[Analysis of factors associated with futile recanalization after endovascular treatment for acute ischemic stroke with large vessels occlusion in anterior intracranial circulation].

Objective: To analyze the related factors of futile recanalization (FR) after emergency endovascular treatment of large artery occlusion in anterior circulation. Methods: Three studies on endovascular treatment of acute anterior circulation large vessels occlusion stroke were selected, and their data were merged for retrospective analysis. Patients were divided into the FR group and favorable prognosis group according to the functional prognosis. Risk factor analysis was conducted using multivariate logistic regression. Results: A total of 1 581 patients were finally included, with 858 (48.9%) patients in favorable prognosis group and 926 (51.91%) patients in FR group. Among them, there were 939 males and 642 females, with a mean age of (65±12) years. Multivariate logistic regression analysis showed that National Institute of Health Stroke Scale (NIHSS) score (OR=1.089,95%CI:1.066-1.113), puncture to recanalization time (OR=0.756, 95%CI:0.586-0.971), age (OR=1.04,95%CI:1.029-1.051), serum glucose (OR=1.101,95%CI:1.062-1.143), systolic blood pressure (OR=1.005,95%CI:1.001-1.010), passes≥3(OR=1.941,95%CI:1.294-2.941)Alberta stroke program early CT (ASPECT) score (OR=0.919,95%CI:0.847-0.996), occlusion site (M1 segment of middle cerebral artery, OR=0.744,95%CI:0.565-0.980) and collateral circulation [(2 points, OR=0.757, 95%CI:0.581-0.985); (3-4 points, adjusted OR=0.640, 95%CI: 0.472-0.866)] were independent factors of FR. Conclusion: The incidence of FR in patients with large artery occlusion in anterior circulation who achieve satisfied reperfusion after endovascular treatment is high. Higher NIHSS score, longer puncture to recanalization time, older age, higher serum glucose and systolic blood pressure are risk factors, while lower ASPECTS, occlusion in cerebral middle M1 segment, better collateral circulation are protective factors.

DWI-Based Radiomics Predicts the Functional Outcome of Endovascular Treatment in Acute Basilar Artery Occlusion.

BACKGROUND AND PURPOSE: Endovascular treatment is a reference treatment for acute basilar artery occlusion (ABAO). However, no established and specific methods are available for the preoperative screening of patients with ABAO suitable for endovascular treatment. This study explores the potential value of DWI-based radiomics in predicting the functional outcomes of endovascular treatment in ABAO. MATERIALS AND METHODS: Patients with ABAO treated with endovascular treatment from the BASILAR registry (91 patients in the training cohort) and the hospitals in the Northwest of China (31 patients for the external testing cohort) were included in this study. The Mann-Whitney U test, random forests algorithm, and least absolute shrinkage and selection operator were used to reduce the feature dimension. A machine learning model was developed on the basis of the training cohort to predict the prognosis of endovascular treatment. The performance of the model was evaluated on the independent external testing cohort. RESULTS: A subset of radiomics features (n = 6) was used to predict the functional outcomes in patients with ABAO. The areas under the receiver operating characteristic curve of the radiomics model were 0.870 and 0.781 in the training cohort and testing cohort, respectively. The accuracy of the radiomics model was 77.4%, with a sensitivity of 78.9%, specificity of 75%, positive predictive value of 83.3%, and negative predictive value of 69.2% in the testing cohort. CONCLUSIONS: DWI-based radiomics can predict the prognosis of endovascular treatment in patients with ABAO, hence allowing a potentially better selection of patients who are most likely to benefit from this treatment.

A Case Report of Hypophosphatemia Leading to the Diagnosis of Mesothelioma.

Hypophosphatemia can be commonly encountered as an electrolyte imbalance and is defined as a value less than 0.8 mmol/l (2.5 mg/dl). It can be an incidental finding, but it is not uncommon to see it presenting with varied symptoms. It is good to have a clear diagnostic approach to this so adequate treatment can be instated. We present a 66-year-old gentleman who presented with hypophosphatemia. Investigations confirmed renal phosphate wasting secondary to fibroblast growth factor-23 (FGF-23). Imaging showed right pleural effusion, and pleural biopsy confirmed malignant mesothelioma. This may just be an association rather than the cause of his hypophosphatemia. It does however highlight the importance of further investigations for patients with tumor-induced osteomalacia.

Multicomponent Bioluminescence Imaging with Naphthylamino Luciferins.

Bioluminescent tools have been used for decades to image processes in complex tissues and preclinical models. However, few distinct probes are available to probe multicellular interactions. We and others are addressing this limitation by engineering new luciferases that can selectively process synthetic luciferin analogues. In this work, we explored naphthylamino luciferins as orthogonal bioluminescent probes. Three analogues were prepared using an optimized synthetic route. The luciferins were found to be robust emitters with native luciferase in vitro and in cellulo. We further screened the analogues against libraries of luciferase mutants to identify unique enzyme-substrate pairs. The new probes can be used in conjunction with existing bioluminescent tools for multi-component imaging.

Clinical Outcomes of Endovascular Treatment within 24 Hours in Patients with Mild Ischemic Stroke and Perfusion Imaging Selection.

BACKGROUND AND PURPOSE: Endovascular thrombectomy has been accepted as the standard of care for patients with acute ischemic stroke. Our aim was to investigate the clinical outcomes of patients with mild ischemic stroke with acute proximal large-vessel occlusion after endovascular treatment within 24 hours of symptom onset. MATERIALS AND METHODS: Between January 2014 and August 2017, ninety-three Chinese patients with mild ischemic stroke (NIHSS scores, 0-8) and large-vessel occlusion with endovascular treatment were retrospectively enrolled from 7 comprehensive stroke centers. They were divided into 2 groups: ≤6 hours and 6-24 hours from symptom onset to groin puncture. We analyzed their modified Rankin Scale scores at 90 days, symptomatic intracranial hemorrhage at 48 hours, and mortality during 90 days. Multivariable linear regression analysis was used to identify predictors for NIHSS shift after discharge. RESULTS: Twenty-nine patients received endovascular treatment within 6-24 hours after symptom onset and had an imaging mismatch based on perfusion CT or diffusion-weighted MR imaging. There were no substantial differences between the 2 groups in 90-day functional independence (P = .54) and the risks of the combination of symptomatic intracranial hemorrhage and death (P = .72). Two significant indicators of NIHSS shift were 48-hour symptomatic intracranial hemorrhage (unstandardized ß = 7.28; 95% CI, 3.48-11.1; P < .001) and baseline systolic blood pressure (unstandardized ß = 0.08; 95% CI, 0.03-0.14; P = .005). CONCLUSIONS: Patients with mild ischemic stroke and large-vessel occlusion in the anterior circulation, an imaging mismatch, and endovascular treatment within 6-24 hours of initial symptoms showed no heterogeneity in the efficacy and safety outcome compared with those treated ≤6 hours from symptom onset.

Effect of Retrievable Stent Size on Endovascular Treatment of Acute Ischemic Stroke: A Multicenter Study.

BACKGROUND AND PURPOSE: In clinical practice, stent diameter is one of the variable properties important for endovascular treatment. A consensus guideline for stent retriever size selection has yet to be established. The aim of this study was to investigate the effects of different diameters of Solitaire retrievers on outcomes. MATERIALS AND METHODS: Of 628 patients enrolled from the Endovascular Treatment for Acute Anterior Circulation Ischemic Stroke Registry, 256 were treated with the Solitaire 4-mm device and 372, with the 6-mm device. We matched patients treated with the 2 stent sizes using propensity score analysis. The successful outcome was reperfusion as measured by the modified Thrombolysis in Cerebral Infarction score immediately postprocedure and the dichotomized modified Rankin Scale score at 90 days. Symptomatic intracerebral hemorrhage and in-hospital mortality were also recorded. RESULTS: After propensity score analysis, group outcomes did not differ. In addition, in patients with atherosclerosis-related occlusion, a higher reperfusion rate (P = .021) was observed in the Solitaire 4 group, as well as a shorter time interval (P = .002) and fewer passes (P = .025). Independent predictors of successful reperfusion in patients with atherosclerotic disease on logistic analysis were the small stent (OR, 3.217; 95% CI, 1.129-9.162; P = .029) and the propensity score acting as a covariate (OR, 52.84; 95% CI, 3.468-805.018; P = .004). CONCLUSIONS: We found no evidence of a differential effect of intra-arterial therapy based on the size of Solitaire retrievers. In patients with atherosclerotic disease, favorable reperfusion was associated with deployment of a small stent.

Direct endovascular treatment: an alternative for bridging therapy in anterior circulation large-vessel occlusion stroke.

BACKGROUND AND PURPOSE: Whether intravenous thrombolysis prior to endovascular treatment in patients with anterior circulation large-vessel occlusion (LVO) is indispensable remains unclear. The aim was to retrospectively compare, in a Chinese population, the effectiveness and safety of direct endovascular treatment (DEVT) initiated within 4.5 h after onset with bridging therapy in acute anterior circulation LVO stroke patients. METHODS: A total of 363 patients, 160 in the bridging therapy group and 203 in the DEVT group, were enrolled between 2014 and 2016. Using propensity score matching analysis, 276 patients were matched. A modified Rankin Scale score of 0-2 was considered as good functional outcome. RESULTS: Good functional outcome at 90 days in the DEVT group [40.6% (56/138)] did not significantly differ from that in the bridging group [44.9% (62/138)] (P = 0.53). Rates of symptomatic intracranial hemorrhage [13.8% (19/138) vs. 13.0% (18/138), P = 1.00] and mortality [25.4% (35/138) vs. 23.9% (33/138), P = 0.88] within 90 days were also not significantly different. Patients in the DEVT group had a lower rate of asymptomatic intracranial hemorrhage [28.3% (39/138) vs. 44.9% (62/138), P = 0.01] and a higher rate of successful reperfusion [92.0% (127/138) vs. 81.9% (113/138), P = 0.02]. CONCLUSIONS: Our results suggest that, in Chinese patients with anterior circulation LVO stroke, direct endovascular mechanical thrombectomy initiated within an intravenous thrombolysis time window carries similar effectiveness to that of bridging therapy and a decreased asymptomatic intracranial hemorrhage risk. DEVT may be an alternative for bridging therapy. Future randomized controlled trials are warranted.

Targeting quinolone- and aminocoumarin-resistant bacteria with new gyramide analogs that inhibit DNA gyrase.

Bacterial DNA gyrase is an essential type II topoisomerase that enables cells to overcome topological barriers encountered during replication, transcription, recombination, and repair. This enzyme is ubiquitous in bacteria and represents an important clinical target for antibacterial therapy. In this paper we report the characterization of three exciting new gyramide analogs-from a library of 183 derivatives-that are potent inhibitors of DNA gyrase and are active against clinical strains of gram-negative bacteria (Escherichia coli, Shigella flexneri, and Salmonella enterica; 3 of 10 wild-type strains tested) and gram-positive bacteria (Bacillus spp., Enterococcus spp., Staphylococcus spp., and Streptococcus spp.; all 9 of the wild-type strains tested). E. coli strains resistant to the DNA gyrase inhibitors ciprofloxacin and novobiocin display very little cross-resistance to these new gyramides. In vitro studies demonstrate that the new analogs are potent inhibitors of the DNA supercoiling activity of DNA gyrase (IC50s of 47-170 nM) but do not alter the enzyme's ATPase activity. Although mutations that confer bacterial cells resistant to these new gyramides map to the genes encoding the subunits of the DNA gyrase (gyrA and gyrB genes), overexpression of GyrA, GyrB, or GyrA and GyrB together does not suppress the inhibitory effect of the gyramides. These observations support the hypothesis that the gyramides inhibit DNA gyrase using a mechanism that is unique from other known inhibitors.

Cognitive impairments associated with periventricular white matter hyperintensities are mediated by cortical atrophy.

BACKGROUND: Previous studies have shown that white matter lesions (WMLs) is an important risk factor for cognitive impairment, but the underlying mechanisms have not been clarified. OBJECTIVE: We tested the hypothesis that the cognitive impairments associated with periventricular white matter hyperintensities (PWMHs) on magnetic resonance imaging (MRI) would be mediated by the cortical thinning of corresponding area. METHOD: Sixteen stroke- and dementia-free subjects with PWMHs and 16 healthy control subjects were enrolled in this study. All participants underwent an examination of cognition, MRI-based cortical thickness measurement and a MRI-DTI scan. Then, the possible relationships among cognitive impairments, PWMHs and the topography of cortical thinning were analyzed. RESULTS: Comparing with the controls, the cognitive tests of the subjects with PWMHs showed significant decline in the domains of verbal fluency and executive function. After accounting for age, gender, years of education, and treatable vascular risk factors related to cognitive performance, cortical thickness had an independent influence on the cognitive impairments, especially in the frontal pole, orbitofrontal cortex, superior and middle frontal gyrus, superior and middle temporal gyrus, insula, and cuneus. CONCLUSIONS: Our results suggest that the association between PWMHs and cognitive impairments is mediated by cortical thinning.

[Volume loading experiment in dogs with large area infarction of right and left ventricles].

In order to study volume loading effect on large area myocardial infarction (MI) in right and left ventricles, large area MI in both ventricles and cardiogenic shock in 12 dogs were induced by occluding coronary arteries. Left ventricular systolic pressure (LVSP) and +/- dp/dt max. dropped markedly by 54%, 51% and 47% respectively, whereas right ventricular systolic pressure (RVSP) and +/- dp/dt max. fell by 9%, 25% and 27% respectively. The condition was obviously worse by rapid volume loading (dextran, 30 ml/kg, i.v. in 20 min.) in group I (n = 6), leading to increased retrograde beat of right ventricle, further decrease of +/- dp/dt max. in both ventricles, significant increase of right atrial pressure (RAP) and left ventricular and diastolic pressure (LEVDP) (2.9 +/- 0.2 kPa, P < 0.01 and 5.0 +/- 0.3 kPa, P < 0.001, respectively), and even ventricular fibrillation. Shock was reversed by combined treatment of dopamine (10 micrograms/kg.min) and glyceryl trinitrate (1 microgram/kg.min) in group II (n = 6) in 30 min, showing evident increase of arterial pressure, cardiac output, LVSP and +/- dp/dt max. without rise in RAP and LVEDP.

[Monetary incentives for a more effective immunization program]. / Incentivos monetarios para una inmunizacion mas eficaz.

PIP: In 1984 an insurance plan for child immunization was introduced in the counties of Wuji, Linzhang, an Zunhua, and in the city of Xingtai in the province of Hebei, China. The remuneration of village physicians and payment for vaccination services was linked to their effectiveness. In Wuji county children under 2 up to the age of 7 could be enrolled. If a child contracted measles, $8.50 was paid as compensation, $29 for tetanus, $43 for diphtheria, and $57 for poliomyelitis. If death was caused by one of these diseases, $85 was paid. 84% of children of this age range participated in the plan. 36% of the money from policy purchases of $36,000 was allocated to compensation and administration and 64% to municipal health centers for replacement of supplies and to village doctors performing vaccinations whose annual income ranged between $86 and $286 plus $37 for vaccinations. In the 1st year 31 cases were compensated for a total of $600. In the other countries similar schemes were operational: rural doctors pitched in with 5-20-25% of compensation, and the health care system paid the rest. In 1987, two-thirds of cities in the province adopted this plan enlisting 2,559,780 children (31% of those under 7) and accumulating a total fund of $2,500,000. A 1987 sample of 36, 992 children indicated a 94% coverage for BCG (bacillus Calmette-Guerin), 85% for poliomyelitis, 80% for DPT (diphtheria-pertussis-tetanus), 80% for measles, 90% for Japanese B encephalitis and epidemic meningitis. In 1986, there were 273,000 fewer cases of measles, polio, diphtheria, pertussis, epidemic meningitis, and Japanese encephalitis with 4200 fewer deaths, and 3000 fewer incapacities (or possibly 1,000,000, 15,000 and 5000 fewer, respectively, because of nonreporting). Measles morbidity declined from 16/100,000 in 1986 to 3.7/100,000 in the first 11 months of 1987.^ieng