Comparison of Risk Factors for Developing Liver Fibrosis in Subjects With and Without Metabolic Syndrome: A Cohort Study.

Background: Metabolic syndrome (MS), a combination of diabetes, high blood pressure and obesity, is a well-known risk factor for developing non-alcoholic fatty liver disease, condition that can lead to serious liver damage such as liver fibrosis (LF), which is characterized by excessive deposition of connective tissue, progressing to cirrhosis and hepatocellular carcinoma. Nevertheless, subjects without MS may also develop LF. Non-invasive LF predictors based upon anthropometric and biochemical data have been reported. Aim: To compare anthropometric, genetic, and biochemical parameters in subjects with or without MS, and at risk for developing liver fibrosis. Methods: A randomized sample of 200 individuals was taken from the 2015 Nuevo León State Health Survey. Inclusion criteria were age ≥18 and a previously stored blood sample. According to the parameters obtained, subjects were classified as either with or without MS and their NAFLD fibrosis score was calculated considering variables such as age, BMI, glycemia, albumin, platelets, and AST/ALT ratio, to establish a high or low risk of LF. Comparisons of weight, age, BMI, blood glucose, total cholesterol, triglycerides, platelets, albumin, AST/ALT ratio, and HDL were made between groups. DNA was extracted from stored blood samples and genotyped, using q-PCR, according to variants in four genes related to: fatty acid (FA) metabolism (PNPLA3, rs738409), adipocyte differentiation (PLIN2, rs35568725), glucose metabolism (GCKR, rs1260326 and rs780094), and BMI (UCP2, rs659366). Statistical analysis was performed with SPSS v.22. A p value <0.05 was taken as level of significance. Results: A total of 134 subjects were included and divided into four groups (n): With MS+ high risk (35), With MS+ low risk (34), Without MS+ high risk (32), Without MS+ low risk (33). Table 1 shows the main significative findings. Higher age, low platelet count, and increased AST/ALT ratio, were significantly different in high risk subjects, independently of the presence of MS. No association between the polymorphisms and risk for fibrosis was found. In subjects at high risk for LF, statistical significance was found for high cholesterol blood levels (OR= 20.0 (95%CI 2.87;139.38) in carriers of the T allele of GCKR rs780094 polymorphism. Conclusion: Aging, thrombocytopenia, and increased transaminases, the last two indicators of liver disfunction, were found as important risk factors for LF in subjects without metabolic syndrome. None of the genetic variants analyzed resulted associated to risk of LF, although sample size could be a factor. GCKR rs780094 variant was found related with risk for hypercholesterolemia, even though dyslipidemia was not found associated with risk of LF in the present study. &nbsp

Do immunoglobulin G and immunoglobulin E anti- l -asparaginase antibodies have distinct implications in children with acute lymphoblastic leukemia? A cross-sectional study

Background: l-Asparaginase is essential in the treatment of childhood acute lymphoblastic leukemia. If immunoglobulin G anti-l-asparaginase antibodies develop, they can lead to faster plasma clearance and reduced efficiency as well as to hypersensitivity reactions, in which immunoglobulin E can also participate. This study investigated the presence of immunoglobulin G and immunoglobulin E anti-l-asparaginase antibodies and their clinical associations. Methods: Under 16-year-old patients at diagnosis of B-cell acute lymphoblastic leukemia confirmed by flow cytometry and treated with a uniform l-asparaginase and chemotherapy protocol were studied. Immunoglobulin G anti-l-asparaginase antibodies were measured using an enzyme-linked immunosorbent assay. Intradermal and prick skin testing was performed to establish the presence of specific immunoglobulin E anti-l-asparaginase antibodies in vivo. Statistical analysis was used to investigate associations of these antibodies with relevant clinical events and outcomes. Results: Fifty-one children were studied with 42 (82.35%) having anti-l-asparaginase antibodies. In this group immunoglobulin G antibodies alone were documented in 10 (23.8%) compared to immunoglobulin E alone in 18 (42.8%) patients. Immunoglobulin G together with immunoglobulin E were simultaneously present in 14 patients. Children who produced exclusively immunoglobulin G or no antibodies had a lower event-free survival (p-value = 0.024). Eighteen children (35.3%) relapsed with five of nine of this group who had negative skin tests suffering additional relapses (range: 2–4), compared to none of the nine children who relapsed who had positive skin tests (p-value < 0.001). Conclusion: Children with acute lymphoblastic leukemia and isolated immunoglobulin G anti-l-asparaginase antibodies had a higher relapse rate, whereas no additional relapses developed in children with immunoglobulin E anti-l-asparaginase antibodies after the first relapse

Long-term efficacy and safety of fostemsavir among subgroups of heavily treatment-experienced adults with HIV-1

Objectives: The aim of this study was to understand how demographic and treatment-related factors impact responses to fostemsavir-based regimens. Design: BRIGHTE is an ongoing phase 3 study evaluating twice-daily fostemsavir 600 mg and optimized background therapy (OBT) in heavily treatment-experienced individuals failing antiretroviral therapy with limited treatment options (Randomized Cohort 1-2 and Nonrandomized Cohort 0 fully active antiretroviral classes). Methods: Virologic response rates (HIV-1 RNA <40 copies/ml, Snapshot analysis) and CD4+ T-cell count increases in the Randomized Cohort were analysed by prespecified baseline characteristics (age, race, sex, region, HIV-1 RNA, CD4+ T-cell count) and viral susceptibility to OBT. Safety results were analysed by baseline characteristics for combined cohorts (post hoc). Results: In the Randomized Cohort, virologic response rates increased between Weeks 24 and 96 across most subgroups. Virologic response rates over time were most clearly associated with overall susceptibility scores for new OBT agents (OSS-new). CD4+ T-cell count increases were comparable across subgroups. Participants with baseline CD4+ T-cell counts less than 20 cells/μl had a mean increase of 240 cells/μl. In the safety population, more participants with baseline CD4+ T-cell counts less than 20 vs. at least 200 cells/μl had grade 3/4 adverse events [53/107 (50%) vs. 24/96 (25%)], serious adverse events [58/107 (54%) vs. 25/96 (26%)] and deaths [16/107 (15%) vs. 2/96 (2%)]. There were no safety differences by other subgroups. Conclusion: Week 96 results for BRIGHTE demonstrate comparable rates of virologic and immunologic response (Randomized Cohort) and safety (combined cohorts) across subgroups. OSS-new is an important consideration when constructing optimized antiretroviral regimens for heavily treatment-experienced individuals with limited remaining treatment options

Endodontic regenerative treatment for internal radicular resorption using bio-ceramic material, case report

The internal resorption of the internal radicular conduct is a process than can be both physiological or pathological, being the osteoclasts, odontoclasts and dentinoclast responsible for said process. 49-year-old female patient, refers orthodontic treatment at age 20, attends a dental check-up due to pain when chewing. Dental organ (DO) #11 was diagnosed with internal root resorption and symptomatic, suppurative apical periodontitis. Treatment started performing an endodontic access and taking a conductometry reading with an apical foramen locator, using a precision hybrid instrumentation technique and applying hypochlorite irrigation, the intra-canal was medicated with chemically pure calcium hydroxide for 7 days. The canal obturation was repaired infiltrating a bio-ceramic material (BIO-C Sealer) followed by the placement of the single cone using a vertical condensation technique

Guía Mexicana de Práctica Clínica de Inmunoterapia 2011

Existen varias guías internacionales para la práctica clínica de in- munoterapia, que aplican solo parcialmente en México. La primera guía mexicana de inmunoterapia data de 1998

Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children

We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-alpha 2 in 10 patients: IFN-alpha 2 only in three, IFN-alpha 2 plus IFN-omega in five, and IFN-alpha 2, IFN-omega plus IFN-beta in two; IFN-omega only in nine patients). Seven children (3.8%) had Abs neutralizing at least 10 ng/ml of one IFN, whereas the other 12 (6.6%) had Abs neutralizing only 100 pg/ml. The auto-Abs neutralized both unglycosylated and glycosylated IFNs. We also detected auto-Abs neutralizing 100 pg/ml IFN-alpha 2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-omega in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-alpha 2 only (OR [95% CI] = 67.6 [5.7-9,196.6]) than for auto-Abs neutralizing IFN-. only (OR [95% CI] = 2.6 [1.2-5.3]). ORs were also higher for auto-Abs neutralizing high concentrations (OR [95% CI] = 12.9 [4.6-35.9]) than for those neutralizing low concentrations (OR [95% CI] = 5.5 [3.1-9.6]) of IFN-omega and/or IFN-alpha 2

Centrality evolution of the charged-particle pseudorapidity density over a broad pseudorapidity range in Pb-Pb collisions at root s(NN)=2.76TeV

Peer reviewe