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The pathogenesis of ovarian cancer (OC) is complex. Serine Protease 8 (PRSS8) is a potential biomarker for early detection of OC. Multiple databases were used to predict the expression of PRSS8, Sterol regulatory element binding protein (SREBP) and sodium channel epithelial 1alpha subunit (SCNN1A) in OC patients and to detect the relationship among the three. The expressions of PRSS8, SREBF2, SCNN1A and related factors of the pathway were detected by RT-qPCR and Western blot. The cell transfection was used to overexpress or inhibit the expression of PRSS8 and SREBF2, so as to explore its mechanism. MTT assay and Colony formation assay were used to detect cell proliferation. The Transwell and Wound Healing assays were utilized to measure cell invasion and migration. We have further confirmed cell-level studies in animals. We found that PRSS8 expression was up-regulated in OC patients and cell lines. Knocking down PRSS8 reduced the proliferation, migration and epithelial-mesenchymal transition (EMT) of OC cells, which was realized by SREBF2 transcriptional regulation. Knocking down SREBF2 reduced PRSS8 and then inhibited the expression of SCNN1A, thus affecting the proliferation, migration and EMT of OC cells. These results also applied to animals experiments. In conclusion, SREBF2 activates the PRSS8/SCNN1A axis to accelerate cell proliferation, migration and EMT of OC.

The purpose of the study was to conduct a meta-analysis about the effect of the combined application of orthokeratology and single-vision spectacles on slowing the progression of high myopia.The literature was searched in PubMed, EMBASE, the Cochrane Library, Wang Fang Data, CNKI and sinoMed. The Cochrane Handbook was used to evaluate the quality of the included randomized clinical trials, and the Newcastle-Ottawa Scale was used to evaluate the included case-control or cohort studies. The results were analyzed by Revman 5.3.Five studies (2 randomized clinical trials, 2 case-controls, and 1 cohort study) with a total of 360 patients were included in this meta-analysis. The follow-up time was at least 1 year. Combined application of orthokeratology and single-vision spectacles were used in the experimental group. The control group used single-vision spectacles only. The pooled estimates indicated that the standardized mean difference between the 2 groups was -1.46 mm (95% confidence interval: -1.88 to -1.05; P.05) for axial length elongation and -1.85D (95% confidence interval: -2.40 to -1.31; P.05) for change in spherical equivalent refraction. No serious adverse events were reported in all studies.The combined application of orthokeratology and single-vision spectacles is more effective than single-vision spectacles only on slowing the progression of high myopia.

ObjectiveTo evaluate the comparative safety and efficacy of direct endovascular thrombectomy (dEVT) compared to bridging therapy (BT; IV tissue plasminogen activator + EVT) and to assess whether BT potential benefit relates to stroke severity, size, and initial presentation to EVT vs non-EVT center.MethodsIn a prospective multicenter cohort study of imaging selection for endovascular thrombectomy (Optimizing Patient Selection for Endovascular Treatment in Acute Ischemic Stroke [SELECT]), patients with anterior circulation large vessel occlusion (LVO) presenting to EVT-capable centers within 4.5 hours from last known well were stratified into BT vs dEVT. The primary outcome was 90-day functional independence (modified Rankin Scale [mRS] score 0–2). Secondary outcomes included a shift across 90-day mRS grades, mortality, and symptomatic intracranial hemorrhage. We also performed subgroup analyses according to initial presentation to EVT-capable center (direct vs transfer), stroke severity, and baseline infarct core volume.ResultsWe identified 226 LVOs (54% men, mean age 65.6 ± 14.6 years, median NIH Stroke Scale [NIHSS] score 17, 28% received dEVT). Median time from arrival to groin puncture did not differ in patients with BT when presenting directly (dEVT 1.43 [interquartile range (IQR) 1.13–1.90] hours vs BT 1.58 [IQR 1.27–2.02] hours, p = 0.40) or transferred to EVT-capable centers (dEVT 1.17 [IQR 0.90–1.48] hours vs BT 1.27 [IQR 0.97–1.87] hours, p = 0.24). BT was associated with higher odds of 90-day functional independence (57% vs 44%, adjusted odds ratio [aOR] 2.02, 95% confidence interval [CI] 1.01–4.03, p = 0.046) and functional improvement (adjusted common OR 2.06, 95% CI 1.18–3.60, p = 0.011) and lower likelihood of 90-day mortality (11% vs 23%, aOR 0.20, 95% CI 0.07–0.58, p = 0.003). No differences in any other outcomes were detected. In subgroup analyses, patients with BT with baseline NIHSS scores p = 0.006); this association was not evident for patients with NIHSS scores ≥15 (aOR 1.05, 95% CI 0.40–2.74, p = 0.92). Similarly, functional outcomes improvements with BT were detected in patients with core volume strata (ischemic core 3: aOR 2.10, 95% CI 1.02–4.33, p = 0.044 vs ischemic core ≥50 cm3: aOR 0.41, 95% CI 0.01–16.02, p = 0.64) and transfer status (transferred: aOR 2.21, 95% CI 0.93–9.65, p = 0.29 vs direct to EVT center: aOR 1.84, 95% CI 0.80–4.23, p = 0.15).ConclusionsBT appears to be associated with better clinical outcomes, especially with milder NIHSS scores, smaller presentation core volumes, and those who were “dripped and shipped.” We did not observe any potential benefit of BT in patients with more severe strokes.Trial Registration InformationClinicalTrials.gov Identifier: NCT02446587.Classification of EvidenceThis study provides Class III evidence that for patients with ischemic stroke from anterior circulation LVO within 4.5 hours from last known well, BT compared to dEVT leads to better 90-day functional outcomes.

The purpose of the current study was to investigate the biological function of cell division cycle-associated protein 7 (CDCA7) on ovarian cancer (OC) progression and analyze the molecular mechanism of CDCA7 on OC cellular processes and angiogenesis. CDCA7 expression in OC tissues and adjacent normal tissues was obtained from Gene Expression Profiling Interactive Analysis (GEPIA) and in various cancer cell lines was obtained from Cancer Cell Line Encyclopedia (CCLE). Moreover, CDCA7 expression in adjacent normal tissues and tumor tissues of OC patients as well as in normal ovarian epithelial cells (NOEC) and ovarian cancer cells (OVCAR3, SKOV3, CAOV-3, A2780) was further confirmed via Western blot assay and Reverse transcription-quantitative polymerase chain reaction (RT-qPCR). In addition, Immunohistochemistry (IHC) was also applied for determination of CDCA7 expression in tissues of OC patients. Then, SKOV3 cells were introduced with shRNA-CDCA7 for functional experiments. GeneMANIA database analysis and coimmunoprecipitation (Co-IP) assay verified the interaction between CDCA7 and enhancer of zeste homolog 2 (EZH2) to probe the potential mechanism. CDCA7 expression was elevated in tumor tissues of OC patients and OC cell lines. CDCA7 silencing restrained the proliferative, migrative and invasive capacities and arrested cell cycle of OC cells. In addition, CDCA7 knockdown induced a weaker in vitro angiogenesis of HUVECs. Mechanistically, CDCA7 interacted with EZH2. Downregulation of CDCA7 arrested angiogenesis by suppressing EZH2 expression. To sum up, the current study revealed the impact and potential mechanism of CDCA7 on OC cellular processes, developing a promising molecular target for OC therapies., Graphical Abstract

Background Epidural hematomas (EDHs) involving the venous sinuses are uncommon and carry the risk of hemorrhage or venous infarction. We report the largest case series for superior sagittal sinus− and transverse sinus−related EDHs including surgical and nonsurgical management. We compare our findings to the relevant literature. Methods A retrospective review of the EDH cases at our center was performed from 2013–2018. Patients were analyzed by surgical versus conservative management, outcomes, and complications. Results Of the 268 EDH patients identified, 32 involved the venous sinuses (23 supratentorial and 9 infratentorial). Ten of the patients had surgery, and 22 were managed conservatively. No surgical complications occurred, and all had a Glasgow Outcome Scale score of 5 at follow-up. All of the nonsurgical patients had a Glasgow Outcome Scale score of 4 or 5 at follow-up except for 1 patient with prior disability. The literature search resulted in 39 infratentorial and 47 supratentorial EDHs involving venous sinuses. Conclusions Surgical and nonsurgical management of EDHs involving the venous sinuses are both viable options with good outcomes. Surgical intervention is based on location, size, neurologic examination, expansion on serial imaging, and vascular imaging findings. Surgery has the potential for significant complications, but all surgical patients in our series had good outcomes at follow-up. Similarly, nonsurgically managed patients had good outcomes and our overall series demonstrates better outcomes with fewer complications than other similar series in the literature.

Purpose To compare the efficacy and safety of subthreshold micropulse (STMP) laser photocoagulation and half-dose photodynamic therapy (PDT) in the treatment of acute central serous chorioretinopathy (CSC). Methods A total of 39 acute CSC patients were included. 18 patients were treated with STMP laser and 21 patients were treated with half-dose PDT. The main outcome measures were best-corrected visual acuity (BCVA) according to Early Treatment Diabetic Retinopathy Study (ETDRS) chart, the proportion of eyes with complete resolution of subretinal fluid, the number of treatments, and the retinal sensitivity by microperimetry during the 12-month study period. Results The mean number of treatments during the 12-month period was 1.6 in STMP group and 1.3 in half-dose PDT group, respectively (P = 0.174). The proportion of eyes with complete resolution of subretinal fluid was 83.3% in STMP group compared with 90.5% in half-dose PDT group at 12-month (P = 0.647). The mean BCVA at 12-month after treatment was 75.28 ± 12.58 for STMP group and 76.62 ± 11.57 for half-dose PDT group, respectively (P = 0.731). No statistically significant difference was found in the mean retinal sensitivity between the two groups during the 12 months follow-up (P = 0.701 at 3 months; P = 0.725 at 6 months; P = 0.695 at 12 months). Conclusions Subthreshold micropulse Laser Photocoagulation is as effective as half-dose PDT for acute CSC, while minimizing the damage effect on retinal.

To explore the effects of type 2 diabetes mellitus (T2DM) on osteoarthritis (OA), 12 bone tissue samples were obtained surgically from the human total knee arthroplasty patients and analyzed by quantitative proteomics.Based on patient clinical histories, patient samples were assigned to diabetes mellitus osteoarthritis (DMOA) and OA groups. A data-independent acquisition method for data collection was used with proteomic data analysis to assess intergroup proteomic differences. Gene Ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genome pathway enrichment analysis were used to further find the correlation between T2DM and OA.GO functional analysis found 153 differentially expressed proteins between DMOA and OA groups, of which 92 differentially expressed proteins were significantly up-regulated and 61 were significantly down-regulated. Kyoto Encyclopedia of Genes and Genome pathway analysis found 180 pathways, including 9 pathways significantly enriched. Further data analysis revealed that 6 signaling pathways were closely associated with T2DM and OA.OA and DMOA onset and progression were closely related to synthesis and metabolism of extracellular matrix components (e.g., fibronectin, decorin, etc.). The effects of T2DM on OA occur though 2 major ways of oxidative stress and low-grade chronic inflammation, involving in 2 inhibited signaling pathways and 4 activated signaling pathways.

Rationale Randomized evidence for endovascular thrombectomy safety and efficacy in patients with large core strokes is lacking. Aims To demonstrate endovascular thrombectomy efficacy and safety in patients with large core on non-contrast CT or perfusion imaging (CT/MR) and determine if there is heterogeneity of treatment effect in large cores based on the imaging modality. Design SELECT2 is a prospective, randomized, multi-center, assessor-blinded controlled trial with adaptive enrichment design, enrolling up to 560 patients. Procedure Patients who meet the clinical criteria and have anterior circulation large vessel occlusions with large core on either NCCT (ASPECTS 3–5) or perfusion imaging (CTP [rCBF Study outcomes The distribution of 90-day mRS scores is the primary outcome. Functional independence (mRS = 0–2) rate is a secondary outcome. Other secondary outcomes include safety (symptomatic ICH, neurological worsening, mortality) and imaging outcomes. Analysis A normal approximation of the Wilcoxon-Mann-Whitney test (the generalized likelihood ratio test) to assess the primary outcome. Functional independence rates, safety and imaging outcomes will also be compared. Discussion The SELECT2 trial will evaluate endovascular thrombectomy safety and efficacy in large cores on either CT or perfusion imaging and may provide randomized evidence to extend endovascular thrombectomy eligibility to larger population. Registration: ClinicalTrials.gov–NCT03876457

To identify morphologic features of isolated cervical spine facet fractures that can reliably differentiate AOSpine F1 and F2 injuries. Retrospective review of cervical spine CTs on all patients who sustained isolated cervical fractures of the facets presenting to our level 1 trauma center from August 2012 through December 2015. CTs were reviewed for facet fracture characteristics and AOSpine facet fracture classification. Association between facet fracture characteristics and AOSpine classification was assessed through multivariable logistic regression models. Fifty-six patients with cervical spine fractures isolated to the facets were included in the study. The mean age was 36 (range 9–90) years with 55.4% (n = 31) males. A significant correlation was found between subtype F1 and subtype F2 in laterality (left- or right-sided) (p = 0.004), interfacetal fracture involvement (p

Background Moyamoya disease (MMD) is a rare cerebrovascular condition, often presenting as a headache or stroke in adults. Anesthetic management of this illness may challenge providers because it can affect the long-term neurologic outcome and hospital length of stay (LOS) in patients with MMD. Materials and Methods A literature search was conducted to assess etiology and epidemiology, as well as existing reports of intraoperative management of MMD. Due to sparse findings, the search was expanded to include studies of the use of intraoperative anesthetic agents during other neurosurgical procedures. We also retrospectively reviewed all MMD cases from January 1, 2009, to December 31, 2015, at Memorial Hermann Hospital-Texas Medical Center, where intraoperative management involved craniotomy and surgical revascularization. Data were collected primarily on the use of several anesthetic agents. The LOS and any adverse events were also recorded for each case. The data were divided into two equivalent case cohorts: (1) January 1, 2009, to February 18, 2013, and (2) February 19, 2013, to December 31, 2015. Results Remifentanil use notably increased between the first and second time periods while fentanyl use decreased. Desflurane usage also demonstrated an observed increase when our two cohorts were compared. Additionally, there was a decrease in the mean LOS between the first and second periods of 3.9 and 3.3 days, respectively. Conclusion Increasing use of remifentanil in MMD cases could be attributed to its ability to provide more stable hemodynamics during induction, maintenance, and emergence of anesthesia when compared with fentanyl. Lower systolic pressures, diastolic pressures, and heart rates were reported in patients receiving remifentanil over fentanyl.

Introduction It is unknown if treatment with rt‐PA in mild acute ischemic stroke (MIS) is associated with improvement in long term cognition. Methods Forty‐five patients with suspected acute mild stroke or transient ischemic attacks with NIHSS ≤6 were enrolled in a prospective cohort. Cognitive testing was performed within 24 h of symptom onset. Follow‐up assessment was performed at Day 90 on 25 patients. Prestroke baseline cognition was based on age, years of education (YrE), history of cognitive impairment, and the Fazekas score. Results Eighty‐five percent patients with suspected MIS or TIA showed cognitive abnormalities within 24 h of onset. There was no significant difference in age, sex, Fazekas score, or YrE between rt‐PA versus No‐rt‐PA groups (N = 8 vs. 17).Two sample t‐test for change in performance in the WMS‐III sub‐tests (follow‐up – baseline) ± SD, indicated a difference between rt‐PA 0.74 ± 0.77 and no‐rt‐PA groups ‐0.02 ± 0.83 (P = 0.044). Logistic regression for predicting normal status using the mental control subtest, at follow‐up showed an OR 8.96, CI 0.98–82.12 (P = 0.05) favoring the rt‐PA group. Improvement in Mental Control at 90 days occurred in patients with low white matter disease compared to high white matter disease, 0.60 ± 0.46 (P = 0.048). A statistical trend was observed and suggested an improvement on SDMT and Trail Making tests, 1.43 ± 0.8 (P = 0.077). Conclusion Suspected MIS and TIA patients have cognitive impairment within 24 h of onset. rt‐PA administration might be associated with improvement on some cognitive tests at 90 days.

Background: Stroke outcomes have been shown to be worse for patients presenting overnight and on weekends (after-hours) to stroke centers compared with those presenting during business hours (on-hours). Telemedicine (TM) helps provide evaluation and safe management of stroke patients. We compared time metrics and outcomes of stroke patients who were assessed and received intravenous recombinant tissue plasminogen activator (IV-tPA) via TM during after-hours with those during on-hours. Methods: Analysis of our TM registry from September 2015 to December 2016, identified 424 stroke patients who were assessed via TM and received IV-tPA. We compared baseline characteristics, clinical variables, time metrics, and outcomes between the after-hours (5 pm-7:59 am, weekends) and on-hours (weekdays 8 am-4:59 pm) patients. Results: Of the 424 patients, 268 were managed via TM during after-hours, and 156 during on-hours. Baseline characteristics and clinical variables were similar between the groups. Importantly, there were no differences in all relevant time metrics including door to IV-tPA bolus time. IV-tPA complications (including all intracerebral hemorrhage (ICH), any systemic bleeding, and angioedema), discharge disposition, and 90-day modified Rankin Scale were also similar in the groups. Conclusions: There was no difference in IV-tPA treatment times, acute stroke evaluation times, or mortality between the patients treated after-hours versus on-hours. Unlike in-person neurology coverage at many centers, the coverage provided by TM does not differ depending on the hour or day. Access to stroke specialists 24/7 via TM can ensure dependable and timely clinical care for acute stroke patients regardless of the time of day or day of the week.

We propose a Bayesian hierarchical monitoring design for single-arm phase II clinical trials of cancer treatments that incorporates the information on the duration of response into the monitoring rules. To screen a new treatment by evaluating its preliminary therapeutic effect, futility monitoring rules are commonly used in phase II clinical trials to make “go/no-go” decisions timely and efficiently. These futility monitoring rules are usually focused on a single outcome (eg, response rate), although a single outcome may not adequately determine the efficacy of the experimental treatment. For example, targeted agents with a long response duration but a similar response rate may be worth further evaluation in cancer research. To address this issue, we propose Bayesian hierarchical futility monitoring rules to consider both the response rate and duration. The first level of monitoring evaluates whether the response rate provides evidence that the experimental treatment is worthy of further evaluation. If the evidence from the response rate does not support continuing the trial, the second level monitoring rule, which is based on the duration of response, will be triggered. If both stopping rules are satisfied, the trial will be stopped for futility. We conducted simulation studies to evaluate the operating characteristics of the proposed monitoring rules and compared them to those of standard method. We illustrated the proposed design with a single arm phase II cancer clinical trial to assess the safety and efficacy of combined treatment of nivolumab and azacitidine in patients with relapsed/refractory acute myeloid leukemia. The proposed design avoids an aggressive early termination for futility when the experimental treatment substantially prolongs the duration of response but fails to improve the response rate.

Background and Purpose: Time elapsed from last-known well (LKW) and baseline imaging results are influential on endovascular thrombectomy (EVT) outcomes. Methods: In a prospective multicenter cohort study of imaging selection for endovascular thrombectomy (SELECT [Optimizing Patient’s Selection for Endovascular Treatment in Acute Ischemic Stroke], the early infarct growth rate (EIGR) was defined as ischemic core volume on perfusion imaging (relative cerebral blood flow2. The primary outcome was 90-day functional independence (modified Rankin Scale score =0–2). Results: Of 445 consented, 361 (285 EVT, 76 medical management only) patients met the study inclusion criteria. The optimal EIGR was P P P P =0.001). EIGR independently correlated with functional independence after EVT, adjusting for age, National Institutes of Health Stroke Scale, time LKW to groin puncture, reperfusion (modified Thrombolysis in Cerebral Infarction score of ≥2b), IV-tPA (intravenous tissue-type plasminogen activator), and transfer status (aOR: 0.78 [0.65–0.94], P =0.01). Slow progressors had higher functional independence rates (121 [61%] versus 30 [35%], P P =0.001) as compared to fast progressors, who had substantially worse clinical outcomes both in early and late time window. The odds of good outcome decreased by 14% for each 5 mL/h increase in EIGR (aOR, 0.87 [0.80–0.94], P Conclusions: The EIGR strongly correlates with both collateral status and clinical outcomes after EVT. Fast progressors demonstrated worse outcomes when receiving EVT beyond 6 hours of stroke onset as compared to those who received EVT within 6 hours. Registration: URL: https://clinicaltrials.gov . Unique identifier: NCT02446587.

Cervical cancer (CC), an aggressive malignancy, has a high risk of relapse and death, mainly occurring in females. Accumulating investigations have confirmed the critical role of long noncoding RNAs (lncRNAs) in diverse cancers. LncRNA LINC01503 has been reported as an oncogene in several cancers. Nonetheless, its role and molecular mechanism in CC have not been explored. In the present study, we found that FXYD3 expression was considerably up-regulated in CC tissues and cells. Moreover, FXYD3 deficiency conspicuously hampered cell proliferation and migration while facilitated cell apoptosis in CC cells. Subsequently, molecular mechanism experiments implied that FXYD3 was a downstream target gene of miR-342-3p, and FXYD3 expression was reversely mediated by miR-342-3p. Moreover, we discovered that LINC01503 acted as the endogenous sponge for miR-342-3p. Besides, LINC01503 negatively regulated miR-342-3p expression and positively regulated FXYD3 expression in CC. Rescue assays revealed that LINC01503 depletion-induced repression on CC progression could be partly recovered by miR-342-3p inhibition, and then the co-transfection of sh-FXYD3#1 rescued this effect. Conclusively, LINC01503 aggravated CC progression through sponging miR-342-3p to mediate FXYD3 expression, providing promising therapeutic targets for CC patients.

Background The effect and safety of atropine on delaying the progression of myopia has been extensively studied, but its optimal dose is still unclear. Therefore, the purpose of this meta-analysis is to systematically evaluate the safety and effectiveness of atropine in controlling the progression of myopia, and to explore the relationship between the dose of atropine and the effectiveness of controlling the progression of myopia. Methods This work was done through the data searched from PubMed, MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials. The Cochrane Handbook was also used to evaluate the quality of the included studies. In addition, a meta-analysis was performed using Revman5.3 software. Results A total of 10 randomized controlled trials (RCTs) were included. Myopia progression was mitigated greater in the atropine treatment group than that in the control group, with MD = − 0.80, 95% CI (− 0.94, − 0.66) during the whole observation period. There was a statistical difference among 0.05, 0.5, and 1.0% atropine (P = 0.004). In addition, less axial elongation was shown, with MD = − 0.26, 95% CI (− 0.33, − 0.18) during the whole observation period. Conclusion The effectiveness of atropine in controlling the progression of myopia was dose related. A 0.05% atropine was likely to be the optimal dose.

Mobile Stroke Units (MSUs) deliver acute stroke treatment on-scene in coordination with Emergency Medical Services (EMS). One criticism of the MSU approach is the limited range of a single MSU. The Houston MSU is evaluating MSU implementation, and we developed a rendezvous approach as an innovative solution to expand the range and number of patients treated.In addition to direct 911 dispatch of our MSU to the scene within our 7-mile catchment area, we empowered more distant EMS units to activate the MSU. We also monitored EMS radio communications to identify possible patients. For these distant patients, the MSU met the EMS unit en route to the stroke center and treated the patient at that intermediate location. The distribution of the distance from MSU base station to site of stroke and time from 911 alert to tissue plasminogen activator (tPA) bolus were compared between patients treated on-scene and by rendezvous using Wilcoxon rank sum test.Over 4 years, 338 acute ischemic stroke patients were treated with tPA on our MSU. Of these, 169 (50%) were treated on-scene after MSU dispatch at a median of 6.4 miles (IQR 6.4 miles) from MSU base station. 169 (50%) were treated by 'rendezvous' pathway with assessment and treatment of stroke a median of 12.4 miles from base (IQR 5.5 miles) (p0.0001). Time (min) from MSU alert to tPA bolus did not differ: 36.0 ± 10.0 for on-scene vs 37.0 ± 10.0 with rendezvous (p=0.65). 13% of patients alerted via direct 911 dispatch were treated vs 44% of rendezvous patients.Adding a rendezvous approach to an MSU dispatch pathway doubles the range of operations and the number of patients treated by an MSU in an urban area, without incurring delay.

Medical and socioeconomic factors may impact decisions to change the goals of care for patients with intracerebral hemorrhage (ICH) to comfort measures only.We reviewed prospectively collected data on patients with ICH, including baseline patient demographics, Glasgow Coma Scale (GCS), National Institute of Health Stroke Scale (NIHSS), and ICH score. We conducted multivariable logistic regression analysis to identify predictors of change to comfort measures only status.Of 198 patients included in the analysis, 39 (19.7%) were made comfort measures only. Age, gender, insurance status, substance use, and medical comorbidities were similar between groups. Race was significantly different between the comfort measures only (black 15.4%, white 51.3%, other 33.3%) and noncomfort measures only groups (black 39.6%, white 45.9%, other 14.5%; P = .003). Patients changed to comfort measures only had higher mean income based on zip code ($59,264 versus $49,916; P = .021), higher median NIHSS (23 versus 16; P = .0001), higher ICH score (2.7 versus 1.5; P.0001), lower median GCS (7 versus 13; P.0001). Following multivariable analysis, factors associated with comfort measures only were GCS odds ratio (OR) 0.77, 95% confidence interval (CI) 0.68-0.86, P.0001), intraventricular hemorrhage (IVH) volume (OR 1.03, 95% CI 1.01-1.06, P = .002), and black race (OR 0.24, 95% CI 0.07-0.82, P = .022). Mortality, poor outcome, and hospital length of stay were not significantly different between black and white patients.Lower GCS score, higher IVH volume, and race were independent predictors of comfort measures only. Black patients were 76% less likely to withdraw life support than white patients. There were no significant differences in mortality between black and white patients. Providers should be aware of potential racial disparities.

Supplemental Digital Content is available in the text, Enterovirus 71 (EV71) is an important etiological agent of hand, foot, and mouth disease (HFMD), which can also lead to severe neurological complications (eg, encephalitis) in young children. Although a series of reports on EV71 infection have been published, the pathogenic mechanism of EV71 infection is still not fully understood. We evaluated the cerebrospinal fluid (CSF) levels of the inflammatory cytokines interleukin (IL)-8, IL-1β, IL-6, IL-10, tumor necrosis factor (TNF)-α, and IL-12p70 in 88 children with EV71-related encephalitis and 19 children with febrile convulsion (FC) with the use of commercial cytometric bead array kits. The levels of IL-8, IL-1β, IL-6, and IL-10 in CSF were significantly higher in encephalitis group when compared with those observed in FC group, while no significant changes were noted in the levels of TNF-α and IL-12p70. In addition, significant and positive correlations among CSF IL-8, IL-1β, IL-6, and IL-10 were observed in encephalitis group. Furthermore, receiver operator characteristic analysis determined a cut-off value of 10.62 pg/mL for IL-6 to discriminate encephalitis patients from FCs with the sensitivity and specificity of 89.8% and 84.2%, respectively. Moreover, logistic regression analyses revealed that IL-6 was an independent predictor of EV71-related encephalitis (odds ratio = 23.241, P

Correlate body mass index (BMI) with incidence and type of cervical spine injury seen on CT in adult patients presenting with blunt trauma. Retrospective chart review of all adult blunt trauma patients who had a cervical spine CT performed at our level 1 trauma center during an approximately 3-year period. A statistically significant (p = 0.01) difference in cervical spine injury incidence was present between different BMI groups. Cervical spine injury incidence was 7.7% for underweight (BMI ≤ 18) patients, 7.1% for normal weight (BMI 18–25) patients, 6.2% for overweight/obese (BMI 25–35) patients, and 4.7% for morbidly obese (BMI > 35) patients. Using BMI > 18–25 as a reference group, females with BMI > 25–35 had an adjusted odds ratio (aOR) of 0.56 (CI 0.41–0.75) and females with BMI > 35 had an aOR of 0.42 (CI 0.26–0.70). Males with a BMI ≤ 18 had an aOR of 2.20 (CI 1.12–4.32) and males with BMI > 35 had an aOR of 0.66 (CI 0.46–0.95). A particularly low incidence of cervical spine injury was observed in patients older than 65 in the obese group with a cervical spine injury rate of only 1.4% in this patient population. No statistical significant difference was seen in injury morphology across the BMI groups. An inverse relationship exists between BMI and the overall incidence of cervical spine injury. This protective effect appears to be influenced by gender with elevated BMI having lower relative odds of cervical spine injury in women than in men. A particularly low rate of cervical spine injury was identified in obese patients over the age of 65. Routine imaging of all elderly, obese trauma patients with low energy mechanism of injury may not be warranted.

IMPORTANCE: A direct to angiography (DTA) treatment paradigm without repeated imaging for transferred patients with large vessel occlusion (LVO) may reduce time to endovascular thrombectomy (EVT). Whether DTA is safe and associated with better outcomes in the late (>6 hours) window is unknown. Also, DTA feasibility and effectiveness in reducing time to EVT during on-call vs regular-work hours and the association of interfacility transfer times with DTA outcomes have not been established. OBJECTIVE: To evaluate the functional and safety outcomes of DTA vs repeated imaging in the different treatment windows and on-call hours vs regular hours. DESIGN, SETTING, AND PARTICIPANTS: This pooled retrospective cohort study at 6 US and European comprehensive stroke centers enrolled adults (aged ≥18 years) with anterior circulation LVO (internal cerebral artery or middle cerebral artery subdivisions M1/M2) and transferred for EVT within 24 hours of the last-known-well time from January 1, 2014, to February 29, 2020. EXPOSURES: Repeated imaging (computed tomography with or without computed tomographic angiography or computed tomography perfusion) before EVT vs DTA. MAIN OUTCOMES AND MEASURES: Functional independence (90-day modified Rankin Scale score, 0-2) was the primary outcome. Symptomatic intracerebral hemorrhage, mortality, and time metrics were also compared between the DTA and repeated imaging groups. RESULTS: A total of 1140 patients with LVO received EVT after transfer, including 327 (28.7%) in the DTA group and 813 (71.3%) in the repeated imaging group. The median age was 69 (interquartile range [IQR], 59-78) years; 529 were female (46.4%) and 609 (53.4%) were male. Patients undergoing DTA had greater use of intravenous alteplase (200 of 327 [61.2%] vs 412 of 808 [51.0%]; P = .002), but otherwise groups were similar. Median time from EVT center arrival to groin puncture was faster with DTA (34 [IQR, 20-62] vs 60 [IQR, 37-95] minutes; P 6 to 24 hours; P = .88 for interaction). Three-month mortality was lower with DTA (53 of 312 [17.0%] vs 186 of 763 [24.4%]; P = .008). A 10-minute increase in EVT-center arrival to groin puncture in the repeated imaging group correlated with 5% reduction in the functional independence odds (aOR, 0.95 [95% CI, 0.91-0.99]; P = .01). The rates of modified Rankin Scale score of 0 to 2 decreased with interfacility transfer times of greater than 3 hours in the DTA group (96 of 161 [59.6%] vs 15 of 42 [35.7%]; P = .006), but not in the repeated imaging group (75 of 208 [36.1%] vs 71 of 192 [37.0%]; P = .85). CONCLUSIONS AND RELEVANCE: The DTA approach may be associated with faster treatment and better functional outcomes during all hours and treatment windows, and repeated imaging may be reasonable with prolonged transfer times. Optimal EVT workflow in transfers may be associated with faster, safe reperfusion with improved outcomes.

Background Alternative polyadenylation (APA) is emerging as a major post-transcriptional mechanism for gene regulation, and dysregulation of APA contributes to several human diseases. However, the functional consequences of APA in human cancer are not fully understood. Particularly, there is no large-scale analysis in cancer cell lines. Methods We characterized the global APA profiles of 6398 patient samples across 17 cancer types from The Cancer Genome Atlas and 739 cancer cell lines from the Cancer Cell Line Encyclopedia. We built a linear regression model to explore the correlation between APA factors and APA events across different cancer types. We used Spearman correlation to assess the effects of APA events on drug sensitivity and the Wilcoxon rank-sum test or Cox proportional hazards model to identify clinically relevant APA events. Results We revealed a striking global 3'UTR shortening in cancer cell lines compared with tumor samples. Our analysis further suggested PABPN1 as the master regulator in regulating APA profile across different cancer types. Furthermore, we showed that APA events could affect drug sensitivity, especially of drugs targeting chromatin modifiers. Finally, we identified 1971 clinically relevant APA events, as well as alterations of APA in clinically actionable genes, suggesting that analysis of the complexity of APA profiles could have clinical utility. Conclusions Our study highlights important roles for APA in human cancer, including reshaping cellular pathways and regulating specific gene expression, exemplifying the complex interplay between APA and other biological processes and yielding new insights into the action mechanism of cancer drugs.

Background aims Extensive animal data indicate that mesenchymal stromal cells (MSCs) improve outcome in stroke models. Intra-arterial (IA) injection is a promising route of delivery for MSCs. Therapeutic effect of MSCs in stroke is likely based on the broad repertoire of secreted trophic and immunomodulatory cytokines produced by MSCs. We determined the differential effects of exposing MSCs to different types of clinically relevant vehicles, and/or different additives and passage through a catheter relevant to IA injections. Methods MSCs derived from human bone marrow were tested in the following vehicles: 5% albumin (ALB), 6% Hextend (HEX) and 40% dextran (DEX). Each solution was tested (i) alone, (ii) with low-dose heparin, (iii) with 10% Omnipaque, or (iv) a combination of heparin and Omnipaque. Cells in vehicles were collected directly or passed through an IA catheter, and MSC viability and cytokine release profiles were assessed. Results Cell viability remained above 90% under all tested conditions with albumin being the highest at 97%. Viability was slightly reduced after catheter passage or exposure to heparin or Omnipaque. Catheter passage had little effect on MSC cytokine secretion. ALB led to increased release of angiogenic factors such as vascular endothelial growth factor compared with other vehicles, while HEX and DEX led to suppression of pro-inflammatory cytokines such as interleukin-6. However, when these three vehicles were subjected to catheter passage and/or exposure to additives, the cytokine release profile varied depending on the combination of conditions to which MSCs were exposed. Discussion Exposure of MSCs to certain types of vehicles or additives changes the profile of cytokine secretion. The activation phenotype of MSCs may therefore be affected by the vehicles used for these cells or the exposure to the adjuvants used in their administration.

The purpose of the study is to determine the incidence of sacral fracture patterns on CT imaging of pelvic trauma patients with correlation with mechanism of injury and pelvic ring injury pattern using the Young-Burgess classification system. This is a retrospective review of all pelvic CTs with pelvic fractures performed at our level 1 trauma center during a 4-year period from July 2010 to June 2014. Sacral fractures were very common in pelvic trauma patients, being present in 60% of patients presenting to our institution with pelvic fractures. Longitudinal fractures were almost always associated with additional pelvic ring injuries. Denis zone 1 fractures had the highest association with lateral compression pelvic ring injuries. Denis zone 2 and 3 fractures were seen with increased frequency in AP compression and vertical shear injuries. A third of transverse sacral fractures occurred in isolation, with isolated transverse sacral fractures typically occurring in the low (S3–S5) sacrum. Almost half of combined transverse and longitudinal sacral fractures occurred without an additional pelvic fracture present. Sacral avulsions almost always occurred as part of a pelvic ring fracture pattern, most commonly in AP compression injuries. Coccyx fractures frequently occurred in isolation, but were commonly seen in vertical shear injuries when associated with a pelvic ring injury pattern. Avulsion fractures and longitudinal fractures of the sacrum are almost always associated with anterior pelvic ring injury. Conversely, transverse fractures of the lower sacrum and combined longitudinal and transverse sacral fractures are prone to occur in isolation.

Objective Cervical cancer is the most common malignant tumor in gynaecology with high mortality. MiRNA has been reported to regulate cell biological processes in cervical cancer. This study aimed to explore the expression of miR-1258 and role of miR-1258 by targeting E2F1 in cervical cancer cells. Methods The expression of miR-1258 and E2F1 in cervical cancer cells and transfection effects was determined by RT-qPCR analysis. The expression of E2F1, MMP2, MMP7, MMP9, Bcl2, Bax, cleaved caspase3, caspase3, KI67, p-AKT, cyclinD1, CDK2, P53 and AKT in cervical cancer cells was detected by western blot analysis. The proliferation, invasion, migration and apoptosis were respectively analyzed by CCK-8 assay, transwell assay, wound healing assay and flow cytometry analysis. E2F1 was a potential target of miR-1258, which demonstrated by a dual-luciferase reporter assay. Results miR-1258 expression was decreased while E2F1 expression was increased in cervical cancer cells. MiR-1258 overexpression could down-regulate the E2F1 expression. Overexpression of miR-1258 inhibited the proliferation, invasion and migration and promoted the apoptosis of cervical cancer cells by AKT and P53 signal pathway. And, Overexpression of miR-1258 also suppressed the tumor growth by AKT and P53 signal pathway. Overexpression of E2F1 reduced the inhibition effects of miR-1258 in cervical cancer. Conclusion Taken together, miR-1258 overexpression exerts its inhibition effects on the proliferation, invasion and migration and promotion effects on the apoptosis of cervical cancer cells by targeting the E2F1, which might provide new ideas for clinical treatment of cervical cancer.

OBJECTIVE The primary imaging modalities used to select patients for endovascular thrombectomy (EVT) are noncontrast computed tomography (CT) and CT perfusion (CTP). However, their relative utility is uncertain. We prospectively assessed CT and CTP concordance/discordance and correlated the imaging profiles on both with EVT treatment decisions and clinical outcomes. METHODS A phase 2, multicenter, prospective cohort study of large-vessel occlusions presented up to 24 hours from last known well was conducted. Patients received a unified prespecified imaging evaluation (CT, CT angiography, and CTP with Rapid Processing of Perfusion and Diffusion software mismatch determination). The treatment decision, EVT versus medical management, was nonrandomized and at the treating physicians' discretion. An independent, blinded, neuroimaging core laboratory adjudicated favorable profiles based on predefined criteria (CT:Alberta Stroke Program Early CT Score ≥ 6, CTP:regional cerebral blood flow (

Background To describe the clinical characteristics and the outcomes of strabismus surgery for acute acquired comitant esotropia (AACE). Methods Medical records of 45 AACE patients were retrospectively analyzed. The insertion location of medial rectus was compared between the AACE patients and comitant exotropic patients. The location was also compared with those measured in other studies. Surgical outcome measurements included amount of deviation and level of binocularity at last follow-up. Results The distance from medial rectus to limbus was shorter in AACE patients than in patients with comitant exotropia. The distance was also shorter in AACE patients than patients in other studies. Out of the 45 patients, 2 had neurological diseases. Neostigmine test was negative in all patients. The age at onset of AACE was 5–47 years (mean 19.1 ± 7.3 years), one patient was 5 years (2.2%), 20 patients were 11–17 years (44.5%) and the other 24 patients were 18–47 years old (53.3%). The mean cycloplegic refraction was − 4.1 ± 3.0 diopters (D) and 41 patients were myopic (91%). The angle of deviation was 40.5 ± 19.5 prism diopters (PD) at distance and 35.6 ± 19.9PD at near preoperatively. The angle was 0.8 ± 1.6 PD at distance and 0.7 ± 1.8 PD at near postoperatively. Diplopia resolved in patients who underwent strabismus surgery, with no recurrence during the follow-up period. Thirty patients had stereopsis postoperatively. Conclusions AACE seems to occur mostly in older children and adults and myopes. The distance from the insertion to limbus of medial rectus was shorter in patients with AACE. Good results can be achieved by strabismus surgery.

OBJECTIVE For research and risk factor analysis, a reproducible method quantifying atherosclerosis is necessary. Our aim was to develop a computed tomography (CT) angiography grading system to quantify atherosclerotic disease of the head and neck. METHODS Institutional review board-approved, retrospective analysis was performed on 152 patients who underwent head/neck CT angiography. A grading scale was designed to calculate plaque burden at multiple sites with the sum referred to as atherosclerosis score. Three radiologists calculated scores with an overlap of cases to calculate the intraclass correlation coefficient. RESULTS Without any prior training, the intraclass correlation coefficient between readers was considered fair. After a short tutorial, intraclass correlation coefficient was recalculated using separate patients, showing excellent correlation.Statistically significant positive correlation was found between atherosclerosis scale and age, hyperlipidemia, hypertension, and diabetes, but no correlation with sex or smoking status. CONCLUSIONS A simple, visual grading scale for atherosclerosis in head/neck CT angiography was used to standardize reporting and better characterize a patient's risk of stroke.

Background and objective Most stroke patients are prescribed aspirin (ASA) to adjust blood coagulability. Marrow stromal cells (MSCs) are being tested in clinical trials for stroke patients who likely are prescribed aspirin. One of the principal mechanisms of action of MSCs and ASA is modulation of the inflammatory response, including those mediated by monocytes (Mo). Thus, here we tested if aspirin can modify anti-inflammatory properties of MSCs or Mo alone, and in combination. Methods Mo were isolated at 24 h of stroke onset from ischemic stroke patients with NIHSS ranging from 11 to 20 or from healthy controls. Human bone marrow-derived MSCs from healthy subjects were used at passage 3. Mo, MSCs, and MSCs-Mo co-cultures were exposed to ASA at clinically relevant doses. The secretome profile of inflammatory mediators was measured using Magpix multiplex cytokine array. Viability was measured using MTT assay. Linear mixed effect model was used for statistical analysis. Results Overall Mo from control subjects exposed to ASA showed increased secretion of IL-1RA, IL-8, MCP-1, and TNF-α and Mo from stroke patients showed greater release of IL-1RA and MCP-1. In MSCs-Mo co-cultures, ASA added to co-cultures of control Mo reduced fractalkine secretion while it increased the fractalkine secretion when added to Mo from stroke patients. In addition, in co-cultures independent of Mo origin, ASA reduced IL-6, IL-8, MCP-1, and TNF-α. Conclusions Aspirin in acute stroke patients may modulate the secretome profile of Mo and MSCs, thus potentially modulating immune and inflammatory responses associated with stroke. Our results suggest that stroke trials involving the use of intravenous MSCs should consider the effect of aspirin as a confounding factor.

OBJECTIVES Evaluate the time taken to visualize the internal jugular vein and carotid arteries, and subjective image quality assessed on a 0-100 visual analogic scale, on an ultrasound model using either traditional ultrasound gel or normal saline. METHODS Twenty-two anesthesiology residents and twenty anesthesiology faculty were blinded and randomized into four separate groups using gel and saline as a conduction medium, in different sequences. RESULTS Subjective image quality was 12.2 ± 4.2 better with gel than with saline (P

To evaluate chest injury patterns in pediatric patients involved in all-terrain vehicle (ATV) accidents. Retrospective review of patients 0–18 years old admitted to a level I trauma institute following an ATV-related incident from 2004 to 2013 was performed. Chest injury type, accident mechanism, driver/passenger status, and demographic and clinical data were compared between patients with and without chest injury. Chest injury was present in 102 (22%) of total 455 patients. The most common chest injuries were pulmonary contusion (61%), pneumothorax (45%), and rib fracture (34%). There were no cardiac, esophageal, or tracheobronchial injuries. Pulmonary lacerations, hemothoraces, and scapular fractures were predominantly not detected on radiography and recognized on CT only (86–92%). Patients with chest injury had longer median hospital stays (3 days vs 2 days, p = 0.0054). There was no significant difference in admission to intensive care after controlling for injury severity scores in patients with chest injury compared to those without (17 vs 9). Eight patients with chest injury died (8%) compared to 2 patients without chest injury (0.6%) (p = 0.0002). Chest injuries are common in children following ATV accidents and may be a marker of more severe trauma. Increased public awareness of these potentially devastating injuries and continuing safety efforts are needed.

SummaryBackground Functional Fibrinogen assay of the Thromboelastography (FFTEG), a whole blood viscoelastic hemostatic assay, has been used to estimate fibrinogen levels in adult patients undergoing major surgery but its performance in pediatric patients undergoing cardiac surgery requires evaluation. In this study, we evaluate the correlation between FFTEG parameters and standard laboratory tests for fibrinogen and platelet counts before and after cardiopulmonary bypass in children undergoing repair for congenital heart disease. Methods In this prospective observational study, whole blood samples were obtained from children less than 5 years of age undergoing congenital heart surgery with cardiopulmonary bypass before surgical incision and immediately after administration of protamine. Blood samples were analyzed for Thromboelastography, Functional Fibrinogen level measured by FFTEG (FLEV), complete blood counts with platelet count and plasma fibrinogen assay (LFib, Clauss). The primary outcome of this study was to assess the correlation between FFTEG parameters, LFib and platelet counts in neonates, infants, and small children less than 5 years old. Additionally, we studied if postbypass FFTEG parameters could predict critical thresholds of hypofibrinogenemia LFib ≤200 mg·dl−1. Results One hundred and five children (22 neonates, 51 infants, and 32 small children) were included in the final analysis. FLEV estimated higher fibrinogen levels than LFib in all patients. Before bypass, FLEV was on average 133 mg·dl−1 higher than LFib (95% confidence interval, CI, 116–150, P < 0.001) for all the patients; after bypass, FLEV was 48 mg·dl−1 (95% CI: 37–59, P < 0.001) higher than LFib for all the patients. Linear correlation coefficients between FLEV and LFib in all patients were R = 0.41 (95% CI: 0.24–0.56, P < 0.001) before bypass and increased to R = 0.63 (95% CI: 0.51–0.74, P < 0.001) after bypass. Bland Altman analysis performed on postbypass values of FLEV and LFib showed a positive bias of FLEV in estimation of LFib. The magnitude and the variability of the bias for all the patients group was decreased with lower mean of the difference of FLEV and LFib when the average values of FLEV and LFib were

During the 20 years since US Food and Drug Administration approval of IV tissue plasminogen activator for acute ischemic stroke, vascular neurology consultation via telemedicine has contributed to an increased frequency of IV tissue plasminogen activator administration and broadened geographic access to the drug. Nevertheless, a growing demand for acute stroke coverage persists, with the greatest disparity found in rural communities underserved by neurologists. To provide efficient and consistent acute care, formal training in telemedicine during neurovascular fellowship is warranted. Herein, we describe our experiences incorporating telestroke into the vascular neurology fellowship curriculum and propose recommendations on integrating formal telemedicine training into the Accreditation Council for Graduate Medical Education vascular neurology fellowship.

Background and Purpose: Post-stroke anxiety (PSA) is common and disabling. PSA should be considered as an important outcome in stroke. However, there is a lack of understanding of factors that may be linked to PSA. The purpose of this study was to determine the frequency of PSA and sociodemographic and clinical factors associated with PSA in a cohort of racially and ethnically diverse stroke patients. Methods: We conducted a retrospective study of ischemic and hemorrhagic stroke patients seen in a stroke outpatient clinic from August 1, 2017 to June 30, 2018. Patients were eligible if a Generalized Anxiety Disorder 7-Item (GAD-7) instrument was available. GAD-7 scores greater than or equal to 10 indicated the presence of moderate to severe PSA. Multivariable logistic regression was used to identify independent sociodemographic and clinical factors associated with PSA. Results: Records from 289 stroke patients with a GAD-7 instrument were analyzed. PSA was common (21%; GAD-7 ≥ 10). Fifty-seven percent of females had a GAD-7 greater than or equal to 10 compared to 41% of females who had a GAD-7 less than 10 (P = .03). Multivariable analysis found that self-reported nonmarried status (odds ratio, 3.27; 95% confidence interval, 1.44-7.44), excessive fatigue (odds ratio, 4.46; 95% confidence interval, 1.87-10.63), and depression (odds ratio, 1.24; 95% confidence interval, 1.16-1.33) were independently associated with PSA. Conclusions: PSA may occur more frequently in those who report non-married, excessive fatigue, or depression. Trials of PSA interventions should consider the potential impact of social support, depression, and comorbid conditions contributing to post-stroke fatigue, including sleep apnea.

A time-dependent measure, termed the rate ratio, was proposed to assess the local dependence between two types of recurrent event processes in one-sample settings. However, the one-sample work does not consider modelling the dependence by covariates such as subject characteristics and treatments received. The focus of this paper is to understand how and in what magnitude the covariates influence the dependence strength for bivariate recurrent events. We propose the covariate-adjusted rate ratio, a measure of covariate-adjusted dependence. We propose a semiparametric regression model for jointly modeling the frequency and dependence of bivariate recurrent events: the first level is a proportional rates model for the marginal rates and the second level is a proportional rate ratio model for the dependence structure. We develop a pseudo-partial likelihood to estimate the parameters in the proportional rate ratio model. We establish the asymptotic properties of the estimators and evaluate the finite sample performance via simulation studies. We illustrate the proposed models and methods using a soft tissue sarcoma study that examines the effects of initial treatments on the marginal frequencies of local/distant sarcoma recurrence and the dependence structure between the two types of cancer recurrence.

Background and Purpose- Endovascular thrombectomy (EVT) is effective for acute ischemic stroke with large vessel occlusion and National Institutes of Health Stroke Scale (NIHSS) ≥6. However, EVT benefit for mild deficits large vessel occlusions (NIHSS,6) is uncertain. We evaluated EVT efficacy and safety in mild strokes with large vessel occlusion. Methods- A retrospective cohort of patients with anterior circulation large vessel occlusion and NIHSS6 presenting within 24 hours from last seen normal were pooled. Patients were divided into 2 groups: EVT or medical management. Ninety-day mRS of 0 to 1 was the primary outcome, mRS of 0 to 2 was the secondary. Symptomatic intracerebral hemorrhage was the safety outcome. Clinical outcomes were compared through a multivariable logistic regression after adjusting for age, presentation NIHSS, time last seen normal to presentation, center, IV alteplase, Alberta Stroke Program early computed tomographic score, and thrombus location. We then performed propensity score matching as a sensitivity analysis. Results were also stratified by thrombus location. Results- Two hundred fourteen patients (EVT, 124; medical management, 90) were included from 8 US and Spain centers between January 2012 and March 2017. The groups were similar in age, Alberta Stroke Program early computed tomographic score, IV alteplase rate and time last seen normal to presentation. There was no difference in mRS of 0 to 1 between EVT and medical management (55.7% versus 54.4%, respectively; adjusted odds ratio, 1.3; 95% CI, 0.64-2.64; P=0.47). Similar results were seen for mRS of 0 to 2 (63.3% EVT versus 67.8% medical management; adjusted odds ratio, 0.9; 95% CI, 0.43-1.88; P=0.77). In a propensity matching analysis, there was no treatment effect in 62 matched pairs (53.5% EVT, 48.4% medical management; odds ratio, 1.17; 95% CI, 0.54-2.52; P=0.69). There was no statistically significant difference when stratified by any thrombus location; M1 approached significance ( P=0.07). Symptomatic intracerebral hemorrhage rates were higher with thrombectomy (5.8% EVT versus 0% medical management; P=0.02). Conclusions- Our retrospective multicenter cohort study showed no improvement in excellent and independent functional outcomes in mild strokes (NIHSS,6) receiving thrombectomy irrespective of thrombus location, with increased symptomatic intracerebral hemorrhage rates, consistent with the guidelines recommending the treatment for NIHSS ≥6. There was a signal toward benefit with EVT only in M1 occlusions; however, this needs to be further evaluated in future randomized control trials.

Background and purpose Women minorities have an overall increased lifetime incidence of cerebrovascular disease. The provision of risk factor modification in this group can prove difficult. In a population-based study, we used cluster enrollment to identify vascular risk factors in the female caregivers of stroke survivor study participants. Methods Obese women caregivers were identified as part of Swipe out Stroke, a Phase I PROBE study assessing the use of SmartPhone based intervention for dietary modification in minority stroke survivors. After written informed consent was obtained, both patients and caregivers were screened for vascular risk factors at study enrollment. Descriptive statistics were used to depict the study population. Continuous baseline variables were compared using 2 sample t-test or Wilcoxon rank-sum test by caregivers and patients. Categorical baseline variables were compared using Fisher's exact test. Results Thirty-six stroke patients (63.9% African-American, 36.1% Hispanic) and thirteen female caregivers (69.2% African-American, 30.8% Hispanic) were enrolled. Mean age, patients - 54.1 (SD 9.4), caregivers - 51.3 (SD 15.6) years, education, employment status and family history of stroke or obesity did not differ significantly. Compared to stroke patients, female caregivers were significantly less likely to self-report hypertension (69.2 versus 97.2%; P = 0.01) and hyperlipidemia (16.7 versus 60%; P = 0.02). Female caregivers were more likely to have elevated systolic blood pressure (147.6 vs 127.7 mmHg; P = 0.05), total cholesterol (207.5 versus 167 mg/dL; P = 0.01) and low density lipoprotein values (119.5 versus 88 mg/dL; P = 0.03) compared to stroke patients. Conclusions Using cluster enrollment, we discovered minority female caregivers were more likely to have unknown or poorly controlled vascular risk factors compared to stroke patients. Innovative health screening tools may benefit the extended family of minority patients participating in clinical trials.

Background The cortico-ponto-cerebellar tract (CPCT) is the largest projection pathway, which synapses at the pons. Remote effects of supratentorial brain tumors have not been evaluated along the infratentorial course of the CPCT. Aim The purpose of this study is to evaluate the possible lateralization of the diffusion tensor metrics of the affected CPCT in patients with supratentorial brain tumor. Methods and results We included 39 patients with 29 left-sided tumors (LST) and 10 right-sided tumors, retrospectively. We measured the magnitude of changes of the fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values of the CPCT prior to the brain surgery at the level of crus cerebri and middle cerebellar peduncle. Regions of interest (ROIs) were placed on the lateral side of crus cerebri, and ROI-1 (anterior 1/3), ROI-2 (middle 1/3), ROI-3 (posterior 1/3), and ROI-4 were placed at the level of middle cerebellar peduncle. We hypothesized that there would be decreased FA and increased ADC values of the ipsilesional CPCT compared with contralesional CPCT. Ipsilesional FA values were decreased with simultaneous increased ADC value along the CPCT compared with contralesional CPCT in following ROIs, ROI-1 (LST FA: P = .005, ADC: P = .037) and ROI-3 (LST FA: P = .049, ADC: P = .049), respectively. Affected ROI-4 in LST cases also showed lower FA values, although not statistically significant. Conclusion We observed a statistically significant FA value decrease and ADC increase along the left ROI-1 and ROI-3 as well as the nonstatistically significant FA decrease of the left ROI-4 at the second neuron level when there was a related supratentorial tumor. These findings are suggestive of presynaptic and postsynaptic microstructural changes of these tracts following the presynaptic involvement by a primary supratentorial brain tumor.

BACKGROUND: Postcraniotomy pain can be difficult to manage with opioids due to opioid-related side effects, including drowsiness, nausea/vomiting, confusion, and pupillary changes, potentially masking the signs of postoperative neurological deterioration. Intravenous (IV) acetaminophen, a non-opioid analgesic, has been reported to have opioid-sparing effects after abdominal and orthopedic surgeries. This study investigates whether IV acetaminophen has similar effects after craniotomy. METHODS: In this prospective, randomized, placebo-controlled, double-blind clinical trial, 100 adult patients scheduled to undergo supratentorial craniotomy for excision of a brain mass were randomized to receive either IV acetaminophen or placebo pre-incision and then every 6 hours for a total of 24 hours after surgery. Total 24-hour opioid consumption, pain scores, satisfaction with overall pain management, time to meet PACU discharge criteria, and incidence of opioid-related side effects were compared. RESULTS: There was no difference in the 24 hour postoperative opioid consumption in morphine equivalents between the IV acetaminophen group (median 11 mg, n = 45) and the placebo group (median 10.1 mg, n = 41). No statistically significant difference of VAS pain score was observed between two treatment groups. Patient satisfaction with overall postoperative pain management was significantly higher in the IV acetaminophen group than the placebo group on a 1–10 scale (8.1 ± 0.4 vs. 6.9 ± 0.4, p=0.03). There was no significant difference in secondary outcomes, including the incidence of opioid-related side effects. CONCLUSION: IV acetaminophen, as adjunctive therapy for craniotomy procedures, did not show an opioid-sparing effect in patients for the 24 hours after craniotomy; however, it was associated with improved patient satisfaction regarding overall pain control.

To assess the effectiveness of pain relief in patients with grade 2 proximal hamstring injury, treated with platelet-rich plasma (PRP) or corticosteroid injection, by using the primary outcome of visual analog scale (VAS) at 1 week and 4 weeks of follow-up. A single institution retrospective study was performed for image-guided PRP or steroid injections between 12/1/2015 and 10/30/2017 for proximal hamstring injuries. VAS was measured at 1 week and 4 weeks post-injection via telephone interviews and the pain response was recorded into two groups (negative/no change vs. positive). A comparison of pain responses between PRP and steroid was conducted by generalized estimating equation. Among 56 patients, 32 received PRP and 24 received steroid injections with ages from 13 to 75 years old. At 1 week post-injection follow-up, 23 patients (71.9%) from the PRP group and 11 patients (45.8%) from the steroid group showed positive response. After controlling for age, pre-procedure pain level, and gender, the positive response rate in the PRP group was higher than the steroid group (aOR: 4.04, 95% CI: 1.04–15.63, p value = 0.04). At 4 weeks post-injection, 23 patients (71.9%) from the PRP group and 13 patients (54.2%) from the steroid group showed positive response with no statistical significance (aOR: 2.48, 95% CI: 0.63–9.79, p value = 0.19). The PRP group had shown more favorable response compared to steroid group at 1 week post-injection, which suggests that PRP therapy can be considered as a conservative treatment choice for grade 2 proximal hamstring injuries with better short-term pain relief based on limited pilot data.

Background: Dysphagia is a common complication of stroke and can have a lasting impact on morbidity and mortality; yet there are no standards to guide dysphagia management in stroke patients. We assessed predictors of percutaneous endoscopic gastrostomy (PEG) placement in an ischemic stroke cohort and sought to determine the utility of an objective scale in predicting PEG placement in a high-risk sub-set. Methods: Consecutive cases of ischemic stroke were retrospectively, identified and demographic and clinical variables were collected. Penetration-Aspiration (PAS) scores (1-2 normal; 3-5 penetration; 6-8 aspiration) were calculated for patients undergoing Fiberoptic Endoscopic Evaluation of Swallowing (FEES) or Modified Barium Swallowing Studies (MBSS). Multiple logistic regression analysis was used to assess predictors of PEG placement. Results: Among 724 patients, 131 underwent PEG placement. In univariate analysis of the overall cohort, sex, age, insured payer status, arrival National Institute of Health Stroke Scale (NIHSS), NIHSS level of consciousness severity, NIHSS dysarthria severity, diabetes mellitus, and prior International Conference for Harmonization (ICH) were all significantly associated with PEG placement. Among 197 high-risk patients undergoing FEES or MBSS, the multivariate logistic regression analysis showed that PAS scores 6-8 versus 1-2 (odds ratio [OR] 13.2; 95% confidence interval [CI] 4.58, 38.2), PAS score 3-5 versus 1.2 (OR 33.8; 95% CI 11.6, 98.3), Hispanic race (OR, 5.73; 95% CI 1.82, 18.0), male sex (OR, 2.59; 95% CI 1.05, 6.34), and arrival NIHSS (OR, 1.11; 95% CI 1.05, 1.18) were associated with PEG placement. Conclusions: Use of an objective dysphagia scale simplified the prediction model among acute ischemic stroke patients undergoing instrumental assessments of dysphagia with FEES or MBSS. Male sex and Hispanic race were also significantly associated with PEG placement in this analysis. These findings support the need for rigorously designed prospective studies to assess biological and social factors that influence PEG placement and to determine, how to best evaluate and manage patients with dysphagia.

To compare the incidence of rotator cuff tears on shoulder MRI in patients who have rotator cuff calcific tendinopathy with that in patients without calcific tendinopathy in a frequency-matched case–control study. Retrospective review shoulder MRIs of 86 patients with rotator cuff calcific tendinopathy and an 86-patient age-, gender-, and laterality-matched control group using frequency matching. No statistically significant difference (odds ratio: 0.72, 95% confidence interval: 0.38–1.38, p = 0.32) was found in the incidence of rotator cuff tear in the calcific tendinopathy (27.9%) and control groups (34.9%). A significant (p

Enterovirus 71 (EV71) is a major pathogen that causes hand, foot and mouth disease (HFMD) as well as neurological complications, such as encephalitis. The chemokines involved in the migration of leukocytes have increasingly been implicated in infectious diseases of the central nervous system. Few studies have evaluated the levels of chemokines in HMFD children with EV71-related encephalitis. In the present study, we evaluated the cerebrospinal fluid (CSF) levels of the chemokines IL-8, RANTES, MIG, MCP-1 and IP-10 in 99 children with EV71-related encephalitis and 22 children with febrile convulsion (FC). We found that the concentrations of IL-8, RANTES, MIG and IP-10 were significantly higher in HFMD children with encephalitis compared to patients with FC. Additionally, these four chemokines were dramatically reduced during convalescence. Inversely, the level of MCP-1 was lower in encephalitis patients than FC patients and was not significantly reduced during convalescence. Additionally, MIG was strongly correlated with IP-10 in encephalitis patients. Furthermore, the area under the ROC curve (AUC) of CSF MIG and IP-10 in distinguishing encephalitis from FC were 0.869 and 0.876, and the corresponding sensitivities/specificities were 67.7%/100.0% and 67.7%/95.5%, respectively. In conclusion, our results indicate that chemokines play important roles in the pathogenesis of EV71 infection.

Thrombelastography (TEG) measures coagulation in venous blood. We hypothesized that TEG, by reflecting clot subtype and ex vivo fibrinolysis, might predict fibrinolytic response to tPA as reflected by rapid clinical improvement or hemorrhagic transformation of the infarct. 171 acute ischemic stroke patients treated with tPA were prospectively enrolled. Venous blood for TEG was drawn before and 10 min after tPA bolus. We measured rapid clinical improvement (RCI = 8 point improvement on NIHSS or total NIHSS of 0, 1 at 36 h), Hemorrhagic transformation (HT = any blood on imaging within 36 h), and hyperdense middle cerebral artery sign (HDMCA = biomarker for erythrocyte-rich clot). Multivariable regression models compared TEG parameters after adjusting for potential confounders. No differences in pre- or post-tPA TEG were found between patients with or without RCI. Also, there was no correlation between TEG and HDMCA. Clotting was slightly prolonged in patients with HT (p = 0.046). We failed to find a robust association between TEG and clinical response to tPA. It is likely that arterial clot lysis is determined by factors unrelated to coagulation status as measured by TEG in the venous circulation. It is unlikely that TEG will be useful to predict clinical response to tPA, but may help predict bleeding.

Background: Thrombelastography (TEG) provides a global, dynamic measure of coagulation. We examined the effect of antiplatelet (AP) medications on coagulation in patients with acute stroke as measured by TEG. Methods: We reviewed prospectively collected data on patients presenting with acute ischemic stroke (AIS) and spontaneous intracerebral hemorrhage (ICH) between 2009 and 2014. Patient demographics and baseline TEG values were compared among 4 different drug use groups: aspirin only, clopidogrel only, both aspirin and clopidogrel, and no AP. Multivariable regression models were conducted to compare the differences in TEG components. Results: A total of 202 patients were included, 139 with AIS and 63 with ICH. Forty-eight (24%) patients were taking aspirin alone, 12 (6%) were taking clopidogrel, 16 (8%) dual AP, and 126 (62%) no AP. Dual AP use was associated with prolonged mean R (time to initiate clotting) of 5.5 minutes as compared to no AP use (4.6 minutes, P = .04). Additionally, mean maximal amplitude (MA; final clot strength) and angle (rate of clot formation) were decreased in the dual AP group (MA = 59.3 mm, angle = 57.8°) as compared to the no AP group (MA = 64.5 mm, angle = 64.5°; P = .04 and P = .01, respectively). Patients on single AP therapy (either aspirin or clopidogrel) did not differ from those on no AP therapy in any TEG parameters measured. Conclusion: Dual AP therapy is associated with a detectable coagulopathy which may have implications in the management of patients with AIS and hemorrhagic stroke. The effects of single AP therapy may not be demonstrated by TEG.

Importance Intravenous acetaminophen is a commonly prescribed analgesic for the prevention and treatment of postsurgical pain. Its efficacy in the context of endoscopic sinus surgery (ESS) has yielded mixed results. Objective To compare the efficacy of perioperative intravenous acetaminophen (IVAPAP) with that of placebo in improving early postoperative pain after endoscopic sinus surgery (ESS). Design, Setting, and Participants A prospective, randomized clinical trial including 62 patients undergoing ESS for chronic rhinosinusitis in a single tertiary referral hospital. Interventions Participants were randomized to receive 1 g of IVAPAP or 100 mL of placebo consisting of saline infusions immediately before the start of surgery and 4 hours after the initial dose. Main Outcomes and Measures The primary outcome was postoperative pain measured by visual analog scale (VAS) scores up to 24 hours after surgery by blinded observers. Secondary endpoints included postoperative opioid (intravenous and oral) use and adverse events in the 24-hour postoperative period. Results Of the 62 enrolled adult participants, 60 were randomized (31 to IVAPAP intervention and 29 to placebo). The mean (SD) age of participants was 53.7 (14.7) years and 35 (58%) of the participants were men and 25 (42%) were women. Within the first hour, mean pain scores were reduced in the IVAPAP group compared with the control group, reaching a maximum difference of 7.7 mm on a VAS scale favoring the treatment group with a true difference possibly as high as 22 mm, and the data are compatible with a clinically meaningful difference. At 12- and 24-hours, average pain scores were less in the placebo group and the data are compatible with a clinically meaningful difference of 5.8 (−5.2 to 16.8) and 8.2 (−1.9 to 18.4), respectively, favoring the placebo group. However, at all time points the CIs included the null value and were wide, thus preventing definitive conclusions. Inspection of the secondary outcomes favored IVAPAP, but the wide range of the CIs and inclusion of the null value prevent definitive conclusions. Conclusions and Relevance The results of this study are inconclusive. The data suggest that perioperative intravenous acetaminophen may reduce immediate postoperative pain and opioid requirements compared with placebo and these differences could be clinically meaningful. Unfortunately, the imprecision of the estimates prevents definitive conclusion. Use of IVAPAP does not seem to increase adverse events. Trial Registration clinicaltrials.gov Identifier:NCT01608308

SummaryBackground The incidence of infiltration and extravasation when using peripheral intravenous catheters is high in pediatric patients. Due to the lack of a gold standard test to confirm intravascular location of a peripherally placed intravenous catheter, we introduce a novel method, the color-flow injection test to assess the intravascular location of these catheters. For the color-flow injection test, 1 mL of normal saline was injected within 2 seconds in the distal intravenous catheter and changes in color-flow via ultrasonography were observed at the proximal draining veins. The primary objective of the study was to demonstrate feasibility of the color-flow injection test. Methods A prospective study was conducted on children

Tha aims of this study were to identify the incidence of femoral head fractures in the setting of acetabular fractures and to determine the relationship between acetabular fracture pattern, the degree of acetabular fracture displacement, and the incidence of femoral head fractures. This is a retrospective cross-sectional study of 274 patients with 300 acetabular fractures diagnosed on pelvic CT. Acetabular fractures were categorized using the Judet-Letournel classification system. Femoral head fractures were present in 18.0% of acetabular fractures. Fracture patterns with a posterior wall component had a very high (56.3%) incidence of femoral head fracture. Anterior column and anterior column with posterior hemitransverse fractures have a very low (3.4%) incidence of femoral head fracture. Anterior hip dislocation had a 66.7% incidence of femoral head fracture, while posterior dislocation had a 71.9% incidence. Acetabular fractures displaced by more than 5 mm had a 26.9% incidence of femoral head fracture, while acetabular fracture displaced less than 5 mm had only 4.2% incidence of femoral head fracture. Femoral head fractures are a very common associated finding in patients presenting with acetabular fractures. In patients with a posterior wall component of the fracture or associated hip dislocation, a femoral head fracture is more likely than not present. Conversely, in acetabular fractures with less than 5 mm displacement or anterior column fractures without posterior acetabular involvement, femoral head fractures are very unlikely in the absence of a dislocation event.

Objective To assess the safety of probiotic Lactobacillus reuteri strain Deutsche Sammlung von Mikroorganismen (DSM) 17938 with daily administration to healthy infants with colic and to determine the effect of L reuteri strain DSM 17938 on crying, fussing, inflammatory, immune, and microbiome variables. Study design We performed a controlled, double-blinded, phase 1 safety and tolerability trial in healthy breast-fed infants with colic, aged 3 weeks to 3 months, randomly assigned to L reuteri strain DSM 17938 (5 × 108 colony-forming units daily) or placebo for 42 days and followed for 134 days. Results Of 117 screened infants, 20 were randomized to L reuteri strain DSM 17938 or placebo (sunflower oil) (in a 2:1 ratio) with 80% retention. Eleven of the 20 (55%) presented with low absolute neutrophil counts ( Conclusions Daily administration of L reuteri strain DSM 17938 appears to be safe in newborn infants with colic, including those with neutropenia, which frequently coexists. A placebo response of 66% suggests that many infants with colic will have resolution within 3 weeks. Trial registration ClinicalTrials.gov : NCT01849991 .

In literature, there are a few unified approaches to test proof of concept and estimate a target dose, including the multiple comparison procedure using modeling approach, and the permutation approach proposed by Klingenberg. We discuss and compare the operating characteristics of these unified approaches and further develop an alternative approach in a Bayesian framework based on the posterior distribution of a penalized log-likelihood ratio test statistic. Our Bayesian approach is much more flexible to handle linear or nonlinear dose–response relationships and is more efficient than the permutation approach. The operating characteristics of our Bayesian approach are comparable to and sometimes better than both approaches in a wide range of dose–response relationships. It yields credible intervals as well as predictive distribution for the response rate at a specific dose level for the target dose estimation. Our Bayesian approach can be easily extended to continuous, categorical, and time-to-event responses. We illustrate the performance of our proposed method with extensive simulations and Phase II clinical trial data examples.