Update in lean metabolic dysfunction-associated steatotic liver disease.

BACKGROUND: A new nomenclature consensus has emerged for liver diseases that were previously known as non-alcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated fatty liver disease (MAFLD). They are now defined as metabolic dysfunction-associated steatotic liver disease (MASLD), which includes cardiometabolic criteria in adults. This condition, extensively studied in obese or overweight patients, constitutes around 30% of the population, with a steady increase worldwide. Lean patients account for approximately 10%-15% of the MASLD population. However, the pathogenesis is complex and is not well understood. AIM: To systematically review the literature on the diagnosis, pathogenesis, characteristics, and prognosis in lean MASLD patients and provide an interpretation of these new criteria. METHODS: We conducted a comprehensive database search on PubMed and Google Scholar between January 2012 and September 2023, specifically focusing on lean NAFLD, MAFLD, or MASLD patients. We include original articles with patients aged 18 years or older, with a lean body mass index categorized according to the World Health Organization criteria, using a cutoff of 25 kg/m2 for the general population and 23 kg/m2 for the Asian population. RESULTS: We include 85 studies in our analysis. Our findings revealed that, for lean NAFLD patients, the prevalence rate varied widely, ranging from 3.8% to 34.1%. The precise pathogenesis mechanism remained elusive, with associations found in genetic variants, epigenetic modifications, and adaptative metabolic response. Common risk factors included metabolic syndrome, hypertension, and type 2 diabetes mellitus, but their prevalence varied based on the comparison group involving lean patients. Regarding non-invasive tools, Fibrosis-4 index outperformed the NAFLD fibrosis score in lean patients. Lifestyle modifications aided in reducing hepatic steatosis and improving cardiometabolic profiles, with some medications showing efficacy to a lesser extent. However, lean NAFLD patients exhibited a worse prognosis compared to the obese or overweight counterpart. CONCLUSION: MASLD is a complex disease comprising epigenetic, genetic, and metabolic factors in its pathogenesis. Results vary across populations, gender, and age. Limited data exists on clinical practice guidelines for lean patients. Future studies employing this new nomenclature can contribute to standardizing and generalizing results among lean patients with steatotic liver disease.

Association between early sexual initiation and sexually transmitted infections among Peruvian reproductive-age women.

Background: Sexually transmitted infections (STIs) are a serious public health problem worldwide, especially among reproductive-age women. The early sexual onset of sexual intercourse (EOSI) has been suggested as a risk factor, although there is no data at the national level. Objective: To evaluate the association between EOSI and STIs in Peruvian women of childbearing age. Methods: Analytical cross-sectional study with secondary data analyzes of the Peruvian Demographic and Family Health Survey 2018. The outcome was the presence of STIs in the last 12 months and the exposure variable was EOSI (age < 15 years at the time of their first sexual experience). To evaluate the association of interest, crude and adjusted prevalence ratios (aPRs) were calculated using generalized linear models with Poisson family and logarithmic link function. Results: We analyzed data from 31,028 women of childbearing age. The 11.3% reported having STIs in the last 12 months and 20.2% of the participants had an EOSI. After adjusting for potential confounders, we found that EOSI was associated with STIs (aPR: 1.27; 95% CI: 1.08-1.50; p = 0.005). When conducting stratified analysis by area of residence and number of sexual partners, this association was maintained in women living in urban areas (aPR: 1.36; 95% CI: 1.11-1.66; p = 0.003) those who did not report having a history of multiple sexual partners (aPR: 1.27; 95% CI: 1.08-1.51; p = 0.005), and those in the middle (aPR: 1.42; 95% CI: 1.03-1.97; p = 0.034) and highest (aPR: 2.12; 95% CI: 1.33-3.39; p = 0.002) wealth quintiles. Conclusion: Among reproductive-age women from Peru, EOSI was associated with STIs, especially in women living in urban areas, with no history of multiple sexual partners, and belonging to the middle to higher wealth index. The implementation of measures to prevent EOSI and fostering appropriate sexual health counseling for women with EOSI is advised.

Hypertension and Histopathology Severity of Non-Alcoholic Fatty Liver Disease Among Adults with Obesity: A Cross-Sectional Study.

Background: Cardiovascular diseases are responsible for the majority of deaths resulting from non-alcoholic fatty liver disease (NAFLD). NAFLD is associated with hypertension and this is a key predictor of severe liver outcomes and an indicator of nonspecific portal fibrosis. Aim: To assess the association between hypertension and NAFLD severity. Methods: We conducted a secondary analysis of data from Peruvian adults with obesity and NAFLD who attended a Peruvian bariatric center. The severity of NAFLD was assessed using the Fatty Liver Inhibition of Progression algorithm / Steatosis, Activity and Fibrosis score. Hypertension was determined by either being recorded in the medical records or if the patient had a systolic pressure ≥ 140 mmHg or diastolic pressure ≥ 90 mmHg. To evaluate the association of interest, we calculated crude and adjusted prevalence ratios (aPR) using Poisson generalized linear models with logarithmic link function and robust variances. For the multivariable models, we adjusted for age, sex, physical activity and smoking. Results: Our study included 234 participants. The prevalence of hypertension was 19.2%, while the prevalence of severe NAFLD was 46.2%. After adjusting for confounders, the prevalence of hypertension was found to be significantly higher in the severe NAFLD group compared to the non-severe group (aPR = 1.33; 95% CI: 1.03-1.74). When stratified by the presence of metabolic syndrome (MetS), the association remained significant only in the group without MetS (aPR = 1.80; 95% CI: 1.05-3.11). Conclusion: We found an association between hypertension and severe NAFLD in adults with obesity, particularly in those without MetS.

Efficacy of Liraglutide in Non-Diabetic Obese Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Objective: We systematically assessed the efficacy of liraglutide in non-diabetic obese adults. Methods: Six databases were searched up to July 2021 for randomized controlled trials (RCTs) assessing liraglutide versus placebo in obese adults. Primary outcomes were body weight and body mass index (BMI). Secondary outcomes were treatment-emergent adverse events (TEAEs), hypoglycemic episodes, HbA1c, and blood pressure. Effect measures were risk ratio (RR) or mean difference (MD) with their confidence interval (95%CI). Random-effects models and inverse variance meta-analyses were used. Quality of evidence was assessed using GRADE. Results: Twelve RCTs (n = 8249) were included. In comparison to placebo, liraglutide reduced body weight (MD −3.35 kg; 95%CI −4.65 to −2.05; p < 0.0001), and BMI (MD −1.45 kg/m2; 95%CI −1.98 to −0.91; p < 0.0001). Liraglutide did not reduce TEAEs (RR 1.08; 95%CI 0.92 to 1.27; p = 0.25), and Hb1Ac (MD −0.76%; 95%CI −2.24 to 0.72; p = 0.31). Furthermore, it did not increase hypoglycemic episodes (RR 2.01; 95%CI 0.37 to 11.02; p = 0.28). Finally, liraglutide reduced systolic blood pressure (MD −3.07 mmHg; 95%CI −3.66 to −2.48; p < 0.0001) and diastolic blood pressure (MD −1.01 mmHg; 95%CI −1.55 to −0.47; p = 0.0003). Seven RCTs had a high risk of bias. Subgroup analyses by length of treatment and doses had effects similar to the overall analyses. Quality of evidence was low or very low for most outcomes. Conclusions: In non-diabetic obese adults, liraglutide reduced body weight, BMI and blood pressure in comparison to placebo. Adverse events, Hb1Ac levels and hypoglycemic episodes were not different than placebo.

Awareness of primary immunodeficiency diseases at a national pediatric reference center in Peru.

OBJECTIVE: To investigate the level of awareness of primary immunodeficiency diseases among physicians working at Instituto Nacional de Salud del Niño. METHODS: Cross-sectional study including pediatric residents and pediatricians working at the Instituto Nacional de Salud del Niño during the study period (2017-2019). Physicians working at the immunology unit and surgery departments were excluded. Three aspects of awareness of primary immunodeficiency diseases were investigated: education, general knowledge, and diagnostic suspicion and actions taken in the face of suspicion. RESULTS: This sample comprised 83 physicians with a median age of 33 years. Most physicians were women (71.1%) and half were pediatric residents. During their undergraduate studies, 43.1% had taken primary immunodeficiency disease courses, and 39.2% had attended conferences on this topic. During their residency training, 25.9% had taken primary immunodeficiency disease courses, and 60.3% had participated in conferences on this topic. Among pediatricians, 50% had taken primary immunodeficiency disease courses, and 53.1% had attended conferences on this topic. Only 39.8% of physicians reported being familiar with the list of 10 warning signs developed by the Jeffrey Modell Foundation. More than half of physicians considered the lack of access to laboratory tests the major challenge in making diagnosis of primary immunodeficiency diseases. CONCLUSION: This study revealed limited awareness of primary immunodeficiency diseases among physicians working at Instituto Nacional de Salud del Niño. Although most physicians suspected primary immunodeficiency diseases in patients with a history of recurrent infections and frequent use of antibiotics, not all of them were familiar with the list of 10 warning signs proposed by the Jeffrey Modell Foundation, nor were they able to describe ancillary tests requested in suspected cases.

Manejo oportuno de púrpura trombocitopénica trombótica en paciente con lupus eritematoso sistémico: reporte de caso / Timely management of thrombotic thrombocytopenic purpura in a patient with systemic lupus erythematosus: case report

Introducción: La púrpura trombocitopénica trombótica puede presentarse en menos del 2 por ciento de los pacientes con lupus eritematoso sistémico. Esta asociación implica un aumento de la mortalidad y un periodo de remisión más prolongado. Objetivo: Se presenta el caso de paciente peruana que desarrolló esta asociación y presentó complicaciones relacionadas con shock séptico. Caso clínico: Paciente femenina, con antecedente de púrpura trombocitopénica inmunológica y lupus eritematoso sistémico, acudió a emergencia por presentar palidez cutánea generalizada, petequias en miembros inferiores y hematuria. Posteriormente, su estado de salud se complicó con un shock séptico y deterioro del nivel de conciencia. Por todo esto, es referida a un hospital de mayor complejidad y hace su ingreso a la unidad de cuidados intensivos. La clínica y los exámenes de laboratorio revelaron hallazgos compatibles con púrpura trombocitopénica trombótica (anemia grave, plaquetopenia, esquistositosis) y lupus eritematoso sistémico activo grave. Antes de ser referida, recibió pulsos de metilprednisona y prednisona. Ya en unidad de cuidados intensivos, se cambió a soporte ventilatorio y tratamiento antibiótico. Con el diagnóstico presuntivo de púrpura trombocitopénica trombótica, asociada a lupus eritematoso sistémico activo grave, se inició tratamiento oportuno con plasmaféresis, corticoterapia y ciclofosfamida. La paciente recuperó los niveles plaquetarios y el nivel óptimo de conciencia. Actualmente acude a controles. Conclusiones: La púrpura trombocitopénica trombótica es una emergencia hematológica con alta mortalidad en ausencia de tratamiento. Su reconocimiento oportuno, sin dosificación de la proteína ADAMTS13, en esta asociación poco frecuente con lupus eritematoso sistémico es importante en el buen pronóstico del paciente(AU)

Introduction: Thrombotic thrombocytopenic purpura may occur in less than 2 percent of patients with systemic lupus erythematosus. This association implies an increase in mortality and a longer remission period. Objective: We present the case of a Peruvian woman who developed this association, and complicating herself with septic shock. Clinical case: A female patient, with a history of immunological thrombocytopenic purpura and systemic lupus erythematosus, comes to the emergency room due to generalized skin pallor, lower limb petechiae and hematuria. Subsequently, her state of health gets complicated with a septic shock and deterioration of the level of consciousness. For all of this, she was referred to a hospital of greater complexity and makes admission to an intensive care unit. Clinical and laboratory tests revealed findings compatible with thrombotic thrombocytopenic purpura (severe anemia, platelet disease, schistositosis) and severe active systemic lupus erythematosus. Before being referred, she received pulses of methylprednisone and prednisone. When already in the intensive care unit, it was changed to ventilatory support andantibiotic treatment. With the presumptive diagnosis of thrombotic thrombocytopenic purpura, associated with severe active systemic lupus erythematosus, a timely treatment was initiated with plasmapheresis, corticosteroids and cyclophosphamide. The patient recovered platelet levels and optimal level of consciousness. She is currently going to controls. Conclusions: Thrombotic thrombocytopenic purpura is a hematological emergency with high mortality in the absence of treatment. Its timely recognition, without dosing of ADAMTS13 protein, in this rare association with systemic lupus erythematosus is important in the good prognosis of the patient(AU)

Vasoactive Agents for the Management of Acute Variceal Bleeding: A Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: Vasoactive agents with endoscopic therapy are used to treat acute variceal bleeding (AVB). There are two main groups of vasoactive agents: terlipressin and vasopressin (T-V), and octreotide and somatostatin (O-S). However, the benefit/harm balance is unclear. Our aim was to assess the efficacy and safety of T-V versus O-S for the management of AVB. METHODS: We performed a systematic search for randomized controlled trials (RCTs) in PubMed, Scopus, and CENTRAL. Our main outcomes were mortality and adverse events. Secondary outcomes were bleeding control, rebleeding, blood transfusion, hospital stay. We evaluated the certainty of evidence using GRADE methodology. RESULTS: We included 21 RCTs. The risk of mortality (RR: 1.01; 95%CI: 0.83-1.22), bleeding control (RR: 0.96; 95%CI: 0.91-1.02; I 2 =53%), early rebleeding (RR: 0.91; 95%CI: 0.66-1.24: I 2 =0%), late rebleeding (RR: 0.94; 95 CI: 0.56-1.60; I 2 =0%), blood transfusion (MD: 0.04; 95%CI: -0.31-0.39; I 2 =68%) and hospital stay (MD: -1.06; 95%CI: -2.80-0.69; I 2 =0%) were similar between T-V and O-S groups. Only 15 studies reported adverse events, which were significantly higher in the T-V compared to the O-S group (RR 2.39; 95%CI: 1.58-3.63; I 2 =57%). The certainty of evidence was moderate for the main outcomes, and low or very low for others. CONCLUSIONS: In cirrhotic patients with AVB, those treated with T-V had similar mortality risk compared to O-S. However, the use of T-V showed an increased risk of adverse events compared to O-S.

Metodologías cuantitativas: Cálculo del tamaño de muestra con STATA y R / Quantitative methods: Sample size calculation with STATA and R

El cálculo de tamaño de muestra es un aspecto esencial del diseño de estudios cuantitativos. Un adecuado tamaño de muestra nos permite determinar cuál es la mínima cantidad de participantes necesarios para probar nuestra hipótesis de interés. De esta manera, podemos reducir costos, maximizar el uso de nuestros recursos de investigación y garantizar la factibilidad del estudio. Contradictoriamente, a pesar de su relevancia muy pocos investigadores dominan esta habilidad. Esta revisión tiene por objeto revisar los conceptos básicos para realizar un cálculo de tamaño de muestra y compartir códigos de Stata y R específicamente diseñados para facilitar estos cálculos.

The calculation of sample size is an essential aspect of the design of quantitative studies. An adequate sample size allows us to determine the minimum number of participants necessary to test our hypothesis of interest. Hence, we can reduce costs, maximize the use of our research resources and guarantee the feasibility of the study. Contradictorily, despite its relevance, very few researchers dominate this skill. This review aims to review the basics of sample size calculation and share Stata and R codes specifically designed to facilitate these calculations.