Recombinant soluble form of receptor for advanced glycation end products ameliorates microcirculation impairment and neuroinflammation after subarachnoid hemorrhage.

Impaired cerebral microcirculation after subarachnoid hemorrhage (SAH) has been shown to be related to delayed ischemic neurological deficits (DIND). We previously demonstrated the involvement of the receptor for advanced glycation end products (RAGE) in the pathogenesis of SAH related neuronal death. In the present study, we aimed to investigate the therapeutic effects of a recombinant soluble form of RAGE (sRAGE) on microcirculation impairment following SAH. Intrathecal injection of autologous blood in rats, mixed primary astrocyte and microglia cultures exposed to hemolysates and endothelial cells â€‹(ECs) from human brain microvascular exposed to glia-conditioned medium or SAH patient's CSF were used as experimental SAH models in vivo and in vitro. The results indicated that intrathecal administration of recombinant sRAGE significantly ameliorated the vasoconstriction of cortical arterioles and associated perfusion impairment, brain edema, reduced cell death, endothelial dysfunction, and improved motor performance at 24 and 48 â€‹h after SAH induction in rats. The in vitro results further showed that recombinant sRAGE significantly reduced astrocyte swelling and microglia activation, in parallel with decreased mRNA expression levels of pro-inflammatory cytokines including interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) in vitro. Moreover, the in vitro model of SAH-induced p-eNOS and eNOS suppression, along with stress fiber formation in brain microvascular ECs, was effectively reversed by sRAGE treatment and led to a decrease in cleaved-caspase 3 expression. In summary, recombinant sRAGE effectively lessened microcirculation impairment and vascular injury after SAH via the mechanism of anti-inflammation, which may provide a potential therapeutic strategy for SAH.

Rare Cutaneous Manifestations of Erdheim Chester Disease: A Case Report and Literature Review.

Erdheim Chester disease (ECD) is a rare and complex non-Langerhans histiocytic systemic disease that affects multiple organ systems, including the bones, heart, lungs, and central nervous system. Fewer than 1,000 cases have been reported in the medical literature and dermatological manifestations of the disease are rare but can provide valuable diagnostic clues for this challenging disease. The cutaneous manifestations of ECD can take many forms, including nodules, plaques, papules, and xanthomas. These lesions can occur on any part of the body and may be solitary or multiple. Cutaneous manifestations of ECD have been reported to occur in up to 20% of cases, but the true prevalence may be higher, as many cases may go undiagnosed. We present the case of a 62-year-old gentleman with a history of ECD currently on vemurafenib who presented with multiple painless subcutaneous nodules on his back after an excision biopsy under local anesthetic revealed histological features of ECD. The objective of this case report is to raise awareness of ECD and its dermatological manifestations. Further research is warranted to better understand the pathogenesis and morphology of cutaneous involvement in ECD.

Continuous lumbar drainage after aneurysmal subarachnoid hemorrhage decreased malondialdehyde in cerebrospinal fluid and improved outcome.

PURPOSE: The use of a continuous lumbar drain (LD) for the treatment of aneurysmal subarachnoid hemorrhage (aSAH), and malondialdehyde (MDA), a marker of oxidative stress, is correlated with clinical outcome. This study aimed to investigate the relationship between LD placement and MDA level after aSAH. METHODS: Patients with modified Fisher's grade III and IV aSAH who underwent early aneurysm obliteration were enrolled. Cerebrospinal fluid (CSF) was obtained on day 7 after aSAH in non-LD group. In LD group, the LD was inserted on day 3 after aSAH for continuous CSF drainage. The levels of intrathecal hemoglobin, total bilirubin, ferritin, and MDA were measured. RESULTS: There were 41 patients in non-LD group (age: 58.7 ± 13.7 years; female: 61.0%) and 48 patients in LD group (age: 58.3 ± 10.4 years; female: 79.2%). There were more favorable outcomes (Glasgow Outcome Scale ≥4) at 3 months after aSAH in LD group (p = 0.0042). The intrathecal hemoglobin, total bilirubin, ferritin, and MDA levels at day 7 after aSAH were all significantly lower in LD group. An older age (>60 years) (p = 0.0293), higher MDA level in the CSF (p = 0.0208), and delayed ischemic neurological deficit (p = 0.0451) were independent factors associated with unfavorable outcomes. LD placement was associated with a decreased intrathecal MDA level on day 7 after aSAH (p < 0.001). CONCLUSION: The intrathecal MDA level at day 7 after aSAH can be an effective outcome indicator in modified Fisher's grade III/IV aSAH. Continuous CSF drainage via a LD can decrease the intrathecal MDA level and improve the functional outcome.

Dental Pulp Stem Cell-Derived Conditioned Medium Alleviates Subarachnoid Hemorrhage-Induced Microcirculation Impairment by Promoting M2 Microglia Polarization and Reducing Astrocyte Swelling.

Aneurysmal subarachnoid hemorrhage (SAH) can cause severe neurological deficits and high mortality. Early brain edema following SAH contributes to the initiation of microcirculation impairment and may further lead to delayed ischemic neurologic deficit (DIND). This study aimed to investigate whether dental pulp stem cell conditioned medium (DPSC-CM) ameliorates SAH-induced microcirculation impairment and the underlying mechanisms. SAH was induced via intrathecal injection of fresh autologous blood in Wistar male adult rat. DPSC-CM or DPSC-CM + insulin growth factor-1 (IGF-1) antibody was randomly administered by intrathecal route 5 min after SAH induction. To evaluate the underlying mechanisms of DPSC-CM in the treatment of SAH, primary rat astrocyte and microglia co-cultures were challenged with hemolysate or SAH-patient CSF in the presence or absence of DPSC-CM. The results showed that in vivo, DPSC-CM treatment decreased the brain water content, improved microcirculation impairment and enhanced functional recovery at 24 h post-SAH. DPSC-CM treatment also alleviated the expressions of water channel protein aquaporin-4 (AQP4) and pro-inflammatory cytokines, and enhanced the expressions of anti-inflammatory factors in the cortical region. However, all the beneficial effects of DPSC-CM were abrogated after treatment with IGF-1 neutralizing antibody. The in vitro results further showed that DPSC-CM treatment reduced hemolysate/SAH-patient CSF-induced astrocyte swelling and promoted M2 microglia polarization, partially through IGF-1/AKT signaling. The data suggested that DPSC-CM significantly reduced brain edema and rescued microcirculation impairment with concomitant anti-inflammatory benefits after SAH, and may potentially be developed into a novel therapeutic strategy for SAH.

Combination of indirect revascularization and endothelial progenitor cell transplantation improved cerebral perfusion and ameliorated tauopathy in a rat model of bilateral ICA ligation.

OBJECTIVE: Endothelial progenitor cells (EPCs) contribute to the recovery of neurological function after ischemic stroke. Indirect revascularization has exhibited promising effects in the treatment of cerebral ischemia related to moyamoya disease and intracranial atherosclerotic disease. The role of EPCs in augmenting the revascularization effect is not clear. In this study, we investigated the therapeutic effects of indirect revascularization combined with EPC transplantation in rats with chronic cerebral ischemia. METHODS: Chronic cerebral ischemia was induced by bilateral internal carotid artery ligation (BICAL) in rats, and indirect revascularization by encephalo-myo-synangiosis (EMS) was performed 1 week later. During the EMS procedure, intramuscular injection of EPCs and the addition of stromal cell-derived factor 1 (SDF-1), and AMD3100, an SDF-1 inhibitor, were undertaken, respectively, to investigate their effects on indirect revascularization. Two weeks later, the cortical microcirculation, neuronal damage, and functional outcome were evaluated according to the microvasculature density and partial pressure of brain tissue oxygen (PbtO2), regional blood flow, expression of phosphorylated Tau (pTau), TUNEL staining and the rotarod performance test, respectively. RESULTS: The cortical microcirculation, according to PbtO2 and regional blood flow, was impaired 3 weeks after BICAL. These impairments were improved by the EMS procedure. The regional blood flow was further increased by the addition of SDF-1 and decreased by the addition of AMD3100. Intramuscular injection of EPCs further increased the regional blood flow as compared with the EMS group. The rotarod test results showed that the functional outcome was best in the EMS combined with EPC injection group. Western blot analysis showed that the EMS combined with EPC treatment group had significantly decreased expressions of phosphorylated Tau and phosphorylated glycogen synthase kinase 3 beta (Y216 of GSK-3ß). pTau and TUNEL-positive cells were markedly increased at 3 weeks after BICAL induction. Furthermore, the groups treated with EMS combined with SDF-1 or EPCs exhibited marked decreases in the pTau expression and TUNEL-positive cells, whereas AMD3100 treatment increased TUNEL-positive cells. CONCLUSION: The results of this study suggested that indirect revascularization ameliorated the cerebral ischemic changes. EPCs played a key role in augmenting the effect of indirect revascularization in the treatment of chronic cerebral ischemia.

Epidemiology of bla CTX-M-Positive Salmonella Typhimurium From Diarrhoeal Outpatients in Guangdong, China, 2010-2017.

Salmonella enterica can lead to intestinal diarrhea, and the emergence and spread of cephalosporin-resistant Salmonella have brought great challenges to clinical treatment. Therefore, this study investigated the prevalence and transmission of bla CTX-M genes among S. Typhimurium from diarrhoeal outpatients in Guangdong, China, from 2010 to 2017. A total of 221 bla CTX-M-positive isolates were recovered from 1,263 S. Typhimurium isolates from the facal samples of diarrhoea patients in 45 general hospitals from 11 cities. The most popular CTX-M gene was bla CTX-M-55 (39.6%, 72/182) in the CTX-M-1 group, followed by bla CTX-M-14 (22.5%, 41/182) and bla CTX-M-65 (19.2%, 35/182) in the CTX-M-9 group. The isolates that carried bla CTX-M-9G had significantly higher resistance rates to multiple antibacterials compared with bla CTX-M-1G (p < 0.01). Meanwhile, PFGE analysis not only showed the clonal transmission of bla CTX-M-55/14/65-positve isolates of diarrhoeal outpatients' origins from different hospitals in Guangdong province, but also the characteristic of bla CTX-M-55/14/65-positve isolates' bacterial persistence. Multilocus sequence typing (MLST) analysis indicated that these S. Typhimurium isolates possessed ST34 and ST19. Furthermore, genomic Beast phylogenomic analysis provided the evidence of a close relationship of bla CTX-M-positive S. Typhimurium isolates between the outpatients and pork. Most bla CTX-M-55/14/65 genes were transmitted by non-typeable or IncI1/IncFII/IncHI2 plasmids with the size of ranging from ~80 to ~280 kb. Moreover, whole-genome sequencing (WGS) analysis further revealed that bla CTX-M-55/14/65 coexisted with other 25 types of ARGs, of which 11 ARGs were highly prevalent with the detection rates >50%, and it first reported the emergence of bla TEM-141 in S. Typhimurium. This study underscores the importance of surveillance for bla CTX-M-positive microbes in diarrhea patients.

Application of routine laboratory data in combination with machine learning in the differential diagnosis of lung tuberculosis / 中华检验医学杂志

Objective:To investigate the application value of establishing the differential diagnosis model of pulmonary tuberculosis using routine laboratory data.Methods:The retrospective study was conducted. The routine laboratory data of newly diagnosed patients with pulmonary tuberculosis and other pulmonary diseases in Beijng Jishuitan Hospital and Beijing Hepingli Hospital from May 2015 to November 2021were collected. According to the random numbers showed in the computer, all the 11516 patients were divided into training dataset and test dataset with a ratio of 9∶1. Four machine learning algorithms, Support Vector Machine, Random Forest, K-Nearest Neighbor and Logistic Regression, were used to build models and select features. The diagnostic accuracy of each model was verified by using the 10-fold cross-validation method and the performance of each model was evaluated by using the receptor operator of characteristic (ROC) curve.Results:Random Forest was selected as the optimal machine learning algorithm to build the best feature model in the study. According to importance scale of factors, the differential diagnosis model of pulmonary tuberculosis consisting of 37 non-specific test indexes. In the validation set and test set the accuracy and area under curve (AUC) of the models were 0.747 and 0.736, the sensitivity, specificity and accuracy were 68.03% and 68.75%, 70.91% and 67.90%, 70.30% and 68.12%, respectively.Conclusion:A key tool in the differential diagnosis model of pulmonary tuberculosis was established by routine laboratory data in combination with machine learning. The results of this study need to be further verified by more data from medical institutions.

Anorexia nervosa manifesting as massive ascites, hypercholesterolemia, and sequential binge eating in an 11-year-old girl: A case report.

RATIONALE: Anorexia nervosa (AN) is a serious eating disorder associated with a distorted body image. Hypercholesterolemia has been found in patients with AN but the mechanism of hyperlipidemia in AN remains little known. Ascites in patients with AN has been attributed to hypoalbuminemia and liver diseases, but massive ascites without the aforementioned etiologies has never been reported in AN. PATIENT CONCERNS: An 11-year-old girl was admitted for exclusion of organic underlying diseases due to severe body weight loss (18% within 3 weeks), poor appetite, and hypercholesterolemia (274 mg/dL). She complained of heartburn sensation, nausea, vomiting, constipation, and postprandial dull abdominal pain with fullness. DIAGNOSES: The patient's condition met with all 3 of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for diagnosing AN. On admission, her total cholesterol level was 337 mg/dL and hypocomplementemia (C3 55.5 mg/dL) was also found. Abdominal sonography and computed tomography scans showed massive ascites. However, neither proteinuria nor hypoalbuminemia was found. Upper gastroduodenal endoscopy showed chronic superficial gastritis and colonoscopy revealed negative findings. Ascites obtained by paracentesis demonstrated a transudate without bacterial infection, tuberculosis, or pancreatitis. Exploratory laparoscopy showed nonpurulent ascites. However, biopsies from the small intestine, mesentery, and liver showed chronic inflammation and fibrosis. INTERVENTIONS: The intensive nutritional therapy by increasing total energy intake stepwise with a combination of high-energy formula and her favorite foods. OUTCOMES: Her hypercholesterolemia, hypocomplementemia, and massive ascites resolved after her weight was restored. She developed binge eating with continuous weight gain after discharge. Her weight significantly increased to an obese level (body mass index [BMI] 25.9 kg/m) after loss to follow-up for 4 years until she returned to our emergency room due to suicide attempt. CONCLUSION: Diagnostic crossover between subtypes in anorexia nervosa might be a potential risk factor for illness severity and poor prognosis. AN can manifest as massive ascites with normal albumin concentrations that could possibly be due to chronic inflammation of the intestinal serosa, mesentery, and peritoneal surface of the liver.

The Effect of Implementation of a Nursing Information System: Experiences in a Regional Teaching Hospital in Taiwan.

The implementation of a nursing information system is a revolutionary change in that with its help nurses can quickly complete various assessments and treatment records and simplify manual work. Consequently, physicians and interdisciplinary teams can query information and deliver the most accurate treatment. Since the implementation of a nursing information system to the case hospital, the recording time difference between new and senior nurses was reduced; for new nurses, the recording time per shift decreased from 66.2 ± 15.0 minutes to 37.16 ± 15.7 minutes, while for senior nurses with more than 10 years of experience, it decreased from 45.4 ± 6.65 minutes to 29.1 ± 4.23 minutes. With the application of the innovation diffusion theory, the Nursing Department achieved cross-team cooperation with the Information Department and successfully developed the nursing information system, which laid a solid foundation for the case hospital to further develop other information systems.

Early sensory neurophysiological changes in prediabetes.

AIMS/INTRODUCTION: To elucidate whether axonal changes arise in the prediabetic state and to find a biomarker for early detection of neurophysiological changes. MATERIALS AND METHODS: We enrolled asymptomatic diabetes patients, as well as prediabetic and normoglycemic individuals to test sensory nerve excitability, and we analyzed those findings and their correlation with clinical profiles. RESULTS: In nerve excitability tests, superexcitability in the recovery cycle showed increasing changes in the normoglycemic, prediabetes and diabetes cohorts (-19.09 ± 4.56% in normoglycemia, -22.39 ± 3.16% in prediabetes and -23.71 ± 5.15% in diabetes, P = 0.002). Relatively prolonged distal sensory latency was observed in the median nerve (3.12 ± 0.29 ms in normoglycemia, 3.23 ± 0.38 ms in prediabetes and 3.45 ± 0.43 ms in diabetes, P = 0.019). Superexcitability was positively correlated with fasting plasma glucose (r = 0.291, P = 0.009) and glycated hemoglobin (r = 0.331, P = 0.003) in all participants. CONCLUSIONS: Sensory superexcitability and latencies are the most sensitive parameters for detecting preclinical physiological dysfunction in prediabetes. In addition, changes in favor of superexcitability were positively correlated with glycated hemoglobin for all participants. These results suggest that early axonal changes start in the prediabetic stage, and that the monitoring strategy for polyneuropathy should start as early as prediabetes.

Impaired microcirculation after subarachnoid hemorrhage in an in vivo animal model.

The influence of aneurysmal subarachnoid hemorrhage (SAH) on brain microcirculation has not yet been systematically investigated. We established an animal model to examine (1) the brain surface microcirculation (2) the influences of cerebrospinal fluid (CSF) from aneurysmal SAH on the brain surface microcirculation. A rat SAH model was induced by injection of autologous arterial blood into the cisterna magnum, and the brain surface microcirculation was evaluated by a capillary videoscope with craniotomy at the fronto-parietal region. CSF from SAH rats and SAH patients was applied on the brain surface of naïve rats to assess the resulting microcirculatory changes. In the SAH rats, diffuse constriction of cortical arterioles within 24 hours of SAH was observed. Similar patterns of microcirculation impairment were induced on normal rat brain surfaces via application of CSF from SAH rats and SAH patients. Furthermore, the proportion of subjects with arteriolar vasoconstriction was significantly higher in the group of SAH patients with delayed ischemic neurological deficits (DIND) than in those without DIND (p < 0.001). This study demonstrated impaired microcirculation on brain surface arterioles in a rat model of SAH. CSF from SAH rats and patients was responsible for impairment of brain surface microcirculation.

Direct visualization of microcirculation impairment after acute subdural hemorrhage in a novel animal model.

OBJECTIVE: Direct brain compression and secondary injury due to increased intracranial pressure are believed to be the pathognomic causes of a grave outcome in acute subdural hemorrhage (aSDH). However, ischemic damage from aSDH has received limited attention. The authors hypothesized that cerebral microcirculation is altered after aSDH. Direct visualization of microcirculation was conducted in a novel rat model. METHODS: A craniectomy was performed on each of the 18 experimental adult Wistar rats, followed by superfusion of autologous arterial blood onto the cortical surface. Changes in microcirculation were recorded by capillary videoscopy. Blood flow and the partial pressure of oxygen in the brain tissue (PbtO2) were measured at various depths from the cortex. The brain was then sectioned for pathological examination. The effects of aspirin pretreatment were also examined. RESULTS: Instantaneous vasospasm of small cortical arteries after aSDH was observed; thrombosis also developed 120 minutes after aSDH. Reductions in blood flow and PbtO2 were found at depths of 2-4 mm. Blood-brain barrier disruption and thrombi formation were confirmed using immunohistochemical staining, while aspirin pretreatment reduced thrombosis and the impairment of microcirculation. CONCLUSIONS: Microcirculation impairment was demonstrated in this aSDH model. Aspirin pretreatment prevented the diffuse thrombosis of cortical and subcortical vessels after aSDH.

Cerebrospinal fluid high mobility group box 1 is associated with neuronal death in subarachnoid hemorrhage.

We aim to determine the cerebrospinal fluid levels of high mobility group box 1 in subarachnoid hemorrhage patients and to investigate the involvement of the receptor for advanced glycation end products and high mobility group box 1 in the pathogenesis of post-subarachnoid hemorrhage neuronal death. The study included 40 patients (mean age, 59 ± 19 years) with Fisher's grade ≥ III aneurysmal subarachnoid hemorrhage. Cerebrospinal fluid was collected on the seventh day post-hemorrhage. Receptor for advanced glycation end products expression was examined in rat brain tissue following subarachnoid hemorrhage and in cultured neurons exposed to post-subarachnoid hemorrhage cerebrospinal fluid. Therapeutic effects of the recombinant soluble form of RAGE on subarachnoid hemorrhage models were also investigated. The results indicated that a higher level of cerebrospinal fluid high mobility group box 1 was independently associated with unfavorable outcome at three months post-subarachnoid hemorrhage (OR = 1.061, 95% CI: 1.005-1.121). Expression of RAGE increased in post-subarachnoid hemorrhage rat brain cells and in cultured neuron with stimulation of post-subarachnoid hemorrhage cerebrospinal fluid. Administration of recombinant soluble form of RAGE significantly reduced the number of positive TUNEL staining cells in subarachnoid hemorrhage rat and improved cell viability in post-subarachnoid hemorrhage cerebrospinal fluid-treated cultured neurons. Thus, the level of cerebrospinal fluid high mobility group box 1 can be a prognostic indicator for patients with Fisher's grade ≥ III aneurysmal subarachnoid hemorrhage and that treatment with soluble form of RAGE is a novel approach for subarachnoid hemorrhage.

Treatment of arteriovenous malformation with high-flow fistula and bilateral transverse-sigmoid sinuses stenosis resulting diffuse cortical vein engorgement and symptoms resembling carotid-cavernous fistula.

Patients harboring arteriovenous malformations (AVMs) may present with focal neurological deficit, seizures, hemorrhage or be completely asymptomatic. This diversity in manifestation of AVM is related to the individual characteristics of AVMs such as size, location, configuration of feeding arteries, and drainage veins. Treating the AVMs with high-flow fistula and downstream sinuses occlusion is challenging. The authors reported their experience of treating this kind of AVM. The high venous pressure caused diffuse cortical venous regurgitation and engorgement of left superior ophthalmic vein and symptoms resembling carotid-venous fistula. To avoid possible reflux of embolization materials to cortical veins and facilitate surgical treatment, the bilateral transverse sinuses were re-canalized first. The venous pressure was measured through left transverse sinus, and it decreased significantly from 50 mmHg to 20 mmHg after bilateral sinus stenting. The AVM was then embolized and excised uneventfully.

Intrathecal lactate predicting hydrocephalus after aneurysmal subarachnoid hemorrhage.

BACKGROUND: Evidence shows possible benefits from continuous drainage by lumbar drain after aneurysmal subarachnoid hemorrhage (SAH). Under the hypothesis that compartmentalization occurs between the ventricle and subarachnoid space after massive SAH, this study aimed to evaluate the biochemical differences between ventricular and intrathecal cerebrospinal fluid (CSF) and assess the role of CSF lactate in shunt-dependent hydrocephalus (SDHC) after aneurysmal SAH. MATERIALS AND METHODS: Patients with modified Fisher grade III/IV aneurysmal SAH who underwent early obliteration were evaluated. Intrathecal and intraventricular CSF were obtained on day 7 post-SAH to measure their biochemical composition in terms of total protein, glucose, ferritin, and lactate. The associations of SDHC with the clinical parameters and CSF data were analyzed. RESULTS: There were 28 patients (mean age, 55.4 y; males, 46.6%), including 18 (64.3%) with SDHC. Intrathecal CSF had significantly higher levels of total protein, ferritin, hemoglobin, and lactate but lower glucose level than intraventricular CSF (all P < 0.0001). By multivariate analysis of clinical and CSF parameters, elevated intrathecal CSF lactate (P = 0.036) and the presence of intraventricular hemorrhage (P = 0.05) were independent factors associated with SDHC. Moreover, intrathecal lactate >5.5 µM effectively predicted the occurrence of SDHC (odds ratio: 32, 95% confidence interval: 3.8-270.8; P = 0.0015). CONCLUSIONS: By compartmentalization of the subarachnoid space after SAH, intrathecal lactate level is a useful predictive parameter for long-term SDHC in patients with aneurysmal SAH patients.

Effect of Blood Pressure Lowering in Early Ischemic Stroke: Meta-Analysis.

BACKGROUND AND PURPOSE: Elevated blood pressure is common in acute stage of ischemic stroke and the strategy to manage this situation is not well established. We therefore conducted a meta-analysis of randomized controlled trials comparing active blood pressure lowering and control groups in early ischemic stroke. METHODS: Pubmed, EMBASE, and Clinicaltrials.gov from January 1966 to March 2015 were searched to identify relevant studies. We included randomized controlled trials with blood pressure lowering started versus control within 3 days of ischemic stroke onset. The primary outcome was unfavorable outcome at 3 months or at trial end point, defined as dependency or death, and the key secondary outcome was recurrent vascular events. Pooled relative risks and 95% confidence intervals were calculated using random-effects model. RESULTS: The systematic search identified 13 randomized controlled trials with 12 703 participants comparing early blood pressure lowering and control. Pooling the results with the random-effects model showed that blood pressure lowering in early ischemic stroke did not affect the risk of death or dependency at 3 months or at trial end point (relative risk, 1.04; 95% confidence interval, 0.96-1.13; P=0.35). Also, blood pressure lowering also had neutral effect on recurrent vascular events, as well as on disability or death, all-cause mortality, recurrent stroke, and serious adverse events. CONCLUSIONS: This meta-analysis suggested blood pressure lowering in early ischemic stroke had a neutral effect on the prevention of death or dependency.

Prognostic value of intrathecal heme oxygenase-1 concentration in patients with Fisher Grade III aneurysmal subarachnoid hemorrhage.

OBJECT: Experimental studies have demonstrated the crucial role of posthemorrhagic erythrocyte catabolism in the pathogenesis of subarachnoid hemorrhage (SAH). The authors of this study aimed to investigate the prognostic value of a series of CSF biomarkers linked to heme metabolism in SAH patients. METHODS: Patients with Fisher Grade III aneurysmal SAH undergoing early aneurysm obliteration were enrolled. The levels of heme oxygenase-1 (HO-1), oxyhemoglobin, ferritin, and bilirubin in intrathecal CSF were measured on the 7th day posthemorrhage. The associations of functional outcome with clinical and CSF parameters were analyzed. RESULTS: The study included 41 patients (mean age 59 ± 14 years; 16 male, 25 female), 17 (41.5%) of whom had an unfavorable outcome (Glasgow Outcome Scale score ≤ 3) 3 months after SAH. In terms of the clinical data, age > 60 years, admission World Federation of Neurosurgical Societies Grade ≥ III, and the presence of acute hydrocephalus were independent factors associated with an unfavorable outcome. After adjusting for clinical parameters, a higher level of HO-1 appeared to be the most significant CSF parameter related to an unfavorable outcome among all tested CSF molecules (OR 0.934, 95% CI 0.883-0.989, p = 0.018). Further analysis using a generalized additive model identified a cutoff HO-1 value of 81.2 µM, with higher values predicting unfavorable outcome (82.4% accuracy). CONCLUSIONS: The authors propose that the level of intrathecal CSF HO-1 at Day 7 post-SAH can be an effective outcome indicator in patients with Fisher Grade III aneurysmal SAH.

A highly divergent Encephalomyocarditis virus isolated from nonhuman primates in Singapore.

BACKGROUND: In 2001 and 2002, fatal myocarditis resulted in the sudden deaths of four, two adult and two juvenile, orang utans out of a cohort of 26 in the Singapore Zoological Gardens. METHODS: Of the four orang utans that underwent post-mortem examination, virus isolation was performed from the tissue homogenates of the heart and lung obtained from the two juvenile orang utans in Vero cell cultures. The tissue culture fluid was examined using electron microscopy. Reverse transcription and polymerase chain reaction with Encephalomyocarditis virus (EMCV)-specific primers targeting the gene regions of VP3/VP1 and 3D polymerase (3Dpol) confirmed the virus genus and species. The two EMCV isolates were sequenced and phylogenetic analyses of the virus genes performed. Serological testing on other animal species in the Singapore Zoological Gardens was also conducted. RESULTS: Electron microscopy of the two EMCV isolates, designated Sing-M100-02 and Sing-M105-02, revealed spherical viral particles of about 20 to 30 nm, consistent with the size and morphology of members belonging to the family Picornaviridae. In addition, infected-Vero cells showed positive immunoflorescence staining with antiserum to EMCV. Sequencing of the viral genome showed that the two EMCV isolates were 99.9% identical at the nucleotide level, indicating a similar source of origin. When compared with existing EMCV sequences in the VP1 and 3Dpol gene regions, the nucleotide divergence were at a maximum of 38.8% and 23.6% respectively, while the amino acid divergence were at a maximum of 33.9% and 11.3% respectively. Phylogenetic analyses of VP1 and 3Dpol genes further grouped the Sing-M100-02 and Sing-M105-02 isolates to themselves, away from existing EMCV lineages. This strongly suggested that Sing-M100-02 and Sing-M105-02 isolates are highly divergent variants of EMCV. Apart from the two deceased orang utans, a serological survey conducted among other zoo animals showed that a number of other animal species had neutralizing antibodies to Sing-M105-02 isolate, indicating that the EMCV variant has a relatively wide host range. CONCLUSIONS: The etiological agent responsible for the fatal myocarditis cases among two of the four orang utans in the Singapore Zoological Gardens was a highly divergent variant of EMCV. This is the first report of an EMCV infection in Singapore and South East Asia.