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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.

Background: The effect of anesthesia choice on endovascular thrombectomy (EVT) outcomes is unclear. Collateral status on perfusion imaging may help identify the optimal anesthesia choice. Methods: In a pooled patient level analysis of EXTEND-IA, EXTEND-IA TNK, EXTEND-IA TNK part II and SELECT, EVT Functional outcomes (mRS distribution) were compared between general anesthesia (GA) vs non-general anesthesia (non-GA). Further, we assessed the impact of collateral flow on perfusion imaging evaluated by hypoperfusion intensity ratio (HIR) - Tmax10 sec/Tmax6 sec) on the association between anesthesia type and EVT outcomes. Results: Of 731 treated with EVT, 305 (42%) received GA and 426 (58%) non-GA. The baseline characteristics were similar, except for presentation NIHSS (median [IQR] GA 18 [13-22], non-GA 16[11-20], p Conclusion: GA was associated with worse functional outcomes after EVT, particularly in patients with poor collaterals. These findings have implications for randomized trials of GA vs non-GA.

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

Background One factor that contributes to the difficulty during intubation is poor visualization of the airway anatomy during laryngoscopy. Aim To compare the efficacy and first-pass success rate of the King Vision® Video Laryngoscopes against the GlideScope® Video Laryngoscope in patients with anticipated difficult airways. Methods 225 adult patients scheduled for surgery requiring general anesthesia and tracheal intubation that met ≥2 of the following inclusion criteria: Mallampati classification (MP) III-IV, inter-incisor distance 43 cm, and/or thyromental distance Results The rate of success of tracheal intubation was 96% for GS, 81.3% for KV-Ch, and 96% for KV-NCh. Furthermore, first-pass success was highest for the KV-NCh at 89.3%, with GS and KV-Ch having a significant difference (P = 0.0083). Conclusion The GS and KV-NCh performed similarly in facilitating successful tracheal intubation during the first attempt. In contrast, the KV-Ch was less successful overall.

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.

This study (NCT02428413) evaluated waste anesthetic gas (WAG) in the postanesthesia care unit (PACU) and assessed the utility of the ISO-Gard(®) mask in reducing nursing exposure to WAG. We hypothesized that WAG levels in the patient’s breathing zone upon recovery would exceed the recommended levels, leading to increased exposure of the PACU nurses, with use of the ISO-Gard mask limiting this exposure. A total of 125 adult patients were recruited to participate. Patients were randomized to receive the standard oxygen delivery mask or the ISO-Gard face mask postoperatively. Continuous particulate concentrations were measured using infrared spectrophotometers placed within the patients’ and nurses’ 6-inch breathing zone. Maximum WAG measurements were obtained every 30 seconds, and the duration of maximum WAG >2 ppm and its proportion relative to the total collection period were calculated. We observed a statistically significant difference in desflurane duration and proportion of maximum WAG >2 ppm in both patient and PACU nurse breathing zones. Therefore, patients and PACU nurses using routine care were exposed to WAG levels >2 ppm during the 1-hour postoperative period, and the ISO-Gard mask effectively reduced the amount of WAG detected in the immediate 1-hour postoperative recovery phase.

Background: Acute subdural hematoma (aSDH) in the elderly is an increasingly important public health issue. Mortality rate in this population can be as high as 90% (Copper et al., 1976; Cagetti et al., 1992; Taussky et al., 2012; Hanif, 2009; Raj et al., 2016; Luerssen et al., 1988). Objective: The goal of this study is to examine outcomes for patients 70 years and older who underwent craniotomy for aSDH. Methods: This is a retrospective study of patients 70 years and older who underwent craniotomy for evacuation of aSDH between 2006 and 2016. Patients with subacute, chronic, acute-on-chronic SDH and those considered too neurologically devastated to benefit from surgery were excluded. A multivariable logistic regression was performed to identify independent clinical factors associated with mortality. Results: A total of 1953 elderly patients with SDH were seen between 2006 and 2016. 1325 patients had non-surgical SDH, 307 were too neurologically devastated to benefit from surgery, and 321 elderly patients had surgery. 112 patients had a craniotomy for aSDH. The overall mortality rate was 42%. 24% of patients were discharged to home or a rehabilitation facility. Multivariable logistic regression analysis showed that age, Glasgow Coma Scale (GCS) score, and surgery type had a significant impact on mortality. Conclusion: Elderly patients with aSDH requiring surgery have a high likelihood of mortality. 24% of surgical patients were functional enough to go home or to a rehabilitation facility from the hospital. Age over 80 years old, GCS

Background and Purpose: Marrow stromal cells (MSCs) are being tested in clinical trials for stroke patients. MSCs appear to promote recovery through secretomes that promote modulation of immune cells, including myeloid phagocytes. Many stroke patients have comorbidities such as metabolic syndrome, hypertension, hypercholesterolemia, and diabetes for which they are prescribed medications that might affect the function of MSCs and monocytes (Mo) when they are administered in stroke patients. We studied the effects of the two most commonly prescribed stroke medications, statin and statin plus aspirin, on the secretomes of MSCs and their modulation of Mo derived from stroke patients.Methods: Human MSCs, Mo and their co-cultures were exposed to atorvastatin or atorvastatin plus aspirin followed by secretome analysis at 24 h. Monocytes were isolated from healthy controls as well as stroke patients with NIHSS ranging from 11 to 20. Secretome composition was measured using multiplex immunoassay. We used MTT assay to measure proliferation of monocytes. The mixed model was used to analyze experimental data. p-values less than 0.05 were considered significant.Results: Atorvastatin and aspirin combination increased the release of IL-1RA from stroke Mo. In MSCs, atorvastatin and aspirin combination reduced the release of pro-inflammatory cytokines such as IL-6, IL-8, MCP-1 and IFN-γ. Atorvastatin alone reduced the release of IL-6, IL-8 and MCP-1 from co-cultures of stroke monocytes and MSCs. Combination of atorvastatin and aspirin had additive effect on reducing the secretion of IL-6 from co-cultures of stroke Mo and MSCs.Conclusion: Atorvastatin, alone and in combination with aspirin can promote anti-inflammatory effect by modulating the secretome profile of Mo and MSCs. Our results suggest that stroke trials involving the use of intravenous MSCs should consider the effect of aspirin and atorvastatin, both of which are administered to the majority of hospitalized ischemic stroke patients.

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.

Background: The effect of anesthesia choice on endovascular thrombectomy (EVT) outcomes is unclear. Methods: In the prospective multicenter cohort study of imaging selection for EVT (SELECT), patients were stratified based on their anesthesia type into general anesthesia (GA) and conscious sedation (CS). EVT times and outcomes were compared. Further we assessed the impact of ischemic core size (rCBF Results: Of 361 enrolled, 285 received EVT. 129 (45%%) received GA and 156 (54%) CS. The baseline characteristics were similar, except for presentation NIHSS (GA 17(13-21), CS 15(11-20), p=0.027) and ischemic core volume (GA 14.1 cc (0-38) vs CS 6.3(0-26.1), p=0.034). GA was associated with numerically longer arrival to GP times 92 (68—115) vs. 85(60-117) mins, p=0.58. After adjustment for baseline imbalances, patients who received CS had a shift toward better outcome (adj cOR 1.72, 95% CI=1.08-2.75, p=0.022) with higher functional independence rates 56.8% vs 48.8%, p=0.75. Furthermore, GA was associated with higher mortality rates (19% vs 9%, p=0.017), figure 1A. In patients with core volume ≥ 50 cc, there was a trend for a shift towards better outcomes (adj cOR=5.84, 95%CI= 0.90-38.00, P=0.065), figure 1B while there was no difference in patients with core volume < 50 cc (adj cOR=1.01 (95%CI 0.53-1.94, P=0.96), figure 1C. There was an interaction between core volume size and anesthesia type on functional outcome (p=0.042). For every 10cc increase in the core volume, the odds of attaining better functional outcome decreased by 29% (adjusted cOR: 0.71, 95% CI=0.61-0.83, p Conclusion: Conscious sedation was associated with a shift towards better EVT outcomes. This effect was driven by patients with larger ischemic core volumes and has implications for randomized trials of conscious sedation vs general anesthesia.

Background: Whether IV tPA has adjunctive benefit to endovascular thrombectomy (EVT) is unclear. Methods: In a prospective multicenter cohort study of imaging selection for EVT (SELECT), patients who received IV tPA vs. no IV tPA were compared stratified by stroke severity and ischemic core size (rCBF Results: Of 361 enrolled, 285 received EVT; 226 presented within 4.5 hrs, 162 (72%) received IV tPA. IV tPA patients had lower median ASPECTS (8 vs 9, p=0.007) and larger ischemic core size (11.4 (1.5-37) vs 3.9 (0-32.15), p=0.042, otherwise similar at baseline. There were no delays in EVT delivery associated with tPA: median time (IQR) from arrival to groin puncture 95.0 min (66.0, 118.0) tPA vs 81.5 (63.5, 107.5) no tPA, p=0.21. IV tPA use was associated with higher mRS 0-2 rates (57% vs 44%), aOR 2.02 (95% CI 1.01-4.03, p=0.046) after adjustment for baseline differences with a shift towards better outcomes on all mRS levels (cOR 2.06, 95% CI 1.18-3.59, p=0.01) with lower mortality (11% vs 22%, p=0.026) and similar sICH rates (and 6% vs 6%, p=1.0). In patients with NIHSS Conclusion: IV tPA did not result in thrombectomy delivery delays and may result in better outcomes. Patients with less severe strokes and smaller infarct size had a stronger association between the use of IV tPA and favorable outcomes.

Background: Whether Endovascular Thrombectomy (EVT) is cost-effective in large ischemic core infarcts is unknown. Methods: In the prospective multicenter cohort study of imaging selection study (SELECT), large core was defined as CT ASPECTS < 6 or CTP ischemic core volume (rCBF Results: Of 361 enrolled, 105 had large core on CT or CTP (EVT 62, MM 43). 19 (31%) EVT patients achieved mRS 0-2 vs 6 (14%) MM (aOR: 3.27, 95% CI: 1.11-9.62; P = .03) with a shift towards better mRS (adj cOR: 2.12, 95% CI: 1.05-4.31, P = .04). Over 20 years EVT was associated with $26589 (C.I. $8672- $43978) incremental costs and a gain of 1.18 QALYs (C.I. 0.091- 2.2) per patient. EVT could avert 75 deaths over a theoretical cohort of 1000 patients (MM 861 vs EVT 786) thus the ICER of EVT compared to MM was $22400 per QALY (CI. $10109 - $66140), which is EVT has a higher NMB compared to MM at the lower and upper WTP thresholds (EVT $86,3 and 271,4 million vs MM $53,6-$179,3 million), Tab 2. The PSA confirmed the results (fig 1). The CEAC showed 94% and 97% cost-effectiveness probability of EVT at the lower and upper values respectively of the maximum WTP, fig 2. EVT ICER in SELECT large core ($22400/QALY) was higher but still comparable to those in HERMES ($16882/QALY), DAWN ($7335/QALY) and DEFUSE3 ($14673/QALY), Tab 3. Conclusion: EVT may result in better outcomes and more lives saved in large core patients with higher QALYs, NMB and an acceptable ICER. The results were comparable to other EVT RCTs.

Background: The efficacy of endovascular thrombectomy (EVT) in M2 occlusions is uncertain. Methods: In a prospective multicenter cohort study of imaging selection (SELECT), EVT outcomes were compared to medical managment (MM) in M2 occlusions. Further, we assessed for potential treatment benefit in patients with higher stroke severity (NIHSS) and a larger perfusion deficit on CTP (Tmax > 6 sec - ischemic core volume)The primary outcome was excellent outcome (mRS 0-1). Results: of 361 patients enrolled in SELECT, 87 had isolated M2 occlusion (EVT 59, MM 28). Baseline NIHSS median (IQR) (EVT 14 (10-20), MM 15 (9.5-19.5), p=0.72) and infarct volume rCBF10 had better outcomes with EVT (46%) vs MM (10%), aOR=11.39, 95% CI=1.80-72.11, p=0.01 as shown in figure 1. As perfusion deficit lesion size increased, the odds of achieving excellent outcomes was reduced (for each 10cc by 11%, aOR: 0.89, 95% CI=0.79-1.00, p=0.05). Excellent outcomes declined in patients with MM as perfusion deficit lesion size increased, yet in the EVT they were maintained as shown in figure 2. Similar results were obtained for mRS 0-2. Conclusion: EVT may result in better rates of excellent outcomes in isolated M2 occlusions, especially those with more severe strokes and larger perfusion deficits who are more likely to have worse outcomes without emergent reperfusion.