Roberto Añez

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are potentially life-threatening type IV immune reactions characterized by systemic inflammation mediated by cytotoxic T lymphocytes resulting in epidermal detachment and extensive necrosis. Although infrequent, the main concern across the SJS/TEN spectrum is its mortality, morbidity and associated financial burden. To date, there are no definitive recommendations regarding optimal treatment regimens; therefore, early diagnosis, prompt withdrawal of the culprit drug, and interdisciplinary consultations are vital to avoid disease progression. It is hard to assess the efficacy of novel therapies when the “conventional”, well-founded therapies with corticosteroids and cyclosporine are still under investigation. However, optimal posology is still under debate, as well as possible combined therapies. Other drugs that have shown to have a possible beneficial effect, like etanercept and n-Acetylcysteine, are still under investigation, given the insufficient number of investigations and small samples. New pharmacological approaches have been proposed in the last decade to improve outcomes across the SJS/TEN spectrum. This review aims to analyze novel approaches for SJS/TEN and assess their efficacy and safety compared to currently available treatments.

Introduction. Inflammation, insulin resistance, and dyslipidemia are key pathophysiological mechanisms involved in atherosclerotic cardiovascular disease which may be quantified by the systemic immune-inflammation index (SII), the triglyceride-glucose index (TyG), and the lipid accumulation product (LAP), respectively. Objective. To compare the predictive capacity of the SII, TyG and LAP for coronary artery disease (CAD) severity. Methodology. A cross-sectional study was conducted on 73 patients with chronic CAD; cardiovascular risk factors, statin use and laboratory values were used. CAD severity was determined through assessment of angiographic features for the application of the SYNTAX score. The SII was calculated as absolute platelet count × (absolute neutrophil count / absolute lymphocyte count); while the TyG index was calculated using the formula: ln [triglycerides × fasting glucose] / 2, on a logarithmic scale; and LAP was calculated as waist circumference (cm) – 65 × triglycerides (mmol/L) for men; and waist circumference – 58 × triglycerides for women. Results. The average age was 59.5±7.7 years, with a predominance of men in the sample (50.7%; n = 37). Of the indices evaluated, SII showed the greatest area under the curve (AUC) for the prediction of moderate to severe CAD (AUC: 0.73 CI95%: 0.61-0.85), a cut-off point off 378.4 with a sensitivity of 71.4% and specificity of 66.6%. In the multivariate analysis, subjects with an SII value ≥378.4 displayed an increased risk for higher CAD severity (OR: 7.56; CI95%: 1.62-35.28; P = 0.01). Conclusions. SII had a greater predictive capacity for moderate to severe CAD in comparison to TyG and LAP, demonstrating the importance of inflammation in chronic atherosclerotic disease.

Patients undergoing metabolic surgery have factors ranging from anatomo-surgical, endocrine metabolic, eating patterns and physical activity, mental health and psychological factors. Some of the latter can explain the possible pathophysiological neuroendocrine, metabolic, and adaptive mechanisms that cause the high prevalence of weight regain in postbariatric patients. Even metabolic surgery has proven to be effective in reducing excess weight in patients with obesity; some of them regain weight after this intervention. In this vein, several studies have been conducted to search factors and mechanisms involved in weight regain, to stablish strategies to manage this complication by combining metabolic surgery with either lifestyle changes, behavioral therapies, pharmacotherapy, endoscopic interventions, or finally, surgical revision. The aim of this revision is to describe certain aspects and mechanisms behind weight regain after metabolic surgery, along with preventive and therapeutic strategies for this complication.

Cardiovascular disease (CVD) is a global public health issue due to its high morbidity, mortality, and economic impact. The implementation of innovative therapeutic alternatives for CVD is urgently required. Specialized proresolving lipid mediators (SPMs) are bioactive compounds derived from ω-3 and ω-6 fatty acids, integrated into four families: Lipoxins, Resolvins, Protectins, and Maresins. SPMs have generated interest in recent years due to their ability to promote the resolution of inflammation associated with the pathogeneses of numerous illnesses, particularly CVD. Several preclinical studies in animal models have evidenced their ability to decrease the progression of atherosclerosis, intimal hyperplasia, and reperfusion injury via diverse mechanisms. Large-scale clinical trials are required to determine the effects of SPMs in humans. This review integrates the currently available knowledge of the therapeutic impact of SPMs in CVD from preclinical and clinical studies, along with the implicated molecular pathways. In vitro results have been promising, and as such, SPMs could soon represent a new therapeutic alternative for CVD.

Background. Visceral adiposity is related to insulin resistance (IR), a metabolic state considered as a risk factor for other cardiometabolic diseases. In that matter, mathematical indexes such as the visceral adiposity index (VAI) and the lipid accumulation product (LAP) could indirectly assess IR based on visceral adiposity. Objective. To evaluate the association and diagnostic accuracy of VAI and LAP to diagnose IR in the adult population of Maracaibo city. Methods. This is a cross-sectional descriptive study with multistage sampling. Receiver operating characteristic (ROC) curves were built to determine VAI and LAP cutoff points to predict IR. A set of logistic regression models was constructed according to sociodemographic, psychobiologic, and metabolic variables. Results. 1818 subjects were evaluated (51.4% women). The area under the curve (AUC) values for LAP and VAI were 0.689 (0.665–0.714) and 0.645 (0.619–0.670), respectively. Both indexes showed a higher IR risk in the upper tertile in bivariate analysis. However, in the logistic regression analysis for the IR risk, only the 2nd (OR: 1.91; 95% CI: 1.37–2.65; p < 0.01 ) and 3rd (OR: 5.40; 95% CI: 3.48–8.39; p < 0.01 ) LAP tertiles showed a significant increase. This behaviour was also observed after adjusting for hs-C-reactive protein (hs-CPR). Conclusion. Although both indexes show a low predictive capacity in individuals with IR in the Maracaibo city population, the LAP index was more strongly associated with IR.

Background: In 1980, Reuben Andresen observed that in certain individuals, obesity did not increase mortality, introducing an atypical phenotype called “healthy obese”. Other studies reported that 10-15 % of lean individuals presented insulin resistance, hyperglycemia and dyslipidemia. The objective of this study was to evaluate biochemical and clinical characteristics of metabolic phenotypes in Maracaibo city. Methods: A descriptive, cross-sectional sub-analysis of The Maracaibo City Metabolic Syndrome Prevalence Study, with a randomized multistage sampling was performed including 1226 non diabetic individuals from both sexes. For phenotype definition, the subjects were first classified according to their BMI into Normal-Weight, Overweight and Obese; then divided in metabolically healthy and unhealthy using a two-step analysis cluster being predictive variables: HOMA2-IR, HOMA2-βcell, triglycerides. To evaluate the relationship with coronary risk, a multiple logistic regression model was performed. Results: In the studied population, 43.9% (n=538) were healthy normal weight, 5.2% (n=64) unhealthy normal weight, 17.4% (n=217) healthy obese and 33.5% (n=411) unhealthy obese subjects. Atypical phenotypes, Metabolically Unhealthy Normal-Weight (MUNW) was more frequent in males (56.3%), whereas Metabolically Unhealthy Obese (MUO) was more frequent in females (51.3%). This phenotypes had a higher coronary event risk, especially for obese individuals (MHO: OR=1.85 CI95%: 1.11-3.09; p=0.02 and MUO: OR=2.09 CI95%: 1.34-3.28; p<0.01). Conclusion: Individuals with atypical metabolic phenotypes are common in Maracaibo city. Related factors may include insulin resistance, basal glucose, and triglycerides levels. Lastly, obese subjects show a higher coronary event risk even those with normal metabolic status.

Diabetes Mellitus (DM) is an inflammatory clinical entity with different mechanisms involved in its physiopathology. Among these, the dysfunction of the gut microbiota stands out. Currently, it is understood that lipid products derived from the gut microbiota are capable of interacting with cells from the immune system and have an immunomodulatory effect. In the presence of dysbiosis, the concentration of lipopolysaccharides (LPS) increases, favoring damage to the intestinal barrier. Furthermore, a pro-inflammatory environment prevails, and a state of insulin resistance and hyperglycemia is present. Conversely, during eubiosis, the production of short-chain fatty acids (SCFA) is fundamental for the maintenance of the integrity of the intestinal barrier as well as for immunogenic tolerance and appetite/satiety perception, leading to a protective effect. Additionally, it has been demonstrated that alterations or dysregulation of the gut microbiota can be reversed by modifying the eating habits of the patients or with the administration of prebiotics, probiotics, and symbiotics. Similarly, different studies have demonstrated that drugs like Metformin are capable of modifying the composition of the gut microbiota, promoting changes in the biosynthesis of LPS, and the metabolism of SCFA.