Broadband photomultiplication organic photodetectors.

Broadband photomultiplication organic photodetectors (PMOPDs) can be achieved with a double-layered active layer prepared from IEICO-4F : PBDB-T blend solutions with different weight ratios (1 : 1 or 3 : 100, wt/wt). The response range of the double-layered PMOPDs covers from 310 nm to 930 nm, determined by the photon harvesting range of the IEICO-4F : PBDB-T (1 : 1, wt/wt) layer. The IEICO-4F : PBDB-T (3 : 100, wt/wt) layer was used as a PM layer in the double-layered PMOPDs, achieving external quantum efficiency (EQE) more than 100% based on the work mechanism of trap-assisted hole tunneling injection. The trapped electrons in PBDB-T/IEICO-4F/PBDB-T near the Al electrode will makeinterfacial-band-bending to narrow the injection barrier, resulting in hole-tunneling-injection from the external circuit. The polymer PBDB-T can provide an efficient charge transport channel for the injected hole from the external circuit. The specific detectivity (D*) and responsivity (R) of the double-layered PMOPDs are 1.05 ± 0.03 × 1012 Jones and 0.94 ± 0.03 A W-1 at 810 nm under a -10 V bias, respectively.

Forkhead box protein P1 is a useful marker for the diagnosis of mucinous minimal deviation adenocarcinoma of uterine cervix.

Mucinous minimal deviation adenocarcinoma (MDA) is a rare highly differentiated tumor of uterine cervix, of which the confusing histopathology resembling some benign lesions usually makes difficulty for pathologic diagnosis. The expression of forkhead box protein P1 (FOXP1) is found in some kinds of human tumors and is considered to be associated with the progression of the tumors. The purpose of this study is to detect the FOXP1 expression in MDA and evaluate its possible role in the diagnosis of MDA. Twenty-two MDA cases and 20 control cases consisting of 10 cases of lobular endocervical glandular hyperplasia and 10 cases of normal endocervical tissue were included in this study. All available clinical data were collected and immunostaining for FOXP1, carcinoembryonic antigen (CEA), human milk fat globule antigen 1 (HMFG1), estrogen receptor, and progesterone receptor were performed on these cases. The nuclear/cytoplasmic expression of FOXP1 was found in 18 of 22 MDA cases while in 1 of 20 control cases, which showed statistical significance (P = .000). The cytoplasmic CEA expression was found in 14 of 22 MDA cases and 2 of 20 control cases (P = .000), whereas cytoplasmic HMFG1 expression was found in 10 of 22 MDA cases and 4 of 20 control cases (P = .081). No statistical difference was found between FOXP1 and CEA expression (P = .083) or between FOXP1 and HMFG1 expression (P = .375) in MDA. Neither estrogen receptor nor PR expression was found in MDA. The significant expression of FOXP1 in MDA may be helpful to some extent in the pathologic diagnosis of cervical MDA. A widened observation range and further researches are needed to elucidate the potential mechanism.

Predictors of dysphagia screening and pneumonia among patients with intracerebral haemorrhage in China: a cross-sectional hospital-based retrospective study.

OBJECTIVES: This study aimed to investigate factors associated with undergoing dysphagia screening (DS) and developing pneumonia, as well as the relationship between DS and pneumonia in patients with intracerebral haemorrhage (ICH). DESIGN: Our study was a cross-sectional hospital-based retrospective study. STUDY DESIGN AND SETTINGS: We derived data from the China Stroke Centre Alliance, a nationwide clinical registry of ICH from 1476 participating hospitals in mainland China. To identify predictors for pneumonia, multivariable logistic regression models were used to identify patient characteristics that were independently associated with DS and pneumonia. PARTICIPANTS: We included 31 546 patients in this study with patient characteristics, admission location, medical history, hospital characteristics and hospital grade from August 2015 to July 2019. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcomes were DS and pneumonia during acute hospitalisation. RESULTS: In total, 25 749 (81.6%) and 7257 (23.0%) patients with ICH underwent DS and developed pneumonia. Compared with patients without pneumonia, those who developed pneumonia were older and had severe strokes (Glasgow Coma Scale 9-13: 52.7% vs 26.9%). Multivariable analyses revealed that a higher pneumonia risk was associated with dysphagia (OR, 4.34; 95% CI, 4.02 to 4.68), heart failure (OR, 1.85; 95% CI, 1.24 to 2.77) and smoking (OR, 1.12; 95% CI, 1.12 to 0.20). DS was associated with lower odds of pneumonia (OR, 0.65; 95% CI, 0.44 to 0.95). CONCLUSION: Our findings further confirm that dysphagia is an independent risk factor for pneumonia; one-fifth of patients with ICH did not undergo DS. However, comprehensive dysphagia evaluation and effective management are crucial. Nursing processes ensure the collection of complete and accurate information during evaluation of patients. There is a need to increase the rate of DS in patients with ICH, especially those with severe stroke or older. Further, randomised controlled trials are warranted to determine the effectiveness of DS on clinical outcomes.

Assessment of Perfusion Volumes by a New Automated Software for Computed Tomography Perfusion.

INTRODUCTION: To compare the perfusion volumes assessed by a new automated CT perfusion (CTP) software iStroke with the circular singular value decomposition software RAPID and determine its predictive value for functional outcome in patients with acute ischaemic stroke (AIS) who underwent endovascular treatment (EVT). METHODS: Data on patients with AIS were collected from four hospitals in China. All patients received CTP followed by EVT with complete recanalisation within 24 hours of symptom onset. We evaluated the agreement of CTP measures between the two softwares by Spearman's rank correlation tests and kappa tests. Bland-Altman plots were used to evaluate the agreement of infarct core volume (ICV) on CTP and ground truth on diffusion-weighted imaging (DWI). Logistic regression models were used to test the association between ICV on these two softwares and functional outcomes. RESULTS: Among 326 patients, 228 had DWI examinations and 40 of them had infarct volume >70 mL. In all patients, the infarct core and hypoperfusion volumes on iStroke had a strong correlation with those on RAPID (ρ=0.68 and 0.66, respectively). The agreement of large infarct core (volume >70 mL) was substantial (kappa=0.73, p<0.001) between these two softwares. The ICV measured by iStroke and RAPID was significantly correlated with independent functional outcome at 90 days (p=0.009 and p<0.001, respectively). In patients with DWI examinations and those with an ICV >70 mL, the ICV of iStroke and RAPID was comparable on individual agreement with ground truth. CONCLUSION: The automatic CTP software iStroke is a reliable tool for assessing infarct core and mismatch volumes, making it clinically useful for selecting patients with AIS for acute reperfusion therapy in the extended time window.

Granular cell tumor of the uterine cervix. A case report.

BACKGROUND: Granular cell tumor (GCT) is a relatively rare and nearly always benign neoplasm that has been described in many sites and organs including the tongue, skin, subcutaneous tissue, breast, and vulva. However, it is rarely seen in the uterine cervix. CASE: We report a case of granular cell tumor of the cervix in a 38-year-old woman. Upon microscopic examination the tumor was found to comprise large polygonal cells with an abundant eosinophilic granular cytoplasm and round to oval nuclei. Upon immunohistochemical staining the large cells showed S-100, neuron specific enolase, and CD68 positive in the cytoplasm. Clinical presentation of the patient, histopathological features of the lesion, and treatment approach are discussed. CONCLUSION: GCTs of the cervix are extremely rare. To the best of our knowledge this report is the first Chinese case of cervical GCT in the English-language literature. GCTs should always be considered during the diagnosis process with large cell lesions of the cervix. Extensive surgical resection appears to be adequate for most GCTs. Because of the unpredictable clinical outcome of this tumor, strict and long-term follow-up are recommended.

[Pathologic features and prognostic factors of ovarian granulose cell tumor].

OBJECTIVE: To identify the pathological features, clinical symptoms and the prognostic factors for adult granulose cell tumor (AGCT) and juvenile granulose cell tumor (JGCT). METHODS: The pathological features and clinical characters of 40 patients with granulose cell tumors (GCT) between April 2002 and September 2011 were reviewed, and the relevant prognostic factors were analyzed. RESULTS: 34 cases (85%) were AGCT, and the average age of onset was 50.1 years old. 6 cases (15%) were JGCT, with an average 35.3 years old age of onset. The difference of average onset age was significant (P = 0.034). The histopathological patterns of AGCT were mainly follicular, insular and trabecular, Call-Exner bodies were found frequently, while the luteinization, hemorrhage and necrosis of tumor cells were not common. In contrast, the histopathological pattern of JGCT was mainly diffuse, Call-Exner bodies were rare, while the luteinization, hemorrhage and necrosis of tumor cells were common. The pathological features of the cases with unfavorable prognosis were: (1) Mixed mode with tumor cell histopathological pattern (follicular, insular, trabecular and diffuse pattern, the tumor cells were mainly organized in two or more than two kinds of patterns above). (2) Call-Exner bodies were rare; (3) mitosis number of tumor cells > or = 3/10 HPF (4) low expression of PTEN and high expression of Ki-67. CONCLUSION: The histological patterns, mitosis number, the expression rate of PTEN and Ki-67 were identified to predict the prognosis for GCT of ovary.

Outcomes in minor stroke patients treated with intravenous thrombolysis.

AIMS: Our study aimed to describe the short-, medium-, and long-term outcomes of intravenous thrombolysis in minor stroke, and to explore the relationship between thrombolysis and clinical outcomes. METHODS: Our study included ischemic minor stroke patients (National Institutes of Health Stroke Scale score ≤ 5) within 4.5 h from symptom onset from the Third China National Stroke Registry (CNSR-III) between August 2015 and March 2018. The primary outcome was a favorable functional outcome, defined as a modified Rankin Scale (mRS) score of 0-1 at 3 months. The secondary outcomes included mRS score of 0-1 at discharge, 6 months, and 1 year. The safety outcomes were symptomatic intracerebral hemorrhage (sICH) at 24-36 h and all-cause mortality. The association between intravenous thrombolysis and clinical outcomes was studied using multivariable models. RESULTS: A total of 1905 minor ischemic stroke patients were included. Overall 527 patients (28%) received intravenous t-PA (IV t-PA) and 1378 patients (72%) in the non-IV t-PA group. Of them, 18.85% (359/1905) participants had a disabled outcome (defined as mRS score ≥ 2) at discharge, 12.8% (242/1885) at 3 months, 13.9% (262/1886) at 6 months, and 13.9% (260/1871) at 1 year. In multivariable analysis, IV t-PA was associated with favorable functional outcomes at discharge (adjusted odds ratio [aOR] 1.49; 95% confidence interval [CI] 1.13-1.96; p = 0.004), 3 months (aOR 1.51; 95% CI 1.09-2.10; p = 0.01), 6 months (aOR 1.64; 95% CI 1.19-2.27; p = 0.003), and 1 year (aOR 1.52; 95% CI 1.10-2.10; p = 0.01). Symptomatic ICH occurred in 3 (0.6%) patients in IV t-PA versus 2 (0.1%) in the non-IV t-PA group. No significant differences were found in all-cause mortality between the two groups. CONCLUSIONS: Intravenous t-PA may be safe and effective in minor stroke (NIHSS ≤ 5) within a 4.5-h window and further randomized controlled trials are warranted.

Intravenous thrombolysis versus antiplatelet therapy in minor stroke patients with large vessel occlusion.

AIM: Our study aimed to explore the effectiveness and safety of intravenous t-PA compared with dual antiplatelet therapy (DAPT) and aspirin alone for minor stroke with National Institutes of Health Stroke Scale (NIHSS) score ≤5 and large vessel occlusion (LVO). METHODS: Patients with minor stroke harboring LVO within 4.5-h time window were included from the Third China National Stroke Registry (CNSR-III) between August 2015 and March 2018 in China. Clinical outcomes including modified Rankin scale (mRS) score, recurrent stroke, and all-cause mortality at 90 days and 36-h symptomatic intracerebral hemorrhage (sICH) were collected. Multivariable logistic regression models and propensity score matching analyses were used to determine the association between treatment groups and clinical outcomes. RESULTS: A total of 1401 minor stroke patients with LVO were included. Overall 251 patients (17.9%) received intravenous t-PA, 722 patients (51.5%) received DAPT, and 428 patients (30.5%) received aspirin alone. The intravenous t-PA was associated with greater proportions of mRS 0-1 (aspirin versus t-PA: adjusted odds ratio [aOR], 0.50; 95% confidence interval [CI], 0.32 to 0.80; p = 0.004; DAPT versus t-PA: aOR, 0.76; 95% CI, 0.49 to 1.19; p = 0.23). Using propensity score matching analyses, the results were similar. There was no difference in 90-day recurrent stroke among the groups. The rates of all-cause mortality in intravenous t-PA, DAPT, and aspirin groups were 0%, 0.55%, 2.34%, respectively. No patient developed sICH within 36 h of intravenous t-PA. CONCLUSION: In patients with minor stroke harboring LVO within 4.5-h time window, intravenous t-PA was associated with higher odds for the excellent functional outcome, as compared with the aspirin alone. Further randomized controlled trials are warranted.

Tenecteplase versus alteplase for acute ischaemic stroke: a meta-analysis of phase III randomised trials.

BACKGROUND: Tenecteplase (TNK) was found non-inferior to alteplase in recent clinical trials. We aimed to elucidate the efficacy and safety of TNK versus alteplase for acute ischaemic stroke (AIS). METHODS: Systematic literature search and a meta-analysis of phase III clinical trials in ischaemic stroke patients with TNK use were conducted. The primary outcome was excellent functional outcome which was defined as modified Rankin Scale score of 0-1 at 90 days and safety outcomes included symptomatic intracerebral haemorrhage and death at 90 days. We used random-effects model to estimate the pooled risk difference and 95% CI in R package 'Meta'. The included trials were adapted to the non-inferiority analysis with a margin of -4%. RESULTS: Three trials enrolling 4094 patients were identified by systematic search. All trials included AIS patients within 4.5 hours time window. Meta-analysis indicated that 1089 (53.0%) of 2056 patients in the TNK arm and 1016 (50.5%) of 2012 in the alteplase arm had excellent functional outcome at 90 days (0.03 (95% CI -0.00 to 0.06); I2=0%), meeting the prespecified non-inferiority threshold. And TNK thrombolysis was not correlated with increased risk of symptomatic intracerebral haemorrhage (0.00 (95% CI -0.01 to 0.01); I2=0%) or death (0.01 (95% CI -0.01 to 0.02); I2=0%) at 90 days. The sensitivity analysis with the 0.25 mg/kg trials exclusively showed similar results to the main analysis. CONCLUSIONS: TNK was non-inferior to alteplase for achieving excellent functional outcome at 90 days without increasing the safety concern in treating patients with AIS. These findings suggest that TNK can be an alternative to alteplase. PROSPERO REGISTRATION NUMBER: CRD42022354342.

Short-term effect of PM2.5 on stroke in susceptible populations: A case-crossover study.

BACKGROUND: Fine particulate matter (PM2.5) is a risk factor for stroke, and patients with pre-existing diseases appear to be particularly susceptible. We conducted a case-crossover study to examine the association between short-term exposure to fine particulate matter (PM2.5) and hospital admission for stroke in individuals with atrial fibrillation (AF), hypertension, diabetes, or hyperlipidemia. METHODS: Patients diagnosed with acute ischemic stroke (AIS) were recruited from 2015 to 2017 in Chinese Stroke Center Alliances. We estimated daily PM2.5 average exposures with a spatial resolution of 0.1° using a data assimilation approach combining satellite measurements, air model simulations, and monitoring values. Conditional logistic regression was used to assess PM2.5-related stroke risk in patients with pre-existing medical co-morbidities. RESULTS: A total of 155,616 patients diagnosed with AIS were admitted. Patients with a history of AF (n = 15,430), hypertension (n = 138,220), diabetes (n = 43,737), or hyperlipidemia (n = 16,855) were assessed separately. A 10 µg/m3 increase in daily PM2.5 was associated with a significant increase in AIS for individuals with AF at lag 4 (odds ratio (OR), 1.008; 95% confidence interval (CI), 1.002-1.014), and with hypertension (OR, 1.008; 95% CI, 1.006-1.010), diabetes (OR, 1.006; 95% CI, 1.003-1.010), and hyperlipidemia (OR, 1.007; 95% CI, 1.001-1.012) at lags 0-7. Elderly (⩾ 65 years old) and female patients with AF had significantly higher associations at lag 5 (OR, 1.009; 95% CI, 1.002-1.015) and lag 5 (OR, 1.010; 95% CI, 1.002-1.018), respectively. CONCLUSION: Short-term exposure to PM2.5 is significantly associated with hospital admission for stroke in individuals with pre-existing medical histories, especially in older or female patients with AF. Preventive measures to reduce PM2.5 concentrations are particularly important in individuals with other medical co-morbidities.

Mediation effect of stroke recurrence in the association between post-stroke interleukin-6 and functional disability.

AIM: Post-stroke inflammation increases the risk of functional disability through enlarged cerebral infarct size directly and follow-up stroke event indirectly. We aimed to use post-stroke proinflammatory cytokine interleukin-6 (IL-6) as a marker of inflammatory burden and quantify post-stroke inflammation's direct and indirect effect on functional disability. METHODS: We analyzed patients with acute ischemic stroke admitted to 169 hospitals in the Third China National Stroke Registry. Blood samples were collected within 24 h of admission. Stroke recurrence and functional outcome measured by the modified Rankin scale (mRS) were assessed via face-to-face interviews at 3 months. Functional disability was defined as an mRS score ≥2. Mediation analyses under the counterfactual framework were performed to examine the potential causal chain in which stroke recurrence may mediate the relationship between IL-6 and functional outcome. RESULTS: Among the 7053 analyzed patients, the median (interquartile range [IQR]) NIHSS score was 3 (1-5), and the median (IQR) level of IL-6 was 2.61 (1.60-4.73) pg/mL. Stroke recurrence was observed in 458 (6.5%) patients, and functional disability was seen in 1708 (24.2%) patients at the 90-day follow-up. Per stand deviation (4.26 pg/mL) increase in the concentration of IL-6 was associated with an increased risk of stroke recurrence (adjusted odds ratio [aOR], 1.19; 95% CI, 1.09-1.29) and disability (aOR, 1.22; 95% CI, 1.15-1.30) within 90 days. Mediation analyses revealed that 18.72% (95% CI, 9.26%-28.18%) of the relationship between IL-6 and functional disability was mediated by stroke recurrence. CONCLUSIONS: Stroke recurrence mediates less than 20% of the association between IL-6 and functional outcome at 90 days among patients with acute ischemic stroke. In addition to typical secondary prevention strategies for preventing stroke recurrence, more attention should be paid to novel anti-inflammatory therapy to improve functional outcomes directly.

U-shaped association between low-density lipoprotein cholesterol levels and risk of all-cause mortality mediated by post-stroke infection in acute ischemic stroke.

During the acute stage of ischemic stroke, it remains unclear how to interpret the low low-density lipoprotein cholesterol (LDL-C) level. We aimed to evaluate the association between LDL-C levels, post-stroke infection, and all-cause mortality. 804,855 ischemic stroke patients were included. Associations between LDL-C levels, infection, and mortality risk were estimated by multivariate logistic regression models and displayed by restricted cubic spline curves. Mediation analysis was performed under counterfactual framework to elucidate the mediation effect of post-stroke infection. The association between LDL-C and mortality risk was U-shaped. The nadir in LDL-C level with the lowest mortality risk was 2.67 mmol/L. Compared with the group with LDL-C = 2.50-2.99 mmol/L, the multivariable-adjusted odds ratio for mortality was 2.22 (95% confidence intervals (CI): 1.77-2.79) for LDL-C <1.0 mmol/L and 1.22 (95% CI: 0.98-1.50) for LDL-C ≥5.0 mmol/L. The association between LDL-C and all-cause mortality was 38.20% (95% CI: 5.96-70.45, P = 0.020) mediated by infection. After stepwise excluding patients with increasing numbers of cardiovascular risk factors, the U-shaped association between LDL-C and all-cause mortality and the mediation effects of infection remained consistent with the primary analysis, but the LDL-C interval with the lowest mortality risk increased progressively. The mediation effects of infection were largely consistent with the primary analysis in subgroups of age ≥65 years, female, body mass index <25 kg/m2, and National Institutes of Health Stroke Scale ≥16. During the acute stage of ischemic stroke, there is a U-shaped association between LDL-C level and all-cause mortality, where post-stroke infection is an important mediating mechanism.

Langerhans cell histiocytosis of the female genital tract: a literature review with additional three case studies in China.

PURPOSE: To summarize the clinical and pathological features of all reported Langerhans cell histiocytosis (LCH) cases of female genital tract and to provide our additional three cases, and the emphasis is put on the pathological diagnosis to remind both gynecologists and pathologists of this rare disease. METHODS: Literatures available are reviewed and the routine hematoxylin and eosin stained sections and immunohistochemical stained sections are studied for the diagnosis of our cases. RESULTS: Only 18 female genital tract LCH cases have been previously reported in medical literatures. The three cases we provide are diagnosed as LCH by both morphology and immunochemical staining after biopsy. All the patients presented papulous or ulcerative lesions on vulva or cervix, and the following systemic laboratory and radiologic examinations demonstrated no other affected site. After various treatments based on surgery and chemotherapy, most patients showed no signs of local or systemic recurrence. CONCLUSIONS: 'Pure' LCH of female genital tract without any other spreading is a quite rare disease and it might be misrecognized as some other diseases, so both gynecologists and pathologists should keep it in mind when encountered with such cases. The three patients we reported appeared to be the first cases having 'pure' lesion of female genital tract in China.

[Primitive neuroectodermal tumor in female genital tract: a clinicopathologic study].

OBJECTIVE: To study the clinicopathologic features of primitive neuroectodermal tumor (PNET) in female genital tract. METHODS: Six cases of PNET arising in female genital tract were retrospectively reviewed. The clinicopathologic features, immunohistochemical findings and EWS gene translocation study results were analyzed. RESULTS: The age of patients ranged from 10 to 27 years (mean = 20 years). The sites of involvement included ovary (1 case), uterus (1 case), vulva (2 cases) and vagina (2 cases). The greatest diameter of the tumor ranged from 2 to 10 cm (mean = 5.4 cm). The tumor had nodular appearance and showed grayish-pink fleshy cut surface, accompanied by foci of hemorrhage and necrosis. Histologically, the tumor was composed of malignant small round cells with indistinct cell borders, hyperchromatic nuclei, dense chromatin, tiny nucleoli and scanty cytoplasm. The tumor cells were arranged in sheets or lobules. Homer-Wright rosettes were identified in 1 case. Immunohistochemical study showed that the tumor cells were positive for CD99, FLI-1 and CD56 (6/6). Focal expression of vimentin (5/6), NSE (5/6), nestin (4/6), synaptophysin (4/6), S-100 protein (2/6) and chromogranin A (1/6) was also demonstrated. EWS gene translocation was detected in 5 cases studied. Follow-up information was available in 2 patients (7 and 17 months of follow up, respectively). One of them died of tumor metastasis 17 months after diagnosis. The other patient was still alive. CONCLUSIONS: PNET arising in female genital tract is rare. It mainly involves ovary, uterus, vulva and vagina. Immunohistochemical study using a panel of antibodies and fluorescence in-situ hybridization play an important role in definitive diagnosis of this rare malignancy.

[Effect of FK506 and CsA on vascular endothelium of hyperlipidemic rats].

OBJECTIVE: To observe the influence of ciclosporin A (CsA) or/and FK506 on vascular endothelium of hyperlipidemic rats. METHODS: Hyperlipidemic rat model was established as previously described. The injury of vascular endothelium of these rats was observed after stimulation with FK506 or/and CsA. The mRNA transcription and protein expression of the vascular endothelium growth factor (VEGF), decay-accelerating factor (DAF) and C reactive protein (CRP) in vascular endothelium of rats were measured. The serum reactive oxygen species (ROS) was detected. RESULTS: Compared with FK506, CsA was more likely to cause injury of vascular endothelium, damaging the integrity of endothelium of hyperlipidemic rats. CsA inhibited the expression of VEGF and the complement inhibitor DAF and increased the expression of CRP of vascular endothelial cells. CsA also up-regulated the serum level of ROS. FK506 showed no such impacts. CONCLUSION: CsA can damage vascular endothelium of hyperlipidemic rats by activating the complement system induced by VEGF/DAF and ROS/CRP pathway. FK506 has no influence on the VEGF/DAF pathway and the expression of ROS/CRP.

Organocatalytic inverse-electron-demand Diels-Alder reaction between 5-alkenyl thiazolones and ß,γ-unsaturated carbonyl compounds.

An inverse-electron-demand oxa-Diels-Alder reaction of 5-alkenyl thiazolones with ß,γ-unsaturated carbonyl compounds enabled by quinine thiourea was studied, which allows the enantioselective synthesis of a broad range of highly functionalized pyranthiazoles bearing three continuous stereocenters. This protocol is adaptable to a wide scope of substrates and has great potential for scale-up synthesis and facile transformation.

Solvent directed chemically divergent synthesis of ß-lactams and α-amino acid derivatives with chiral isothiourea.

A protocol for the chemically divergent synthesis of ß-lactams and α-amino acid derivatives with isothiourea (ITU) catalysis by switching solvents was developed. The stereospecific Mannich reaction occurring between imine and C(1)-ammonium enolate generated zwitterionic intermediates, which underwent intramolecular lactamization and afforded ß-lactam derivatives when DCM and CH3CN were used as solvents. However, when EtOH was used as the solvent, the intermediates underwent an intermolecular esterification reaction, and α-amino acid derivatives were produced. Detailed mechanistic experiments were conducted to prove that these two kinds of products came from the same intermediates. Furthermore, chemically diversified transformations of ß-lactam and α-amino acid derivatives were achieved.

External validation of ABCD series scores for predicting early stroke events following transient ischemic attack in a large nationwide registry.

Introduction: In the context of modern guideline-based strategies, new validations of prognostic scores for predicting early stroke risk are needed. We aimed to compare the validity of the ABCD series scores and assess the incremental values of risk components for predicting in-hospital stroke events in patients with transient ischemic attack (TIA). Patients and methods: We abstracted data from the Chinese Stroke Center Alliance (CSCA), a nationwide registry with 68,433 TIA patients admitted within 7 days of symptom onset from 1476 hospitals. TIA was defined by time-based criteria according to the World Health Organization (WHO). The discrimination of ABCD, ABCD2, ABCD2-I, and ABCD3 scores for predicting in-hospital stroke events was assessed by the area under the receiver-operating characteristics curves (AUC). The incremental predictive values of added risk predictor were determined by net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Results: A total of 29,286 TIA patients were included, of whom 1466 (5.0%) had in-hospital stroke events. Compared with ABCD2-I score (AUC 0.79, 95% confidence interval [CI] 0.77-0.80), ABCD (AUC 0.58, 95% CI 0.57-0.60), ABCD2 (AUC 0.58, 95% CI 0.56-0.59), and ABCD3 (AUC 0.58, 95% CI 0.56-0.60) had lower predictive utility. An incremental value was observed when adding infarction on DWI (IDI = 0.0597, NRI = 1.1036) into ABCD2 score to be ABCD2-I. Conclusion: The traditional scales utilizing medical history (ABCD, ABCD2, and ABCD3 scores) show fair ability for predicting in-hospital stroke events after TIA, but the ABCD2-I score, which adds infarction on DWI, improves the predictive ability.

Pre-stroke dementia and in-hospital outcomes in the Chinese Stroke Center Alliance.

Background: Little is known about the impact of prevalent dementia on in-hospital outcomes of patients with incident stroke in China. Using data from the Chinese Stroke Center Alliance (CSCA), we aim to quantify the prevalence of pre-stroke dementia and whether this group is at higher risk of adverse in-hospital outcomes compared to those without pre-stroke dementia. Methods: We used multivariable logistic regression models to assess the associations between pre-stroke dementia and ambulation by day 2, in-hospital mortality, in-hospital complications, and being discharged home. Covariates included age, sex, comorbidities [dyslipidemia, atrial fibrillation, peripheral vascular disease (PVD), smoking, and alcohol use], medication history (antiplatelet drugs or lipid-lowering drugs), stroke severity [measured by the National Institute of Health Stroke Scale (NIHSS)], administration of intravenous tissue plasminogen activator (IV tPA) within 4.5 hours of stroke onset, and receipt of deep vein thrombosis (DVT) prophylaxis if indicated. Results: In the final analytic sample of 559,070 ischemic stroke patients with no prior stroke history enrolled across 1,476 hospitals, those with pre-stroke dementia (n=1,511; 0.3%) were older and more likely to be female. Despite having received similar treatment, patients with pre-stroke dementia had lower odds of ambulating by day 2 [odds ratio (OR) =0.69; 95% confidence interval (CI): 0.62-0.78], higher odds of in-hospital mortality (OR =2.01; 95% CI: 1.35-2.99) or complications (OR =2.17; 95% CI: 1.93-2.44), and lower odds of being discharged home compared to those without pre-stroke dementia (OR =0.71; 95% CI: 0.62-0.83). Conclusions: Worse in-hospital outcomes among patients with pre-stroke dementia may be explained by pre-existing cognitive impairment that limited their ability to advocate for care needs. Further research is needed to determine whether a different care pathway or additional attention from clinicians is necessary for patients with pre-stroke dementia.

Association between high-sensitivity C-reactive protein, functional disability, and stroke recurrence in patients with acute ischaemic stroke: A mediation analysis.

BACKGROUND: Post-stroke inflammation biomarker high-sensitivity C-reactive protein (hsCRP) increases cerebral infarct size and results in functional disability directly, it also contributes to the formation and maturation of atherosclerotic plaques, which increase the risk of stroke recurrence and results in functional disability indirectly. However, no study has quantified how much functional disability was mediated by stroke recurrence. METHODS: Patients with acute ischaemic stroke within 7 days and admitted to 169 hospitals in the Third China National Stroke Registry were analyzed. Blood samples were collected within 24 h of admission. Stroke recurrence and functional disability (defined as a modified Rankin scale score ≥ 2) were assessed via face-to-face interviews at three months. Mediation analysis under the counterfactual framework was performed to examine the potential causal chain in which stroke recurrence may mediate the relationship between hsCRP and functional outcome. Sensitivity analyses were performed across different subgroups and on different scales of hsCRP measurement. FINDINGS: Of the 7603 analyzed patients (mean [SD] age, 62.3 [11.3] years; 2392 [31.5%] women), the median (interquartile range [IQR]) of NIHSS score was 3.0 (1.0-6.0). The median (IQR) level of hsCRP was 1.73 (0.81-4.38) mg/L. A total of 496 (6.5%) cases of stroke recurrence and 1884 (24.8%) cases of functional disability were observed at the 90-day follow-up. Each SD increase in the concentration of hsCRP was associated with an increased risk of stroke recurrence (adjusted odds ratio [aOR], 1.11; 95% CI, 1.04-1.18) and disability (aOR, 1.14; 95% CI, 1.08-1.20) within 90 days. Of 1884 functionally disabled patients, only 16.0 % (n = 302) of patients experienced stroke recurrence before functional disability. Stroke recurrence during follow-up explained 16.52% (95% CI, 5.79%-27.25%) of the relationship between hsCRP and functional disability. Sensitivity analyses in different subgroups and on different scales of hsCRP measurement showed comparable results. INTERPRETATION: Stroke recurrence mediates less than 20% of the association between hsCRP and functional disability at 90 days among patients with acute ischaemic stroke. In addition to typical secondary prevention strategies for preventing stroke recurrence, more attention should be paid to novel anti-inflammatory therapy to improve functional outcomes. FUNDING: Beijing Natural Science Foundation, the National Key R&D Program of China, the National Natural Science Foundation of China, and the Beijing Municipal Science & Technology Commission.