Polygenic Score for Physical Activity Is Associated with Multiple Common Diseases.

INTRODUCTION: Genetic pleiotropy, in which the same genes affect two or more traits, may partially explain the frequently observed associations between high physical activity (PA) and later reduced morbidity or mortality. This study investigated associations between PA polygenic risk scores (PRS) and cardiometabolic diseases among the Finnish population. METHODS: PRS for device-measured overall PA were adapted to a FinnGen study cohort of 218,792 individuals with genomewide genotyping and extensive digital longitudinal health register data. Associations between PA PRS and body mass index, diseases, and mortality were analyzed with linear and logistic regression models. RESULTS: A high PA PRS predicted a lower body mass index (ß = -0.025 kg·m-2 per one SD change in PA PRS, SE = 0.013, P = 1.87 × 10-80). The PA PRS also predicted a lower risk for diseases that typically develop later in life or not at all among highly active individuals. A lower disease risk was systematically observed for cardiovascular diseases (odds ratio [OR] per 1 SD change in PA PRS = 0.95, P = 9.5 × 10-19) and, for example, hypertension [OR = 0.93, P = 2.7 × 10-44), type 2 diabetes (OR = 0.91, P = 4.1 × 10-42), and coronary heart disease (OR = 0.95, P = 1.2 × 10-9). Participants with high PA PRS had also lower mortality risk (OR = 0.97, P = 0.0003). CONCLUSIONS: Genetically less active persons are at a higher risk of developing cardiometabolic diseases, which may partly explain the previously observed associations between low PA and higher disease and mortality risk. The same inherited physical fitness and metabolism-related mechanisms may be associated both with PA levels and with cardiometabolic disease risk.

Complicações metabólicas relacionadas à terapia de nutrição parenteral em pacientes hospitalizados / Metabolic complications related to parenteral nutrition therapy in hospitalized patients

Investigar as complicações metabólicas relacionadas à administração da terapia nutricional parenteral (TNP) e sua relação com o desfecho clínico de pacientes hospitalizados. Métodos: Estudo longitudinal retrospectivo realizado com pacientes internados em hospital público referência no atendimento de urgências e emergências da cidade de Goiânia no período de setembro de 2020 a fevereiro de 2021. A coleta de dados foi realizada por meio de consulta aos prontuários eletrônicos. As informações foram coletadas após o primeiro dia de uso da NP até o desfecho clínico -alta, óbito ou descontinuidade da NP. Resultados: A amostra foi constituída por 28 pacientes em uso de nutrição parenteral no hospital durante a etapa de coleta dedados. Desses pacientes a maioria era do sexo masculino, com média de idade de 46,78 anos. As indicações mais frequentes para o uso da terapia nutricional parenteral foram: repouso,abdome agudo e pós-operatório. As complicações mais prevalentes foram a hipocalemia, hipomagnesemia, uremia e a hiponatremia e o desfecho clínico mais frequente foi o óbito. Encontrou-se relação entre desfecho clínico e presença de hipernatremia (p=0,010), ocorrendo a alta hospitalar exclusivamente naqueles pacientes que não apresentaram hipernatremia. E ainda houve relação marginal (p=0,053) entre desfecho clínico e local da internação, sendo que foi mais frequente o óbito naqueles admitidos na unidade de terapia intensiva. Conclusão: Não houve associação entre a TNP e as complicações metabólicas. Todavia, observou-se relação entre hipernatremia e mortalidade, sendo esta mais prevalente em pacientes internados nas unidades de terapia intensiva (UTIs). Nessa amostra, a complicação metabólica mais observada foi a hipocalemia

To investigate the metabolic complication related to administration of the Parenteral Nutrition Therapy (PNT) and their relation to the clinical outcome of hospitalized patients. Methods: retrospective longitudinal study carried with interned patients at a public hospital of standart in the urgency and emergency care from the Goiânia city during the period from september2020 to february 2021. The data capture was realized through consultation to the electronic record. The information was collected after the first day use of NP to clinical outcome -discharge, death or discontinuation of NP. Results: The sample was composed by 28 patients in use of parenteral nutrition at hospital during the data capture. The majority of these patients were male, with mean age of 46-78 anos. The indications more frequent to the use of parenteral nutrition therapy were: rest, acute abdomen and pos-operative. The complications more prevalent were hypokalemia, hypomagnesemia, uremia and hyponatremia. And the clinical outcome more frequent was death. A relationship between clinical outcome and hypernatremia presence (p=0,010) was found, occurring the hospitalar discharge exclusively in those patients which did not submit to hypernatremia. And there was still a marginal relationship (p=0,053) between clinical outcome and hospitalization, which was more frequent the death in those admitted in intensive care units. Conclusion: There was no association between the PNT and the metabolic complications. However, there was an observed relationship between hypernatremia and mortality, while more prevalent in patients staying in the intensive care unit (ICU). In this sample, the metabolic complication most observed was hypokalemia

Mortalidad por COVID-19 en México y las enfermedades metabólicas durante el año crítico de la pandemia / COVID-19 mortality in Mexico and metabolic diseases during a critical pandemic year

Conocer la asociación específica de las enfermedades metabólicas en la mortalidad por COVID-19, ocurrida en México durante el año crítico de la pandemia de marzo 2020 a marzo 2021. Método. Se utilizó la base nacional de COVID-19 de la Dirección General de Epidemiología. Se analizaron los casos positivos que presentaron las enfermedades metabólicas: cardiovasculares, hipertensión, diabetes y obesidad. Se realizó un análisis descriptivo para conocer la distribución de los casos fallecidos y no fallecidos. Se empleó la prueba de ji cuadrada para la diferencia de las proporciones. Se utilizaron análisis de regresión logística para conocer la asociación entre las enfermedades metabólicas y la mortalidad por COVID-19 en personas positivas al virus SARS-CoV-2. Los datos fueron ajustados por edad y sexo. Resultados. Se observó la asociación de las enfermedades metabólicas en la mortalidad. La diabetes tuvo mayor porcentaje de letalidad 18,4%. Cuando se conjuntaron las enfermedades cardiovasculares y diabetes el porcentaje de letalidad subió a 31,5%; la conjunción de las enfermedades cardiovasculares, con hipertensión y diabetes fue la de mayor porcentaje de letalidad 38,7%. La obesidad fue la que tuvo menor incidencia. Conclusiones. Las enfermedades metabólicas en México son un problema de salud pública que afectó la mortalidad por covid-19. Es prioritario atender con políticas públicas preventivas y efectivas en favor de un modelo de consumo alimentario sano, acorde con las necesidades nutrimentales de la población(AU)

To know the specific association of metabolic disease on COVID-19 mortality, occurred during the critical year of the pandemic, from march 2020 to march 2021. Method: The Covid-19 national base of the General Directorate of Epidemiology was used. Positive cases of metabolic diseases were analyzed: cardiovascular disease, hypertension, diabetes and obesity. A descriptive analysis was carried out to find out the distribution of deceased and non-deceased cases. The chi-square test was used for the difference in proportions. Logistic regression analysis was used to understand the association between metabolic diseases and COVID 19 mortality in people who tested positive for the SARS-CoV-2 virus. The data were adjusted for age and gender. Results: The association of metabolic diseases on mortality was observed. Diabetes had a higher percentage of lethality 18,4%. When cardiovascular disease and diabetes were combined, the fatality rate rose to 31,5%; the combination of cardiovascular diseases, with hypertension and diabetes was the highest percentage of lethality 38,7%. Obesity had the least incidence. Conclusions: Metabolic diseases in México are a public health problem that affected COVID-19 mortality. It is a priority to deal with preventive and effective public policies in favor of a healthy food consumption model, in line with the nutritional needs of the population(AU)

Efficacy and safety of direct-acting oral anticoagulants compared to vitamin K antagonists in COVID-19 outpatients with cardiometabolic diseases.

BACKGROUND: It remains uncertain if prior use of oral anticoagulants (OACs) in COVID-19 outpatients with multimorbidity impacts prognosis, especially if cardiometabolic diseases are present. Clinical outcomes 30-days after COVID-19 diagnosis were compared between outpatients with cardiometabolic disease receiving vitamin K antagonist (VKA) or direct-acting OAC (DOAC) therapy at time of COVID-19 diagnosis. METHODS: A study was conducted using TriNetX, a global federated health research network. Adult outpatients with cardiometabolic disease (i.e. diabetes mellitus and any disease of the circulatory system) treated with VKAs or DOACs at time of COVID-19 diagnosis between 20-Jan-2020 and 15-Feb-2021 were included. Propensity score matching (PSM) was used to balance cohorts receiving VKAs and DOACs. The primary outcomes were all-cause mortality, intensive care unit (ICU) admission/mechanical ventilation (MV) necessity, intracranial haemorrhage (ICH)/gastrointestinal bleeding, and the composite of any arterial or venous thrombotic event(s) at 30-days after COVID-19 diagnosis. RESULTS: 2275 patients were included. After PSM, 1270 patients remained in the study (635 on VKAs; 635 on DOACs). VKA-treated patients had similar risks and 30-day event-free survival than patients on DOACs regarding all-cause mortality, ICU admission/MV necessity, and ICH/gastrointestinal bleeding. The risk of any arterial or venous thrombotic event was 43% higher in the VKA cohort (hazard ratio 1.43, 95% confidence interval 1.03-1.98; Log-Rank test p = 0.029). CONCLUSION: In COVID-19 outpatients with cardiometabolic diseases, prior use of DOAC therapy compared to VKA therapy at the time of COVID-19 diagnosis demonstrated lower risk of arterial or venous thrombotic outcomes, without increasing the risk of bleeding.

Metabolic dysfunction-associated fatty liver disease is associated with increased all-cause mortality in the United States.

BACKGROUND & AIMS: Recently, international experts proposed redefining non-alcoholic fatty liver disease (NAFLD) as metabolic dysfunction-associated fatty liver disease (MAFLD), based on modified criteria. It is suspected that outcomes such as mortality may differ for these clinical entities. We studied the impact of MAFLD and NAFLD on all-cause and cause-specific mortality in US adults. METHODS: We analyzed data from 7,761 participants in the Third National Health and Nutrition Examination Survey and their linked mortality through 2015. NAFLD was diagnosed by ultrasonographic evidence of hepatic steatosis without other known liver diseases. MAFLD was defined based on the criteria proposed by an international expert panel. The Cox proportional hazard model was used to study all-cause mortality and cause-specific mortality between MAFLD and NAFLD, with adjustments for known risk factors. RESULTS: During a median follow-up of 23 years, individuals with MAFLD had a 17% higher risk of all-cause mortality (hazard ratio [HR] 1.17; 95% CI 1.04-1.32). Furthermore, MAFLD was associated with a higher risk of cardiovascular mortality. NAFLD per se did not increase the risk of all-cause mortality. Individuals who met both definitions had a higher risk of all-cause mortality (HR 1.13, 95% CI 1.00-1.26), while individuals who met the definition for MAFLD but not NAFLD had a 1.7-fold higher risk of all-cause mortality (HR 1.66, 95% CI 1.19-2.32). Estimates for all-cause mortality were higher for those with advanced fibrosis and MAFLD than for those with advanced fibrosis and NAFLD. CONCLUSIONS: In this US population-based study, MAFLD was associated with an increased risk of all-cause mortality, while NAFLD demonstrated no association with all-cause mortality after adjusting for metabolic risk factors. LAY SUMMARY: Our findings provide further support for the idea that non-alcoholic fatty liver disease (NAFLD) is a part of a broader multi-system disease that also includes obesity, diabetes, high blood pressure, and high cholesterol. Therefore, re-defining NAFLD as metabolic dysfunction-associated fatty liver disease (MAFLD) may help improve our understanding of predictors that increase the risk of death.

Ten-year risk of fatal cardiovascular disease and its association with metabolic risk factors among waste pickers in South Africa.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death among non-communicable diseases in South Africa. Several metabolic risk factors contribute to the development of CVD. Informal workers such as waste pickers could be unhealthy lifestyle naive, and most public health research on CVD does not include this understudied population. This study estimated the 10-year risk of fatal CVD and its association with metabolic risk factors in an understudied study population of waste pickers in Johannesburg, South Africa. METHODS: A cross-sectional survey was conducted among waste pickers in two landfill sites in Johannesburg. We used the Systematic Coronary Risk Evaluation (SCORE) risk charts to estimate the 10-year risk of fatal CVD. We then employed ordinary least squares regression to assess the association between the 10-year risk of fatal CVD with metabolic risk factors. Other variables adjusted in the regression model were HIV status, education, income, injuries from work, clinic visits in the previous 12 months, and alcohol consumption. RESULTS: A total of 370 waste pickers were included in this analysis, 265 (73.41%) were males. The mean age of the participants was 34 years. The majority were between the age of 20 and 39 years. More than 55% of the waste pickers did not visit a clinic in the previous 12 months, and 68.57% were smoking. The 10-year survival probability from CVD was more than 99% for both males and females. In the multivariable regression model, elevated blood glucose showed a non-significant increase in the mean percentage of 10-year risk of fatal CVD. Waste pickers who were overweight/obese, and hypertensive had high statistically significant mean percentages of the 10-year risk of fatal CVD compared to those who did not have the metabolic risk factors. CONCLUSIONS: Prevention of 10-year risk of fatal CVD in this understudied population of waste pickers should target the control of obesity, hypertension, and diabetes. Health awareness and education for waste pickers will be an important step in reducing the burden of these metabolic risk factors. We further recommend that health systems should recognize waste pickers as a high-risk group and consider extensive CVDs surveillance.

Indirect impact of the COVID-19 pandemic on hospitalisations for cardiometabolic conditions and their management: A systematic review.

BACKGROUND: The Coronavirus disease 2019 (COVID-19) pandemic has led to a dramatic crisis in health care systems worldwide. These may have significant implications for the management of cardiometabolic diseases. We conducted a systematic review of published evidence to assess the indirect impact of the COVID-19 pandemic on hospitalisations for cardiovascular diseases and their management. METHODS: Studies that evaluated volume of hospitalisations for cardiometabolic conditions and their management with comparisons between the COVID-19 and pre-COVID periods were identified from MEDLINE, Embase and the reference list of relevant studies from January 2020 to 25 February 2021. RESULTS: We identified 103 observational studies, with most studies assessing hospitalisations for acute cardiovascular conditions such as acute coronary syndrome, ischemic strokes and heart failure. About 89% of studies reported a decline in hospitalisations during the pandemic compared to pre-pandemic times, with reductions ranging from 20.2 to 73%. Severe presentation, less utilization of cardiovascular procedures, and longer patient- and healthcare-related delays were common during the pandemic. Most studies reported shorter length of hospital stay during the pandemic than before the pandemic (1-8 vs 2-12 days) or no difference in length of stay. Most studies reported no change in in-hospital mortality among hospitalised patients. CONCLUSION: Clinical care of patients for acute cardiovascular conditions, their management and outcomes have been adversely impacted by the COVID-19 pandemic. Patients should be educated via population-wide approaches on the need for timely medical contact and health systems should put strategies in place to provide timely care to patients at high risk. SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2021: CRD42021236102.

Cardiometabolic Outcomes and Mortality in Patients with Adrenal Adenomas in a Population-based Setting.

CONTEXT: While adrenal adenomas have been linked with cardiovascular morbidity in convenience samples of patients from specialized referral centers, large-scale population-based data are lacking. OBJECTIVE: To determine the prevalence and incidence of cardiometabolic disease and assess mortality in a population-based cohort of patients with adrenal adenomas. DESIGN: Population-based cohort study. SETTING: Olmsted County, Minnesota, USA. PATIENTS: Patients diagnosed with adrenal adenomas without overt hormone excess and age- and sex-matched referent subjects without adrenal adenomas. MAIN OUTCOME MEASURE: Prevalence, incidence of cardiometabolic outcomes, mortality. RESULTS: (Adrenal adenomas were diagnosed in 1004 patients (58% women, median age 63 years) from 1/01/1995 to 12/31/2017. At baseline, patients with adrenal adenomas were more likely to have hypertension [adjusted odds ratio (aOR) 1.96, 95% CI 1.58-2.44], dysglycemia (aOR 1.63, 95% CI 1.33-2.00), peripheral vascular disease (aOR 1.59, 95% CI 1.32-2.06), heart failure (aOR 1.64, 95% CI 1.15-2.33), and myocardial infarction (aOR 1.50, 95% CI 1.02-2.22) compared to referent subjects. During median follow-up of 6.8 years, patients with adrenal adenomas were more likely than referent subjects to develop de novo chronic kidney disease [adjusted hazard ratio (aHR) 1.46, 95% CI 1.14-1.86], cardiac arrhythmia (aHR 1.31, 95% CI 1.08-1.58), peripheral vascular disease (aHR 1.28, 95% CI 1.05-1.55), cardiovascular events (aHR 1.33, 95% CI 1.01-1.73), and venous thromboembolic events (aHR 2.15, 95% CI 1.48-3.13). Adjusted mortality was similar between the 2 groups. CONCLUSION: Adrenal adenomas are associated with an increased prevalence and incidence of adverse cardiometabolic outcomes in a population-based cohort.

Moderate Consumption of Beer and Its Effects on Cardiovascular and Metabolic Health: An Updated Review of Recent Scientific Evidence.

There is growing interest in the potential health-related effects of moderate alcohol consumption and, specifically, of beer. This review provides an assessment of beer-associated effects on cardiovascular and metabolic risk factors to identify a consumption level that can be considered "moderate". We identified all prospective clinical studies and systematic reviews that evaluated the health effects of beer published between January 2007 and April 2020. Five of six selected studies found a protective effect of moderate alcohol drinking on cardiovascular disease (beer up to 385 g/week) vs. abstainers or occasional drinkers. Four out of five papers showed an association between moderate alcohol consumption (beer intake of 84 g alcohol/week) and decreased mortality risk. We concluded that moderate beer consumption of up to 16 g alcohol/day (1 drink/day) for women and 28 g/day (1-2 drinks/day) for men is associated with decreased incidence of cardiovascular disease and overall mortality, among other metabolic health benefits.

Poor Metabolic Health Increases COVID-19-Related Mortality in the UK Biobank Sample.

Previous studies link obesity and components of metabolic health, such as hypertension or inflammation, to increased hospitalizations and mortality of patients with COVID-19. Here, in two overlapping samples of over 1,000 individuals from the UK Biobank we investigate whether metabolic health as measured by waist circumference, dyslipidemia, hypertension, type 2 diabetes, and systemic inflammation is related to increased COVID-19 infection and mortality rate. Using logistic regression and controlling for confounding variables such as socioeconomic status, age, sex or ethnicity, we find that individuals with worse metabolic health (measured on average eleven years prior to 2020) have an increased risk for COVID-19-related death (adjusted odds ratio: 1.75). We also find that specific factors contributing to increased mortality are increased serum glucose levels, systolic blood pressure and waist circumference.

Non-COVID-19 patients in times of pandemic: Emergency department visits, hospitalizations and cause-specific mortality in Northern Italy.

The COVID-19 pandemic forced healthcare services organization to adjust to mutating healthcare needs. Not exhaustive data are available on the consequences of this on non-COVID-19 patients. The aim of this study was to assess the impact of the pandemic on non-COVID-19 patients living in a one-million inhabitants' area in Northern Italy (Bologna Metropolitan Area-BMA), analyzing time trends of Emergency Department (ED) visits, hospitalizations and mortality. We conducted a retrospective observational study using data extracted from BMA healthcare informative systems. Weekly trends of ED visits, hospitalizations, in- and out-of-hospital, all-cause and cause-specific mortality between December 1st, 2019 to May 31st, 2020, were compared with those of the same period of the previous year. Non-COVID-19 ED visits and hospitalizations showed a stable trend until the first Italian case of COVID-19 has been recorded, on February 19th, 2020, when they dropped simultaneously. The reduction of ED visits was observed in all age groups and across all severity and diagnosis groups. In the lockdown period a significant increase was found in overall out-of-hospital mortality (43.2%) and cause-specific out-of-hospital mortality related to neoplasms (76.7%), endocrine, nutritional and metabolic (79.5%) as well as cardiovascular (32.7%) diseases. The pandemic caused a sudden drop of ED visits and hospitalizations of non-COVID-19 patients during the lockdown period, and a concurrent increase in out-of-hospital mortality mainly driven by deaths for neoplasms, cardiovascular and endocrine diseases. As recurrencies of the COVID-19 pandemic are underway, the scenario described in this study might be useful to understand both the population reaction and the healthcare system response at the early phases of the pandemic in terms of reduced demand of care and systems capability in intercepting it.

Indicadores de desigualdad y mortalidad por enfermedades cardiometabólicas en Guatemala / Inequality indicators and cardiometabolic diseases mortality in Guatemalahttps

La medición de las desigualdades en salud al interior de los países de ingresos bajos y medios es necesaria para la planificación, monitoreo y evaluación de intervenciones de salud pública, especialmente para problemas que contribuyen altamente a la carga de enfermedad, como las enfermedades cardiometabólicas. El objetivo de este estudio fue caracterizar los patrones de desigualdad de las tasas de mortalidad para las principales causas cardiometabólicas en Guatemala. Se usó datos del Censo Nacional de Población, y estadísticas oficiales de de-función de 2018 para calcular tasas crudas de mortalidad para diabetes (DM), infarto agudo de miocardio (IAM), y accidente cerebrovascular (ACV). Se calcularon indicadores simples y complejos de desigualdad absoluta y relativa (diferencia, razón, índice de pendiente, índice de concentración, distancia de la media, índice de Theil, riesgo atribuible poblacional, y porcentaje de riesgo atribuible poblacional) para seis dimensiones de desigualdad: sexo, pueblo de pertenencia, nivel educativo, tipo de ocupación, departamento y municipio. Se documentaron 6,445 muertes por DM, 5,761 por IAM, y 3,218 por ACV. Los indicadores mostraron marcadas desigualdades para las seis dimensiones estudiadas. El patrón de desigualdad predominante para sexo, pueblo de pertenencia y departamento fue de privación masiva. Para nivel educativo y ocupación predominó un patrón de incrementos escalonados. Se identificó exclusión marginal superpuesta en nivel educativo, ocupación y municipio. Se concluye que los patrones de desigualdad de las tasas de mortalidad para estas tres enfermedades sugieren la superposición de patrones de privación masiva, incrementos escalonados, y exclusión marginal.

Measuring health inequalities within low- and middle-income countries is needed for planning, monitoring, and evaluation of public health interventions, especially for problems that represent a high burden of disease, like cardio metabolic diseases. The goal of this study was to characterize inequality patterns in mortality rates from cardio metabolic causes in Guatemala. Data from the 2018 National Population Census, and official vital statistics were used to estimate crude mortality rates for diabetes (DM), acute myocardial infarction (IAM), and stroke (ACV). Simple and complex indicators of absolute and relative inequality (difference, ratio, slope index, concentration index, distance from the mean, Theil index, population attributable risk, and percentage of popula-tion attributable risk) were calculated for six dimensions of inequality: sex, race/ethnicity, education level, type of occupation, department, and municipality. A total of 6,445 DM deaths, 5,761 IAM deaths, and 3,218 ACV deaths were documented. Indicators showed marked inequalities for the six dimensions studied. Massive deprivation was the predominant inequality pattern for sex, race/ethnicity, and department. Staggered increments were iden-tified for education level and type of occupation. Overlapping marginal exclusion was found for education level, occupation, and municipality. We conclude that inequality patterns found for the three causes of death suggest overlapping patterns of mass deprivation, staggered increments, and marginal exclusion.

PPARγ agonists delay age-associated metabolic disease and extend longevity.

Aging leads to a number of disorders caused by cellular senescence, tissue damage, and organ dysfunction. It has been reported that anti-inflammatory and insulin-sensitizing compounds delay, or reverse, the aging process and prevent metabolic disorders, neurodegenerative disease, and muscle atrophy, improving healthspan and extending lifespan. Here we investigated the effects of PPARγ agonists in preventing aging and increasing longevity, given their known properties in lowering inflammation and decreasing glycemia. Our molecular and physiological studies show that long-term treatment of mice at 14 months of age with low doses of the PPARγ ligand rosiglitazone (Rosi) improved glucose metabolism and mitochondrial functionality. These effects were associated with decreased inflammation and reduced tissue atrophy, improved cognitive function, and diminished anxiety- and depression-like conditions, without any adverse effects on cardiac and skeletal functionality. Furthermore, Rosi treatment of mice started when they were 14 months old was associated with lifespan extension. A retrospective analysis of the effects of the PPARγ agonist pioglitazone (Pio) on longevity showed decreased mortality in patients receiving Pio compared to those receiving a PPARγ-independent insulin secretagogue glimepiride. Taken together, these data suggest the possibility of using PPARγ agonists to promote healthy aging and extend lifespan.

Mortality patterns in patients with diabetes mellitus at a Nigerian tertiary hospital: A 10-Year autopsy study.

OBJECTIVES: Diabetes mellitus (DM) is a global health problem with associated high morbidity and mortality. This study was a retrospective review of post-mortem examination findings of hospitalised patients with DM for causes of death. MATERIALS AND METHODS: A retrospective, cross-sectional autopsy review of all the patients with DM in our hospital between January 2008 and December 2017 was conducted. The causes of death were classified into cardiovascular, cerebrovascular, acute diabetic emergencies, infection, cancers and unnatural deaths. The demographic data and clinicopathological parameters were extracted, and the data were analysed using the SPSS software version 23. RESULTS: A total of 1092 cases of autopsy were done within the study period, of which 91 cases were on patients with diabetes accounting for 8.3%. Infections with sepsis were the major cause of death, accounting for 51.6% followed by cardiovascular diseases (16.5%), cancers (14.3%), acute diabetic emergencies (6.6%) and cerebrovascular accidents (6.6%), with renal complications and road traffic accidents accounting for 2.2% each. Patients' age ranged from 31 to 84 years, with a modal age of 57 years. There was a male predominance with a male-to-female ratio of 1.5:1. Systemic hypertension co-morbidity was statistically significantly more common in patients aged 60 and above (P = 0.035). The most common lesion observed in the kidneys was benign nephrosclerosis (43.2%). CONCLUSIONS: This study suggests that majority of our patients with diabetes mellitus die from infections with attendant sepsis. Older patients appear to have co-morbid systemic hypertension. Patient education on infection prevention and prompt treatment might be life-saving.

Metabolic Disorders with Kidney Transplant.

Metabolic disorders are highly prevalent in kidney transplant candidates and recipients and can adversely affect post-transplant graft outcomes. Management of diabetes, hyperparathyroidism, and obesity presents distinct opportunities to optimize patients both before and after transplant as well as the ability to track objective data over time to assess a patient's ability to partner effectively with the health care team and adhere to complex treatment regimens. Optimization of these particular disorders can most dramatically decrease the risk of surgical and cardiovascular complications post-transplant. Approximately 60% of nondiabetic patients experience hyperglycemia in the immediate post-transplant phase. Multiple risk factors have been identified related to development of new onset diabetes after transplant, and it is estimated that upward of 7%-30% of patients will develop new onset diabetes within the first year post-transplant. There are a number of medications studied in the kidney transplant population for diabetes management, and recent data and the risks and benefits of each regimen should be optimized. Secondary hyperparathyroidism occurs in most patients with CKD and can persist after kidney transplant in up to 66% of patients, despite an initial decrease in parathyroid hormone levels. Parathyroidectomy and medical management are the options for treatment of secondary hyperparathyroidism, but there is no randomized, controlled trial providing clear recommendations for optimal management, and patient-specific factors should be considered. Obesity is the most common metabolic disorder affecting the transplant population in both the pre- and post-transplant phases of care. Not only does obesity have associations and interactions with comorbid illnesses, such as diabetes, dyslipidemia, and cardiovascular disease, all of which increase morbidity and mortality post-transplant, but it also is intimately inter-related with access to transplantation for patients with kidney failure. We review these metabolic disorders and their management, including data in patients with kidney transplants.

Impact of graft-versus-host disease on the clinical outcome of allogeneic hematopoietic stem cell transplantation for non-malignant diseases.

The impact of acute and chronic graft-versus-host disease (GVHD) on clinical outcomes was retrospectively analyzed in 960 patients with non-malignant diseases (NMD) who underwent a first allogeneic hematopoietic stem cell transplantation (HSCT). Grade III-IV acute GVHD (but not grade I-II) was significantly associated with a lower rate of overall survival (OS), and higher non-relapse mortality (NRM) than that seen in patients without acute GVHD. Extensive (but not limited) GVHD was significantly associated with a lower OS rate and higher NRM than that seen in patients without chronic GVHD. Any grade of acute (but not chronic) GVHD was significantly associated with a lower incidence of relapse and a lower proportion of patients requiring a second HSCT or donor lymphocyte infusion for graft failure or mixed chimerism, but its impact on OS was almost negligible. Acute GVHD was significantly associated with lower OS rates in all disease groups, whereas chronic GVHD was significantly associated with lower OS rates in the primary immunodeficiency and histiocytosis groups. In conclusion, acute and chronic GVHD, even if mild, was associated with reduced OS in patients receiving HSCT for NMD and effective strategies should, therefore, be implemented to minimize GVHD.

Role of gut microbiota in sex- and diet-dependent metabolic disorders that lead to early mortality of androgen receptor-deficient male mice.

The gut microbiota is involved in metabolic disorders induced by androgen deficiency after sexual maturation in males (late-onset hypogonadism). However, its role in the energy metabolism of congenital androgen deficiency (e.g., androgen-insensitive syndrome) remains elusive. Here, we examined the link between the gut microbiota and metabolic disease symptoms in androgen receptor knockout (ARKO) mouse by administering high-fat diet (HFD) and/or antibiotics. HFD-fed male, but not standard diet-fed male or HFD-fed female, ARKO mice exhibited increased feed efficiency, obesity with increased visceral adipocyte mass and hypertrophy, hepatic steatosis, glucose intolerance, insulin resistance, and loss of thigh muscle. In contrast, subcutaneous fat mass accumulated in ARKO mice irrespective of the diet and sex. Notably, all HFD-dependent metabolic disorders observed in ARKO males were abolished after antibiotics administration. The ratios of fecal weight-to-food weight and cecum weight-to-body weight were specifically reduced by ARKO in HFD-fed males. 16S rRNA sequencing of fecal microbiota from HFD-fed male mice revealed differences in microbiota composition between control and ARKO mice. Several genera or species (e.g., Turicibacter and Lactobacillus reuteri, respectively) were enriched in ARKO mice, and antibiotics treatment spoiled the changes. Furthermore, the life span of HFD-fed ARKO males was shorter than that of control mice, indicating that androgen deficiency causes metabolic dysfunctions leading to early death. These findings also suggest that AR signaling plays a role in the prevention of metabolic dysfunctions, presumably by influencing the gut microbiome, and improve our understanding of health consequences in subjects with hypogonadism and androgen insensitivity.

Comparison of the beta-hydroxybutyrate, glucose, and lactate concentrations derived from postmortem proton magnetic resonance spectroscopy and biochemical analysis for the diagnosis of fatal metabolic disorders.

PURPOSE: The detection and quantification of metabolites relevant for the diagnosis of fatal metabolic disorders by proton magnetic resonance spectroscopy (1H-MRS) was recently demonstrated. This prospective study aimed to compare the concentrations of beta-hydroxybutyrate (BHB), glucose (GLC), and lactate (LAC) derived from both biochemical analyses and 1H-MRS for the diagnosis of fatal metabolic disorders. METHODS: In total, 20 cases with suspected fatal metabolic disorders were included in the study. For the agreement based on thresholds, the concentrations of BHB and GLC in the vitreous humor (VH) from the right vitreous and in cerebrospinal fluid (CSF) from the right lateral ventricle were derived from 1H-MRS and biochemical analyses. The predefined thresholds for pathological elevations were 2.5 mmol/l for BHB and 10 mmol/l for GLC based on the literature. In addition, concentrations of the same metabolites in white matter (WM) tissue from the corona radiata of the right hemisphere were analyzed experimentally using both methods. To enable the biochemical analysis, a dialysate of WM tissue was produced. For all three regions, the LAC concentration was determined by both methods. RESULTS: The conclusive agreement based on thresholds was almost perfect between both methods with only one disagreement in a total of 70 comparisons due to the interference of a ferromagnetic dental brace. The differences in the concentrations between both methods showed high standard deviations. Confidence intervals of the bias not including 0 were found in CSF-GLC (- 3.1 mmol/l), WM-GLC (1.1 mmol/l), and WM-LAC (- 6.5 mmol/l). CONCLUSION: Despite a considerable total error attributable to both methods, MRS derives the same forensic conclusions as conventional biochemical analyses. An adaptation of the protocol to reduce the detected errors and more data are needed for the long-term validation of MRS for the diagnosis of fatal metabolic disorders. The production of WM dialysates cannot be recommended due to high glycolytic loss.

Risks of cause-specific mortality in offspring of pregnancies complicated by hypertensive disease of pregnancy.

BACKGROUND: Fetal environment has a substantial influence on an individual's health throughout their life course. Animal models of hypertensive disease of pregnancy have demonstrated adverse health outcomes among offspring exposed to hypertensive disease of pregnancy in utero. Although there are numerous descriptions of the neonatal, infant, and pediatric outcomes of human offspring affected by hypertensive disease of pregnancy, there are few data in US populations on later life outcomes, including mortality. OBJECTIVE: To assess risk for early mortality among offspring of pregnancies complicated by hypertensive disease of pregnancy. STUDY DESIGN: This is a retrospective cohort study of offspring born to women with singleton or twin pregnancies between 1947 and 1967 with birth certificate information in the Utah Population Database. We identified offspring from delivery diagnoses of gestational hypertension, preeclampsia, or eclampsia. Offspring from these pregnancies (exposed) were matched to offspring of pregnancies without hypertensive disease of pregnancy (unexposed) by maternal age at delivery, birth year, sex, and multiple gestation. We also identified unexposed siblings of exposed offspring for a separate sibling analysis. Mortality follow-up of all offspring continued through 2016, at which time they would have been 49-69 years old. Adjusted hazard ratios for cause-specific mortality comparing exposed with unexposed offspring were estimated using Cox proportional hazard models. RESULTS: We compared mortality risks for 4050 exposed offspring and 6989 matched unexposed offspring from the general population and 7496 unexposed siblings. Mortality risks due to metabolic, respiratory, digestive, nervous, and external causes of death did not differ between exposed and unexposed groups. Mortality risks from cardiovascular disease were greater in exposed offspring compared with unexposed offspring (adjusted hazard ratio, 1.57; 95% confidence interval, 1.16-2.12). In sex-specific models among the general population, cardiovascular disease mortality was significantly associated with exposure among male patients (adjusted hazard ratio, 1.92; 95% confidence interval, 1.27-2.88) but not among female patients (adjusted hazard ratio, 0.97; 95% confidence interval, 0.81-1.94). An interaction between hypertensive disease of pregnancy exposure and birth order on cardiovascular disease mortality was significant (P=.047), suggesting that the effect of hypertensive disease of pregnancy on cardiovascular disease mortality increased with higher birth order. Among siblings, the association between hypertensive disease of pregnancy exposure and cardiovascular disease mortality was not significant (adjusted hazard ratio, 1.39; 95% confidence interval, 0.99-1.95), and this was also true for sex-specific analyses of males (adjusted hazard ratio, 1.26; 95% confidence interval, 0.81-1.94) and females (adjusted hazard ratio, 1.71; 95% confidence interval, 0.96-3.04). As in the general population, there was a significant interaction between hypertensive disease of pregnancy exposure and birth order on cardiovascular disease mortality (P=.011). CONCLUSION: In a US population, overall mortality risks are greater for offspring of pregnancies complicated by hypertensive disease of pregnancy compared with unexposed offspring. Among siblings, there was not a significant association between hypertensive disease of pregnancy exposure and cardiovascular disease mortality.

Effect of Androgen Deprivation Therapy on Metabolic Complications and Cardiovascular Risk.

Androgen deprivation therapy (ADT) has been the cornerstone of prostate cancer treatment. ADT delays cancer progression, alleviates cancer-related symptoms, and is associated with survival gains. Despite these established benefits, the extended duration of therapy comes with known side effects. Furthermore, research from the past decade has generated increased awareness for more potentially lethal cardiometabolic consequences of ADT. In this review, we explore the relationship between ADT and cardiometabolic effects. Current literature on this complex relationship remains conflicting, due to a variety of factors, including study design (randomized vs. observational), treatment decision-making, and patient factors. Looking to the future, a combination of well-designed, randomized controlled trials and high-quality, real-world evidence are needed to definitely establish any ADT cardiovascular safety signal and to evaluate the efficacy of potential screening and therapeutic interventions. Furthermore, a collaborative, integrated approach among all health care professionals is critical to accurately delineate patients' potential risk/benefit treatment options.