Acute ischemic stroke in tuberculous meningitis.

Background: The underlying mechanism for stroke in patients with tuberculous meningitis (TBM) remains unclear. This study aimed to investigate the predictors of acute ischemic stroke (AIS) in TBM and whether AIS mediates the relationship between inflammation markers and functional disability. Methods: TBM patients admitted to five hospitals between January 2011 and December 2021 were consecutively observed. Generalized linear mixed model and subgroup analyses were performed to investigate predictors of AIS in patients with and without vascular risk factors (VAFs). Mediation analyses were performed to explore the potential causal chain in which AIS may mediate the relationship between neuroimaging markers of inflammation and 90-day functional outcomes. Results: A total of 1,353 patients with TBM were included. The percentage rate of AIS within 30 days after admission was 20.4 (95% CI, 18.2-22.6). A multivariate analysis suggested that age ≥35 years (OR = 1.49; 95% CI, 1.06-2.09; P = 0.019), hypertension (OR = 3.56; 95% CI, 2.42-5.24; P < 0.001), diabetes (OR = 1.78; 95% CI, 1.11-2.86; P = 0.016), smoking (OR = 2.88; 95% CI, 1.68-4.95; P < 0.001), definite TBM (OR = 0.19; 95% CI, 0.06-0.42; P < 0.001), disease severity (OR = 2.11; 95% CI, 1.50-2.90; P = 0.056), meningeal enhancement (OR = 1.66; 95% CI, 1.19-2.31; P = 0.002), and hydrocephalus (OR = 2.98; 95% CI, 1.98-4.49; P < 0.001) were associated with AIS. Subgroup analyses indicated that disease severity (P for interaction = 0.003), tuberculoma (P for interaction = 0.008), and meningeal enhancement (P for interaction < 0.001) were significantly different in patients with and without VAFs. Mediation analyses revealed that the proportion of the association between neuroimaging markers of inflammation and functional disability mediated by AIS was 16.98% (95% CI, 7.82-35.12) for meningeal enhancement and 3.39% (95% CI, 1.22-6.91) for hydrocephalus. Conclusion: Neuroimaging markers of inflammation were predictors of AIS in TBM patients. AIS mediates < 20% of the association between inflammation and the functional outcome at 90 days. More attention should be paid to clinical therapies targeting inflammation and hydrocephalus to directly improve functional outcomes.

Efficacy of local hemostatic agents after endoscopic submucosal dissection: a meta-analysis.

INTRODUCTION: Topical hemostatic agents have been used to reduce bleeding rates after endoscopic submucosal dissection (ESD) for gastric cancer. However, to date, no review has summarized evidence on their efficacy. MATERIAL AND METHODS: PubMed, Embase, ScienceDirect, CENTRAL, and Google Scholar were searched for studies comparing bleeding rates after ESD with and without local hemostatic agents. RESULTS: Eleven studies were included. The studies used polyglycolic acid (PGA) sheets and fibrin glue, fibrin glue, oxidized regenerated cellulose, polysaccharide hemostatic powder, or polyethylene oxide adhesive. Meta-analysis revealed a statistically significant reduction in the risk of delayed bleeding with the use of PGA sheets & fibrin glue (six studies; RR: 0.35 95% CI: 0.20, 0.63 p = 0.0005). However, meta-analysis of two studies showed no difference in the risk of bleeding based on the use of fibrin glue (RR: 0.44 95% CI: 0.03, 7.17 p = 0.56). Scarce data were available for the remaining hemostatic agents. CONCLUSION: A large number of different hemostatic agents have been used to reduce the risk of bleeding after ESD for gastric cancer. Observational studies indicate that the use of PGA with fibrin glue could reduce the risk of bleeding after ESD. However, evidence for other agents was too scarce to derive conclusions.

Continuous Observation of Serum Total Magnesium Level in Patients Undergoing Hemodialysis.

BACKGROUND: Magnesium is an indispensable cation and plays an important physiological role in the body. Most previous studies focused on the single measurement of serum magnesium in patients undergoing hemodialysis. However, scant studies focused on continuous observations of serum magnesium levels. OBJECTIVE: To provide continuous observations of serum magnesium levels in patients on maintenance hemodialysis (MHD). The levels of magnesium in patients initiating hemodialysis are also recorded and analyzed in the present study. METHODS: In this retrospective study, we serially investigated the measurements of serum total magnesium in MHD patients and patients initiating hemodialysis. Our data were followed up for one year. We provided real-time update on the levels of serum magnesium in patients on hemodialysis. RESULTS: On January 1, 2019, a total of 356 end-stage renal disease patients were receiving hemodialysis in our hospital. On December 31, 2019, the number had increased to 383. We found that serum total magnesium levels were in the normal range before initiating hemodialysis. With the initiation of hemodialysis, the levels of serum total magnesium increased. In patients on MHD, hypermagnesemia was very common. Hypomagnesemia was rare when 0.5 mmol/L magnesium dialysate was used. We did not find proton pump inhibitor associated hypomagnesemia. CONCLUSION: We find that serum total magnesium levels are in the normal range before initiating hemodialysis. However, in patients on MHD, hypermagnesemia is common when 0.5 mmol/L magnesium dialysate is used. Hypomagnesemia is very rare. Hypomagnesemia in patients on MHD is an indicator of poor condition.

Association between the NFKB1-94ins/del ATTG polymorphism and cancer risk: an updated meta-analysis.

To assess the effect of the NFKB1 -94ins/del polymorphism on cancer, we conducted a meta-analysis based on 25 studies including 8,750 cases and 9,170 controls. Overall, the -94ins/del polymorphism was associated with cancer risk in the pooled analysis and in Asian population, whereas no association was observed in Caucasian population. Stratified analysis by subtypes of cancer showed that the -94ins/del polymorphism was associated with oral squamous cell carcinoma and ovarian cancer risk, but had no association with colorectal cancer, bladder cancer, and renal cell cancer. Our meta-analysis suggests the NFKB1 -94ins/del polymorphism affects cancer susceptibility, and the association is ethnic-specific.

Association of two variants in SMAD7 with the risk of congenital heart disease in the Han Chinese population.

SMAD7 is a general antagonist of TGF-ß signaling and has been found to be involved in cardiogenesis in mouse models, but its role in human congenital heart disease (CHD) has yet to be investigated. To examine if SMAD7 is associated with CHD, we conducted a case-control study in the Han Chinese population. Exon1 and exon4 of SMAD7, which encode the functional MH1 and MH2 domains, were directly sequenced in 1,201 sporadic CHD patients and 1,116 control individuals. A total of 18 sequence variations were identified. Two common variants rs3809922 and rs3809923 are located at exon4 of SMAD7, and were found in strong linkage disequilibrium with each other (r²â€Š= 0.93). We analyzed the association of these two loci with CHD in 3 independent subgroup case-control studies, and found that in some subgroups, rs3809922 and rs3809923 were significantly associated with CHD through genetic model analysis. In the combined data set, TT genotype in rs3809922 significantly increased the risk of CHD compared with CC and CT, while GG genotype in rs3809923 significantly increased the risk of CHD compared with CC and CG, particularly in the recessive model. In addition, haplotype analyses showed that haplotype TG significantly increased the risk of CHD (P = 6.9×10⁻6); this finding supports the results from the analyses based on single locus. According to data from the 1000 Genomes Project, the frequencies of the two risk alleles varied greatly between populations worldwide, which indicate the identified associations might have a population difference. To our knowledge, this is the first report that genetic variants in SMAD7 influence susceptibility to CHD risk.

Identification of functional mutations in GATA4 in patients with congenital heart disease.

Congenital heart disease (CHD) is one of the most prevalent developmental anomalies and the leading cause of noninfectious morbidity and mortality in newborns. Despite its prevalence and clinical significance, the etiology of CHD remains largely unknown. GATA4 is a highly conserved transcription factor that regulates a variety of physiological processes and has been extensively studied, particularly on its role in heart development. With the combination of TBX5 and MEF2C, GATA4 can reprogram postnatal fibroblasts into functional cardiomyocytes directly. In the past decade, a variety of GATA4 mutations were identified and these findings originally came from familial CHD pedigree studies. Given that familial and sporadic CHD cases allegedly share a basic genetic basis, we explore the GATA4 mutations in different types of CHD. In this study, via direct sequencing of the GATA4 coding region and exon-intron boundaries in 384 sporadic Chinese CHD patients, we identified 12 heterozygous non-synonymous mutations, among which 8 mutations were only found in CHD patients when compared with 957 controls. Six of these non-synonymous mutations have not been previously reported. Subsequent functional analyses revealed that the transcriptional activity, subcellular localization and DNA binding affinity of some mutant GATA4 proteins were significantly altered. Our results expand the spectrum of GATA4 mutations linked to cardiac defects. Together with the newly reported mutations, approximately 110 non-synonymous mutations have currently been identified in GATA4. Our future analysis will explore why the evolutionarily conserved GATA4 appears to be hypermutable.

Genetic polymorphisms of the TYMS gene are not associated with congenital cardiac septal defects in a Han Chinese population.

BACKGROUND: Clinical research indicates that periconceptional administration of folic acid can reduce the occurrence of congenital cardiac septal defects (CCSDs). The vital roles of folate exhibits in three ways: the unique methyl donor for DNA expression regulation, the de novo biosynthesis of purine and pyrimidine for DNA construction, and the serum homocysteine removal. Thymidylate synthase (TYMS) is the solo catalysis enzyme for the de novo synthesis of dTMP, which is the essential precursor of DNA biosynthesis and repair process. To examine the role of TYMS in Congenital Cardiac Septal Defects (CCSDs) risk, we investigated whether genetic polymorphisms in the TYMS gene associated with the CCSDs in a Han Chinese population. METHOD: Polymorphisms in the noncoding region of TYMS were identified via direct sequencing in 32 unrelated individuals composed of half CCSDs and half control subjects. Nine SNPs and two insertion/deletion polymorphisms were genotyped from two independent case-control studies involving a total of 529 CCSDs patients and 876 healthy control participants. The associations were examined by both single polymorphism and haplotype tests using logistic regression. RESULT: We found that TYMS polymorphisms were not related to the altered CCSDs risk, and even to the changed risk of VSDs subgroup, when tested in both studied groups separately or in combination. In the haplotype analysis, there were no haplotypes significantly associated with risks for CCSDs either. CONCLUSION: Our results show no association between common genetic polymorphisms of the regulatory region of the TYMS gene and CCSDs in the Han Chinese population.