Association of Pre-S/S and Polymerase Mutations with Acute and Chronic Hepatitis B Virus Infections in Patients from Rio de Janeiro,Brazil

Several hepatitis B virus (HBV)-related factors, including the viral load, genotype, and genomic mutations, have been linked to the development of liver diseases. Therefore, in this study we aimed to investigate the influence of HBV genetic variability during acute and chronic infection phases. A real-time nested PCR was used to detect HBV DNA in all samples (acute, n = 22; chronic, n = 49). All samples were sequenced for phylogenetic and mutation analyses. Genotype A, sub-genotype A1, was the most common genotype in the study population. A total of 190 mutations were found in the pre-S/S gene area and the acute profile revealed a greater number of nucleotide mutations (p < 0.05). However, both profiles contained nucleotide mutations linked to immune escape and an increased risk of hepatocellular carcinomas (acute, A7T; chronic, A7Q). Furthermore, 17 amino acid substitutions were identified in the viral polymerase region, including the drug resistance mutations lamivudine and entecavir (rtL180M), with statistically significant differences between the mutant and wild type strains. Owing to the natural occurrence of these mutations, it is important to screen for resistance mutations before beginning therapy.     

Association study of the I/D polymorphism and plasma angiotensin-converting enzyme (ACE) as risk factors for stent restenosis

The ID (insertion/deletion) polymorphism of the ACE (angiotensin-converting enzyme) gene controls plasma ACE levels. Both have been correlated with ISR (in-stent restenosis) in preliminary analyses, but not confirmed in larger studies. In the present study, baseline and 6-month quantitative coronary analysis were performed in 897 patients who had stent implantation and the ID polymorphism genotyped. Plasma ACE levels were measured in 848 patients (95%). Restenosis rates among genotypes were 31.2% DD, 25.5% ID and 28.8% II (not significant). Plasma ACE levels were significantly higher in restenotic patients compared with patients without restenosis (30.7+/-18.6 units/l compared with 22.8+/-12.8 units/l; P=0.0001) and a strong independent predictor of ISR [OR (odds ratio)=3.70; 95% CI (confidence interval), 2.40-5.71; P<0.0001], except in diabetics. In the subgroup of diabetics and patients with AMI (acute myocardial infarction), the DD genotypes actually had a lower risk of ISR than the II genotypes (diabetics, OR=0.16; 95% CI, 0.04-0.69; P=0.014; and patients with AMI, OR=0.21; 95% CI, 0.061-0.749; P=0.016). After exclusion of diabetics and patients with AMI, ISR rates for genotypes in 632 patients were 31.7% DD, 24.3% ID and 17.6% II (P=0.02; DD compared with non-DD OR=1.57; 95% CI, 1.09-2.25). The association between the D allele and ISR observed in selected populations does not hold with a larger sample size. Other than sample size, clinical variables can modulate the association between ID polymorphism and ISR. Plasma ACE level is a risk factor for ISR, independently of the ID genotype.     

Multiple cerebral infarctions from nonbacterial thrombotic endocarditis mimicking cerebral vasculitis.

Primary vasculitis of the central nervous system (PVCNS) is an uncommon disorder that can present with a variety of symptoms, making diagnosis and management difficult. We describe a case of cerebral infarction that occurred from nonbacterial thrombotic endocarditis (NBTE) and presented with clinical and radiologic imaging features that suggested PVCNS. The patient was a 58-year-old woman with left hemiparesis, aphasia, and episodic confusion. Magnetic resonance imaging of the brain demonstrated multifocal lesions consistent with infarction involving both cerebral hemispheres, and cerebral angiography showed changes consistent with vasculitis. Although brain biopsy findings were normal, the patient was treated for presumed vasculitis with cyclophosphamide and prednisone. Four months later respiratory failure secondary to polymicrobial pneumonia and adult respiratory distress syndrome developed, and she died. Autopsy revealed multiple infarcts in the heart, lungs, right kidney, spleen, and brain. Multiple thrombotic platelet-fibrin vegetations consistent with NBTE were found on all cardiac valves. Examination of the brain revealed no evidence of active or healed vasculitis. Cerebral angiography may show findings that suggest vasculitis, but it is not diagnostic, as several other conditions may cause similar changes. Nonbacterial thrombotic endocarditis may cause multiple cerebral infarctions and can be difficult to distinguish from vasculitis, as specific diagnostic tests for PVCNS are lacking.     

Five year time course of celiac disease serology during gluten free diet: results of a community based “CD-Watch” program

Background

Little information is available on the effect of a follow-up strategy in celiac disease patients during gluten-free diet.

Aims

To assess 5 year time course of t-transglutaminase antibodies (t-TG) in celiac disease patients enrolled in a community based follow-up program.

Methods

Annual t-TG testing and periodical clinic visit in 2245 patients.

Results

Proportion of patients with negative t-TG progressively increased from 83% to 93% during the 5-year follow-up: poor adherence to gluten-free diet (HR 4.764), long duration of gluten-free diet (HR 0.929) and female gender (HR 1.472) were independently associated with serological outcome. In individual patients, 69% tested t-TG “persistently negative”, 1% “persistently positive” and 30% “intermittently negative or positive”. By applying mathematical modelling to t-TG conversion rates observed in this latter group at beginning and end of the follow-up program, the predicted proportion of t-TG negative population increased from 90% to 95% over 5 years.

Conclusions

Time-course of t-TG serology in the community fluctuates in 1/3 of celiac disease patients suggesting inconstant adherence to gluten-free diet and need of follow-up strategy. Periodical serological and clinical follow-up is a viable and efficacious strategy to promote adherence to gluten-free diet as inferred from time-course of t-TG serology.     

Correction to “Retrospective analysis of anti-inflammatory therapies during the first wave of COVID-19 at a community hospital”

Correction to: “Iglesias JI et al. Retrospective analysis of anti-inflammatory therapies during the first wave of COVID-19 at a community hospital. World J Crit Care Med 2021 Sep 9; 10(5): 244-259. DOI: 10.5492/wjccm.v10.i5.244. PMID: 34616660; PMCID: PMC8462025.” In this article, corrections were made to Tables.     

Platelet‐rich plasma counteracts detrimental effect of high‐glucose concentrations on mesenchymal stem cells from Bichat fat pad

Diabetic patients display increased risk of periodontitis and failure in bone augmentation procedures. Mesenchymal stem cells (MSCs) and platelet‐rich plasma (PRP) represent a relevant advantage in tissue repair process and regenerative medicine. We isolated MSCs from Bichat's buccal fat pad (BFP) and measured the effects of glucose and PRP on cell number and osteogenic differentiation potential. Cells were cultured in the presence of 5.5‐mM glucose (low glucose [LG]) or 25‐mM glucose (high glucose [HG]). BFP–MSC number was significantly lower when cells were cultured in HG compared with those in LG. Following osteogenic differentiation procedures, calcium accumulation, alkaline phosphatase activity, and expression of osteogenic markers were significantly lower in HG compared with LG. Exposure of BFP–MSC to PRP significantly increased cell number and osteogenic differentiation potential, reaching comparable levels in LG and in HG. Thus, high‐glucose concentrations impair BFP–MSC growth and osteogenic differentiation. However, these detrimental effects are largely counteracted by PRP.