Dr. Hasan Sadikin General Hospital

BACKGROUND: The Direct Repeat locus of the Mycobacterium tuberculosis complex (MTC) is a member of the CRISPR (Clustered regularly interspaced short palindromic repeats) sequences family. Spoligotyping is the widely used PCR-based reverse-hybridization blotting technique that assays the genetic diversity of this locus and is useful both for clinical laboratory, molecular epidemiology, evolutionary and population genetics. It is easy, robust, cheap, and produces highly diverse portable numerical results, as the result of the combination of (1) Unique Events Polymorphism (UEP) (2) Insertion-Sequence-mediated genetic recombination. Genetic convergence, although rare, was also previously demonstrated. Three previous international spoligotype databases had partly revealed the global and local geographical structures of MTC bacilli populations, however, there was a need for the release of a new, more representative and extended, international spoligotyping database. RESULTS: The fourth international spoligotyping database, SpolDB4, describes 1939 shared-types (STs) representative of a total of 39,295 strains from 122 countries, which are tentatively classified into 62 clades/lineages using a mixed expert-based and bioinformatical approach. The SpolDB4 update adds 26 new potentially phylogeographically-specific MTC genotype families. It provides a clearer picture of the current MTC genomes diversity as well as on the relationships between the genetic attributes investigated (spoligotypes) and the infra-species classification and evolutionary history of the species. Indeed, an independent Naïve-Bayes mixture-model analysis has validated main of the previous supervised SpolDB3 classification results, confirming the usefulness of both supervised and unsupervised models as an approach to understand MTC population structure. Updated results on the epidemiological status of spoligotypes, as well as genetic prevalence maps on six main lineages are also shown. Our results suggests the existence of fine geographical genetic clines within MTC populations, that could mirror the passed and present Homo sapiens sapiens demographical and mycobacterial co-evolutionary history whose structure could be further reconstructed and modelled, thereby providing a large-scale conceptual framework of the global TB Epidemiologic Network. CONCLUSION: Our results broaden the knowledge of the global phylogeography of the MTC complex. SpolDB4 should be a very useful tool to better define the identity of a given MTC clinical isolate, and to better analyze the links between its current spreading and previous evolutionary history. The building and mining of extended MTC polymorphic genetic databases is in progress.

Abstract Objective Clinical and laboratory biomarkers to predict the severity of coronavirus disease 2019 (COVID-19) are essential in this pandemic situation of which resource allocation must be urgently prepared especially in the context of respiratory support readiness. Lymphocyte count has been a marker of interest since the first COVID-19 publication. We conducted a systematic review and meta-analysis in order to investigate the association of lymphocyte count on admission and the severity of COVID-19. We would also like to analyze whether patient characteristics such as age and comorbidities affect the relationship between lymphocyte count and COVID-19. Methods Comprehensive and systematic literature search was performed from PubMed, SCOPUS, EuropePMC, ProQuest, Cochrane Central Databases, and Google Scholar. Research articles in adult patients diagnosed with COVID-19 with information on lymphocyte count and several outcomes of interest, including mortality, acute respiratory distress syndrome (ARDS), intensive care unit (ICU) care, and severe COVID-19, were included in the analysis. Inverse variance method was used to obtain mean differences and its standard deviations. Maentel-Haenszel formula was used to calculate dichotomous variables to obtain odds ratios (ORs) along with its 95% confidence intervals. Random-effect models were used for meta-analysis regardless of heterogeneity. Restricted-maximum likelihood random-effects meta-regression was performed for age, gender, cardiac comorbidity, hypertension, diabetes mellitus, COPD, and smoking. Results There were a total of 3099 patients from 24 studies. Meta-analysis showed that patients with poor outcome have a lower lymphocyte count (mean difference − 361.06 μL [− 439.18, − 282.95], p < 0.001; I 2 84%) compared to those with good outcome. Subgroup analysis showed lower lymphocyte count in patients who died (mean difference − 395.35 μL [− 165.64, − 625.07], p < 0.001; I 2 87%), experienced ARDS (mean difference − 377.56 μL [− 271.89, − 483.22], p < 0.001; I 2 0%), received ICU care (mean difference − 376.53 μL [− 682.84, − 70.22], p = 0.02; I 2 89%), and have severe COVID-19 (mean difference − 353.34 μL [− 250.94, − 455.73], p < 0.001; I 2 85%). Lymphopenia was associated with severe COVID-19 (OR 3.70 [2.44, 5.63], p < 0.001; I 2 40%). Meta-regression showed that the association between lymphocyte count and composite poor outcome was affected by age ( p = 0.034). Conclusion This meta-analysis showed that lymphopenia on admission was associated with poor outcome in patients with COVID-19.

Background: Patients critically ill with coronavirus disease-2019 (COVID-19) feature hyperinflammation, and the associated biomarkers may be beneficial for risk stratification. We aimed to investigate the association between several biomarkers, including serum C-reactive protein (CRP), procalcitonin (PCT), D-dimer, and serum ferritin, and COVID-19 severity. Methods: We performed a comprehensive systematic literature search through electronic databases. The outcome of interest for this study was the composite poor outcome, which comprises mortality, acute respiratory distress syndrome, need for care in an intensive care unit, and severe COVID-19. Results: A total of 5350 patients were pooled from 25 studies. Elevated CRP was associated with an increased composite poor outcome [risk ratio (RR) 1.84 (1.45, 2.33), p < 0.001; I 2 : 96%] and its severe COVID-19 (RR 1.41; I 2 : 93%) subgroup. A CRP ⩾10 mg/L has a 51% sensitivity, 88% specificity, likelihood ratio (LR) + of 4.1, LR- of 0.5, and an area under curve (AUC) of 0.84. An elevated PCT was associated with an increased composite poor outcome [RR 3.92 (2.42, 6.35), p < 0.001; I 2 : 85%] and its mortality (RR 6.26; I 2 : 96%) and severe COVID-19 (RR 3.93; I 2 : 63%) subgroups. A PCT ⩾0.5 ng/ml has an 88% sensitivity, 68% specificity, LR+ of 2.7, LR- of 0.2, and an AUC of 0.88. An elevated D-dimer was associated with an increased composite poor outcome [RR 2.93 (2.14, 4.01), p < 0.001; I 2 : 77%], including its mortality (RR 4.15; I 2 : 83%) and severe COVID-19 (RR 2.42; I 2 : 58%) subgroups. A D-dimer >0.5 mg/L has a 58% sensitivity, 69% specificity, LR+ of 1.8, LR- of 0.6, and an AUC of 0.69. Patients with a composite poor outcome had a higher serum ferritin with a standardized mean difference of 0.90 (0.64, 1.15), p < 0.0001; I 2 : 76%. Conclusion: This meta-analysis showed that an elevated serum CRP, PCT, D-dimer, and ferritin were associated with a poor outcome in COVID-19. The reviews of this paper are available via the supplemental material section.

Objective: To investigate the association between hypertension and outcome in patients with Coronavirus Disease 2019 (COVID-19) pneumonia. Methods: We performed a systematic literature search from several databases on studies that assess hypertension and outcome in COVID-19. Composite of poor outcome, comprising of mortality, severe COVID-19, acute respiratory distress syndrome (ARDS), need for intensive care unit (ICU) care and disease progression were the outcomes of interest. Results: A total of 6560 patients were pooled from 30 studies. Hypertension was associated with increased composite poor outcome (risk ratio (RR) 2.11 (95% confidence interval (CI) 1.85, 2.40), p < 0.001; I 2 , 44%) and its sub-group, including mortality (RR 2.21 (1.74, 2.81), p < 0.001; I 2 , 66%), severe COVID-19 (RR 2.04 (1.69, 2.47), p < 0.001; I 2 31%), ARDS (RR 1.64 (1.11, 2.43), p = 0.01; I 2 ,0%, p = 0.35), ICU care (RR 2.11 (1.34, 3.33), p = 0.001; I 2 18%, p = 0.30), and disease progression (RR 3.01 (1.51, 5.99), p = 0.002; I 2 0%, p = 0.55). Meta-regression analysis showed that gender ( p = 0.013) was a covariate that affects the association. The association was stronger in studies with a percentage of males < 55% compared to ⩾ 55% (RR 2.32 v. RR 1.79). Conclusion: Hypertension was associated with increased composite poor outcome, including mortality, severe COVID-19, ARDS, need for ICU care and disease progression in patients with COVID-19.

OBJECTIVE: To assess the number of adult critical care beds in Asian countries and regions in relation to population size. DESIGN: Cross-sectional observational study. SETTING: Twenty-three Asian countries and regions, covering 92.1% of the continent's population. PARTICIPANTS: Ten low-income and lower-middle-income economies, five upper-middle-income economies, and eight high-income economies according to the World Bank classification. INTERVENTIONS: Data closest to 2017 on critical care beds, including ICU and intermediate care unit beds, were obtained through multiple means, including government sources, national critical care societies, colleges, or registries, personal contacts, and extrapolation of data. MEASUREMENTS AND MAIN RESULTS: Cumulatively, there were 3.6 critical care beds per 100,000 population. The median number of critical care beds per 100,000 population per country and region was significantly lower in low- and lower-middle-income economies (2.3; interquartile range, 1.4-2.7) than in upper-middle-income economies (4.6; interquartile range, 3.5-15.9) and high-income economies (12.3; interquartile range, 8.1-20.8) (p = 0.001), with a large variation even across countries and regions of the same World Bank income classification. This number was independently predicted by the World Bank income classification on multivariable analysis, and significantly correlated with the number of acute hospital beds per 100,000 population (r = 0.19; p = 0.047), the universal health coverage service coverage index (r = 0.35; p = 0.003), and the Human Development Index (r = 0.40; p = 0.001) on univariable analysis. CONCLUSIONS: Critical care bed capacity varies widely across Asia and is significantly lower in low- and lower-middle-income than in upper-middle-income and high-income countries and regions.

Despite high rates of exposure, only 5-10% of people infected with Mycobacterium tuberculosis will develop active tuberculosis (TB) disease, suggesting a significant role for genetic variation in the human immune response to this infection. Here, we studied TB association and expression of 18 genes involved in the Toll-like receptor (TLR) pathways. Initially, we genotyped 149 sequence polymorphisms in 375 pulmonary TB patients and 387 controls from Indonesia. We found that four polymorphisms in the TLR8 gene on chromosome X showed evidence of association with TB susceptibility in males, including a non-synonymous polymorphism rs3764880 (Met1Val; P = 0.007, odds ratio (OR) = 1.8, 95% c.i. = 1.2-2.7). We genotyped these four TLR8 polymorphisms in an independent collection of 1,837 pulmonary TB patients and 1,779 controls from Russia and again found evidence of association in males (for rs3764880 P = 0.03, OR = 1.2, 95% c.i. = 1.02-1.48). Combined evidence for association is P = 1.2x10(-3)-6x10(-4). In addition, a quantitative PCR analysis indicated that TLR8 transcript levels are significantly up-regulated in patients during the acute phase of disease (P = 9.36x10(-5)), relative to baseline levels following successful chemotherapy. A marked increase in TLR8 protein expression was also observed directly in differentiated macrophages upon infection with M. bovis bacille Calmette-Guérin (BCG). Taken together, our results provide evidence, for the first time, of a role for the TLR8 gene in susceptibility to pulmonary TB across different populations.

BACKGROUND: Type 2 diabetes (DM) is a strong risk factor for tuberculosis (TB) and is associated with a slower response to TB treatment and a higher mortality rate. Because lower concentrations of anti-TB drugs may be a contributing factor, we compared the pharmacokinetics of rifampicin in patients with TB, with and without DM. METHODS: Seventeen adult Indonesian patients with TB and DM and 17 age- and sex-matched patients with TB and without DM were included in the study during the continuation phase of TB treatment. All patients received 450 mg of rifampicin (10 mg/kg) and 600 mg of isoniazid 3 times weekly. Steady-state plasma concentrations of rifampicin and its metabolite desacetylrifampicin were assessed at 0, 2, 4, and 6 h after drug intake. RESULTS: Geometric means of rifampicin exposure (AUC(0-6 h)) were 12.3 mg x h/L (95% confidence interval [CI], 8.0-24.2) in patients with TB and DM, and 25.9 mg x h/L (95% CI, 21.4-40.2) in patients with TB only (P=.003). Similar differences were found for the maximum concentration of rifampicin. No significant differences in time to maximum concentration of rifampicin were observed. The AUC(0-6 h) of desacetylrifampicin was also much lower in patients with TB and DM versus patients with TB only (geometric mean, 0.60 vs. 3.2 mg x h/L; P=.001). Linear regression analysis revealed that higher body weight (P<.001), the presence of DM (P=.06), and plasma glucose concentration (P=.016) were correlated with exposure to rifampicin. CONCLUSION: Exposure (AUC(0-6 h)) to rifampicin was 53% lower in Indonesian patients with TB and DM, compared with patients with TB only. Patients with TB and DM who have a higher body weight may need a higher dose of rifampicin.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb), remains the leading cause of mortality from a single infectious agent. Each year around 9 million individuals newly develop active TB disease, and over 2 billion individuals are latently infected with M.tb worldwide, thus being at risk of developing TB reactivation disease later in life. The underlying mechanisms and pathways of protection against TB in humans, as well as the dynamics of the host response to M.tb infection, are incompletely understood. We carried out whole-genome expression profiling on a cohort of TB patients longitudinally sampled along 3 time-points: during active infection, during treatment, and after completion of curative treatment. We identified molecular signatures involving the upregulation of type-1 interferon (α/β) mediated signaling and chronic inflammation during active TB disease in an Indonesian population, in line with results from two recent studies in ethnically and epidemiologically different populations in Europe and South Africa. Expression profiles were captured in neutrophil-depleted blood samples, indicating a major contribution of lymphocytes and myeloid cells. Expression of type-1 interferon (α/β) genes mediated was also upregulated in the lungs of M.tb infected mice and in infected human macrophages. In patients, the regulated gene expression-signature normalized during treatment, including the type-1 interferon mediated signaling and a concurrent opposite regulation of interferon-gamma. Further analysis revealed IL15RA, UBE2L6 and GBP4 as molecules involved in the type-I interferon response in all three experimental models. Our data is highly suggestive that the innate immune type-I interferon signaling cascade could be used as a quantitative tool for monitoring active TB disease, and provide evidence that components of the patient's blood gene expression signature bear similarities to the pulmonary and macrophage response to mycobacterial infection.

OBJECTIVES: To investigate the safety and efficacy of durable polymer drug eluting stents (DES) and biodegradable polymer biolimus eluting stents (biolimus-ES). DESIGN: Network meta-analysis of randomised controlled trials. DATA SOURCES AND STUDY SELECTION: Medline, Google Scholar, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) database search for randomised controlled trials comparing at least two of durable polymer sirolimus eluting stents (sirolimus-ES) and paclitaxel eluting stents (paclitaxel-ES), newer durable polymer everolimus eluting stents (everolimus-ES), Endeavor and Resolute zotarolimus eluting stents (zotarolimus-ES), and biodegradable polymer biolimus-ES. PRIMARY OUTCOMES: Safety (death, myocardial infarction, definite or probable stent thrombosis) and efficacy (target lesion and target vessel revascularisation) assessed at up to one year and beyond. RESULTS: 60 randomised controlled trials were compared involving 63,242 patients with stable coronary artery disease or acute coronary syndrome treated with a DES. At one year, there were no differences in mortality among devices. Resolute and Endeavor zotarolimus-ES, everolimus-ES, and sirolimus-ES, but not biodegradable polymer biolimus-ES, were associated with significantly reduced odds of myocardial infarction (by 29-34%) compared with paclitaxel-ES. Compared with everolimus-ES, biodegradable polymer biolimus-ES were associated with significantly increased odds of myocardial infarction (by 29%), while Endeavor zotarolimus-ES and paclitaxel-ES were associated with significantly increased odds of stent thrombosis. All investigated DES were similar with regards to efficacy endpoints, except for Endeavor zotarolimus-ES and paclitaxel-ES, which were associated with significantly increased the odds of target lesion and target vessel revascularisations compared with other devices. Direction of results beyond one year did not diverge from the findings for up to one year follow-up. Bayesian probability curves showed a gradient in the magnitude of effect, with everolimus-ES and Resolute zotarolimus-ES offering the highest safety profiles. CONCLUSIONS: The newer durable polymer everolimus-ES and Resolute zotarolimus-ES and the biodegradable polymer biolimus-ES maintain the efficacy of sirolimus-ES; however, for safety endpoints, differences become apparent, with everolimus-ES and Resolute zotarolimus-ES emerging as the safest stents to date.

Objectives To review the current knowledge about tuberculosis (TB) and diabetes, assessing the implication of the global increase of diabetes for TB control and patient care. Methods Systematic literature review. Results Using public databases, it can be estimated that 12.6% (95% CI 9.2–17.3%) of new TB cases in the 10 countries with the highest TB burden will be attributable to TB in 2030, a relative increase of 25.5% compared to 2010. Diabetes is associated with a higher age and body weight among patients with TB, but probably not with a specific clinical presentation of TB. Rifampicin hampers glycemic control by increasing the metabolism of most oral antidiabetic drugs, while diabetes patients may have lower concentrations of anti-TB drugs. This might be one factor contributing to higher TB treatment failure rates. Conclusions The global epidemic of diabetes has implications for control and treatment of TB. Prospective studies are needed to improve prevention, early detection and treatment of concomitant diabetes and TB, especially in developing countries. Implications de l’augmentation mondiale du diabète dans la lutte antituberculeuse et les soins aux patients Objectifs: Passer en revue les connaissances actuelles sur la tuberculose et le diabète, évaluer l’implication de l’augmentation mondiale du diabète dans la lutte antituberculeuse et les soins aux patients. Méthodes: Revue systématique de la littérature. Résultats: Sur base des données publiques, on peut estimer que 12,6% [IC95%: 9,2 à 17,3%] des nouveaux cas de tuberculose dans les 10 pays avec la plus forte charge de tuberculose seront attribuables à la tuberculose en 2030, une augmentation relative de 25,5% par rapport à 2010. Le diabète est associéà l’âge plus avancé et au poids corporel chez les patients atteints de tuberculose, mais probablement pas avec une présentation clinique spécifique de tuberculose. La rifampicine entrave le contrôle glycémique en augmentant le métabolisme de la plupart des antidiabétiques oraux, alors que les patients diabétiques peuvent avoir de faibles concentrations de médicaments antituberculeux. Cela pourrait être un facteur contribuant à la hausse des taux d’échec du traitement de la tuberculose. Conclusions: L’épidémie mondiale de diabète a des implications pour le contrôle et le traitement de la tuberculose. Des études prospectives sont nécessaires pour améliorer la prévention, la détection précoce et le traitement du diabète et la tuberculose concomitante, en particulier dans les pays en développement. Implicaciones del aumento global de la diabetes para el control de la tuberculosis y el cuidado de los pacientes Objetivos: Revisar el conocimiento actual sobre la tuberculosis y la diabetes, evaluando las implicaciones del aumento global de diabetes sobre el control de la TB y el cuidado de los pacientes. Métodos: Revisión sistemática de literatura Resultados: Utilizando bases de datos públicas, se puede estimar que un 12.6% [95%IC 9.2-17.3%] de los nuevos casos de tuberculosis en los 10 países con la mayor carga mundial de tuberculosis podrán atribuirse a la TB en el 2030, un aumento relativo del 25.5% comparado con el 2010. La diabetes está asociada con una mayor edad y mayor peso corporal entre los pacientes de TB, pero probablemente no con una presentación clínica específica de la TB. La rifampicina interfiere con el control de la glucemia, aumentando el metabolismo de la mayoría de las medicinas anti-diabéticas, mientras que los pacientes con diabetes pueden tener concentraciones menores de medicación antituberculosa. Este podría ser un factor que contribuye a unas mayores tasas de fallo en el tratamiento de la TB. Conclusiones: La epidemia global de diabetes tiene implicaciones para el control y el tratamiento de la tuberculosis. Se requieren estudios prospectivos para mejorar la prevención, la detección temprana y el tratamiento de la diabetes y la tuberculosis concomitantes, especialmente en países en vías de desarrollo. The association between tuberculosis (TB) and diabetes mellitus (DM) was well known in the early 20th century, but somewhat forgotten in the second half of the 20th century with the advent of widely available treatment for both diseases. In the last decades, with the current global growth of diabetes, the link between TB and DM is re-emerging. The epidemic growth of DM especially occurs in developing countries, where TB is highly endemic. As a result, DM and TB will increasingly present together, and this calls for renewed interest in this topic. Several questions can be asked. First, what is the effect of DM on the TB epidemic, and what projections can be made in light of the global emergence of DM? Second, what is the effect of DM on the clinical presentation of TB? Finally, what is known about combined treatment of DM and TB? In this review, we discuss these various aspects of the interaction between DM and TB. Data for this review were identified by searches of PubMed combining ‘Tuberculosis’ and ‘Diabetes Mellitus’ as free text and MeSH terms, combined with other terms including ‘cohort’, ‘risk factors’, ‘odds ratio’, ‘case control’, ‘cohort study’, ‘therapy’, ‘treatment’, ‘antituberculous’. We systematically checked full text papers referenced in retrieved articles. We also obtained data made available by public databases [http://www.who.int/tb/publications/global_report/2009 for TB and http://www.diabetesatlas.org (accessed 23 November 2009) for prevalence of DM] to calculate the current proportion of patients with TB attributable to DM in different countries and make predictions about the future. Studies from different parts of the world have shown that 5–30% of patients with TB present with concomitant DM (Pablos-Mendez et al. 1997, Feleke et al. 1999; Ponce-de-Leon et al. 2004; Wang et al. 2005; Alisjahbana et al. 2006; Singla et al. 2006) and available evidence indicates that DM acts as risk factor for development of TB. Data from the 1930s have shown that patients with DM had a threefold to fourfold increased risk of developing TB (Root 1934; Boucot et al. 1952). More recent studies have confirmed this association (Mugusi et al. 1990; Kim et al. 1995; Ponce-de-Leon et al. 2004; Alisjahbana et al. 2006, Balde et al. 2006; Coker et al. 2006; Perez et al. 2006; Shetty et al. 2006). In 2008, a meta-analysis was performed, using 13 observational studies, which showed that people with DM had a 3.11 times higher risk of getting TB (95% CI 2.27–4.26) compared to people without DM (Jeon & Murray 2008). Furthermore, it appeared that young patients with diabetes are at higher risk of TB and that the relative risk is also higher in countries with a higher incidence of TB (Jeon & Murray 2008), meaning that a similar prevalence (%) of DM may contribute more to the TB epidemic in developing countries. HIV is by far the strongest risk factor for TB at an individual level, but DM may be more important at the population level. For example in India, a recent study estimated that DM accounts for 14.8% of pulmonary TB cases, while HIV accounts for 3.4% of cases (Stevenson et al. 2007). A recent study in California showed that the estimated risk of TB attributable to DM (25.2%) was equivalent to that attributable to HIV (25.5%) (Pablos-Mendez et al. 1997). Possible interactions between HIV and DM and their risk on TB remain to be determined. Only few studies specified whether TB patients with DM had type 1 or type 2 DM. Type 2 DM is more prevalent, but type 1 DM is associated with a higher risk of TB. Studies from Ethiopia and Tanzania showed that patients with type 1 DM had a threefold to fivefold higher risk of developing TB than patients with type 2 DM (Swai et al. 1990; Feleke et al. 1999). Long duration of illness and poor glucose control may increase the risk of TB (Banyai 1959; Swai et al. 1990). Type 2 DM among patients with TB is often unrecognized. A study in Tanzania found that among 34 TB patients with DM, 73% of DM was newly diagnosed (Mugusi et al. 1990). Also in a recent study from Indonesia, among 94 TB patients with DM, 61% of DM was newly diagnosed (Alisjahbana et al. 2007). The chance of finding TB in a patient with diabetes will depend on the incidence of TB in a particular setting. Also relevant is the capacity of the health system in a particular setting to diagnose DM at an early stage, as DM is a time-dependent risk factor for TB. Socio-economic and life style changes in the developing countries lead to an increase of DM, especially type 2 DM. Table 1 shows the contribution of DM to TB in ten countries with the highest number of new TB cases. The total number of people with DM worldwide is projected to rise from 285 million in 2010 to 439 million in 2030 (http://www.diabetesatlas.org), and similar to the situation now, an estimated 70% of patients with diabetes in 2030 will live in TB-endemic countries (WHO report 2009; http://www.diabetesatlas.org). As to TB, it is predicted that its incidence in most parts of the world will stabilize or drop in the coming decades (WHO report 2009). However, because of a rising prevalence of DM, the relative contribution of DM to the TB epidemic will increase. Assuming similar population growth and change in TB incidence across countries over time, the estimated proportion of TB attributable to DM in 2030 will be 12.6% (95% CI 9.2–17.3%), a relative increase of 25.5% compared to 2010 (see legend of Table 1 for calculations). The top-three countries for TB (India, China and Indonesia) will witness some of the largest effects of rising prevalence rates for DM (Table 1). In the 10 countries with the highest numbers of DM cases (http://www.diabetesatlas.org), the estimated proportion of new TB cases attributable to DM will be 11.4% (95% CI 8.3–15.6%) in 2010 and is predicted to be 14.1% (95% CI 10.3–19.3%) in 2030, a relative increase of 23.7%. In summary, both type 1 and type 2 DM are associated with an increased risk of TB and type 2 DM is often undiagnosed among patients with TB. Given its worldwide prevalence, DM may contribute significantly to the TB epidemic, and the problem will increase in the near future. Several researchers have addressed the question whether DM affects the clinical presentation of TB. First, there is no evidence that DM is preferentially associated with so-called ‘primary tuberculosis’, nor with ‘reactivation tuberculosis’ (Ponce-de-Leon et al. 2004). In one study, when DNA fingerprints of Mycobacterium tuberculosis isolates from DM and non-DM patients were compared, DM was equally found among clustered cases (which typically represent ‘primary tuberculosis’) and unique DNA-fingerprint patterns (which more likely represent ‘reactivation tuberculosis’). Second, published studies found no difference in terms of gender between diabetic and non-diabetic patients, as shown in Table 2. Third, DM does not appear to affect the clinical manifestation of TB. Several studies showed a similar occurrence of symptoms between diabetic and non-diabetic TB patients (Table 2). More sputum smear-negative cases were found among hospitalized TB patients with DM than in age- and sex-matched non-diabetic TB patients in Turkey (Bacakoglu et al. 2001), as in Indonesia (Alisjahbana et al. 2007). But in other studies (Singla et al. 2006;Restrepo et al. 2007; Dooley et al. 2009), more smear-positive cases were found. A retrospective study in Texas showed more sputum smear positive test results in diabetic TB patients than in non-diabetics (Restrepo et al. 2007). Fourth, studies about the effects of DM on the radiological appearance of TB generated conflicting results (Table 3). Finally, extra-pulmonary involvement was less common in diabetic TB patients than in non-diabetic TB patients (Bacakoglu et al. 2001; Nissapatorn et al. 2005; Balde et al. 2006; Restrepo et al. 2007; Dooley et al. 2009). Diabetic TB patients are usually 10–20 years older than those without DM (Table 2), as type 2 DM is associated with older age. In addition, compared to non-DM patients, TB patients with DM usually have a higher body weight before start of treatment, and even more after treatment. In a recent study from West Africa, 23% of TB-DM patients were obese (BMI > 30 kg/m2), compared with 3% of non-diabetic patients (OR: 10.1; 95% CI, 3.1–21.2) (Balde et al. 2006). In Indonesia, 53% of TB patients with DM weighed more than 50 kg before treatment started, compared to only 16.5% of non-diabetic patients (P < 0.01) (Alisjahbana et al. 2007). The higher body weight of TB patients with DM may have implications for the dosing of antituberculous treatment. In conclusion, based on the available literature, TB patients with DM are usually older and have higher body weight, but it remains uncertain whether DM affects clinical presentation of TB. Differences in patient selection and case definitions used for DM may explain some of the discrepancy between different studies. Almost all of the above-mentioned studies lack detail regarding the diagnosis, possible complications and regulation of DM. Below we will review the limited data, which are available about treatment of diabetes in patients with TB and treatment and outcome of TB in patients with diabetes. Many antidiabetic drugs are currently available. The most important ones are classified as insulin secretogogue (sulphonylureas and metiglinides), biguanide (metformin), thiazolidinediones (TZD) and insulin. Among them, sulphonylureas and TZDs are metabolized by cytochrome P450 (CYP) enzymes in the liver. Rifampicin is a very potent inducer of these enzymes (Venkatesan 1992, Burman et al. 2001; Niemi et al. 2003a). Plasma levels of several antidiabetic drugs are significantly lower when co-administered with rifampicin (Table 4). Isoniazid is an inhibitor (rather than an inducer) of some of the enzymes that are induced by rifampicin, most notably CYP2C9 that is relevant to the metabolism of sulphonylureas. However, the inductive effect of rifampicin generally outweighs the inhibitory effect of isoniazid on the same enzyme, so that the overall effect of isoniazid plus rifampicin probably is a decrease in the concentrations of other drugs (Venkatesan 1992). Nothing is known about the effect of rifampicin and INH on metabolism of insulin, but it is unlikely to be significant as insulin is mostly degraded in the liver by hydrolysis of disulphide connections between the A and B chains through the action of insulin degrading enzyme (IDE) (Duckworth et al. 1998). It is unlikely that other first-line TB drugs like pyrazinamide and ethambutol interact with any antidiabetic drugs, but fluoroquinolones, especially gatifloxacin, are associated with hyper- and et al. 2006). on the glucose levels be after start and of rifampicin in patients using oral antidiabetic drugs. of enzymes is in about 1 after rifampicin treatment and the in 2 after rifampicin et al. 2003a). which is not metabolized by rifampicin, might be a has a for type 2 DM et al. 2006) as it has several to control and does not lead to et al. is widely available and associated with less weight increase than other oral antidiabetic drugs. The of when it is combined with antituberculous drugs is that to of patients may effects et al. to and poor treatment In conclusion, rifampicin hampers glycemic for the of higher of sulphonylureas and This may not be and other drugs be As lack of in often the of insulin, may be a antidiabetic TB treatment, but this has not with tuberculosis TB treatment, of antituberculous drugs for 2 pyrazinamide and by drugs and for Rifampicin is the for TB treatment. action is and the of rifampicin is 10 body weight et al. which might be at the lower of the are probably more and treatment duration In most for patients 50 kg and for patients 50 that patients with diabetes are usually and more weight TB treatment, of especially in the of treatment, highly relevant for patients with diabetes. is antidiabetic drugs not affect the concentrations of antituberculous drugs (Venkatesan 1992). important question is whether DM affects TB treatment In the before insulin patients with type 1 DM in the world appeared to from pulmonary TB (Root the of insulin in this the risk of developing TB especially in and DM patients et al. 1952). TB often a and in patients with DM. Among 2010 patients with DM between and 53% and the 1 early studies not outcome with non-diabetic patients. of the antituberculous drugs, and isoniazid the of DM patients with TB More a number of studies have the effect of DM on outcome of TB treatment, as in Table The for after 2 of treatment was in diabetic than non-diabetic TB patients (Singla et al. 2006; Restrepo et al. Dooley et al. 2009). In studies that after of treatment, the of patients with were similar between in diabetic and non-diabetic TB patients et al. 2007; Dooley et al. 2009). A study in Indonesia also showed that DM is not a risk factor for positive after 2 of treatment (Alisjahbana et al. 2007). studies have outcome of treatment. In a of patients in patients with diabetes were more often than but no outcome was et al. In et al. 2009), patients with diabetes a which or treatment but no were no data were A study in found there was no significant difference of of patients with treatment failure et al. 2009), and a study from (Singla et al. 2006) found no difference in confirmed Finally, in a of patients with TB, patients with diabetes had a significantly higher of positive sputum at (Alisjahbana et al. 2007). In conclusion, studies the effect of DM on treatment outcome are to and few have used (Table studies with more are needed to DM to more TB treatment Several studies that diabetes is a risk factor for the in patient with TB et al. Dooley et al. 2009; Wang et al. 2009). studies showed that the risk of was times higher in TB patients with DM (Table In a recent report from was higher among TB patients with DM than among those without et al. 2009). DM has a effect on TB treatment, what be the possible to TB treatment and of tuberculosis are the most important risk for treatment failure and TB However, to TB treatment among patients with DM was similar or than among non-diabetic TB patients et al. 2005; Alisjahbana et al. and some studies have a higher of among TB patients with DM (Bacakoglu et al. 2001; et al. 2001; et al. 2008), have found the et al. Ponce-de-Leon et al. 2004; Singla et al. 2006). it is TB patients with DM might have a higher risk of with a possible may be that TB patients with DM have an with of However, studies have with conflicting results (Restrepo et al. et al. 2008). As a patients with diabetes might have lower concentrations of TB drugs, contributing to higher rates of treatment failure et al. et al. et al. study in TB-DM patients found that to rifampicin was lower in TB patients with DM compared to patients without DM the of treatment et al. 2006). However, in the same the of TB treatment, among TB patients with and without diabetes, not any difference in of TB drugs et al. The results of both studies may be because of increased body weight of patients with diabetes the studies are needed to DM patients with TB at risk for treatment failure and TB patients with DM, especially a higher of The relative risk of TB associated with DM similar across the but the public health implications of the association depend on the prevalence of TB in a specific the highest prevalence of DM is found in countries, the proportion of patients with diabetes developing TB in these will be and common or other will be more In other parts of the TB has a times higher with patients with diabetes an threefold higher risk of TB. In the proportion of patients with diabetes with TB will be In addition, in early and glycemic control of DM is more and this will probably increase the proportion of patients with diabetes with TB. and treatment of TB among patients with DM is especially relevant in TB-endemic countries et al. 2009). in some & this is no in most the of patients with DM for TB, the significant prevalence of DM among patients with TB of the incidence of it that patients with TB be for DM. However, it remains to be what and be used and often of patients with TB for DM and to be & 2009; et al. A review of the of and TB for people with DM has published (Jeon et The association of DM and TB is important in the light of epidemic of type 2 DM in TB-endemic DM is associated with higher age and body weight, but data regarding the effect of DM on clinical presentation are to treatment, rifampicin the metabolism of most oral antidiabetic drugs, glycemic control TB treatment. The and of for glucose control is when combined with TB drugs. the same time, TB treatment failure and may be common among patients with diabetes. However, these and the be data of combined treatment are and studies nor have compared treatment with or TB treatment. Finally, it to for TB in patients with DM and as this will have implications for control and treatment of both in developing countries. of on a will in a of both diseases. This is an important of DM, TB and HIV might be a but this has not in the current literature, which is mostly and contribute to the lack of We for more interest and studies clinical or which will to improve and treatment of concomitant DM and TB, especially in developing countries. We and for their is by a from the of and by the for of was also by a

Dengue viruses (DV), composed of four distinct serotypes (DV1 to DV4), cause 50 to 100 million infections annually. Durable homotypic immunity follows infection but may predispose to severe subsequent heterotypic infections, a risk conferred in part by the immune response itself. Antibody-dependent enhancement (ADE), a process best described in vitro, is epidemiologically linked to complicated DV infections, especially in Southeast Asia. Here we report for the first time the ADE phenomenon in primary human dendritic cells (DC), early targets of DV infection, and human cell lines bearing Fc receptors. We show that ADE is inversely correlated with surface expression of DC-SIGN (DC-specific intercellular adhesion molecule-3-grabbing nonintegrin) and requires Fc gamma receptor IIa (FcgammaRIIa). Mature DC exhibited ADE, whereas immature DC, expressing higher levels of DC-SIGN and similar FcgammaRIIa levels, did not undergo ADE. ADE results in increased intracellular de novo DV protein synthesis, increased viral RNA production and release, and increased infectivity of the supernatants in mature DC. Interestingly, tumor necrosis factor alpha and interleukin-6 (IL-6), but not IL-10 and gamma interferon, were released in the presence of dengue patient sera but generally only at enhancement titers, suggesting a signaling component of ADE. FcgammaRIIa inhibition with monoclonal antibodies abrogated ADE and associated downstream consequences. DV versatility in entry routes (FcgammaRIIa or DC-SIGN) in mature DC broadens target options and suggests additional ways for DC to contribute to the pathogenesis of severe DV infection. Studying the cellular targets of DV infection and their susceptibility to ADE will aid our understanding of complex disease and contribute to the field of vaccine development.

Kasus pernikahan usia dini banyak terjadi di berbagai penjuru dunia dengan berbagai latarbelakang. Telah menjadi perhatian komunitas internasional mengingat risiko yang timbul akibat pernikahan yang dipaksakan, hubungan seksual pada usia dini, kehamilan pada usia muda, dan infeksi penyakit menular seksual. Kemiskinan bukanlah satu-satunya faktor penting yang berperan dalam pernikahan usia dini. Hal lain yang perlu diperhatikan yaitu risiko komplikasi yang terjadi di saat kehamilan dan saat persalinan pada usia muda, sehingga berperan meningkatkan angka kematian ibu dan bayi. Selain itu, pernikahan di usia dini juga dapat menyebabkan gangguan perkembangan kepribadian dan menempatkan anak yang dilahirkan berisiko terhadap kejadian kekerasan dan keterlantaran. Masalah pernikahan usia dini ini merupakan kegagalan dalam perlindungan hak anak. Dengan demikian diharapkan semua pihak termasuk dokter anak, akan meningkatkan kepedulian dalam menghentikan praktek pernikahan usia dini

Rifampin is a key drug for tuberculosis (TB) treatment. The available data suggest that the currently applied 10-mg/kg of body weight dose of rifampin may be too low and that increasing the dose may shorten the treatment duration. A double-blind randomized phase II clinical trial was performed to investigate the effect of a higher dose of rifampin in terms of pharmacokinetics and tolerability. Fifty newly diagnosed adult Indonesian TB patients were randomized to receive a standard (450-mg, i.e., 10-mg/kg in Indonesian patients) or higher (600-mg) dose of rifampin in addition to other TB drugs. A full pharmacokinetic curve for rifampin, pyrazinamide, and ethambutol was recorded after 6 weeks of daily TB treatment. Tolerability was assessed during the 6-month treatment period. The geometric means of exposure to rifampin (area under the concentration-time curve from 0 to 24 h [AUC(0-24)]) were increased by 65% (P < 0.001) in the higher-dose group (79.7 mg.h/liter) compared to the standard-dose group (48.5 mg.h/liter). Maximum rifampin concentrations (C(max)) were 15.6 mg/liter versus 10.5 mg/liter (49% increase; P < 0.001). The percentage of patients for whom the rifampin C(max) was > or =8 mg/liter was 96% versus 79% (P = 0.094). The pharmacokinetics of pyrazinamide and ethambutol were similar in both groups. Mild (grade 1 or 2) hepatotoxicity was more common in the higher-dose group (46 versus 20%; P = 0.054), but no patient developed severe hepatotoxicity. Increasing the rifampin dose was associated with a more than dose-proportional increase in the mean AUC(0-24) and C(max) of rifampin without affecting the incidence of serious adverse effects. Follow-up studies are warranted to assess whether high-dose rifampin may enable shortening of TB treatment.

BACKGROUND: The long duration of the current tuberculosis (TB) treatment is demanding and warrants the development of new drugs. Moxifloxacin shows promising results and may be combined with rifampicin to shorten the duration of TB treatment. Rifampicin induces the phase II metabolic enzymes that are involved in the biotransformation of moxifloxacin. Therefore, the interaction between rifampicin and moxifloxacin should be investigated. PATIENTS AND METHODS: Nineteen Indonesian patients with pulmonary TB who were in the last month of their TB treatment completed a 1-arm, 2-period, fixed-order pharmacokinetic study. In phase 1 of the study, they received 400 mg of moxifloxacin every day for 5 days in addition to 450 mg of rifampicin and 600 mg of isoniazid 3 times per week. In phase 2 of the study, after a 1-month washout period, patients received moxifloxacin for another 5 days (without rifampicin and isoniazid). A 24-h pharmacokinetic curve for moxifloxacin was recorded on the last day of both study periods, and its pharmacokinetic parameters were evaluated for an interaction with rifampicin, using a bioequivalence approach. RESULTS: Coadministration of moxifloxacin with rifampicin and isoniazid resulted in an almost uniform decrease in moxifloxacin exposure (in 18 of 19 patients). The geometric means for the ratio of phase 1 area under the curve to phase 2 area under the curve and for the ratio of phase 1 peak plasma concentration to phase 2 peak plasma concentration were 0.69 (90% confidence interval, 0.65-0.74) and 0.68 (90% confidence interval, 0.64-0.73), respectively. The median time to reach peak plasma concentration for moxifloxacin was prolonged from 1 h to 2.5 h when combined with rifampicin and isoniazid (P=.003). CONCLUSIONS: Coadministration of moxifloxacin with intermittently administered rifampicin and isoniazid results in reduced moxifloxacin plasma concentrations, which is most likely the result of induced glucuronidation or sulphation by rifampicin. Further studies are warranted to evaluate the impact of the interaction on the outcome of TB treatment.

A prospective study of dengue fever (DF) and dengue hemorrhagic fever (DHF) was conducted in a cohort of adult volunteers from two textile factories located in West Java, Indonesia. Volunteers in the cohort were bled every three months and were actively followed for the occurrence of dengue (DEN) disease. The first two years of the study showed an incidence of symptomatic DEN disease of 18 cases per 1,000 person-years and an estimated asymptomatic/ mild infection rate of 56 cases per 1,000 person-years in areas of high disease transmission. In areas where no symptomatic cases were detected, the incidence of asymptomatic or mild infection was 8 cases per 1,000 person-years. Dengue-2 virus was the predominant serotype identified, but all four serotypes were detected among the cohort. Four cases of DHF and one case of dengue shock syndrome (DSS) were identified. Three of the four DHF cases were due to DEN-3 virus. The one DSS case occurred in the setting of a prior DEN-2 virus infection, followed by a secondary infection with DEN-1 virus. To our knowledge, this is the first report of a longitudinal cohort study of naturally acquired DF and DHF in adults.

Probiotics and synbiotics are used to treat chronic illnesses due to their roles in immune system modulation and anti-inflammatory response. They have been shown to reduce inflammation in a number of immune-related disorders, including systemic lupus erythematosus (SLE), human immunodeficiency virus (HIV), and chronic inflammatory skin conditions such as psoriasis and atopic dermatitis (AD). Akkermansia muciniphila (A. muciniphila) and Faecalibacterium prausnitzii (F. prausnitzii) are two different types of bacteria that play a significant part in this function. It has been established that Akkermansia and Faecalibacterium are abundant in normal populations and have protective benefits on digestive health while also enhancing the immune system, metabolism, and gut barrier of the host. They have the potential to be a therapeutic target in diseases connected to the microbiota, such as immunological disorders and cancer immunotherapy. There has not been a review of the anti-inflammatory effects of Akkermansia and Faecalibacterium, particularly in immunological diseases. In this review, we highlight the most recent scientific findings regarding A. muciniphila and F. prausnitzii as two significant gut microbiota for microbiome alterations and seek to provide cutting-edge insight in terms of microbiome-targeted therapies as promising preventive and therapeutic tools in immune-related diseases and cancer immunotherapy.

BACKGROUND: The WHO declared COVID-19 a pandemic on March 11th, 2020. This serious outbreak and the precipitously increasing numbers of deaths worldwide necessitated the urgent need to develop an effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. The development of COVID-19 vaccines has moved quickly. In this study, we assessed the efficacy, safety, and immunogenicity of an inactivated (SARS-CoV-2) vaccine. METHODS: We conducted a randomized, double-blind, placebo-controlled trial to evaluate the efficacy, immunogenicity, and safety of an inactivated SARS-CoV-2 vaccine and its lot-to-lot consistency. A total of 1620 healthy adults aged 18-59 years were randomly assigned to receive 2 injections of the trial vaccine or placebo on a day 0 and 14 schedule. This article was based on an interim report completed within 3 months following the last dose of study vaccine. The interim analysis includes safety and immunogenicity data for 540 participants in the immunogenicity subset and an efficacy analysis of the 1620 subjects. For the safety evaluation, solicited and unsolicited adverse events were collected after the first and second vaccination within 14 and 28 days, respectively. Blood samples were collected for an antibody assay before and 14 days following the second dose. RESULTS: Most of the adverse reactions were in the solicited category and were mild in severity. Pain at the injection site was the most frequently reported symptom. Antibody IgG titer determined by enzyme-linked immunosorbent assay was 97.48% for the seroconversion rate. Using a neutralization assay, the seroconversion rate was 87.15%. The efficacy in preventing symptomatic confirmed cases of COVID-19 occurring at least 14 days after the second dose of vaccine using an incidence rate was 65.30%. CONCLUSIONS: From the 3-month interim analysis, the vaccine exhibited a 65.30% efficacy at preventing COVID-19 illness with favorable safety and immunogenicity profiles.

Background: Abnormalities in hematologic, biochemical, and immunologic biomarkers have been shown to be associated with severity and mortality in Coronavirus Disease 2019 (COVID-19). Therefore, early evaluation and monitoring of both liver and kidney functions, as well as hematologic parameters, are pivotal to forecast the progression of COVID-19. Objectives: In this study, we performed a systematic review and meta-analysis to investigate the association between several complications, including acute kidney injury (AKI), acute liver injury (ALI), and coagulopathy, with poor outcomes in COVID-19. Design: Systematic review and meta-analysis Setting: Observational studies reporting AKI, ALI, and coagulopathy along with the outcomes of clinically validated death, severe COVID-19, or intensive care unit (ICU) care were included in this study. The exclusion criteria were abstract-only publications, review articles, commentaries, letters, case reports, non-English language articles, and studies that did not report key exposures or outcomes of interest. Patients: Adult patients diagnosed with COVID-19. Measurements: Data extracted included author, year, study design, age, sex, cardiovascular diseases, hypertension, diabetes mellitus, respiratory comorbidities, chronic kidney disease, mortality, severe COVID-19, and need for ICU care. Methods: We performed a systematic literature search from PubMed, SCOPUS, EuropePMC, and the Cochrane Central Database. AKI and ALI follow the definition of the included studies. Coagulopathy refers to the coagulopathy or disseminated intravascular coagulation defined in the included studies. The outcome of interest was a composite of mortality, need for ICU care, and severe COVID-19. We used random-effects models regardless of heterogeneity to calculate risk ratios (RRs) for dichotomous variables. Heterogeneity was assessed using I 2 . Random effects meta-regression was conducted for comorbidities and the analysis was performed for one covariate at a time. Results: There were 3615 patients from 15 studies. The mean Newcastle-Ottawa scale of the included studies was 7.3 ± 1.2. The AKI was associated with an increased the composite outcome (RR: 10.55 [7.68, 14.50], P &lt; .001; I 2 : 0%). Subgroup analysis showed that AKI was associated with increased mortality (RR: 13.38 [8.15, 21.95], P &lt; .001; I 2 : 24%), severe COVID-19 (RR: 8.12 [4.43, 14.86], P &lt; .001; I 2 : 0%), and the need for ICU care (RR: 5.90 [1.32, 26.35], P = .02; I 2 : 0%). The ALI was associated with increased mortality (RR: 4.02 [1.51, 10.68], P = .005; I 2 : 88%) in COVID-19. Mortality was higher in COVID-19 with coagulopathy (RR: 7.55 [3.24, 17.59], P &lt; .001; I 2 : 69%). The AKI was associated with the composite outcome and was not influenced by age ( P = .182), sex ( P = .104), hypertension ( P = .788), cardiovascular diseases ( P = .068), diabetes ( P = .097), respiratory comorbidity ( P = .762), and chronic kidney disease ( P = .77). Limitations: There are several limitations of this study. Many of these studies did not define the extent of AKI (grade), which may affect the outcome. Acute liver injury and coagulopathy were not defined in most of the studies. The definition of severe COVID-19 differed across studies. Several articles included in the study were published at preprint servers and are not yet peer-reviewed. Most of the studies were from China; thus, some patients might overlap across the reports. Most of the included studies were retrospective in design. Conclusions: This meta-analysis showed that the presence of AKI, ALI, and coagulopathy was associated with poor outcomes in patients with COVID-19.

INTRODUCTION: Blockage of the cerebral arteries due to thrombosis and embolism resulting in decreased blood flow to the brain, reduced oxygen supply to the brain, resulting in neuronal damage and causes astrocyte cells to secrete glial fibrillary acidic protein (GFAP). The objective of this study was to determine the correlation between GFAP levels serum and clinical outcome in patients with acute ischemic stroke. METHODS: This was observational with a cross-sectional design on acute ischemic stroke patients confirmed by CT scans and divided into large vessel occlusion and small-vessel occlusion. Clinical outcome was measured using the National Institutional Health Stroke Scale (NIHSS) tool. Statistical analysis uses Spearman's rank correlation test and Mann Whitney's test, significant if p < 0.05. RESULTS: After collecting 33 research subjects, we found 16 people with large vessel occlusion and 17 people with small vessel occlusion. Serum GFAP levels were 0.2-1.9 ng/mL, 9.1% with a mild neurological deficit, 45.45% were moderate neurological deficits, and 45.45% were severe neurological deficits. There was a significant positive correlation (r = 0.522; p = 0.002) between serum GFAP levels and the degree of neurological deficit in ischemic stroke patients. There was a statistically significant difference between serum GFAP levels in ischemic stroke patients with CT scan results of large artery occlusion compared to small artery occlusion (0.7 vs 0.4ng/mL; p = 0.001). CONCLUSION: There was a positive correlation between GFAP level serum and NIHSS score on acute ischemic stroke. The higher the value of GFAP serum level, the higher the value for NIHSS and correlated with stroke severity and the extent of brain damage in ischemic stroke patients.

Abstract Background The Ginkgo biloba special extract, EGb 761 ® has been widely used in the treatment of neuropsychiatric disorders, including Alzheimer’s disease (AD). Methods To guide clinical practice in the Asian region, the Asian Clinical Expert Group on Neurocognitive Disorders compiled evidence‐based consensus recommendations regarding the use of EGb 761 ® in neurocognitive disorders with/without cerebrovascular disease. Results Key randomized trials and robust meta‐analyses have demonstrated significant improvement in cognitive function, neuropsychiatric symptoms, activities of daily living (ADL) and quality of life with EGb 761 ® versus placebo in patients with mild‐to‐moderate dementia. In those with mild cognitive impairment (MCI), EGb 761 ® has also demonstrated significant symptomatic improvement versus placebo. World Federation of Societies of Biological Psychiatry guidelines list EGb 761 ® with the same strength of evidence as acetylcholinesterase inhibitors and N‐methyl‐D‐aspartate (NMDA) antagonists e.g. memantine (Grade 3 recommendation; Level B evidence). Only EGb 761 ® had Level B evidence in improving cognition, behaviour, and ADL in both AD and vascular dementia patients. Safety analyses show EGb 761 ® to have a positive risk‐benefit profile. While concerns have been raised regarding a possible increased bleeding risk, several randomized trials and two meta‐analyses have not supported this association. Conclusions The Expert Group foresee an important role for EGb 761 ® , used alone or as an add‐on therapy, in the treatment of MCI and dementias, particularly when patients do not derive benefit from acetylcholinesterase inhibitors or NMDA antagonists. EGb 761 ® should be used in alignment with local clinical practice guidelines.