COVID-19 Computed tomography patterns in renal replacement therapy patients / Padrões de tomografia computadorizada da COVID-19 em pacientes em terapia renal substitutiva

ABSTRACT Introduction: Lung diseases are common in patients with end stage kidney disease (ESKD), making differential diagnosis with COVID-19 a challenge. This study describes pulmonary chest tomography (CT) findings in hospitalized ESKD patients on renal replacement therapy (RRT) with clinical suspicion of COVID-19. Methods: ESKD individuals referred to emergency department older than 18 years with clinical suspicion of COVID-19 were recruited. Epidemiological baseline clinical information was extracted from electronic health records. Pulmonary CT was classified as typical, indeterminate, atypical or negative. We then compared the CT findings of positive and negative COVID-19 patients. Results: We recruited 109 patients (62.3% COVID-19-positive) between March and December 2020, mean age 60 ± 12.5 years, 43% female. The most common etiology of ESKD was diabetes. Median time on dialysis was 36 months, interquartile range = 12-84. The most common pulmonary lesion on CT was ground glass opacities. Typical CT pattern was more common in COVID-19 patients (40 (61%) vs 0 (0%) in non-COVID-19 patients, p < 0.001). Sensitivity was 60.61% (40/66) and specificity was 100% (40/40). Positive predictive value and negative predictive value were 100% and 62.3%, respectively. Atypical CT pattern was more frequent in COVID-19-negative patients (9 (14%) vs 24 (56%) in COVID-19-positive, p < 0.001), while the indeterminate pattern was similar in both groups (13 (20%) vs 6 (14%), p = 0.606), and negative pattern was more common in COVID-19-negative patients (4 (6%) vs 12 (28%), p = 0.002). Conclusions: In hospitalized ESKD patients on RRT, atypical chest CT pattern cannot adequately rule out the diagnosis of COVID-19.

RESUMO Introdução: Doenças pulmonares são comuns em pacientes com doença renal em estágio terminal (DRET), dificultando o diagnóstico diferencial com COVID-19. Este estudo descreve achados de tomografia computadorizada de tórax (TC) em pacientes com DRET em terapia renal substitutiva (TRS) hospitalizados com suspeita de COVID-19. Métodos: Indivíduos maiores de 18 anos com DRET, encaminhados ao pronto-socorro com suspeita de COVID-19 foram incluídos. Dados clínicos e epidemiológicos foram extraídos de registros eletrônicos de saúde. A TC foi classificada como típica, indeterminada, atípica, negativa. Comparamos achados tomográficos de pacientes com COVID-19 positivos e negativos. Resultados: Recrutamos 109 pacientes (62,3% COVID-19-positivos) entre março e dezembro de 2020, idade média de 60 ± 12,5 anos, 43% mulheres. A etiologia mais comum da DRET foi diabetes. Tempo médio em diálise foi 36 meses, intervalo interquartil = 12-84. A lesão pulmonar mais comum foi opacidades em vidro fosco. O padrão típico de TC foi mais comum em pacientes com COVID-19 (40 (61%) vs. 0 (0%) em pacientes sem COVID-19, p < 0,001). Sensibilidade 60,61% (40/66), especificidade 100% (40/40). Valores preditivos positivos e negativos foram 100% e 62,3%, respectivamente. Padrão atípico de TC foi mais frequente em pacientes COVID-19-negativos (9 (14%) vs. 24 (56%) em COVID-19-positivos, p < 0,001), enquanto padrão indeterminado foi semelhante em ambos os grupos (13 (20%) vs. 6 (14%), p = 0,606), e padrão negativo foi mais comum em pacientes COVID-19-negativos (4 (6%) vs. 12 (28%), p = 0,002). Conclusões: Em pacientes com DRET em TRS hospitalizados, um padrão atípico de TC de tórax não pode excluir adequadamente o diagnóstico de COVID-19.

Risk factors for acute kidney injury in patients hospitalized with COVID-19 / Fatores de risco para lesão renal aguda em pacientes hospitalizados com COVID-19

Abstract Introduction: Acute kidney injury (AKI) occurs frequently in COVID-19 patients and is associated with greater morbidity and mortality. Knowing the risks of AKI allows for identification, prevention, and timely treatment. This study aimed to identify the risk factors associated with AKI in hospitalized patients. Methods: A descriptive, retrospective, cross-sectional, and analytical component study of adult patients hospitalized with COVID-19 from March 1 to December 31, 2020 was carried out. AKI was defined by the creatinine criteria of the KDIGO-AKI guidelines. Information, regarding risk factors, was obtained from electronic medical records. Results: Out of the 934 patients, 42.93% developed AKI, 60.59% KDIGO-1, and 9.9% required renal replacement therapy. Patients with AKI had longer hospital stay, higher mortality, and required more intensive care unit (ICU) admission, mechanical ventilation, and vasopressor support. Multivariate analysis showed that age (OR 1.03; 95% CI 1.02-1.04), male sex (OR 2.13; 95% CI 1.49-3.04), diabetes mellitus (DM) (OR 1.55; 95% CI 1.04-2.32), chronic kidney disease (CKD) (OR 2.07; 95% CI 1.06-4.04), C-reactive protein (CRP) (OR 1.02; 95% CI 1.00-1.03), ICU admission (OR 1.81; 95% CI 1.04-3.16), and vasopressor support (OR 7.46; 95% CI 3.34-16.64) were risk factors for AKI, and that bicarbonate (OR 0.89; 95% CI 0.84-0.94) and partial pressure arterial oxygen/inspired oxygen fraction index (OR 0.99; 95% CI 0.98-0.99) could be protective factors. Conclusions: A high frequency of AKI was documented in COVID-19 patients, with several predictors: age, male sex, DM, CKD, CRP, ICU admission, and vasopressor support. AKI occurred more frequently in patients with higher disease severity and was associated with higher mortality and worse outcomes.

RESUMO Introdução: Lesão renal aguda (LRA) ocorre frequentemente em pacientes com COVID-19 e associa-se a maior morbidade e mortalidade. Conhecer riscos da LRA permite a identificação, prevenção e tratamento oportuno. Este estudo teve como objetivo identificar fatores de risco associados à LRA em pacientes hospitalizados. Métodos: Realizou-se estudo descritivo, retrospectivo, transversal e de componente analítico de pacientes adultos hospitalizados com COVID-19 de 1º de março a 31 de dezembro, 2020. Definiu-se a LRA pelos critérios de creatinina das diretrizes KDIGO-LRA. Informações sobre fatores de risco foram obtidas de prontuários eletrônicos. Resultados: Dos 934 pacientes, 42,93% desenvolveram LRA, 60,59% KDIGO-1 e 9,9% necessitaram de terapia renal substitutiva. Pacientes com LRA apresentaram maior tempo de internação, maior mortalidade e necessitaram de mais internações em UTIs, ventilação mecânica e suporte vasopressor. A análise multivariada mostrou que idade (OR 1,03; IC 95% 1,02-1,04), sexo masculino (OR 2,13; IC 95% 1,49-3,04), diabetes mellitus (DM) (OR 1,55; IC 95% 1,04-2,32), doença renal crônica (DRC) (OR 2,07; IC 95% 1,06-4,04), proteína C reativa (PCR) (OR 1,02; IC 95% 1,00-1,03), admissão em UTI (OR 1,81; IC 95% 1,04-3,16) e suporte vasopressor (OR 7,46; IC 95% 3,34-16,64) foram fatores de risco para LRA, e que bicarbonato (OR 0,89; IC 95% 0,84-0,94) e índice de pressão parcial de oxigênio arterial/fração inspirada de oxigênio (OR 0,99; IC 95% 0,98-0,99) poderiam ser fatores de proteção. Conclusões: Documentou-se alta frequência de LRA em pacientes com COVID-19, com diversos preditores: idade, sexo masculino, DM, DRC, PCR, admissão em UTI e suporte vasopressor. LRA ocorreu mais frequentemente em pacientes com maior gravidade da doença e associou-se a maior mortalidade e piores desfechos.

Type 2 diabetes patients requiring empagliflozin in Southeast of Iran: Frequency and guideline adherence (2022–2023) / Pacientes con diabetes tipo 2 que requieren empagliflozina en el sureste de Irán: frecuencia y cumplimiento de las directrices (2022-2023)

Introduction: Empagliflozin plays a beneficial role in individuals with type 2 diabetes at high risk of cardiovascular complications. This study aimed to assess the prevalence of individuals with type 2 diabetes who required empagliflozin based on clinical guidelines between the years 2022 and 2023. Material and methods: This study was a descriptive-analytical cross-sectional study conducted on a target population of patients with type 2 diabetes. Patient data, including demographic characteristics, smoking status, hypertension, hyperlipidemia, renal insufficiency, retinopathy, and proteinuria, were collected. The indication for prescribing empagliflozin was determined based on the risk of cardiovascular complications. Results: A total of 398 individuals with type 2 diabetes with a mean age of 58.4 years were examined. Overall, 87.4% of the patients had an indication for empagliflozin prescription. The indication for empagliflozin prescription was significantly higher in men, individuals with hyperlipidemia, those over 55 years of age, obese individuals, and smokers. The mean age, body mass index, and triglyceride levels were higher in candidates for empagliflozin prescription. Male candidates for empagliflozin had significantly higher rates of smoking and systolic blood pressure compared to females. Conclusions: The findings of this study demonstrated that a significant percentage of individuals with type 2 diabetes had an indication for empagliflozin prescription based on clinical and laboratory criteria. (AU)

Introducción: La empagliflozina tiene un papel beneficioso en las personas con diabetes tipo 2 con alto riesgo de complicaciones cardiovasculares. Este estudio tuvo como objetivo evaluar la prevalencia de pacientes con este padecimiento que requerían empagliflozina según las guías clínicas entre los años 2022 y 2023. Material y métodos: Se trata de un estudio transversal descriptivo-analítico realizado en una población objetivo de personas con diabetes tipo 2. Se recogieron los datos de los pacientes, incluyendo las características demográficas, el hábito tabáquico, la hipertensión, la hiperlipidemia, la insuficiencia renal, la retinopatía y la proteinuria. La indicación para prescribir empagliflozina se determinó en función del riesgo de complicaciones cardiovasculares. Resultados: Se examinaron un total de 398 individuos con diabetes tipo 2 con una edad media de 58,4 años. En general, 87,4% de estos tenía una indicación para la prescripción de empagliflozina, la cual fue significativamente mayor en los hombres, aquellos con hiperlipidemia, obesidad, los mayores de 55 años y los fumadores. La edad media, el índice de masa corporal y los niveles de triglicéridos fueron mayores en los candidatos a la prescripción de este medicamento. Los candidatos masculinos a este fármaco tenían tasas significativamente más altas de tabaquismo y presión arterial sistólica, en comparación con las mujeres. Conclusiones: Los resultados de este estudio demostraron que un porcentaje significativo de personas con diabetes tipo 2 tenía una indicación para la prescripción de empagliflozina según los criterios clínicos y de laboratorio. (AU)

Renin–angiotensin–aldosterone system blockers effect in chronic kidney disease progression in hypertensive elderly patients without proteinuria: PROERCAN trial / Efecto de los bloqueantes del sistema renina-angiotensina-aldosterona en la progresión de enfermedad renal crónica en pacientes hipertensos añosos sin proteinuria: ensayo clínico Progresión de Enfermedad Renal Crónica en Ancianos

Introduction: Evidence about nefroprotective effect with RAAS blockers in elderly patients with chronic kidney disease (CKD) without proteinuria is lacking. The primary outcome of our study is to evaluate the impact of RAAS blockers in CKD progression in elderly patients without proteinuria. Materials and methods: Multicenter open-label, randomized controlled clinical trial including patients over 65 year-old with hypertension and CKD stages 3–4 without proteinuria. Patients were randomized in a 1:1 ratio to either receive RAAS blockers or other antihypertensive drugs and were followed up for three years. Primary outcome is estimated glomerular filtration rate (eGFR) decline at 3 years. Secondary outcome measures include BP control, renal and cardiovascular events and mortality. Results: 88 patients were included with a mean age of 77.9±6.1 years and a follow up period of 3 years: 40 were randomized to RAAS group and 48 to standard treatment. Ethiology of CKD was: 53 vascular, 16 interstitial and 19 of unknown ethiology. In the RAAS group eGFR slope during follow up was −4.3±1.1ml/min, whereas in the standard treatment group an increase on eGFR was observed after 3 years (+4.6±0.4ml/min), p=0.024. We found no differences in blood pressure control, number of antihypertensive drugs, albuminuria, potassium serum levels, incidence of cardiovascular events nor mortality during the follow up period. Conclusions: In elderly patients without diabetes nor cardiopathy and with non proteinuric CKD the use of RAAS blockers does not show a reduction in CKD progression. The PROERCAN (PROgresión de Enfermedad Renal Crónica en ANcianos) trial (trial registration: NCT03195023). (AU)

Introducción: Actualmente no existe suficiente evidencia sobre el efecto nefroprotector de los bloqueantes del sistema renina-angiotensina-aldosterona (BSRAA) en pacientes añosos con enfermedad renal crónica (ERC) sin proteinuria y sin cardiopatía. El objetivo es evaluar el efecto de los BSRAA en la progresión de la ERC en este grupo poblacional. Métodos: Se trata de un estudio prospectivo, aleatorizado, que compara la eficacia de los BSRAA vs. otros tratamientos antihipertensivos en la progresión renal en personas mayores de 65 años con ERC estadios 3 y 4 e índice albúmina/creatinina<30mg/g. Aleatorización 1:1 BSRAA o tratamiento antihipertensivo estándar. Se recogieron cifras tensionales y parámetros analíticos de un año previo a la aleatorización y durante el seguimiento. Resultados: Se incluyeron 88 pacientes seguidos durante tres años con edad media de 77,9±6,1 años. De estos, se aleatorizaron 40 al grupo BSRAA y 48 al estándar. La etiología de ERC fue: 53 vascular, 16 intersticial y 19 no filiada. En el primer grupo se observó una progresión de la ERC con una caída del filtrado glomerular estimado (FGe) de -4,3±1,1mL/min, mientras que en el grupo estándar un aumento del FGe durante el seguimiento de 4,6±0,4mL/min, p=0,024. No se apreciaron diferencias entre ambos en el control tensional, el número de antihipertensivos, la albuminuria, los niveles de potasio, la incidencia de eventos cardiovasculares ni la mortalidad durante el seguimiento. Conclusiones: En pacientes añosos no diabéticos con ERC no proteinúrica y sin cardiopatía el uso de BSRAA no añade beneficio en la progresión de la ERC. Ensayo clínico Progresión de Enfermedad Renal Crónica en Ancianos (PROERCAN) (NCT03195023). (AU)

Asociación entre Glucemia inestable, tiempo de estancia y mortalidad de pacientes en estado críticos: Estudio de cohorte / Associação Entre Glicemia Instável, Tempo de Permanência e Mortalidade de Pacientes Críticos: Estudo de Coorte / Relationships between unstable Glycemia, Hospital Length Of Stay, and mortality In Critically Ill patients: A cohort study

Resumen Introducción: El control y la evaluación de los niveles glucémicos de pacientes en estado críticos es un desafío y una competencia del equipo de enfermería. Por lo que, determinar las consecuencias de esta durante la hospitalización es clave para evidenciar la importancia del oportuno manejo. Objetivo: Determinar la asociación entre la glucemia inestable (hiperglucemia e hipoglucemia), el resultado de la hospitalización y la duración de la estancia de los pacientes en una unidad de cuidados intensivos. Metodología: Estudio de cohorte prospectivo realizado con 62 pacientes a conveniencia en estado crítico entre marzo y julio de 2017. Se recogieron muestras diarias de sangre para medir la glucemia. Se evaluó la asociación de la glucemia inestable con la duración de la estancia y el resultado de la hospitalización mediante ji al cuadrado de Pearson. El valor de p<0.05 fue considerado significativo. Resultados: De las 62 personas participantes, 50 % eran hombres y 50 % mujeres. La edad media fue de 63.3 años (±21.4 años). La incidencia de glucemia inestable fue del 45.2 % y se asoció con una mayor duración de la estancia en la UCI (p<0.001) y una progresión a la muerte como resultado de la hospitalización (p=0.03). Conclusión: Entre quienes participaron, la glucemia inestable se asoció con una mayor duración de la estancia más prolongada y con progresión hacia la muerte, lo que refuerza la importancia de la actuación de enfermería para prevenir su aparición.

Resumo Introdução: O controle e avaliação dos níveis glicêmicos em pacientes críticos é um desafio e uma competência da equipe de enfermagem. Portanto, determinar as consequências da glicemia instável durante a hospitalização é chave para evidenciar a importância da gestão oportuna. Objetivo: Determinar a associação entre glicemia instável (hiperglicemia e hipoglicemia), os desfechos hospitalares e o tempo de permanência dos pacientes em uma unidade de terapia intensiva. Métodos: Um estudo de coorte prospectivo realizado com 62 pacientes a conveniência em estado crítico entre março e julho de 2017. Foram coletadas amostras diariamente de sangue para medir a glicemia. A associação entre a glicemia instável com o tempo de permanência e o desfecho da hospitalização foi avaliada pelo teste qui-quadrado de Pearson. O valor de p <0,05 foi considerado significativo. Resultados: Das 62 pessoas participantes, 50% eram homens e 50% mulheres. A idade média foi de 63,3 anos (±21,4 anos). A incidência de glicemia instável foi de 45,2% e se associou a um tempo de permanência mais prolongado na UTI (p <0,001) e uma progressão para óbito como desfecho da hospitalização (p = 0,03). Conclusão: Entre os participantes, a glicemia instável se associou a um tempo mais longo de permanência e com progressão para óbito, enfatizando a importância da actuação da equipe de enfermagem para prevenir sua ocorrência.

Abstract Introduction: The control and evaluation of glycemic levels in critically ill patients is a challenge and a responsibility of the nursing team; therefore, determining the consequences of this during hospitalization is key to demonstrate the importance of timely management. Objective: To determine the relationship between unstable glycemia (hyperglycemia and hypoglycemia), hospital length of stay, and the hospitalization outcome of patients in an Intensive Care Unit (ICU). Methods: A prospective cohort study conducted with 62 critically ill patients by convenience sampling between March and July 2017. Daily blood samples were collected to measure glycemia. The correlation of unstable glycemia with the hospital length of stay and the hospitalization outcome was assessed using Pearson's chi-square. A p-value <0.05 was considered significant. Results: Among the 62 patients, 50% were male and 50% were female. The mean age was 63.3 years (±21.4 years). The incidence of unstable glycemia was 45.2% and was associated with a longer ICU stay (p<0.001) and a progression to death as a hospitalization outcome (p=0.03). Conclusion: Among critically ill patients, unstable glycemia was associated with an extended hospital length of stay and a progression to death, emphasizing the importance of nursing intervention to prevent its occurrence.

Enzyme Inhibitory and Anti-cancer Properties of Moringa peregrina / Propiedades inhibidoras Enzimáticas y Anticancerígenas de la Moringa peregrina

Background: Moringa peregrina is widely used in the traditional medicine of the Arabian Peninsula to treat various ailments, because it has many pharmacologically active components with several therapeutic effects. Objective: This study aimed to investigate the inhibitory effect of Moringaperegrina seed ethanolic extract (MPSE) against key enzymes involved in human pathologies, such as angiogenesis (thymidine phosphorylase), diabetes (α-glucosidase), and idiopathic intracranial hypertension (carbonic anhydrase). In addition, the anticancer properties were tested against the SH-SY5Y (human neuroblastoma). Results: MPSE extract significantly inhibited α-glucosidase, thymidine phosphorylase, and carbonic anhydrase with half-maximal inhibitory concentrations (IC50) values of 303.1 ± 1.3, 471.30 ± 0.3, and 271.30 ± 5.1 µg/mL, respectively. Furthermore, the antiproliferative effect of the MPSE was observed on the SH-SY5Y cancer cell line with IC50 values of 55.1 µg/mL. Conclusions: MPSE has interesting inhibitory capacities against key enzymes and human neuroblastoma cancer cell line.

Antecedentes: La Moringa peregrina se utiliza ampliamente en la medicina tradicional de la Península Arábiga para tratar diversas dolencias, ya que posee numerosos componentes farmacológicamente activos con varios efectos terapéuticos. Objetivo: Este estudio tenía como objetivo investigar el efecto inhibidor del extracto etanólico de semillas de Moringaperegrina (MPSE) frente a enzimas clave implicadas en patologías humanas, como la angiogénesis (timidina fosforilasa), la diabetes (α-glucosidasa) y la hipertensión intracraneal idiopática (anhidrasa carbónica). Además, se comprobaron las propiedades anticancerígenas frente al SH-SY5Y (neuroblastoma humano). Resultados: El extracto de MPSE inhibió significativamente la α-glucosidasa, la timidina fosforilasa y la anhidrasa carbónica con concentraciones inhibitorias semimáximas (IC50) de 303,1 ± 1,3, 471,30 ± 0,3 y 271,30 ± 5,1 µg/mL, respectivamente. Además, se observó el efecto antiproliferativo del MPSE en la línea celular del cáncer SH-SY5Y con valores de IC50 de 55,1 µg/mL. Conclusiones: MPSE posee interesantes capacidades inhibitorias frente a enzimas clave y línea celular de neuroblastoma canceroso humano.

Mapa de evidências - Doenças Crônicas Não Transmissíveis

Este mapa de evidências apresenta estratégias para o cuidado de pessoas com as seguintes Doenças Crônicas Não Transmissíveis (DCNT): Diabetes Mellitus Tipo 2, Hipertensão Arterial sistêmica e Obesidade. A partir de uma ampla busca bibliográfica realizada para o desenvolvimento de 7 revisões rápidas, 93 estudos de revisão foram incluídos no mapa (62 revisões sistemáticas, 31 revisões sistemáticas com meta-análise). Com base na ferramenta AMSTAR2, foi avaliado o nível de confiabilidade para a evidência reportada nestes estudos, resultando em 2 revisões de nível alto, 5 revisões de nível moderado, 10 revisões de nível baixo e 76 revisões de nível criticamente baixo. Todos os estudos foram avaliados, caracterizados, categorizados por uma equipe multiprofissional organizada em pares, composta por pesquisadores que atuam nas áreas de Saúde Coletiva e Políticas Informadas por Evidências. Principais Achados: ● As revisões avaliaram o efeito de 26 intervenções distribuídas em 5 grupos: Teleconsulta/eHealth, Tratamento farmacológico, Automonitoramento/autogerenciamento, Educação, e Serviço de saúde; ● As intervenções foram associadas a 22 desfechos relacionados às DCNT distribuídos em 3 grupos: resultados clínicos, resultados não clínicos e segurança; ● No total foram encontradas 196 associações entre intervenções, desfechos e efeitos nos estudos selecionados. A maior parte das associações foi com intervenções de cuidado assistencial (32 associações) e intervenções combinadas (24 associações); ● Os desfechos que receberam maior número de associações foram: Pressão Arterial (36 associações), Peso corporal (34 associações), Adesão ao tratamento farmacológico (29 associações) e Satisfação do paciente (21 associações).

Baja disponibilidad de recursos y apoyo para atender a personas con diabetes e hipertensión arterial en las Unidades de Salud de la Familia de Paraguay

Introducción: Paraguay asumió el reto de lograr cobertura universal mediante redes basadas en Atención Primaria de la Salud con Unidades de Salud de la Familia (USF) en el primer nivel de atención. Un desafío es la atención integral ante enfermedades no transmisibles, principal causa de mortalidad en el país. Objetivo: analizar la capacidad de las USF para la atención de personas con hipertensión arterial y diabetes en el sistema nacional de salud. El diseño fue no experimental, cuantitativo, transversal, descriptivo con componente analítico. Metodología: Incluyó a 761 USF de 12 regiones sanitarias agrupados en 4 ejes territoriales. Se adaptó el método de evaluación SARA de la OMS con 75 variables, aplicando un cuestionario a profesionales de salud entre noviembre y diciembre de 2022. Se calculó índices de disponibilidad y preparación así como un índice que los integra. La medida continua de estos índices se categorizó en 3 grupos: suficiente >0,75 a 1; intermedio 0,5 a 0,75 y bajo <0,5. Resultados: Solo en el 38 % de las USF el índice de disponibilidad fue suficiente, en el 31,5 % para el índice de preparación y en el 31,1 % para el índice integrador SARA DM/HTA. El desempeño se asoció de forma significativa con el eje territorial no así con el área ni con la cobertura a población indígena Discusión: las USF presentaron limitaciones para la atención de personas con diabetes e hipertensión en estas regiones del país.

Introduction: Paraguay assumed the challenge of achieving universal coverage through networks based on Primary Health Care with Family Health Units (USF) at the first level of care. One challenge is comprehensive care for non-communicable diseases, the main cause of mortality in the country. Objective: to analyze the capacity of the USF to care for people with high blood pressure and diabetes in the national health system. The design was non-experimental, quantitative, cross-sectional, descriptive with an analytical component. Methods: It included 761 USF from 12 health regions grouped into 4 territorial axes. The WHO SARA evaluation method was adapted with 75 variables, applying a questionnaire to health professionals between November and December 2022. Availability and preparation indices were calculated as well as an index that integrates them. The continuous measurement of these indices was categorized into 3 groups: sufficient >0.75 to 1; intermediate 0.5 to 0.75 and low <0.5. Results: Only in 38.0% of the USF the availability index was sufficient, in 31.5% for the readiness index and in 31.1% for the SARA DM/HTA integrating index. The performance was significantly associated with the territorial axis, but not with the area or with the coverage of the indigenous population. Discussion: the USF presented limitations for the care of people with diabetes and hypertension in these regions of the country.

Pyrene Derivative Incorporated Ni MOF as an Enzyme Mimic for Noninvasive Salivary Glucose Detection Toward Diagnosis of Diabetes Mellitus.

Herein, we demonstrate the detection of glucose in a noninvasive and nonenzymatic manner by utilizing an extended gate field-effect transistor (EGFET) based on the organic molecule pyrene phosphonic acid (PyP4OH8) incorporated nickel metal-organic framework (NiOM-MOF). The prepared electrode responds selectively to glucose instead of sucrose, fructose, maltose, ascorbic acid, and uric acid in a 1× phosphate buffer saline solution. Also, utilizing the scanning Kelvin probe system, the sensing electrode's work function (Φ) is measured to validate the glucose-sensing mechanism. The sensitivity, detection range, response time, limit of detection, and limit of quantification of the electrode are determined to be 24.5 µA mM-1 cm-2, 20 µM to 10 mM, less than 5 s, 2.73 µM, and 8.27 µM, respectively. Most interestingly, the developed electrode follows the Michaelis-Menten kinetics, and the calculated rate constant (km) 0.07 mM indicates a higher affinity of NiOM-MOF toward glucose. The real-time analysis has revealed that the prepared electrode is sensitive to detect glucose in real human saliva, and it can be an alternative device for the noninvasive detection of glucose. Overall, the outcomes of the EGFET studies demonstrate that the prepared electrodes are well-suited for expeditious detection of glucose levels in saliva.

Multiple dietary patterns and the association between long-term air pollution exposure with type 2 diabetes risk: Findings from UK Biobank cohort study.

BACKGROUND: Evidence of modifying effect of various dietary patterns (DPs) on risk of type 2 diabetes (T2D) induced by long-term exposure to air pollution (AP) is still rather lacking, which therefore we aimed to explore in this study. METHODS: We included 78,230 UK Biobank participants aged 40-70 years with at least 2 typical 24-hour dietary assessments and without baseline diabetes. The annual average concentration of particulate matter with diameter micrometers ≤2.5 (PM2.5) and ≤10 (PM10), nitrogen dioxide (NO2), and nitrogen oxides (NOX) estimated by land use regression model was the alternative proxy of long-term AP exposure. Three well-known prior DPs such as Mediterranean diet (MED), dietary approaches to stop hypertension diet (DASH), and empirical dietary inflammatory pattern (EDIP), as well as three posterior DPs derived by the rank reduced regression model were used to capture participants' dietary habits. Cox regression models were used to estimate AP-T2D and DP-T2D associations. Modifying effect of DPs on AP-T2D association was assessed using stratified analysis and heterogeneity test. RESULTS: During a median follow-up 12.19 years, 1,693 participants developed T2D. PM2.5, PM10, NO2, and NOX significantly increased the T2D risk (P <0.05), with hazard ratio (HR) and 95% confidence interval (95% CI) for per interquartile range increase being 1.09 (1.02,1.15), 1.04 (1.00, 1.09), 1.11 (1.04, 1.18), and 1.08 (1.03, 1.14), respectively. Comparing high with low adherence, healthy DPs were associated with a 14-41% lower T2D risk. Participants with high adherence to MED, DASH, and anti-EDIP, alongside the posterior anti-oxidative dietary pattern (AODP) had attenuated and statistically non-significant NO2-T2D and NOX-T2D associations (Pmodify <0.05). CONCLUSIONS: Multiple forms of healthy DPs help reduce the T2D risk associated with long-term exposure to NO2 and NOX. Our findings indicate that adherence to healthy DPs is a feasible T2D prevention strategy for people long-term suffering from NO2 and NOX pollution.

Case report: Successful treatment of acute generalized pustular psoriasis with multiple comorbidities with oral tacrolimus.

Acute generalized pustular psoriasis (GPP) is a serious illness. Despite various treatment methods, there is still lack of effective treatment plans for refractory cases with multiple comorbidities. This case report presents a 67-year-old woman with acute GPP, stage 4 chronic kidney disease (CKD), type 2 diabetes, and cardiovascular disease, in whom skin symptom disappearance and kidney function improvement were observed after the use of oral tacrolimus as the sole therapy. This is the first report on the application of tacrolimus in the treatment of acute GPP, especially refractory acute GPP. The successful treatment indicates that there are shared immune pathways between acute GPP and CKD, and the pathways can be interdicted by tacrolimus. Further studies are needed to optimize the therapy to maximize efficacy and minimize toxicity.

Enhanced resolution profiling in twins reveals differential methylation signatures of type 2 diabetes with links to its complications.

BACKGROUND: Type 2 diabetes (T2D) susceptibility is influenced by genetic and environmental factors. Previous findings suggest DNA methylation as a potential mechanism in T2D pathogenesis and progression. METHODS: We profiled DNA methylation in 248 blood samples from participants of European ancestry from 7 twin cohorts using a methylation sequencing platform targeting regulatory genomic regions encompassing 2,048,698 CpG sites. FINDINGS: We find and replicate 3 previously unreported T2D differentially methylated CpG positions (T2D-DMPs) at FDR 5% in RGL3, NGB and OTX2, and 20 signals at FDR 25%, of which 14 replicated. Integrating genetic variation and T2D-discordant monozygotic twin analyses, we identify both genetic-based and genetic-independent T2D-DMPs. The signals annotate to genes with established GWAS and EWAS links to T2D and its complications, including blood pressure (RGL3) and eye disease (OTX2). INTERPRETATION: The results help to improve our understanding of T2D disease pathogenesis and progression and may provide biomarkers for its complications. FUNDING: Funding acknowledgements for each cohort can be found in the Supplementary Note.

Identification of Risk Factors for Gliptin-associated Bullous Pemphigoid among Diabetic Patients.

Drug-associated bullous pemphigoid has been shown to follow long-term gliptin (dipeptidyl-peptidase 4 inhibitors) intake. This study aimed at identifying risk factors for gliptin-associated bullous pemphigoid among patients with type 2 diabetes. A retrospective study was conducted in a tertiary centre among diabetic patients exposed to gliptins between the years 2008-2021. Data including demographics, comorbidities, medications, and laboratory results were collected using the MDClone platform. Seventy-six patients with type 2 diabetes treated with dipeptidyl-peptidase 4 inhibitors who subsequently developed bullous pemphigoid were compared with a cohort of 8,060 diabetic patients exposed to dipeptidyl-peptidase 4 inhibitors who did not develop bullous pemphigoid. Based on a multivariable analysis adjusted for age and other covariates, Alzheimer's disease and other dementias were significantly more prevalent in patients with bullous pemphigoid (p = 0.0013). Concomitant use of either thiazide or loop diuretics and gliptin therapy was associated with drug-associated bullous pemphigoid (p < 0.0001 for both). While compared with sitagliptin, exposure to linagliptin and vildagliptin were associated with bullous pemphigoid with an odds ratio of 5.68 and 6.61 (p < 0.0001 for both), respectively. These results suggest gliptins should be prescribed with caution to patients with type 2 diabetes with coexisting Alzheimer's and other dementias, or patients receiving long-term use of thiazides and loop diuretics. The use of sitagliptin over linagliptin and vildagliptin should be preferred in these patients.

Prevalence of common risk factors of major noncommunicable diseases among sexual and gender minorities in Kathmandu valley, Nepal.

Four noncommunicable diseases (NCDs): cardiovascular diseases, cancers, chronic respiratory diseases, and diabetes, account for 71% of global deaths. However, little is known about the NCDs risk profile of sexual and gender minorities (SGMs). This study aimed to determine the prevalence of NCDs risk factors among the SGMs of Kathmandu valley, Nepal. A cross-sectional study was conducted among SGMs in the Kathmandu valley, Nepal. We recruited 140 participants using the snowball sampling method. A face-to-face interview was done using a structured questionnaire adapted from World Health Organization Step Wise Approach to Surveillance (STEPS instruments V2.2 2019) along with blood pressure and anthropometric measurements. Data were analyzed using Statistical Package for Social Science (SPSS.v20). More than two-thirds of the participants, 96 (68.6%), had co-occurrence of NCDs risk factors. The prevalence of insufficient fruits and vegetables consumption, current smoking, harmful alcohol consumption, overweight/obesity, and hypertension were 95.7%, 40.0%, 32.9%, 28.5%, and 28.6%, respectively. There was a significant association between hypertension, harmful alcohol consumption, and overweight/obesity with the participants' age, employment status, and marital status, respectively. Study findings indicated a higher prevalence of NCDs risk factors among SGMs. National-level NCDs surveillance, policy planning, prevention, and targeted health interventions should prioritize the SGMs.

Extracellular glucose and dysfunctional insulin receptor signaling independently upregulate arterial smooth muscle TMEM16A expression.

Diabetes alters the function of ion channels responsible for regulating arterial smooth muscle membrane potential, resulting in vasoconstriction. Our prior research demonstrated an elevation of TMEM16A in diabetic arteries. Here, we explored the mechanisms involved in Transmembrane protein 16A (TMEM16A) gene expression. Our data indicate that a Snail-mediated repressor complex regulates arterial TMEM16A gene transcription. Snail expression was reduced in diabetic arteries while TMEM16A expression was upregulated. The TMEM16A promoter contained three canonical E-box sites. Electrophoretic mobility and super shift assays revealed that the -154 nt E-box was the binding site of the Snail repressor complex and binding of the repressor complex decreased in diabetic arteries. High glucose induced a biphasic contractile response in pressurized nondiabetic mouse hindlimb arteries incubated ex vivo. Hindlimb arteries incubated in high glucose also showed decreased phospho-protein kinase D1 and TMEM16A expression. In hindlimb arteries from nondiabetic mice, administration of a bolus dose of glucose activated protein kinase D1 signaling to induce Snail degradation. In both in vivo and ex vivo conditions, Snail expression exhibited an inverse relationship with the expression of protein kinase D1 and TMEM16A. In diabetic mouse arteries, phospho-protein kinase D1 increased while Akt2 and pGSK3ß levels declined. These results indicate that in nondiabetic mice, high glucose triggers a transient deactivation of the Snail repressor complex to increase arterial TMEM16A expression independently of insulin signaling. Conversely, insulin resistance activates GSK3ß signaling and enhances arterial TMEM16A channel expression. These data have uncovered the Snail-mediated regulation of arterial TMEM16A expression and its dysfunction during diabetes.NEW & NOTEWORTHY The calcium-activated chloride channel, TMEM16A, is upregulated in the diabetic vasculature to cause increased vasoconstriction. In this paper, we have uncovered that the TMEM16A gene expression is controlled by a Snail-mediated repressor complex that uncouples with both insulin-dependent and -independent pathways to allow for upregulated arterial protein expression thereby causing vasoconstriction. The paper highlights the effect of short- and long-term glucose-induced dysfunction of an ion channel expression as a causative factor in diabetic vascular disease.

Smoking is not closely related to revision for periprosthetic joint infection after primary total knee and hip arthroplasty.

BACKGROUND: The influence of smoking on the risk of periprosthetic joint infection (PJI) remains unclear. The objective was to explore the impact of smoking on PJI after primary total knee (TKA) and hip (THA) arthroplasty. HYPOTHESIS: Current smoking patients should have an increased risk of PIJ compared with nonsmoking patients. PATIENTS AND METHODS: A prospective registry-based observational cohort study was performed. A total of 4591 patients who underwent primary TKA (3076 patients) or THA (1515) were included. According to the smoking status at the time of arthroplasty, patients were classified as nonsmokers (3031 patients), ex-smokers (688), and smokers (872). Multivariate analysis included smoking status, age, gender, education level, body mass index, American Society of Anesthesiologists class, diagnosis (osteoarthritis, rheumatism), diabetes, chronic obstructive pulmonary disease, perioperative blood transfusion, site of arthroplasty (knee, hip), length of operation, and length of stay. RESULTS: There were PJI after 59 (1.9%) TKA and 27 (1.8%) THA (p=0.840). There were PJI in 47 (1.6%) nonsmokers, 12 (1.7%) ex-smokers, and 17 (1.9%) smokers (p=0.413). There were wound complications (delayed wound healing and superficial wound infection) in 34 (0.7%) nonsmokers, 9 (1.3%) in ex-smokers, and 17 (1.9%) in smokers (p=0.045). In multivariate analysis, only the female gender was a significant predictor of PJI (OR 1.3, 95% CI 1.1-2.4 [p=0.039]). Specifically, the categories of ex-smokers (OR 0.8, 95% CI 0.2-1.7 [p=0.241]) and smokers (OR 1.1, 95% CI 0.6-1.5 [p=0.052]) were not significant predictors. The 4-year arthroplasty survival with PJI as the endpoint was 99.1% (95% CI: 99.0-99.7) for nonsmokers, 99.0% (95% CI: 98.8-99.2) for ex-smokers, and 98.7% (95% CI: 98.2-99.0) for smokers was not significantly different between smoking status groups (p=0.318). DISCUSSION: Smoking was not identified as a significant predictor for PJI following primary TKA or THA. LEVEL OF EVIDENCE: III, prospective cohort study.

Factors associated with incident cardiovascular disease in patients with rheumatoid arthritis: A scoping review.

INTRODUCTION: Rheumatoid arthritis (RA) is the most common form of autoimmune inflammatory arthritis and is associated with various comorbidities including cardiovascular disease (CVD). This scoping review summarizes the current evidence on longitudinal cohort studies assessing potential factors associated with the incidence of cardiovascular events among patients with RA. METHODS: Scopus, PubMed, Ovid MEDLINE and Cochrane databases were used to identify longitudinal cohort studies investigating the incidence of CVD among RA patients. Using predetermined inclusion and exclusion criteria, two reviewers screened and extracted the relevant studies independently to map the existing literature on this topic. The extracted data included study characteristics, demographics, comorbidities, behavioural and RA-related factors. RESULTS: Thirty-three research papers were included with a mean follow-up duration of 7.8 years. The sample size of the studies ranged from 182 to 4,311,022 subjects, the mean age from 46.1 to 72.3 years, and on average, 34.6% of the participants were male. The following factors were reported to be associated with a higher incidence of CVD in RA patients: older age, male sex, co-morbid hypertension, diabetes, and/or dyslipidemia, the presence of rheumatoid factor (RF) and/or acute phase reactants. Among RA treatments, glucocorticoids were shown to increase CVD incidence while DMARDs, especially methotrexate, were associated with a lower incidence of CVD. CONCLUSION: This review offers a comprehensive summary of the current literature reporting on risk factors for CVD incidence among RA patients. Future research should focus on the less studied factors, including socioeconomic status, physical inactivity, alcohol consumption, sleep habits and dietary patterns as well as some RA-related factors such as anti-citrullinated protein antibodies and functional impairment.

Sedentary lifestyle, physical activity, and gastrointestinal diseases: evidence from mendelian randomization analysis.

BACKGROUND: The causal associations of physical activity and sedentary behavior with the risk of gastrointestinal disease are unclear. We performed a Mendelian randomization analysis to examine these associations. METHODS: Genetic instruments associated with leisure screen time (LST, an indicator of a sedentary lifestyle) and moderate-to-vigorous intensity physical activity (MVPA) at the genome-wide significance (P < 5 × 10-8) level were selected from a genome-wide association study. Summary statistics for gastrointestinal diseases were obtained from the UK Biobank study, the FinnGen study, and large consortia. Multivariable MR analyses were conducted for genetically determined LST with adjustment for MVPA and vice versa. We also performed multivariable MR with adjustment for genetically proxied smoking, body mass index (BMI), waist-to-hip ratio, type 2 diabetes, and fasting insulin for both exposures. FINDINGS: Genetically proxied longer LST was associated with an increased risk of gastrointestinal reflux, gastric ulcer, duodenal ulcer, chronic gastritis, irritable bowel syndrome, diverticular disease, Crohn's disease, ulcerative colitis, non-alcoholic fatty liver disease, alcoholic liver disease, cholangitis, cholecystitis, cholelithiasis, acute pancreatitis, chronic pancreatitis, and acute appendicitis. Most associations remained after adjustment for genetic liability to MVPA. Genetic liability to MVPA was associated with decreased risk of gastroesophageal reflux, gastric ulcer, chronic gastritis, irritable bowel syndrome, cholecystitis, cholelithiasis, acute and chronic pancreatitis. The associations attenuated albeit directionally remained after adjusting for genetically predicted LST. Multivariable MR analysis found that BMI and type 2 diabetes mediated the associations of LST and MVPA with several gastrointestinal diseases. INTERPRETATION: The study suggests that a sedentary lifestyle may play a causal role in the development of many gastrointestinal diseases. FUNDING: Natural Science Fund for Distinguished Young Scholars of Zhejiang Province (LR22H260001), Natural Science Foundation of Hunan Province (2021JJ30999), Swedish Heart-Lung Foundation (Hjärt-Lungfonden, 20210351), Swedish Research Council (Vetenskapsrådet, 2019-00977), Swedish Cancer Society (Cancerfonden), the Wellcome Trust (225790/7/22/Z), United Kingdom Research and Innovation Medical Research Council (MC_UU_00002/7) and National Institute for Health Research Cambridge Biomedical Research Centre (NHIR203312).

MITOCHONDRIA-ASSOCIATED MEMBRANES ARE NOT ALTERED IN IMMUNE CELLS IN T2D.

Metabolism research is increasingly recognizing the contributions of organelle crosstalk to metabolic regulation. Mitochondria-associated membranes (MAMs), which are structures connecting the mitochondria and endoplasmic reticulum (ER), are critical in a myriad of cellular functions linked to cellular metabolism. MAMs control calcium signaling, mitochondrial transport, redox balance, protein folding/degradation, and in some studies, metabolic health. The possibility that MAMs drive changes in cellular function in individuals with Type 2 Diabetes (T2D) is controversial. Although disruptions in MAMs that change the distance between the mitochondria and ER, MAM protein composition, or disrupt downstream signaling, can perpetuate inflammation, one key trait of T2D. However, the full scope of this structure's role in immune cell health and thus T2D-associated inflammation remains unknown. We show that human immune cell MAM proteins and their associated functions are not altered by T2D and thus unlikely to contribute to metaflammation.

A Novel Digital Twin Strategy to Examine the Implications of Randomized Control Trials for Real-World Populations.

Randomized clinical trials (RCTs) are essential to guide medical practice; however, their generalizability to a given population is often uncertain. We developed a statistically informed Generative Adversarial Network (GAN) model, RCT-Twin-GAN, that leverages relationships between covariates and outcomes and generates a digital twin of an RCT (RCT-Twin) conditioned on covariate distributions from a second patient population. We used RCT-Twin-GAN to reproduce treatment effect outcomes of the Systolic Blood Pressure Intervention Trial (SPRINT) and the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Blood Pressure Trial, which tested the same intervention but had different treatment effect results. To demonstrate treatment effect estimates of each RCT conditioned on the other RCT patient population, we evaluated the cardiovascular event-free survival of SPRINT digital twins conditioned on the ACCORD cohort and vice versa (SPRINT-conditioned ACCORD twins). The conditioned digital twins were balanced by the intervention arm (mean absolute standardized mean difference (MASMD) of covariates between treatment arms 0.019 (SD 0.018), and the conditioned covariates of the SPRINT-Twin on ACCORD were more similar to ACCORD than a sprint (MASMD 0.0082 SD 0.016 vs. 0.46 SD 0.20). Most importantly, across iterations, SPRINT conditioned ACCORD-Twin datasets reproduced the overall non-significant effect size seen in ACCORD (5-year cardiovascular outcome hazard ratio (95% confidence interval) of 0.88 (0.73-1.06) in ACCORD vs median 0.87 (0.68-1.13) in the SPRINT conditioned ACCORD-Twin), while the ACCORD conditioned SPRINT-Twins reproduced the significant effect size seen in SPRINT (0.75 (0.64-0.89) vs median 0.79 (0.72-0.86)) in ACCORD conditioned SPRINT-Twin). Finally, we describe the translation of this approach to real-world populations by conditioning the trials on an electronic health record population. Therefore, RCT-Twin-GAN simulates the direct translation of RCT-derived treatment effects across various patient populations with varying covariate distributions.