Hepatic steatosis, metabolic dysfunction and risk of mortality: findings from a multinational prospective cohort study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS) are implicated in the aetiology of non-communicable diseases. Our study aimed to evaluate associations between NAFLD and MetS with overall and cause-specific mortality. METHODS: We used dietary, lifestyle, anthropometric and metabolic biomarker data from a random subsample of 15,784 EPIC cohort participants. NAFLD was assessed using the fatty liver index (FLI) and MetS using the revised definition. Indices for metabolic dysfunction-associated fatty liver disease (MAFLD) were calculated. The individual associations of these indices with overall and cause-specific mortality were assessed using multivariable Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (95%CIs). As a subobjective, risk associations with adaptations of new classifications of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic and alcohol-related liver disease (MetALD) were also assessed. RESULTS: Among the 15,784 sub-cohort participants, a total of 1997 deaths occurred (835 due to cancer, 520 to CVD, 642 to other causes) over a median 15.6 (IQR, 12.3-17.1) years of follow-up. Compared to an FLI < 30, FLI ≥ 60 was associated with increased risks of overall mortality (HR = 1.44, 95%CI = 1.27-1.63), and deaths from cancer (HR = 1.32, 95%CI = 1.09-1.60), CVD (HR = 2.06, 95% CI = 1.61-2.63) or other causes (HR = 1.21, 95%CI = 0.97-1.51). Mortality risk associations were also elevated for individuals with MAFLD compared to those without. Individuals with MetS were at increased risk of all mortality endpoints, except cancer-specific mortality. MASLD and MetALD were associated with higher risk of overall mortality. CONCLUSIONS: Our findings based on a prospective cohort suggest that individuals with hepatic steatosis or metabolic dysfunction have a higher overall and cause-specific mortality risk.

Hypoglycemia during hyperosmolar hyperglycemic crises is associated with long-term mortality.

BACKGROUND: Previous research has indicated that hypoglycemia during hospitalization is a predictor of unfavorable outcomes in patients with diabetes. However, no studies have examined the long-term impact of hypoglycemia in adults admitted for hyperglycemic crises. The study was aimed to investigate the long-term implications of hypoglycemia during hyperosmolar hyperglycemic crises, particularly in terms of all-cause mortality. METHODS: This retrospective cohort study included 170 patients (82 men [48.2%], median age 72 years) admitted to a university hospital for hyperosmolar hyperglycemic crises, including pure hyperosmolar hyperglycemic states and hyperosmolar diabetic ketoacidoses. We separately investigated the prognostic significance of hypoglycemia on mortality during the initial intravenous insulin therapy phase and during the later subcutaneous insulin therapy phase, both during hospitalization and in the long term (median follow-up, 652 days; range 2-3460 days). RESULTS: Both hypoglycemia during the initial intravenous insulin therapy phase (observed in 26.5% of patients) and hypoglycemia during the later subcutaneous insulin therapy phase (observed in 52.7% of patients) were associated with long-term mortality. After adjusting for potential confounders, hypoglycemia during the initial intravenous insulin therapy phase remained associated with mortality (hazard ratio 2.10, 95% CI 1.27-3.46, p = 0.004). CONCLUSIONS: Hypoglycemia during hyperosmolar hyperglycemic crises is a marker of long-term mortality, especially when it occurs during the initial intravenous insulin therapy phase.

Metformin and Glucose Concentration as Limiting Factors in Retinal Pigment Epithelial Cell Viability and Proliferation.

Metformin is a well-established drug for the treatment of type 2 diabetes; however, the mechanism of action has not been well described and many aspects of how it truly acts are still unknown. Moreover, regarding in vitro experiments, the glycaemic status when metformin is used is generally not considered, which, added to the suprapharmacological drug concentrations that are commonly employed in research, has resulted in gaps of its mechanism of action. The aim of this study was to determine how glucose and metformin concentrations influence cell culture. Considering that diabetic retinopathy is one of the most common complications of diabetes, a retinal pigment epithelial cell line was selected, and cell viability and proliferation rates were measured at different glucose and metformin concentrations. As expected, glucose concentration by itself positively influenced cell proliferation rates. When the metformin was considered, results were conditioned, as well, by metformin concentration. This conditioning resulted in cell death when high concentrations of metformin were used under physiological concentrations of glucose, while this did not happen when clinically relevant concentrations of metformin were used independently of glucose status. Our study shows the importance of in vitro cell growth conditions when drug effects such as metformin's are being analysed.

Treatment of high-risk Hodgkin lymphoma with a modified Stanford V regimen in the AHOPCA: Substituting chemotherapy agents and hampered outcomes.

BACKGROUND/OBJECTIVES: High-risk Hodgkin lymphoma (HRHL) in children is curable with combined modality therapy. The Association of Pediatric Hematology-Oncology of Central America (AHOPCA) is a consortium of cancer centers from Central America. In 2004, AHOPCA implemented a guideline with a short course of chemotherapy (mStanfordV), strict diagnostics, and radiation guidelines, aimed at reducing abandonment and improving outcomes. METHODS: Newly diagnosed children less than 18 years of age with high-risk HL (Ann Arbor stages: IIB, IIIB, IV) from AHOPCA centers were staged with chest radiography and ultrasound or computed tomography. Therapy was a modified Stanford V (mStanfordV), substituting cyclophosphamide for mechlorethamine and involved field radiation. RESULTS: Of 219 patients with HRHL, 181 patients were eligible and evaluable; 146 (81%) were boys, 22% being less than 6 years; 43 were stage IIB, 84 IIIB, and 54 IV. Thirty-one (17%) abandoned therapy, 28 (15%) progressed, 30 (17%) relapsed, and eight (4%) died of toxicity. Radiation guidelines were not followed. Five-year abandonment-sensitive event-free survival and overall survival (AS-EFS, AS-OS ± SE) for the cohort were 46% ± 4% and 56% ± 4%; 5-year AS-OS for stages IIB, IIIB, and IV was 76% ± 7%, 59% ± 7%, and 35% ± 7% (p = .0006). CONCLUSION: Despite instituting a short treatment guideline, it did not improve the abandonment rate (17%) and did not achieve the reported outcomes of Stanford V. The cyclophosphamide dose used to replace merchlorethamine was inadequate. Despite strict guidelines, the radiation therapy application was inaccurate. Weekly chemotherapy may have adversely affected abandonment of therapy by increasing the burden of travel time. Based on these results, AHOPCA established a new abandonment strategy and a new guideline.

A cross-sectional study evaluating the prevalence and predictors of malnutrition among children and adolescents visiting an urban academic hospital in Nepal.

OBJECTIVE: To examine the prevalence of malnutrition among children and adolescents visiting Kanti Children's Hospital (KCH) and identify predictors associated with malnutrition. Results will guide the development of a newly established nutrition programme at KCH. DESIGN: This cross-sectional pilot study recruited children and adolescents over a 1-month period. Nutritional anthropometrics (height, weight and mid-upper arm circumference (MUAC)) and socio-demographic questionnaires were administered. Clinical data were abstracted from the medical chart. SETTING: KCH in Kathmandu, Nepal. PARTICIPANTS: 370 children and adolescents. RESULTS: Most participants were male (65·1 %); mean age was 3·9 years (±3·4 years). The prevalence of stunting was 25·9 %, wasting was 17·3 % and 24·0 % when classified by BMI-for-age Z-score or MUAC, respectively. Two percent of participants were overweight. Notably, 32·1 % of children ≥5 years were classified with wasting based on MUAC-for-age Z-score, which is higher than that observed in children <5 (20·2 %). Food insecurity was reported among 58·2 % of children with stunting and 34·0 % with wasting. Chronic medical conditions predicted stunting and wasting. The lowest level of wealth predicted stunting, while ethnicity predicted wasting. Ethnicity and education level predicted food insecurity. CONCLUSIONS: We found that the prevalence of stunting and wasting at KCH are higher than previously published studies in Nepal. Malnutrition persists beyond 5 years, and we identified several predictors of malnutrition. Increased provision of and access to clinical nutrition programmes is an essential need for KCH. Twinning programs that provide local clinicians with increased opportunities for education and mentorship of local staff remains a pressing need in Nepal.

Improving the Quality of the Delivery of Nutritional Care Among Children Undergoing Treatment for Cancer in a Low- and Middle-Income Country.

PURPOSE: International twinning programs have been well-established between institutions in childhood cancer and have led to pediatric cancer units in low- and middle-income countries (LMICs) adopting multidisciplinary forms of care. To advance nutritional care in LMICs, the International Initiative for Pediatrics and Nutrition (IIPAN) provided the structural framework and personnel for the delivery of nutritional care. We describe the impact of a newly established nutrition program on the delivery of nutritional care and nutrition-related clinical outcomes in children and adolescents undergoing treatment for cancer in Nicaragua and Honduras. METHODS: A prospective cohort (N = 126) collected clinical data over a 2-year period. Collection of IIPAN's nutritional services received during treatment and clinical data were abstracted from medical charts and registered in Research Electronic Data Capture (REDCap) database. Chi-square, ANOVA, and generalized linear mixed models were used; P < .05 was considered statistically significant. RESULTS: Nutritional assessments led to a higher number of patients receiving recommended standard of care. Children classified as underweight during treatment presented higher number of infections and toxicities, length of hospital stay, and days of treatment delays during treatment. Overall, from the start to end of treatment, 32.5% of patients improved nutritional status, 35.7% maintained it, and 17.5% worsened. On the basis of metrics, the cost per consultation was less than 4.80 US dollars (USD; Honduras) and 1.60 USD (Nicaragua). CONCLUSION: Integration and equitable access of the nutritional care process for all patients needs to be recognized as a component of the basic management in pediatric oncology care. IIPAN's nutritional program demonstrates that nutritional care is economical and feasible in a limited resource setting.

Circulating miRNA expression in long-standing type 1 diabetes mellitus.

Type 1 diabetes is a chronic autoimmune disease which results in inefficient regulation of glucose homeostasis and can lead to different vascular comorbidities through life. In this study we aimed to analyse the circulating miRNA expression profile of patients with type 1 diabetes, and with no other associated pathology. For this, fasting plasma was obtained from 85 subjects. Next generation sequencing analysis was firstly performed to identify miRNAs that were differentially expressed between groups (20 patients vs. 10 controls). hsa-miR-1-3p, hsa-miR-200b-3p, hsa-miR-9-5p, and hsa-miR-1200 expression was also measured by Taqman RT-PCR to validate the observed changes (34 patients vs. 21 controls). Finally, through a bioinformatic approach, the main pathways affected by the target genes of these miRNAs were studied. Among the studied miRNAs, hsa-miR-1-3p expression was found significantly increased in patients with type 1 diabetes compared to controls, and positively correlated with glycated haemoglobin levels. Additionally, by using a bioinformatic approach, we could observe that changes in hsa-miR-1-3p directly affect genes involved in vascular development and cardiovascular pathologies. Our results suggest that, circulating hsa-miR-1-3p in plasma, together with glycaemic control, could be used as prognostic biomarkers in type 1 diabetes, helping to prevent the development of vascular complications in these patients.

A long non-coding RNA that harbors a SNP associated with type 2 diabetes regulates the expression of TGM2 gene in pancreatic beta cells.

Introduction: Most of the disease-associated single nucleotide polymorphisms (SNPs) lie in non- coding regions of the human genome. Many of these variants have been predicted to impact the expression and function of long non-coding RNAs (lncRNA), but the contribution of these molecules to the development of complex diseases remains to be clarified. Methods: Here, we performed a genetic association study between a SNP located in a lncRNA known as LncTGM2 and the risk of developing type 2 diabetes (T2D), and analyzed its implication in disease pathogenesis at pancreatic beta cell level. Genetic association study was performed on human samples linking the rs2076380 polymorphism with T2D and glycemic traits. The pancreatic beta cell line EndoC-bH1 was employed for functional studies based on LncTGM2 silencing and overexpression experiments. Human pancreatic islets were used for eQTL analysis. Results: We have identified a genetic association between LncTGM2 and T2D risk. Functional characterization of the LncTGM2 revealed its implication in the transcriptional regulation of TGM2, coding for a transglutaminase. The T2Dassociated risk allele in LncTGM2 disrupts the secondary structure of this lncRNA, affecting its stability and the expression of TGM2 in pancreatic beta cells. Diminished LncTGM2 in human beta cells impairs glucose-stimulated insulin release. Conclusions: These findings provide novel information on the molecular mechanisms by which T2D-associated SNPs in lncRNAs may contribute to disease, paving the way for the development of new therapies based on the modulation of lncRNAs.

miR-24-3p and Body Mass Index as Type 2 Diabetes Risk Factors in Spanish Women 15 Years after Gestational Diabetes Mellitus Diagnosis.

Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance that is diagnosed for the first time during pregnancy. The objective of this study is to know the glucose tolerance status after 15 years of pregnancy in patients diagnosed with gestational diabetes and to assess the long-term effect of GDM on the circulating miRNA profile of these women. To answer these, 30 randomly selected women diagnosed with GDM during 2005-2006 were included in the study, and glucose tolerance was measured using the National Diabetes Data Group criteria. Additionally, four miRNAs (hsa-miR-1-3p, hsa-miR-24-3p, hsa-miR-329-3p, hsa-miR-543) were selected for their analysis in the plasma of women 15 years after the diagnosis of GDM. In our study we discovered that, fifteen years after the diagnosis of GDM, 50% of women have some degree of glucose intolerance directly related to body weight and body mass index during pregnancy. Dysglycemic women also showed a significantly increased level of circulating hsa-miR-24-3p. Thus, we can conclude that initial weight and BMI, together with circulating expression levels of hsa-miR-24-3p, could be good predictors of the future development of dysglycemia in women with a previous diagnosis of GDM.

Rhabdomyosarcoma in low- and middle-income countries: A report from the Asociacion de Hemato-oncología Pediatrica de Centro América (AHOPCA).

This report describes the results of an observational study dedicated to rhabdomyosarcoma developed by the Asociación de Hemato-oncología Pediatrica de Centro América (AHOPCA) between 2001 and 2018. Overall, 337 previously untreated patients < 18 years old were included in the analysis; 58% had unresected disease, and 19% were metastatic at diagnosis. With a median follow-up of 6.6 years, five-year event-free and overall survival rates were 30% and 33%, respectively. Local progression/relapse was the main cause of treatment failure.

Correlation between glucose measurement parameters of continuous flash monitoring and HbA1c. Real life experience in Asturias.

INTRODUCTION: Despite continuous glucose monitoring having been proven useful in patients with type 1 diabetes mellitus, A1C remains the gold standard for assessing disease management. MATERIAL AND METHODS: Descriptive, retrospective study which included 252 patients, 40.5% male, mean age 44.91±14.57 years, mean duration of diabetes 22.21±13.12 years, 88.1% on basal-bolus insulin therapy and 11.9% users of continuous subcutaneous insulin infusion. Glucose measurement, analytical and anthropometric data were obtained. RESULTS: The mean time in range was 60.18±15.60% and was associated with A1C after adjusting for age, gender, duration of diabetes, BMI, insulin regimen, %CV and time below range (ß: -0.548; p<0.01). The glucose management indicator (GMI) was 7.19±0.69% and was also associated with A1C (ß: 0.957; p<0.01) regardless of age, gender, duration of diabetes, BMI, insulin treatment, %CV and time in range. The average difference between A1C and GMI was 0.17±0.65% (-2.70-3.40%), being higher as A1C increased, in a linear and significant manner, without being influenced by the duration of diabetes or CV. CONCLUSIONS: Although we found a positive correlation between continuous glucose monitoring glucose measurement parameters and A1C, there is still not enough evidence to replace one parameter with another.

Didática de professores e habilidades cognoscitivas de crianças no início de idade escolar / Didáctica de maestros y habilidades cognoscitivas de niños en inicio de edad escolar / Teacher didactics and children's cognitive skills in early school age

RESUMEN El estudio analizó el vínculo entre la didáctica de maestros y las habilidades cognoscitivas de atención, memoria, velocidad y fluidez verbal en estudiantes de primeros grados de un colegio público en Cúcuta-Colombia. Se propuso un diseño exploratorio concurrente con análisis cualitativo y recolección de datos de fuente mixta, con muestreo intencional de 22 estudiantes y 4 maestras. Se evaluaron habilidades cognoscitivas mediante pruebas neuropsicológicas estandarizadas para Colombia y la didáctica fue explorada mediante entrevista semiestructurada siguiendo categorías de enseñanza, aprendizaje y técnicas. Las habilidades cognoscitivas se analizaron mediante estadística descriptiva y las entrevistas por análisis de triangulación categorial, concluyendo en los niños sobresaliente memoria-velocidad y disminuida atención y fluidez verbal, hallazgos sobresalientes vinculados a didácticas basadas en uso de fichas de aprendizaje, repetición, mecanización, mientras que los resultados inferiores se asociaron al uso de video y pasatiempos.

RESUMO O estudo analisou a relação entre a didática de professores e as habilidades cognoscitivas de atenção, memória, velocidade e fluidez verbal em estudantes de primeiros anos de uma escola pública em Cúcuta - Colômbia. Utilizou-se um roteiro exploratório junto com análises qualitativa e levantamento de dados de fonte mista, com amostra intencional de 22 estudantes e 4 professores. Avaliaram-se habilidades cognoscitivas mediante testes neuropsicológicos normatizados para Colômbia e a didática foi explorada mediante entrevista semiestruturada seguindo categorias de ensino, aprendizagem e técnicas. As habilidades cognoscitivas foram analisadas mediante estatística descritiva e as entrevistas por análise de triangulação categorial, concluindo-se nas crianças importantes memória-velocidade e diminuída atenção e fluidez verbal, achados marcantes vinculados a didáticas baseadas no uso de fichas de aprendizagem, repetição, mecanização, enquanto os resultados inferiores foram associados ao uso de vídeo e passatempos.

ABSTRACT The study analyzed the relationship between teacher didactics and cognitive skills of attention, memory, speed and verbal fluidity in first-year students of a public school in Cúcuta-Colombia. An exploratory script was used, together with qualitative analysis and mixed-source data collection, with an intentional sample of 22 students and 4 teachers. Cognitive abilities were evaluated through neuropsychological tests standardized for Colombia, and didactics were explored through semi-structured interviews following categories of teaching, learning and techniques. Cognitive skills were analyzed using descriptive statistics and interviews by categorical triangulation analysis, concluding in important children memory-speed and reduced attention and verbal fluidity, remarkable findings linked to didactics based on the use of learning sheets, repetition, mechanization, while lower results were associated with the use of video and hobbies.

Prevalence of diabetes mellitus in Spain in 2016 according to the Primary Care Clinical Database (BDCAP). / Prevalencia de diabetes mellitus en 2016 en España según la Base de Datos Clínicos de Atención Primaria (BDCAP).

The prevalence of type 2 diabetes mellitus is increasing worldwide, including in Spain, and this disease has become a major challenge for health care. In Spain, the computerization of medical records in primary care, in the Primary Care Clinical Database (BDCAP), has made possible the diagnoses of diabetes in a representative sample of the nation as a whole. This article analyzes the prevalence of diabetes recorded in this database and compares the data of the different autonomous communities. The prevalence of diabetes in Spain is 6.66% of the total population assigned to primary care in the National Health System, is higher in men than in women (7.27% vs. 6.06%), and increases with age up to 80 years. There are significant differences in the adjusted prevalence of diabetes between autonomous communities, with lower prevalence rates in North and Central Spain and higher rates in the South and East, as well as the islands. The lowest prevalence is seen in Castile and Leon (4.51%), and the highest in the Canary Islands (9.72%).

[Gender differences in the mortality of people with type 2 diabetes: Asturias Study 2018]. / Diferencias de género en la mortalidad de personas con diabetes tipo 2: Estudio Asturias 2018.

OBJECTIVE: To investigate the influence of gender on mortality according to the presence or absence of type 2 diabetes mellitus (DM2) and other cardiovascular risk factors in the Asturias Study cohort. METHOD: The Asturias Study (started in 1998) is an observational, prospective cohort study of a representative sample of a population of Asturias aged 30-75 years. The population was divided into groups according to the presence or absence of DM2 and according to gender to assess control of cardiovascular risk factors. In addition, aware of the vital status of the cohort 18 years after the beginning of the study, we analyzed differences in causes of mortality according to the previous categories. RESULTS: In 1998, 1034 people started the study, 561 women (54.25%) and 473 men (45.75%). Of these, 131 (12.66%) had diabetes (75 men and 56 women). The women with T2D presented a hazard ratio (HR) for total mortality of 1.64 (95% confidence interval [95%CI]: .97-2.77), which was 1.63 (95%CI: 1.07-2.50) for the men and, for cardiovascular mortality, 3.06 (95%CI: 1.44-6.47) for the females, versus 1.49 (95%CI: 0.64-3.46) for the males. The mortality rate for people with T2D of both sexes was higher than for people without T2D. CONCLUSIONS: Women with T2D have a risk more than three times higher than women without diabetes of dying from cardiovascular causes. We should implement treatment strategies in women with this condition.

Estimation of body fat mass using the CUN-BAE index and mortality risk by sex in the Asturias Study cohort. / Estimación de grasa corporal según ecuación CUN-BAE e IMC y riesgo de mortalidad por sexos en la cohorte del Estudio Asturias.

INTRODUCTION AND OBJECTIVES: In epidemiological studies, excess body fat (BF) has been associated with cardiometabolic risk factors, some types of cancer, and other causes of death. A new anthropometric method has been defined: The CUN-BAE index (University of Navarra Clinic-Body Fat Estimator), which is based on BMI, sex, and age. BMI and CUN-BAE index were used to assess their contribution to mortality risk from any cause in the Asturias Study cohort. MATERIAL AND METHODS: The Asturias study is a cohort study including 1.034 individuals aged 30-75years who participated in the first study phase (1998-1999). The study included a clinical survey, physical examination, and an oral glucose tolerance test. Vital status was determined in the cohort after 18years of follow-up. RESULTS: Two hundred and four subjects died: 93 females and 111 males (16.6% and 23.5% respectively men). Baseline values of both BMI and %BF suggesting obesity (BMI>30kg/m2 and CUN-BAE >25% in males and >35% in females) were found in most subjects. After adjusting for T2DM, HBP, CVD, and tobacco, the risk of all-cause and cardiovascular mortality was significantly higher as CUN-BAE increased, especially in females. CONCLUSIONS: The CUN-BAE equation is a useful tool, especially in females, to detect those who will have a greater risk of mortality, regardless of cardiovascular risk factors.

Nutritional status at diagnosis of cancer in children and adolescents in Guatemala and its relationship to socioeconomic disadvantage: A retrospective cohort study.

BACKGROUND: At least 80% of children with cancer live in low- and middle-income countries where the prevalence of malnutrition and socioeconomic disadvantage is high. We examined the relationship between nutritional status (NS), assessed by arm anthropometry, and socioeconomic status (SES) in children diagnosed with cancer at Unidad Nacional de Oncologia Pediatrica (UNOP) in Guatemala over a three-year period. METHOD: Patients aged 0 to 18 years of age diagnosed between January 2015 and December 2017 were included. NS was evaluated by mid-upper arm circumference, triceps skin fold thickness, and serum albumin level, and subjects were classified as adequately nourished, moderately depleted, and severely depleted nutritionally. SES was measured by a 15-item instrument developed at UNOP. RESULTS: Of 1365 patients diagnosed in the study period, 1060 (78%) fulfilled the eligibility criteria. Only 6% of patients were classified as medium to high, the remainder as medium-low to extremely low SES. Almost 47% were severely depleted at diagnosis, 19% moderately depleted, and 34% adequately nourished. SES was shown to be a determinant of NS; with progressively lower SES, the probability of a decline in NS increased by a factor of 1.04 points (P < 0.0001). Leukemia and lymphoma were also important predictors of nutritional depletion with odds ratios of 6.08 (95% CI, 1.74-28.28; P = 0.008) for leukemias and 4.83 (95% CI, 1.33-23.03; P = 0.03) for lymphomas. CONCLUSION: Both low SES and a diagnosis of leukemia or lymphoma are strong predictors of poor NS at diagnosis in children with cancer in Guatemala.