Corrigendum to: "Endoscopic duodenal mucosal resurfacing improves glycaemic and hepatic indices in type 2 diabetes: 6-month multicentre results" [JHEP Reports 5 (2019) 101041].

[This corrects the article DOI: 10.1016/j.jhepr.2019.10.006.].

Biphasic papillary (biphasic squamoid alveolar) renal cell carcinoma: a clinicopathologic and molecular study of 17 renal cell carcinomas including 10 papillary adenomas.

Biphasic papillary renal cell carcinoma (synonymous with biphasic squamoid alveolar renal cell carcinoma) is considered within the spectrum of papillary renal cell carcinoma (PRCC). With < 70 reported cases of biphasic PRCC, there is limited data on the pathologic spectrum and clinical course. Seventeen biphasic PRCC cases and 10 papillary adenomas with similar biphasic morphology were assessed. The mean age of the biphasic PRCC patients was 62 years (male to female ratio of 1.8:1), from 10 partial nephrectomies, 6 radical nephrectomies, and 1 biopsy. The mean tumor size was 3.6 cm (range 1.6-8 cm), with 24% showing multifocality. Fifteen out of 17 cases were limited to the kidney (one of which was staged as pT2a but had lung metastases at diagnosis) and 2/17 cases were staged as T3a. All tumors showed typical biphasic morphology with an extent of squamoid foci widely variable from 10 to 95%. Emperipolesis was identified in 88% of cases. All biphasic PRCC tested exhibited positivity for PAX8 (16/16), keratin 7 (17/17), EMA (15/15), AMACR (17/17), and vimentin (12/12) in both large and small cells; cyclin D1 was only expressed in the large cells (16/16). The 10 papillary adenomas showed a similar immunoprofile to biphasic PRCC. NGS testing performed on 13 biphasic PRCC revealed 4 (31%) harboring MET SNVs. In 1/5 (20%) papillary adenomas, a pathogenic MET SNV was identified. Biphasic PRCC is rare with a generally similar immunoprofile to "type 1" PRCC but with notable strong positivity for cyclin D1 in the large cell component. Although most of the biphasic PRCC cases were of small size, low stage, and with an indolent behavior, one patient had metastatic disease and one patient died of the disease.

[Numerical expression of the clinical course of the disease. Data management]. / Expresión numérica del curso clínico de la enfermedad. Manejo de datos.

Data management "behind the scenes" refers to collection, cleaning, imputation, and demarcation; and despite of being indispensable processes, they are usually neglected and thus, generate erroneous information. During the collection are errors: omission of covariates, deviation from the objective, and insufficient quality. The omission of covariates distorts the result attributed to the main manoeuvre. Deviation from the primary objective commonly occurs when the outcome is rare, delayed, or subjective and promotes substitution by non-equivalent surrogate variables. Moreover, insufficient quality occurs due to inadequate instruments, omission of the measurement procedure, or measurements out of context, such as attribution at the wrong time or equivalent. Furthermore, cleaning implies identifying erroneous, extreme, and missing values, which may or may not be imputed, depending on the percentage. The values of the manoeuvre or the outcome are never imputed, nor are patients eliminated due to a lack of values. Finally, the demarcation of each variable seeks to give it a clinical meaning about the outcome, for which a hierarchical sequence of criteria is followed: 1) previous clinical study, 2) expert agreement, 3) clinical judgment of the investigator/investigators, and 4) statistics. Acting without quality controls in data management frequently causes involuntary lies and confuses instead of clarifying.

El manejo de datos "tras bambalinas" se refiere a los procesos de recopilación, limpieza, imputación y demarcación; los cuales, aun siendo indispensables, usualmente suelen ser descuidados, por lo que generan información errónea. Durante la recopilación son errores: omisión de covariables, desvío del objetivo, y calidad insuficiente. La omisión de covariables distorsiona el resultado atribuido a la maniobra principal. El desvío del objetivo primario es común cuando el desenlace es raro, tardado o subjetivo y promueve la sustitución por variables subrogadas no equivalentes. Además, la calidad insuficiente, sucede por instrumentos inadecuados, omisión del procedimiento de medición, o medición fuera de contexto -como atribución a destiempo o equivalente-. Por otro lado, la limpieza implica identificar valores erróneos, extremos y faltantes, que podrán ser o no imputados, dependiendo del porcentaje se imputará comúnmente por la medida de resumen. Nunca se imputan los valores de la maniobra ni del desenlace, ni se eliminan pacientes por falta de valores. Finalmente, la demarcación de cada variable busca un significado clínico en referencia al desenlace, para ello se sigue una secuencia jerárquica de criterios: 1) estudio clínico previo, 2) acuerdo de expertos, 3) juicio clínico del investigador/investigadores y 4) estadística. Actuar sin controles de calidad en el manejo de datos provoca frecuentemente mentiras involuntarias y confunde en lugar de esclarecer.

[Risk management system to reduce COVID-19 infection in health personnelSistema de gestão de riscos para reduzir o contágio de COVID-19 em profissionais de saúde]. / Sistema de gestión de riesgos para reducir el contagio de COVID-19 en el personal de salud.

Objective: To assess the occupational factors associated with the occurrence of COVID-19 in health personnel who were exposed to different magnitudes of risk and who followed the United Nations crisis management policy for COVID-19. Methods: Cross-sectional survey conducted between April and May 2021. The low-risk group (LRG) were considered to be those who had minimal contact with patients; the medium-risk group (MRG) had contact with non-COVID-19 patients and did not perform instrumental airway intervention; and the high-risk group (HRG) were those who cared for COVID-19 patients and performed instrumental intervention with aerosol generation. Diagnosed COVID-19 disease and the presence of positive IgG antibodies for SARS-CoV-2 measured with Elecsys® anti-SARS-CoV-2 were considered as outcomes. Results: Outcome recorded in 43.8% of the LRG, versus 46.7% in the MRG (odds ratio [OR]: 1.125; 95% confidence interval [CI 95% ]: 0.896-1.414; p = 0.311), and 48.6% in the HRG (OR: 1,214; CI 95%: 0.964-1.530; p= 0.10). Conclusion: Belonging to the high-risk group and the medium-risk group, based on the degree of exposure to confirmed COVID-19 patients in the work area, was not associated with a higher occurrence of disease or seroconversion.

Objetivo: Avaliar os fatores ocupacionais associados à ocorrência de COVID-19 em profissionais de saúde expostos a diferentes níveis de risco utilizando a política de gestão de crises elaborada pelas Nações Unidas para a COVID-19. Métodos: Pesquisa transversal realizada entre abril e maio de 2021. O grupo de risco baixo (GRB) consistia em profissionais que tinham contato mínimo com os pacientes; o grupo de risco médio (GRM) incluía profissionais que tinham contato com pacientes sem COVID-19 e não realizavam intervenções instrumentais nas vias aéreas; e grupo de risco alto (GRA), profissionais que cuidavam de pacientes com COVID-19 e realizavam intervenções instrumentais com geração de aerossóis. Para estabelecer o desfecho, considerou-se a história de COVID-19 do profissional de saúde e a detecção de anticorpos IgG anti- SARS-CoV-2 por Elecsys® Anti-SARS-CoV-2. Resultados: A doença foi diagnosticada em 43,8% dos profissionais no GRB, 46,7% no GRM (razão de chances ajustada: 1,125; intervalo de confiança de 95% [IC95%]: 0,896-1,414; p = 0,311) e 48,6% no GRA (razão de chances: 1,214; IC95%: 0,964-1,530; p = 0,10). Conclusões: Pertencer ao GRM e ao GRA em função do nível de exposição a pacientes confirmados com COVID-19 no ambiente de trabalho não foi associado a um aumento da ocorrência da doença ou da soroconversão.

Sistema de gestión de riesgos para reducir el contagio de COVID-19 en el personal de salud

[RESUMEN]. Objetivo. Evaluar los factores laborales asociados con la ocurrencia de COVID-19 en el personal de salud expuesto a distinta magnitud de riesgo con el uso de la política de gestión de crisis de las Naciones Unidas para COVID-19. Métodos. Encuesta transversal realizada entre abril y mayo del 2021. Se consideraron como grupo de riesgo bajo (GRB) quienes tenían contacto mínimo con pacientes; de riesgo medio (GRM) a quienes tenían contacto con pacientes no-COVID-19 y no realizaban intervención instrumental de vías respiratorias; y de riesgo alto (GRA) a quienes atendían pacientes COVID-19 y realizaban intervención instrumental con generación de aerosoles. Se consideró como desenlace el antecedente de enfermedad diagnosticada de COVID-19 y la presencia de anticuerpos IgG positivos contra el SARS-CoV-2 medida con Elecsys® anti-SARS-CoV-2. Resultados. Desenlace en 43,8% en el GRB; 46,7% en el GRM (razón de momios [RM]: 1,125; intervalo de confianza de 95% [IC95%]: 0,896-1,414; p = 0,311); y 48,6% en el GRA (RM: 1,214; IC95%: 0,964-1,530; p = 0,10). Conclusión. Pertenecer al GRM y al GRA por el grado de exposición a pacientes confirmados de COVID-19 en el área de trabajo no se asoció con mayor ocurrencia de enfermedad o de seroconversión.

[ABSTRACT]. Objective. To document trends in inequity in homicide rates in Mexico for the period 2000–2021, at the state and national levels. Methods. An observational, longitudinal ecological study was conducted in which standardized homicide mortality rates were estimated, by municipality and sex. Municipalities were classified in five groups, accor- ding to the Social Lag Index. The absolute inequality gap was obtained, as well as differences between groups with very high and very low social lag, for each year of the study period. Results. In the 32 states, an increase was observed in the rate of death by homicide, with higher rates among men but a greater relative increase among women (+127.86% vs. +110.03%). The absolute gap between municipalities with very high and very low social lag narrowed in the period, due to higher homicide rates in municipalities with low social lag and a modest reduction in municipalities with very high social lag. Conclusions. In Mexico, between 2000 and 2021, the absolute gap in deaths by homicide between municipa- lities with very high and very low social lag declined due to higher homicide rates in municipalities with lower social lag. It is necessary to strengthen policies and actions aimed at addressing the social determinants of interpersonal violence.

[RESUMO]. Objetivo. Avaliar os fatores ocupacionais associados à ocorrência de COVID-19 em profissionais de saúde expostos a diferentes níveis de risco utilizando a política de gestão de crises elaborada pelas Nações Unidas para a COVID-19. Métodos. Pesquisa transversal realizada entre abril e maio de 2021. O grupo de risco baixo (GRB) consistia em profissionais que tinham contato mínimo com os pacientes; o grupo de risco médio (GRM) incluía profis- sionais que tinham contato com pacientes sem COVID-19 e não realizavam intervenções instrumentais nas vias aéreas; e grupo de risco alto (GRA), profissionais que cuidavam de pacientes com COVID-19 e realiza- vam intervenções instrumentais com geração de aerossóis. Para estabelecer o desfecho, considerou-se a história de COVID-19 do profissional de saúde e a detecção de anticorpos IgG anti- SARS-CoV-2 por Elecsys® Anti-SARS-CoV-2. Resultados. A doença foi diagnosticada em 43,8% dos profissionais no GRB, 46,7% no GRM (razão de chan- ces ajustada: 1,125; intervalo de confiança de 95% [IC95%]: 0,896-1,414; p = 0,311) e 48,6% no GRA (razão de chances: 1,214; IC95%: 0,964-1,530; p = 0,10). Conclusões. Pertencer ao GRM e ao GRA em função do nível de exposição a pacientes confirmados com COVID-19 no ambiente de trabalho não foi associado a um aumento da ocorrência da doença ou da soroconversão.

Diet Quality, Physical Activity, and Weight Changes and Their Association With 6-Year Risk of Metabolic Syndrome in Mexican Adults.

Background. Among lifestyle factors, obesity has been postulated as the most important risk factor for metabolic syndrome (MS). Lifestyle factors such as physical activity (PA), diet quality, and weight management are so closely related, it is not clear if the role of lifestyle factors is exclusively through its effect on weight, or if they contribute independently. Objective. To examine the effect of lifestyle factors such as diet quality, weight change, and leisure time PA on MS occurrence in lean and overweight/obese (OW/OB) adults over a 6-year period. Methods. This was a longitudinal analysis of data from adults participating in the Health Workers Cohort Study. Results. A total of 1046 participants were included; 37.2% of the OW/OB group and 16.2% of the lean participants developed MS. Becoming overweight had a hazard ratio (HR) of 3.06 for developing MS compared with remaining lean (95% CI = 1.98, 4.74). Going from OW/OB to lean was associated with lower risk of MS (HR = 0.41; 95% CI = 0.22, 0.79). Among OW/OB, becoming active was associated with lower risk (HR = 0.63; 95% CI = 0.42, 0.95) in comparison with an inactive pattern; diet quality was not associated with occurrence of MS. Conclusion. Weight change was the most relevant factor predicting MS over a 6-year period.

Risk Assessment of Dyslipidemias, Hyperglycemia, Hyperuricemia, and Hypertension Utilizing Self-Reported Body Silhouettes.

Objective: Self-reported body silhouette is an anthropometric instrument that has been utilized as a screening tool for underweight, overweight, obesity, and other abnormal anthropometric variables. Herein, we analyzed the risk associated with the self-reported body silhouette in the scope of dyslipidemias, hyperglycemia, hyperuricemia, and hypertension. Methods: Adult participants of the Health Workers Cohort Study enrolled between March 2004 and April 2006 were included. Then, risk analysis was performed considering dyslipidemias as serum triglycerides, high total cholesterol, high LDL-C, low HDL-C, hyperglycemia, hyperuricemia, and hypertension. Results: A total of 2,297 males and 5,003 females were analyzed. The median ages of the studied population was 39 (30-49) and 41 (31-50) years for males and females, respectively. Overall, there is a stepwise increase in the risk of presenting dyslipidemias, hyperglycemia, hyperuricemia, and hypertension as the self-reported body silhouette number increases, this tendency was observed in both males and females. Conclusion: Self-reported body silhouette is a useful risk assessment tool for dyslipidemias, hyperglycemia, hyperuricemia, and hypertension in Mexican adults. Applications of questioners containing this silhouette might be considered a valuable public health instrument due to their low cost, relative simplicity, and absence of specialized equipment, training, or respondent knowledge.

Risk symptoms for progression in Covid-19. Telemedicine cohort study.

Not available.

Sistema de gestión de riesgos para reducir el contagio de COVID-19 en el personal de salud / Risk management system to reduce COVID-19 infection in health personnel / Sistema de gestão de riscos para reduzir o contágio de COVID-19 em profissionais de saúde

RESUMEN Objetivo. Evaluar los factores laborales asociados con la ocurrencia de COVID-19 en el personal de salud expuesto a distinta magnitud de riesgo con el uso de la política de gestión de crisis de las Naciones Unidas para COVID-19. Métodos. Encuesta transversal realizada entre abril y mayo del 2021. Se consideraron como grupo de riesgo bajo (GRB) quienes tenían contacto mínimo con pacientes; de riesgo medio (GRM) a quienes tenían contacto con pacientes no-COVID-19 y no realizaban intervención instrumental de vías respiratorias; y de riesgo alto (GRA) a quienes atendían pacientes COVID-19 y realizaban intervención instrumental con generación de aerosoles. Se consideró como desenlace el antecedente de enfermedad diagnosticada de COVID-19 y la presencia de anticuerpos IgG positivos contra el SARS-CoV-2 medida con Elecsys® anti-SARS-CoV-2. Resultados. Desenlace en 43,8% en el GRB; 46,7% en el GRM (razón de momios [RM]: 1,125; intervalo de confianza de 95% [IC95%]: 0,896-1,414; p = 0,311); y 48,6% en el GRA (RM: 1,214; IC95%: 0,964-1,530; p = 0,10). Conclusión. Pertenecer al GRM y al GRA por el grado de exposición a pacientes confirmados de COVID-19 en el área de trabajo no se asoció con mayor ocurrencia de enfermedad o de seroconversión.

ABSTRACT Objective. To assess the occupational factors associated with the occurrence of COVID-19 in health personnel who were exposed to different magnitudes of risk and who followed the United Nations crisis management policy for COVID-19. Methods. Cross-sectional survey conducted between April and May 2021. The low-risk group (LRG) were considered to be those who had minimal contact with patients; the medium-risk group (MRG) had contact with non-COVID-19 patients and did not perform instrumental airway intervention; and the high-risk group (HRG) were those who cared for COVID-19 patients and performed instrumental intervention with aerosol generation. Diagnosed COVID-19 disease and the presence of positive IgG antibodies for SARS-CoV-2 measured with Elecsys® anti-SARS-CoV-2 were considered as outcomes. Results. Outcome recorded in 43.8% of the LRG, versus 46.7% in the MRG (odds ratio [OR]: 1.125; 95% confidence interval [CI 95% ]: 0.896-1.414; p = 0.311), and 48.6% in the HRG (OR: 1,214; CI 95%: 0.964-1.530; p= 0.10). Conclusion. Belonging to the high-risk group and the medium-risk group, based on the degree of exposure to confirmed COVID-19 patients in the work area, was not associated with a higher occurrence of disease or seroconversion.

RESUMO Objetivo. Avaliar os fatores ocupacionais associados à ocorrência de COVID-19 em profissionais de saúde expostos a diferentes níveis de risco utilizando a política de gestão de crises elaborada pelas Nações Unidas para a COVID-19. Métodos. Pesquisa transversal realizada entre abril e maio de 2021. O grupo de risco baixo (GRB) consistia em profissionais que tinham contato mínimo com os pacientes; o grupo de risco médio (GRM) incluía profissionais que tinham contato com pacientes sem COVID-19 e não realizavam intervenções instrumentais nas vias aéreas; e grupo de risco alto (GRA), profissionais que cuidavam de pacientes com COVID-19 e realizavam intervenções instrumentais com geração de aerossóis. Para estabelecer o desfecho, considerou-se a história de COVID-19 do profissional de saúde e a detecção de anticorpos IgG anti- SARS-CoV-2 por Elecsys® Anti-SARS-CoV-2. Resultados. A doença foi diagnosticada em 43,8% dos profissionais no GRB, 46,7% no GRM (razão de chances ajustada: 1,125; intervalo de confiança de 95% [IC95%]: 0,896-1,414; p = 0,311) e 48,6% no GRA (razão de chances: 1,214; IC95%: 0,964-1,530; p = 0,10). Conclusões. Pertencer ao GRM e ao GRA em função do nível de exposição a pacientes confirmados com COVID-19 no ambiente de trabalho não foi associado a um aumento da ocorrência da doença ou da soroconversão.

DIA-Person Integration Model to increase the quality of teaching, research and medical care. A person-oriented strategy.

Current model of medicine has made for medical care, teaching and research to be driven apart, with an impact on the patient: during the process of care, the doctor fails to apply the scientific method, he only treats the ailment without accompanying the patient. The medical researcher looks for answers to questions far removed from patient ailments and, in the best-case scenario, conducts research on patient specimens. In addition, the student-teacher dyad is characterized by the transmission of knowledge and leaves aside understanding of the patient. Patients, doctors, researchers and students are oblivious to decision-making and, without questioning, they merely follow processes. One way to address the problem is to return to the DIA-person Integration Model: "concern and doing for the person, accompanied by the integration of teaching, research and medical care", which would allow the transfer of knowledge, skills and benefits from one activity to others. The model consists of contrasting the patient condition with knowledge, carrying out research during and parallel to the medical care-teaching process, as well as applying the architecture of research model "clinical judgment structured description", as a reference and reflection process that integrates the activities of teaching-research and person-oriented medical care.

El modelo actual de la medicina ha distanciado la atención médica, la docencia y la investigación, con impacto en el paciente: durante la atención, el médico omite aplicar el método científico, solo atiende la dolencia sin acompañar al paciente; el investigador médico busca respuestas a preguntas alejadas de las dolencias del paciente y, en el mejor de los casos, realiza investigación en especímenes provenientes de este; la díada estudiante-profesor se caracteriza por la transmisión de conocimiento y deja de lado la comprensión del paciente. Pacientes, médicos, investigadores y estudiantes son ajenos a la toma de decisiones y sin cuestionamientos solo siguen procesos. Una manera de abordar el problema es regresar al Modelo de Integración DIA-persona: "la preocupación y el hacer por la persona, acompañados por la integración de docencia, investigación y atención médica", lo que permitiría el traslado del conocimiento, destrezas y beneficios de una actividad a otra. El modelo consiste en contrastar la condición del paciente con el conocimiento, realizar investigación durante y en paralelo al proceso de atención-docencia médica, así como aplicar el modelo arquitectónico de la investigación "descripción estructurada del juicio clínico", como proceso de referencia y reflexión que integra las actividades de docencia-investigación y atención médica orientadas a la persona.

Modelo de Integración DIA-Persona para incrementar la calidad de la docencia, investigación y atención médica. Estrategia orientada a la persona / DIA-Person Integration Model to increase the quality of teaching, research and medical care. A person-oriented strategy

Resumen El modelo actual de la medicina ha distanciado la atención médica, la docencia y la investigación, con impacto en el paciente: durante la atención, el médico omite aplicar el método científico, solo atiende la dolencia sin acompañar al paciente; el investigador médico busca respuestas a preguntas alejadas de las dolencias del paciente y, en el mejor de los casos, realiza investigación en especímenes provenientes de este; la díada estudiante-profesor se caracteriza por la transmisión de conocimiento y deja de lado la comprensión del paciente. Pacientes, médicos, investigadores y estudiantes son ajenos a la toma de decisiones y sin cuestionamientos solo siguen procesos. Una manera de abordar el problema es regresar al Modelo de Integración DIA-persona: "la preocupación y el hacer por la persona, acompañados por la integración de docencia, investigación y atención médica", lo que permitiría el traslado del conocimiento, destrezas y beneficios de una actividad a otra. El modelo consiste en contrastar la condición del paciente con el conocimiento, realizar investigación durante y en paralelo al proceso de atención-docencia médica, así como aplicar el modelo arquitectónico de la investigación "descripción estructurada del juicio clínico", como proceso de referencia y reflexión que integra las actividades de docencia-investigación y atención médica orientadas a la persona.

Abstract Current model of medicine has made for medical care, teaching and research to be driven apart, with an impact on the patient: during the process of care, the doctor fails to apply the scientific method, he only treats the ailment without accompanying the patient. The medical researcher looks for answers to questions far removed from patient ailments and, in thebest-case scenario, conducts research on patient specimens. In addition, the student-teacher dyad is characterized by thetransmission of knowledge and leaves aside understanding of the patient. Patients, doctors, researchers and students are oblivious to decision-making and, without questioning, they merely follow processes. One way to address the problem is to return to the DIA-person Integration Model "concern and doing for the person, accompanied by the integration of teaching, research and medical care", which would allow the transfer of knowledge, skills and benefits from one activity to others. The model consists of contrasting the patient condition with knowledge, carrying out research during and parallel to the medical care-teaching process, as well as applying the architecture of research model "clinical judgment structured description", as a reference and reflection process that integrates the activities of teaching-research and person-oriented medical care.

Durable metabolic improvements 2 years after duodenal mucosal resurfacing (DMR) in patients with type 2 diabetes (REVITA-1 Study).

AIMS: Duodenal mucosal resurfacing (DMR) is an endoscopic procedure developed to improve metabolic parameters and restore insulin sensitivity in patients with diabetes. Here we report long-term DMR safety and efficacy from the REVITA-1 study. MATERIALS AND METHODS: REVITA-1 was a prospective, single-arm, open-label, multicenter study of DMR feasibility, safety, and efficacy in patients with type 2 diabetes (hemoglobin A1c [HbA1c] of 7.5-10.0% (58-86 mmol/mol)) on oral medication. Safety and glycemic (HbA1c), hepatic (alanine aminotransferase [ALT]), and cardiovascular (HDL, triglyceride [TG]/HDL ratio) efficacy parameters were assessed (P values presented for LS mean change). RESULTS: Mean ± SD HbA1c levels reduced from 8.5 ± 0.7% (69.1 ± 7.1 mmol/mol) at baseline (N = 34) to 7.5 ± 0.8% (58.9 ± 8.8 mmol/mol) at 6 months (P < 0.001); and this reduction was sustained through 24 months post-DMR (7.5 ± 1.1% [59.0 ± 12.3 mmol/mol], P < 0.001) while in greater than 50% of patients, glucose-lowering therapy was reduced or unchanged. ALT decreased from 38.1 ± 21.1 U/L at baseline to 32.5 ± 22.1 U/L at 24 months (P = 0.048). HDL and TG/HDL improved during 24-months of follow-up. No device- or procedure-related serious adverse events, unanticipated device effects, or hypoglycemic events were noted between 12 and 24 months post-DMR. CONCLUSIONS: DMR is associated with durable improvements in insulin sensitivity and multiple downstream metabolic parameters through 24 months post-treatment in type 2 diabetes. Clinical trial reg. no. NCT02413567, clinicaltrials.gov.

A Gut-Centric Model of Metabolic Homeostasis.

Modern changes in diet and lifestyle have led to an explosion of insulin resistance and metabolic diseases around the globe which, if left unchecked, will become a principal driver of morbidity and mortality in the 21st century. The nature of the metabolic homeostatic shift within the body has therefore become a topic of considerable interest. While the gut has long been recognized as an acute nutrient sensor with signaling mechanisms to the other metabolic organs of the body, its role in regulating the body's metabolic status over longer periods of time has been underappreciated. Recent insights from bariatric surgery and intestinal nutrient stimulation experiments provide a window into the adaptive role of the intestinal mucosa in a foregut/hindgut metabolic balance model that helps to define metabolic parameters within the body-informing the metabolic regulation of insulin resistance versus sensitivity, hunger versus satiety, energy utilization versus energy storage, and protection from hypoglycemia versus protection from hyperglycemia. This intestinal metabolic balance model provides an intellectual framework with which to understand the distinct roles of proximal and distal intestinal segments in metabolic regulation. The model may also aid in the development of novel disease-modifying therapies that can correct the dysregulated metabolic signals from the intestine and stem the tide of metabolic diseases in society.

Safety and efficacy of hydrothermal duodenal mucosal resurfacing in patients with type 2 diabetes: the randomised, double-blind, sham-controlled, multicentre REVITA-2 feasibility trial.

OBJECTIVE: Hydrothermal duodenal mucosal resurfacing (DMR) is a safe, outpatient endoscopic procedure. REVITA-2, a double-blind, superiority randomised controlled trial, investigates safety and efficacy of DMR using the single catheter Revita system (Revita DMR (catheter and system)), on glycaemic control and liver fat content in type 2 diabetes (T2D). DESIGN: Eligible patients (haemoglobin A1c (HbA1c) 59-86 mmol/mol, body mass index≥24 and ≤40 kg/m2, fasting insulin >48.6 pmol/L, ≥1 oral antidiabetic medication) enrolled in Europe and Brazil. Primary endpoints were safety, change from baseline in HbA1c at 24 weeks, and liver MRI proton-density fat fraction (MRI-PDFF) at 12 weeks. RESULTS: Overall mITT (DMR n=56; sham n=52), 24 weeks post DMR, median (IQR) HbA1c change was -10.4 (18.6) mmol/mol in DMR group versus -7.1 (16.4) mmol/mol in sham group (p=0.147). In patients with baseline liver MRI-PDFF >5% (DMR n=48; sham n=43), 12-week post-DMR liver-fat change was -5.4 (5.6)% in DMR group versus -2.9 (6.2)% in sham group (p=0.096). Results from prespecified interaction testing and clinical parameter assessment showed heterogeneity between European (DMR n=39; sham n=37) and Brazilian (DMR n=17; sham n=16) populations (p=0.063); therefore, results were stratified by region. In European mITT, 24 weeks post DMR, median (IQR) HbA1c change was -6.6 mmol/mol (17.5 mmol/mol) versus -3.3 mmol/mol (10.9 mmol/mol) post-sham (p=0.033); 12-week post-DMR liver-fat change was -5.4% (6.1%) versus -2.2% (4.3%) post-sham (p=0.035). Brazilian mITT results trended towards DMR benefit in HbA1c, but not liver fat, in context of a large sham effect. In overall PP, patients with high baseline fasting plasma glucose ((FPG)≥10 mmol/L) had significantly greater reductions in HbA1c post-DMR versus sham (p=0.002). Most adverse events were mild and transient. CONCLUSIONS: DMR is safe and exerts beneficial disease-modifying metabolic effects in T2D with or without non-alcoholic liver disease, particularly in patients with high FPG. TRIAL REGISTRATION NUMBER: NCT02879383.

Effect of a ready-to-use supplementary food on the recovery of preschool children with malnutrition.

INTRODUCTION: In developing countries, protein-energy malnutrition causes 60% of deaths in children < 5 years of age. OBJECTIVE: To evaluate the effect of a ready-to-use supplementary food (RUSF) on moderate acute malnutrition (MAM) in preschool children. METHOD: Clinical trial that included 155 children with MAM (weight/height Z-score > -3 and ≤ -2). Each child received RUSF in the form of biscuits, four per day (250 kcal), for 12 months. The tutor received education on nutrition, health and hygiene. Recovery (weight/height Z-score > -2) at four, six, and 12 months was assessed using intent-to-treat (ITT) and per protocol (PP) analyses. Changes in chronic malnutrition were also analyzed. RESULTS: In the first semester, adequate RUSF consumption was observed in 61% of the children, and in 42% in the second semester. In the ITT analysis, 78% were identified to have recovered, with 38% reaching normal nutritional values; in the PP analysis, > 90% recovered and > 40% reached normal values. Recovery from chronic malnutrition was also observed. CONCLUSIONS: The consumption of RUSF and an educational program reduced MAM.

INTRODUCCIÓN: En países en desarrollo, la desnutrición proteico-energética causa 60 % de las muertes en los niños menores de cinco años. OBJETIVO: Evaluar el efecto de un suplemento alimenticio listo para consumir (SALC) en la desnutrición aguda moderada (DAM) en niños preescolares. MÉTODO: Ensayo clínico que incluyó 155 niños con DAM (puntuación Z de peso/talla [pZ] mayor de −3 y menor o igual a −2). Cada niño recibió SALC en forma de galletas, cuatro por día (250 kcal), durante 12 meses. El tutor recibió educación sobre nutrición, salud e higiene. La recuperación (pZ peso/talla mayor de −2) a los cuatro, seis y 12 meses se evaluó con un análisis por intención a tratar (AIT) y por protocolo (APP). También se analizaron cambios en la desnutrición crónica. RESULTADOS: En el primer semestre se observó consumo adecuado del SALC en 61 % de los niños y en 42 % en el segundo semestre. Con el AIT se identificó que 78 % se recuperó y 38 % alcanzó valores normales de nutrición; con el APP, > 90 % se recuperó y > 40 % alcanzó valores normales. Se observó recuperación de la desnutrición crónica. CONCLUSIONES: El consumo de SALC y un programa educativo redujeron la DAM.

U-shaped-aggressiveness of SARS-CoV-2: Period between initial symptoms and clinical progression to COVID-19 suspicion. A population-based cohort study.

BACKGROUND: Early identification of different COVID-19 clinical presentations may depict distinct pathophysiological mechanisms and guide management strategies. OBJECTIVE: To determine the aggressiveness of SARS-CoV-2 using symptom progression in COVID-19 patients. DESIGN: Historic cohort study of Mexican patients. Data from January-April 2020 were provided by the Health Ministry. SETTING: Population-based. Patients registered in the Epidemiologic Surveillance System in Mexico. PARTICIPANTS: Subjects who sought medical attention for clinical suspicion of COVID-19. All patients were subjected to RT-PCR testing for SARS-CoV-2. MEASUREMENTS: We measured the Period between initial symptoms and clinical progression to COVID-19 suspicion (PISYCS) and compared it to the primary outcomes (mortality and pneumonia). RESULTS: 65,500 patients were included. Reported fatalities and pneumonia were 2176 (3.32%), and 11568 (17.66%), respectively. According to the PISYCS, patients were distributed as follows: 14.89% in <24 hours, 43.25% between 1-3 days, 31.87% between 4-7 days and 9.97% >7 days. The distribution for mortality and pneumonia was 5.2% and 22.5% in <24 hours, 2.5% and 14% between 1-3 days, 3.6% and 19.5% between 4-7 days, 4.1% and 20.6% >7 days, respectively (p<0.001). Adjusted-risk of mortality was (OR [95% CI], p-value): <24 hours = 1.75 [1.55-1.98], p<0.001; 1-3 days = 1 (reference value); 4-7 days = 1.53 [1.37-1.70], p<0.001; >7 days = 1.67 [1.44-1.94], p<0.001. For pneumonia: <24 hours = 1.49 [1.39-1.58], p<0.001; 1-3 days = 1; 4-7 days = 1.48 [1.41-1.56], p<0.001; >7 days = 1.57 [1.46-1.69], p<0.001. LIMITATIONS: Using a database fed by large numbers of people carries the risk of data inaccuracy. However, this imprecision is expected to be random and data are consistent with previous studies. CONCLUSION: The PISYCS shows a U-shaped SARS-CoV-2 aggressiveness pattern. Further studies are needed to corroborate the time-related pathophysiology behind these findings.

Back to the clinic. Methods II. The Architecture of Clinical Research. Subject interaction, maneuvers and disease throughout time.

Medicine is characterized by the application of the scientific method through clinical judgment, by correct interpretation and use of the clinical course and/or natural history of the disease; its best description is observed in the architecture of clinical research. Through a temporal sequence, this model explains the phenomenon of causality with three sections: baseline status, maneuver, and outcome. The baseline status assesses who the patient is, where does he come from, his general conditions, the diagnosis, stage and aggressiveness of the pathology, complications, previous therapies, socioeconomic-cultural level, habits, therapeutic indications or contraindications, and the expected evolution is anticipated. In the maneuver, risk or prognostic factors, specific or symptomatic treatment, and general measures can be evaluated. In the outcome, early and late evolution are monitored. The model also allows the causes of follow-up loss to be determined. Anticipating patient evolution by recognizing his condition, disease, and expected effect of medical decisions allows acting in advance, since waiting for the manifestations of the evolutionary process of disease results in detriment to the patient.

La medicina se caracteriza por la aplicación del método científico a través del juicio clínico, por la correcta interpretación y el uso del curso clínico o historia natural de la enfermedad; su descripción más lograda la observamos en la arquitectura de la investigación clínica. A través de una secuencia temporal, este modelo explica el fenómeno de causalidad con tres apartados: estado basal, maniobra y desenlace. En el estado basal se evalúa quién es el paciente, de donde proviene, sus condiciones generales, el diagnóstico, el estadio y la agresividad de la patología, las complicaciones, terapias previas, nivel socioeconómi­co-cultural, hábitos, indicaciones o contraindicaciones terapéuticas y se prevé la evolución esperada. De la maniobra se pueden evaluar los factores de riesgo o pronóstico, tratamiento específico, sintomático y medidas generales. En el desenlace se vigila la evolución temprana y tardía. El modelo también permite determinar las causas de pérdida de seguimiento. Anticipar la evo­lución del paciente al reconocer su condición, enfermedad y efecto esperado de la decisiones médicas permite actuar antici­padamente, ya que esperar las manifestaciones del proceso evolutivo de la enfermedad resulta en detrimento del paciente.

Sensitivity and specificity of increased pulse pressure as a diagnostic test for K/DOQI stage III-b CKD.

BACKGROUND: Increased pulse pressure (IPP) is associated with an estimated glomerular filtration ≤ 60/mL/min/1.73 m2; thus, it can be useful as a diagnostic test to identify people with K/DOQI stage III-b chronic kidney disease (CKD). OBJECTIVE: To determine the usefulness of IPP as a diagnostic test for K/DOQI stage III-b CKD. METHOD: Diagnostic test study that included adult patients without comorbidities, registered in the Health Workers Cohort. The CKD-EPI formula was used to calculate glomerular filtration. Pulse pressure was determined by subtracting diastolic from systolic blood pressure. Sensitivity, specificity, positive predictive value, negative predictive value and prevalence were calculated using standard formulas. A ROC curve was generated to determine the area under the curve. RESULTS: A total of 6,215 patients were included. An IPP ≥ 50 mmHg was observed to have a sensitivity of 74 %, specificity of 70 %, positive predictive value of 1 %, negative predictive value of 100 % and a prevalence of 1 %. The inflection point in the ROC curve to identify K/DOQI III-b CKD was 0.71. CONCLUSION: An IPP ≥ 50 mmHg is useful as a diagnostic test to identify people with K/DOQI stage III-b CKD.

INTRODUCCIÓN: La presión de pulso ampliada (PPA) se asocia a un filtrado glomerular calculado ≤ 60/mL/minuto/1.73 m2, por lo que puede ser útil como prueba diagnóstica para identificar a personas con insuficiencia renal crónica (IRC) estadio K/DOQI III-b. OBJETIVO: Determinar la utilidad de la PPA como prueba diagnóstica de IRC estadio K/DOQI III-b. MÉTODO: Estudio de prueba diagnóstica que incluyó a pacientes adultos sin comorbilidades, registrados en la Cohorte de Trabajadores de la Salud. Se utilizó la fórmula CKD-EPI para calcular la filtración glomerular. Se determinó la presión de pulso restando la presión arterial diastólica a la presión arterial sistólica. Se calculó sensibilidad, especificidad, valor predictivo positivo, valor predictivo negativo y prevalencia. Se elaboró una curva ROC para determinar el área bajo la curva. RESULTADOS: Se incluyeron 6215 pacientes. Se observó que una PPA ≥ 50 mm Hg tuvo sensibilidad de 74 %, especificidad de 70 %, valor predictivo positivo de 1 %, valor predictivo negativo de 100 % y prevalencia de 1 %. El punto de inflexión en la curva ROC para identificar IRC K/DOQI III-b fue de 0.71. CONCLUSIÓN: La PPA ≥ 50 mm Hg es útil como prueba diagnóstica para identificar a personas con IRC estadio K/DOQI III-b.

Prevención de desnutrición aguda moderada con un suplemento alimenticio listo para consumir en niños preescolares de comunidades rurales / Moderate acute malnutrition prevention with a ready-to-use therapeutic food in pre-school children from rural communities

Resumen Introducción: La desnutrición infantil en México alcanza prevalencias de 27.5 % en zonas rurales. Objetivo: Evaluar la efectividad de un suplemento alimenticio listo para consumir (SALC) para corregir desnutrición aguda leve y prevenir desnutrición aguda moderada en preescolares de comunidades rurales. Método: Ensayo clínico aleatorizado por grupos: con y sin SALC (g-SALC y g-S/SALC); se incluyeron niños de dos a cinco años, con puntuaciones-Z de peso para la talla (pZ-P/T) mayor de −2 y menor de −1 y nivel socioeconómico bajo. Todos recibieron educación sobre nutrición, salud e higiene dos veces al mes; los niños del g-SALC debieron consumir diariamente una porción del suplemento. Se evaluó pZ-P/T al inicio y a los cuatro, seis y 12 meses. La comparación entre grupos se realizó con el modelo de riesgos proporcionales de Cox. Resultados: Respecto a la recuperación de desnutrición aguda leve, en g-SALC se observó 68.7 versus 52.1% en el grupo control en el análisis de intención para tratar, con una razón de riesgo (HR) = 1.25; en el análisis por protocolo del primer semestre se observó una HR = 1.48 y en el segundo semestre, HR = 1.56. Un paciente progresó a desnutrición aguda moderada. Conclusiones: El g-SALC mostró resolución significativamente mayor de desnutrición aguda leve.

Abstract Introduction: Child malnutrition in Mexico reaches a prevalence as high as 27.5 % in rural areas. Objective: To assess the effectiveness of a ready-to-use supplementary food (RUSF) to correct mild acute malnutrition and prevent moderate acute malnutrition in preschool children from rural communities. Method: Randomized clinical trial, with assignment to two groups: group with RUSF (RUSF-g) or group without it (non-RUSF-g); children aged from two to five years, with weight-for-height Z-scores (WHZ) between -2 and -1 and low socioeconomic status were included. All received education on nutrition, health and hygiene twice monthly; the RUSF-g children had to consume four biscuits of the supplement every day. WHZ was assessed at baseline and at four, six, and 12 months. The comparison between groups was carried out with Cox proportional hazards model. Results: With regard to mild acute malnutrition correction in the RUSF-g, 68.7 versus 52.1 % in the control group was observed in the intent-to-treat analysis, with a hazard ratio (HR) = 1.25; in the per-protocol analysis of first semester, a HR = 1.48 was observed, and in the second semester, HR = 1.56. One patient progressed to moderate acute malnutrition. Conclusions: The RUSF-g showed a significantly higher resolution of mild acute malnutrition.

Sensibilidad y especificidad de la presión de pulso ampliada como prueba diagnóstica de IRC estadio K/DOQI III-b / Sensitivity and specificity of increased pulse pressure as a diagnostic test for K/DOQI III-b

Resumen Introducción: La presión de pulso ampliada (PPA) se asocia a un filtrado glomerular calculado ≤ 60/mL/minuto/1.73 m2, por lo que puede ser útil como prueba diagnóstica para identificar a personas con insuficiencia renal crónica (IRC) estadio K/DOQI III-b. Objetivo: Determinar la utilidad de la PPA como prueba diagnóstica de IRC estadio K/DOQI III-b. Método: Estudio de prueba diagnóstica que incluyó a pacientes adultos sin comorbilidades, registrados en la Cohorte de Trabajadores de la Salud. Se utilizó la fórmula CKD-EPI para calcular la filtración glomerular. Se determinó la presión de pulso restando la presión arterial diastólica a la presión arterial sistólica. Se calculó sensibilidad, especificidad, valor predictivo positivo, valor predictivo negativo y prevalencia. Se elaboró una curva ROC para determinar el área bajo la curva. Resultados: Se incluyeron 6215 pacientes. Se observó que una PPA ≥ 50 mm Hg tuvo sensibilidad de 74 %, especificidad de 70 %, valor predictivo positivo de 1 %, valor predictivo negativo de 100 % y prevalencia de 1 %. El punto de inflexión en la curva ROC para identificar IRC K/DOQI III-b fue de 0.71. Conclusión: La PPA ≥ 50 mm Hg es útil como prueba diagnóstica para identificar a personas con IRC estadio K/DOQI III-b.

Abstract Introduction: Increased pulse pressure (IPP) is associated an estimated glomerular filtration ≤ 60/mL/min/1.73 m2; thus, it can be useful as a diagnostic test to identify people with K/DOQI stage III-b chronic kidney disease (CKD). Objective: To determine the usefulness of IPP as a diagnostic test for K/DOQI stage III-b CKD. Method: Diagnostic test study that included adult patients without comorbidities, registered in the Health Workers Cohort. The CKD-EPI formula was used to calculate glomerular filtration. Pulse pressure was determined by subtracting diastolic from systolic blood pressure. Sensitivity, specificity, positive predictive value, negative predictive value and prevalence were calculated using standard formulas. A ROC curve was generated to determine the area under the curve. Results: A total of 6,215 patients were included. An IPP ≥ 50 mmHg was observed to have a sensitivity of 74 %, specificity of 70 %, positive predictive value of 1 %, negative predictive value of 100 % and a prevalence of 1 %. The inflection point in the ROC curve to identify K/DOQI III-b CKD was 0.71. Conclusion: An IPP ≥ 50 mmHg is useful as a diagnostic test to identify people with K/DOQI stage III-b CKD.