issues to achieve HRQoL benefits. Our analysis provides insight for improving individualized care for persons with opioid use disorder seeking treatment.

There is a critical need to improve our understanding of the pathogenesis of melanoma brain metastases (MBM). Thus, we performed RNA sequencing on 88 resected MBMs and 42 patient-matched extracranial metastases; tumors with sufficient tissue also underwent whole-exome sequencing, T-cell receptor sequencing, and IHC. MBMs demonstrated heterogeneity of immune infiltrates that correlated with prior radiation and post-craniotomy survival. Comparison with patient-matched extracranial metastases identified significant immunosuppression and enrichment of oxidative phosphorylation (OXPHOS) in MBMs. Gene-expression analysis of intracranial and subcutaneous xenografts, and a spontaneous MBM model, confirmed increased OXPHOS gene expression in MBMs, which was also detected by direct metabolite profiling and [U-13C]-glucose tracing in vivo. IACS-010759, an OXPHOS inhibitor currently in early-phase clinical trials, improved survival of mice bearing MAPK inhibitor–resistant intracranial melanoma xenografts and inhibited MBM formation in the spontaneous MBM model. The results provide new insights into the pathogenesis and therapeutic resistance of MBMs. Significance: Improving our understanding of the pathogenesis of MBMs will facilitate the rational development and prioritization of new therapeutic strategies. This study reports the most comprehensive molecular profiling of patient-matched MBMs and extracranial metastases to date. The data provide new insights into MBM biology and therapeutic resistance. See related commentary by Egelston and Margolin, p. 581. This article is highlighted in the In This Issue feature, p. 565

This paper discusses computational modeling of predictive risk factors for neonates undergoing a Norwood surgical procedure, a multi-stage cardiac procedure that restores functional systemic circulation in patients such as neonates with Hypoplastic Left Heart Syndrome (HLHS). In this model, we apply machine learning based binary classication to 549 cases reported by the Pediatric Heart Networks Single Ventricle Reconstruction Trial. We use neural networks classier to predict risk factors for individual patients undergoing a Norwood procedure for the repair of HLHS. Results indicate that independent risk can be calculated with 85% accuracy and 0.94 area under the receiver operating characteristics curve. This model may help physicians provide counseling for families and medically optimize patients prior to surgery by modifying individual risk factors.

Background: There have been few studies of sufficient size to address the relationship between glioma risk and the use of aspirin or NSAIDs, and results have been conflicting. The purpose of this study was to examine the associations between glioma and aspirin/NSAID use, and to aggregate these findings with prior published studies using meta-analysis. Methods: The Glioma International Case-Control Study (GICC) consists of 4,533 glioma cases and 4,171 controls recruited from 2010 to 2013. Interviews were conducted using a standardized questionnaire to obtain information on aspirin/NSAID use. We examined history of regular use for ≥6 months and duration-response. Restricted maximum likelihood meta-regression models were used to aggregate site-specific estimates, and to combine GICC estimates with previously published studies. Results: A history of daily aspirin use for ≥6 months was associated with a 38% lower glioma risk, compared with not having a history of daily use [adjusted meta-OR = 0.62; 95% confidence interval (CI), 0.54–0.70]. There was a significant duration-response trend (P = 1.67 × 10−17), with lower ORs for increasing duration of aspirin use. Duration-response trends were not observed for NSAID use. In the meta-analysis aggregating GICC data with five previous studies, there was a marginally significant association between use of aspirin and glioma (mOR = 0.84; 95% CI, 0.70–1.02), but no association for NSAID use. Conclusions: Our study suggests that aspirin may be associated with a reduced risk of glioma. Impact: These results imply that aspirin use may be associated with decreased glioma risk. Further research examining the association between aspirin use and glioma risk is warranted.

Periventricular leukomalacia (PVL) is brain injury that develops commonly in neonates after cardiac surgery. Earlier identification of patients who are at higher risk for PVL may improve clinicians’ ability to optimize care for these challenging patients. The aim of this study was to apply machine learning algorithms and wavelet analysis to vital sign and laboratory data obtained from neonates immediately after cardiac surgery to predict PVL occurrence. We analyzed physiological data of patients with and without hypoplastic left heart syndrome (HLHS) during the first 12 h after cardiac surgery. Wavelet transform was applied to extract time-frequency information from the data. We ranked the extracted features to select the most discriminative features, and the support vector machine with radial basis function as a kernel was selected as the classifier. The classifier was optimized via three methods: (1) mutual information, (2) modified mutual information considering the reliability of features, and (3) modified mutual information with reliability index and maximizing set’s mutual information. We assessed the accuracy of the classifier at each time point. A total of 71 neonates met the study criteria. The rates of PVL occurrence were 33% for all patients, with 41% in the HLHS group and 25% in the non-HLHS group. The F-score results for HLHS patients and non-HLHS patients were 0.88 and 1.00, respectively. Using maximizing set’s mutual information improved the classifier performance in the all patient groups from 0.69 to 0.81. The novel application of a modified mutual information ranking system with the reliability index in a PVL prediction model provided highly accurate identification. This tool is a promising step for improving the care of neonates who are at higher risk for developing PVL following cardiac surgery.

Despite the recognition that inguinal hernia (IH) repair is cost-effective, repair rates in low- and middle-income countries remain low. Estimated use of mesh in low- and middle-income countries also remains low despite publications about low-cost, noncommercial mesh. The purpose of our study was to assess the current state of IH repair in the northern and transitional zone of Ghana.A retrospective review of surgical case logs of IH repairs from 2013 to 2017 in 41 hospitals was performed. Multivariate logistic regression was used to determine predictors of mesh use.Eight thousand eighty male patients underwent IH repair. The range of IH repair in each region was 96 to 295 (overall 123) per 100,000 population. Most cases were performed at district hospitals (84%) and repaired nonurgently (93%) by nonsurgeon physicians (66%). Suture repair was most common (85%) although mesh was used in 15%. The strongest predictor of mesh use was when a surgeon performed surgery (odds ratio [OR] 3.13, P 0.001), followed by surgery being performed in a teaching hospital (OR 2.31, P 0.001). Repair at a regional hospital was a negative predictor of mesh use (OR 0.08, P 0.001) as was the use of general anesthesia (OR 0.40, P = 0.001).Most IH repairs are performed in district hospitals, by nonsurgeon physicians, and without mesh. Rates of repair and the use of mesh are higher than previous estimates in Ghana and Sub-Saharan Africa but not as high as high-income countries.

Epithelial tumor cells undergo epithelial-to-mesenchymal transition (EMT) to gain metastatic activity. Competing endogenous RNAs (ceRNAs) have binding sites for a common set of microRNAs (miRs) and regulate each other's expression by sponging miRs. Here, we address whether ceRNAs govern metastasis driven by the EMT-activating transcription factor ZEB1. High miR-181b levels were correlated with an improved prognosis in human lung adenocarcinomas, and metastatic tumor cell lines derived from a murine lung adenocarcinoma model in which metastasis is ZEB1-driven were enriched in miR-181b targets. ZEB1 relieved a strong basal repression of α1 integrin (ITGA1) mRNA, which in turn upregulated adenylyl cyclase 9 mRNA (ADCY9) by sponging miR181b. Ectopic expression of the ITGA1 3'-untranslated region reversed miR-181b-mediated metastasis suppression and increased the levels of adenylyl cyclase 9 protein (AC9), which promoted tumor cell migration and metastasis. In human lung adenocarcinomas, ITGA1 and ADCY9 levels were positively correlated, and an AC9-activated transcriptomic signature had poor-prognostic value. Thus, ZEB1 initiates a miR-181b-regulated ceRNA network to drive metastasis.

Introduction. The quality of cardiopulmonary resuscitation (CPR) has been shown to impact patient outcomes. However, post-CPR morbidity and mortality remain high, and CPR optimization is an area of active research. One approach to optimizing CPR involves establishing reliable CPR performance measures and then modifying CPR parameters, such as compressions and ventilator breaths, to enhance these measures. We aimed to define a reliable CPR performance measure, optimize the CPR performance based on the defined measure and design a dynamically optimized scheme that varies CPR parameters to optimize CPR performance. Materials and Methods. We selected total blood gas delivery (systemic oxygen delivery and carbon dioxide delivery to the lungs) as an objective function for maximization. CPR parameters were divided into three categories: rescuer dependent, patient dependent, and constant parameters. Two optimization schemes were developed using simulated annealing method: a global optimization scheme and a sequential optimization scheme. Results and Discussion. Variations of CPR parameters over CPR sequences (cycles) were analyzed. Across all patient groups, the sequential optimization scheme resulted in significant enhancement in the effectiveness of the CPR procedure when compared to the global optimization scheme. Conclusions. Our study illustrates the potential benefit of considering dynamic changes in rescuer-dependent parameters during CPR in order to improve performance. The advantage of the sequential optimization technique stemmed from its dynamically adapting effect. Our CPR optimization findings suggest that as CPR progresses, the compression to ventilation ratio should decrease, and the sequential optimization technique can potentially improve CPR performance. Validation in vivo is needed before implementing these changes in actual practice.