Delayed Closure of Guillotine Lower Extremity Amputation in Obese Patients is Associated with Increased Mortality.

BACKGROUND: Staged surgery with open guillotine amputation (OGA) prior to a definitive major lower extremity amputation (LEA) has been shown to be effective for sepsis control and improving wound healing. Studies have evaluated postoperative complications including infection, return to the operating room for re-amputation, and amputation failure following OGA. However, the role of timing to close OGA for predictive outcomes remains poorly understood. We aim to assess outcomes of major LEA related to the time of OGA closure. METHODS: Data from patients who underwent major LEA from 2015 to 2021 were collected retrospectively. The study included all patients undergoing below-knee, through-knee, or above-knee amputations. Next, patients who had OGA prior to a definitive amputation were selected. Patients who died before amputation closure were excluded. Postamputation outcomes such as surgical site infection, postoperative sepsis, postoperative ambulation, hospital length of stay, and 30-day, 1-year, and 5-year mortality were reviewed. The study cohort was stratified by demographics and comorbidities. Receiver operating characteristic curve analysis was performed to determine the time of closure (TOC) cutoff value. Univariate and multivariate analysis was performed to assess outcomes. Statistical significance was set at P < 0.05. RESULTS: Of 688 patients who underwent major LEA, 322 underwent staged amputation with OGA before the formalization procedure and were included. The TOC ranged from 1-47 days with a median of 4 days (interquartile range from 3 to 7). The optimal TOC point of 8 days (ranging from 2-42 days) in obese patients (199/322) for predicting mortality showed the largest area under the curve (0.709) with 64.71% sensitivity and 78.3% specificity. Patients who are obese and grouped in TOC less than 8 days had no 30-day mortality, significantly lower 1-year mortality, better survival, and a lower rate of deep venous thrombosis complication. There was no significant difference in length of stay, postoperative surgical site infection, sepsis, and ambulation between the 2 subgroups of obese patients. Multivariable analysis showed that gender, chronic kidney disease, and postoperative ambulation independently predict overall mortality in obese patients. CONCLUSIONS: TOC cutoff in obese patients showed statistically significant results in predicting mortality. Our findings indicated better survival in obese patients with a lower TOC (less than 8 days). This emphasizes the importance of earlier closure of OGA in obese patients.

Association of Bariatric Surgery With Cancer Risk and Mortality in Adults With Obesity.

Importance: Obesity increases the incidence and mortality from some types of cancer, but it remains uncertain whether intentional weight loss can decrease this risk. Objective: To investigate whether bariatric surgery is associated with lower cancer risk and mortality in patients with obesity. Design, Setting, and Participants: In the SPLENDID (Surgical Procedures and Long-term Effectiveness in Neoplastic Disease Incidence and Death) matched cohort study, adult patients with a body mass index of 35 or greater who underwent bariatric surgery at a US health system between 2004 and 2017 were included. Patients who underwent bariatric surgery were matched 1:5 to patients who did not undergo surgery for their obesity, resulting in a total of 30 318 patients. Follow-up ended in February 2021. Exposures: Bariatric surgery (n = 5053), including Roux-en-Y gastric bypass and sleeve gastrectomy, vs nonsurgical care (n = 25 265). Main Outcomes and Measures: Multivariable Cox regression analysis estimated time to incident obesity-associated cancer (a composite of 13 cancer types as the primary end point) and cancer-related mortality. Results: The study included 30 318 patients (median age, 46 years; median body mass index, 45; 77% female; and 73% White) with a median follow-up of 6.1 years (IQR, 3.8-8.9 years). The mean between-group difference in body weight at 10 years was 24.8 kg (95% CI, 24.6-25.1 kg) or a 19.2% (95% CI, 19.1%-19.4%) greater weight loss in the bariatric surgery group. During follow-up, 96 patients in the bariatric surgery group and 780 patients in the nonsurgical control group had an incident obesity-associated cancer (incidence rate of 3.0 events vs 4.6 events, respectively, per 1000 person-years). The cumulative incidence of the primary end point at 10 years was 2.9% (95% CI, 2.2%-3.6%) in the bariatric surgery group and 4.9% (95% CI, 4.5%-5.3%) in the nonsurgical control group (absolute risk difference, 2.0% [95% CI, 1.2%-2.7%]; adjusted hazard ratio, 0.68 [95% CI, 0.53-0.87], P = .002). Cancer-related mortality occurred in 21 patients in the bariatric surgery group and 205 patients in the nonsurgical control group (incidence rate of 0.6 events vs 1.2 events, respectively, per 1000 person-years). The cumulative incidence of cancer-related mortality at 10 years was 0.8% (95% CI, 0.4%-1.2%) in the bariatric surgery group and 1.4% (95% CI, 1.1%-1.6%) in the nonsurgical control group (absolute risk difference, 0.6% [95% CI, 0.1%-1.0%]; adjusted hazard ratio, 0.52 [95% CI, 0.31-0.88], P = .01). Conclusions and Relevance: Among adults with obesity, bariatric surgery compared with no surgery was associated with a significantly lower incidence of obesity-associated cancer and cancer-related mortality.

Obesidad en la mortalidad de pacientes con insuficiencia cardiaca y fracción de eyección reducida / Obesity in the mortality of patients with heart failure and reduced ejection fraction

Introducción: La asociación entre obesidad y menor mortalidad en pacientes con insuficiencia cardiaca y fracción de eyección del ventrículo izquierdo es controversial. Objetivo: Evaluar la asociación entre obesidad y mortalidad en pacientes con insuficiencia cardiaca y fracción de eyección reducida. Métodos: Se realizó un estudio observacional de cohorte prospectivo en pacientes con insuficiencia cardiaca y fracción de eyección reducida en el período comprendido entre enero del 2010 y diciembre de 2020. La muestra quedó conformada por 173 pacientes. Se evaluó la supervivencia mediante el método de Kaplan-Meier, para estimar el efecto del pronóstico de la variable obesidad sobre la mortalidad. Se utilizó el modelo de regresión de Cox. Resultados: Se observó que los pacientes obesos al año de seguimiento tuvieron mejor supervivencia que los que presentaron normopeso (0,6 versus 0,8) a los cinco años presentaron similar supervivencia los tres subgrupos de índice masa corporal (0,6), la mayor mortalidad la presentaron los pacientes bajo peso. La curva de éstos últimos, se distancia del resto de las categorías de IMC, Log Rank p= 0,001. En el modelo de regresión de Cox la obesidad presentó un odd ration OR=´1,159 p=0,648 (intervalo de confianza de 0,615-2,181). Conclusiones: En los pacientes con insuficiencia cardiaca con fracción de eyección reducida no se observó el fenómeno de obesidad paradójica en relación a la mortalidad(AU)

Introduction: The association between obesity and lower mortality in patients with heart failure and left ventricular ejection fraction is controversial. Objective: To evaluate the association between obesity and mortality in patients with heart failure and reduced ejection fraction. Methods: An observational prospective cohort study was carried out, from January 2010 to December 2020, in patients with heart failure and reduced ejection fraction. The sample was made up of 173 patients. Survival was evaluated using Kaplan-Meier method to estimate the prognostic effect of the obesity variable on mortality. Cox regression model was used. Results: It was observed that obese patients at one year of follow-up had better survival than those with normal weight (0.6 versus 0.8). At five years, the three subgroups of body mass index (0.6) showed similar survival and the highest mortality was observed by low weight patients. The curve of the latter differs from the rest of the BMI categories, Log Rank p=0.001. In the Cox regression model, obesity had an odds ratio OR=´1.159 p=0.648 (confidence interval 0.615-2.181). Conclusions: In patients with heart failure with reduced ejection fraction, the phenomenon of paradoxical obesity was not observed in relation to mortality(AU)

Gene and metabolite expression dependence on body mass index in human myocardium.

We hypothesized that body mass index (BMI) dependent changes in myocardial gene expression and energy-related metabolites underlie the biphasic association between BMI and mortality (the obesity paradox) in cardiac surgery. We performed transcriptome profiling and measured a panel of 144 metabolites in 53 and 55, respectively, myocardial biopsies from a cohort of sixty-six adult patients undergoing coronary artery bypass grafting (registration: NCT02908009). The initial analysis identified 239 transcripts with biphasic BMI dependence. 120 displayed u-shape and 119 n-shape expression patterns. The identified local minima or maxima peaked at BMI 28-29. Based on these results and to best fit the WHO classification, we grouped the patients into three groups: BMI < 25, 25 ≤ BMI ≤ 32, and BMI > 32. The analysis indicated that protein translation-related pathways were downregulated in 25 ≤ BMI ≤ 32 compared with BMI < 25 patients. Muscle contraction transcripts were upregulated in 25 ≤ BMI ≤ 32 patients, and cholesterol synthesis and innate immunity transcripts were upregulated in the BMI > 32 group. Transcripts involved in translation, muscle contraction and lipid metabolism also formed distinct correlation networks with biphasic dependence on BMI. Metabolite analysis identified acylcarnitines and ribose-5-phosphate increasing in the BMI > 32 group and α-ketoglutarate increasing in the BMI < 25 group. Molecular differences in the myocardium mirror the biphasic relationship between BMI and mortality.

Understanding the Link Between Obesity and Severe COVID-19 Outcomes: Causal Mediation by Systemic Inflammatory Response.

BACKGROUND: Obesity is an established risk factor for severe COVID-19 outcomes. The mechanistic underpinnings of this association are not well-understood. OBJECTIVE: To evaluate the mediating role of systemic inflammation in obesity-associated COVID-19 outcomes. METHODS: This hospital-based, observational study included 3828 SARS-CoV-2-infected patients who were hospitalized February to May 2020 at Massachusetts General Hospital (MGH) or Columbia University Irving Medical Center/New York Presbyterian Hospital (CUIMC/NYP). We use mediation analysis to evaluate whether peak inflammatory biomarkers (C-reactive protein [CRP], erythrocyte sedimentation rate [ESR], D-dimer, ferritin, white blood cell count and interleukin-6) are in the causal pathway between obesity (BMI ≥ 30) and mechanical ventilation or death within 28 days of presentation to care. RESULTS: In the MGH cohort (n = 1202), obesity was associated with greater likelihood of ventilation or death (OR = 1.73; 95% CI = [1.25, 2.41]; P = 0.001) and higher peak CRP (P < 0.001) compared with nonobese patients. The estimated proportion of the association between obesity and ventilation or death mediated by CRP was 0.49 (P < 0.001). Evidence of mediation was more pronounced in patients < 65 years (proportion mediated = 0.52 [P < 0.001] vs 0.44 [P = 0.180]). Findings were more moderate but consistent for peak ESR. Mediation by other inflammatory markers was not supported. Results were replicated in CUIMC/NYP cohort (n = 2626). CONCLUSION: Findings support systemic inflammatory pathways in obesity-associated severe COVID-19 disease, particularly in patients < 65 years, captured by CRP and ESR. Contextualized in clinical trial findings, these results reveal therapeutic opportunity to target systemic inflammatory pathways and monitor interventions in high-risk subgroups and particularly obese patients.

The Relationship Between Obesity and Amputation-free Survival in Patients Undergoing Lower-limb Revascularisation for Chronic Limb-threatening Ischaemia: A Retrospective Cohort Study.

BACKGROUND: The obesity paradox is a well-documented phenomenon in cardiovascular disease, however it remains poorly understood. We aimed to investigate the relationship between body mass (as measured by body mass index [BMI]) and 1-year amputation-free survival (AFS) for patients undergoing lower limb revascularisation for chronic limb-threatening ischaemia (CLTI). METHODS: A retrospective analysis was undertaken of all consecutive patients undergoing lower limb revascularisation for CLTI at the Leicester Vascular Institute between February 2018-19. Baseline demographics and outcomes were collected using electronic records. BMI was stratified using the World Health Organization criteria. One-year AFS (composite of major amputation/death) was the primary outcome. Kaplan-Meier survival analysis and adjusted Cox's proportional hazard models were used to compare groups to patients of normal mass. RESULTS: One-hundred and ninety patients were included. Overall, no difference was identified in 1-year AFS across all groups (pooled P = 0.335). Compared to patients with normal BMI (n = 66), obese patients (n = 43) had a significantly lower adjusted combined risk of amputation/death (aHR 0.39, 95% CI 0.16-0.92, P = 0.032), however no significant differences were observed for overweight (aHR 0.89, 95% CI 0.47-1.70, P = 0.741), morbidly obese (aHR 1.15, 95% CI 0.41-3.20, P = 0.797) and underweight individuals (aHR 1.86, 95% CI 0.56-6.20, P = 0.314). CONCLUSIONS: In the context of CLTI, obesity is potentially associated with favourable amputation-free survival at 1 year, compared to normal body mass. The results of this study support the notion of an obesity paradox existing within CLTI and question whether current guidance on weight management requires a more patient-specific approach.

Lipid-Lowering Drug Use and Cancer Incidence and Mortality in the ARIC Study.

Background: Lipid-lowering drugs, particularly statins, are associated with reduced incidence of certain cancers in some studies. Associations with cancer mortality are not well studied, and whether associations are similar across race is unknown. Methods: We conducted a prospective analysis of 12 997 cancer-free participants in the Atherosclerosis Risk in Communities Study who were never users at visit 1 (1987-1989). Ever use, duration of use, and age at first use were modeled as time-dependent variables using Cox regression to estimate associations with total, obesity- and smoking-associated, bladder, breast, colorectal, lung, and prostate cancer incidence and mortality. Results: We ascertained 3869 cancer cases and 1661 cancer deaths in 237 999 or more person-years. At 6 years of follow-up, 70.8% of lipid-lowering drug use was a statin. Compared with never use, ever use was associated with lower total, obesity- and smoking-associated cancer mortality and with colorectal cancer mortality (hazard ratio [HR] = 0.50, 95% confidence interval [CI] = 0.32 to 0.79) and incidence (HR = 0.69, 95% CI = 0.53 to 0.92). Inverse associations were consistent by sex and race. Shorter-term use was associated with bladder cancer incidence in men (<10 years: HR = 1.67, 95% CI = 1.02 to 2.73). First use at age 60 years or older was inversely associated with: total mortality, obesity- and smoking-associated mortality, and colorectal cancer mortality; and total incidence, obesity- and smoking-associated incidence, and breast, colorectal, and prostate cancer incidence. Conclusions: This study provides additional evidence for inverse associations between lipid-lowering drug use and cancer incidence and mortality but a positive association with bladder cancer incidence in men. Evaluation of the impact of chemoprevention strategies that include lipid-lowering drugs on population-level cancer burden is needed.

Intermediate Renal Outcomes, Kidney Failure, and Mortality in Obese Kidney Donors.

BACKGROUND: Obesity is associated with the two archetypal kidney disease risk factors: hypertension and diabetes. Concerns that the effects of diabetes and hypertension in obese kidney donors might be magnified in their remaining kidney have led to the exclusion of many obese candidates from kidney donation. METHODS: We compared mortality, diabetes, hypertension, proteinuria, reduced eGFR and its trajectory, and the development of kidney failure in 8583 kidney donors, according to body mass index (BMI). The study included 6822 individuals with a BMI of <30 kg/m2, 1338 with a BMI of 30-34.9 kg/m2, and 423 with a BMI of ≥35 kg/m2. We used Cox regression models, adjusting for baseline covariates only, and models adjusting for postdonation diabetes, hypertension, and kidney failure as time-varying covariates. RESULTS: Obese donors were more likely than nonobese donors to develop diabetes, hypertension, and proteinuria. The increase in eGFR in obese versus nonobese donors was significantly higher in the first 10 years (3.5 ml/min per 1.73m2 per year versus 2.4 ml/min per 1.73m2 per year; P<0.001), but comparable thereafter. At a mean±SD follow-up of 19.3±10.3 years after donation, 31 (0.5%) nonobese and 12 (0.7%) obese donors developed ESKD. Of the 12 patients with ESKD in obese donors, 10 occurred in 1445 White donors who were related to the recipient (0.9%). Risk of death in obese donors was not significantly increased compared with nonobese donors. CONCLUSIONS: Obesity in kidney donors, as in nondonors, is associated with increased risk of developing diabetes and hypertension. The absolute risk of ESKD is small and the risk of death is comparable to that of nonobese donors.

Rodent diet aids and the fallacy of caloric restriction.

Understanding the molecular mechanisms of normal aging is a prerequisite to significantly improving human health span. Caloric restriction (CR) can delay aging and has served as a yardstick to evaluate interventions extending life span. However, mice given unlimited access to food suffer severe obesity. Health gains from CR depend on control mice being sufficiently overweight and less obese mouse strains benefit far less from CR. Pharmacologic interventions that increase life span, including resveratrol, rapamycin, nicotinamide mononucleotide and metformin, also reduce body weight. In primates, CR does not delay aging unless the control group is eating enough to suffer from obesity-related disease. Human survival is optimal at a body mass index achievable without CR, and the above interventions are merely diet aids that shouldn't slow aging in healthy weight individuals. CR in humans of optimal weight can safely be declared useless, since there is overwhelming evidence that hunger, underweight and starvation reduce fitness, survival, and quality of life. Against an obese control, CR does, however, truly delay aging through a mechanism laid out in the following tumor suppression theory of aging.

Detection of sarcopenic obesity and prediction of long-term survival in patients with gastric cancer using preoperative computed tomography and machine learning.

BACKGROUND: Previous studies evaluating the prognostic value of computed tomography (CT)-derived body composition data have included few patients. Thus, we assessed the prevalence and prognostic value of sarcopenic obesity in a large population of gastric cancer patients using preoperative CT, as nutritional status is a predictor of long-term survival after gastric cancer surgery. METHODS: Preoperative CT images were analyzed for 840 gastric cancer patients who underwent gastrectomy between March 2009 and June 2018. Machine learning algorithms were used to automatically detect the third lumbar (L3) vertebral level and segment the body composition. Visceral fat area and skeletal muscle index at L3 were determined and used to classify patients into obesity, sarcopenia, or sarcopenic obesity groups. RESULTS: Out of 840 patients (mean age = 60.4 years; 526 [62.6%] men), 534 (63.5%) had visceral obesity, 119 (14.2%) had sarcopenia, and 48 (5.7%) patients had sarcopenic obesity. Patients with sarcopenic obesity had a poorer prognosis than those without sarcopenia (hazard ratio [HR] = 3.325; 95% confidence interval [CI] = 1.698-6.508). Multivariate analysis identified sarcopenic obesity as an independent risk factor for increased mortality (HR = 2.608; 95% CI = 1.313-5.179). Other risk factors were greater extent of gastrectomy (HR = 1.928; 95% CI = 1.260-2.950), lower prognostic nutritional index (HR = 0.934; 95% CI = 0.901-0.969), higher neutrophil count (HR = 1.101; 95% CI = 1.031-1.176), lymph node metastasis (HR = 6.291; 95% CI = 3.498-11.314), and R1/2 resection (HR = 4.817; 95% CI = 1.518-9.179). CONCLUSION: Body composition analysis automated by machine learning predicted long-term survival in patients with gastric cancer.

Clinical outcomes in patients infected with different SARS-CoV-2 variants at one hospital during three phases of the COVID-19 epidemic in Marseille, France.

OBJECTIVES: To compare the demographics, clinical characteristics and severity of patients infected with nine different SARS-CoV-2 variants, during three phases of the COVID-19 epidemic in Marseille. METHODS: A single centre retrospective cohort study was conducted in 1760 patients infected with SARS-CoV-2 of Nextstrain clades 20A, 20B, and 20C (first phase, February-May 2020), Pangolin lineages B.1.177 (we named Marseille-2) and B.1.160 (Marseille-4) variants (second phase, June-December 2020), and B.1.1.7 (alpha), B.1.351 (beta), P.1 (gamma) and A.27 (Marseille-501) variants (third phase, January 2021-today). Outcomes were the occurrence of clinical failures, including hospitalisation, transfer to the intensive-care unit, and death. RESULTS: During each phase, no major differences were observed with regards to age and gender distribution, the prevalence of chronic diseases, and clinical symptoms between variants circulating in a given phase. The B.1.177 and B.1.160 variants were associated with more severe outcomes. Infections occurring during the second phase were associated with a higher rate of death as compared to infections during the first and third phases. Patients in the second phase were more likely to be hospitalised than those in the third phase. Patients infected during the third phase were more frequently obese than others. CONCLUSION: A large cohort study is recommended to evaluate the transmissibility and to better characterise the clinical severity of emerging variants.

Re-Evaluating the Effects of Obesity on Cancer Immunotherapy Outcomes in Renal Cancer: What Do We Really Know?

Obesity has reached global epidemic proportions and its effects on interactions between the immune system and malignancies, particularly as related to cancer immunotherapy outcomes, have come under increasing scrutiny. Although the vast majority of pre-clinical murine studies suggest that host obesity should have detrimental effects on anti-tumor immunity and cancer immunotherapy outcomes, the opposite has been found in multiple retrospective human studies. As a result, acceptance of the "obesity paradox" paradigm, wherein obesity increases cancer risk but then improves patient outcomes, has become widespread. However, results to the contrary do exist and the biological mechanisms that promote beneficial obesity-associated outcomes remain unclear. Here, we highlight discrepancies in the literature regarding the obesity paradox for cancer immunotherapy outcomes, with a particular focus on renal cancer. We also discuss multiple factors that may impact research findings and warrant renewed research attention in future studies. We propose that specific cancer patient populations may be affected in fundamentally different ways by host obesity, leading to divergent effects on anti-tumor immunity and/or immunotherapy outcomes. Continued, thoughtful analysis of this critical issue is therefore needed to permit a more nuanced understanding of the complex effects of host obesity on cancer immunotherapy outcomes in patients with renal cancer or other malignancies.

Obesity and revision surgery, mortality, and patient-reported outcomes after primary knee replacement surgery in the National Joint Registry: A UK cohort study.

BACKGROUND: One in 10 people in the United Kingdom will need a total knee replacement (TKR) during their lifetime. Access to this life-changing operation has recently been restricted based on body mass index (BMI) due to belief that high BMI may lead to poorer outcomes. We investigated the associations between BMI and revision surgery, mortality, and pain/function using what we believe to be the world's largest joint replacement registry. METHODS AND FINDINGS: We analysed 493,710 TKRs in the National Joint Registry (NJR) for England, Wales, Northern Ireland, and the Isle of Man from 2005 to 2016 to investigate 90-day mortality and 10-year cumulative revision. Hospital Episodes Statistics (HES) and Patient Reported Outcome Measures (PROMs) databases were linked to the NJR to investigate change in Oxford Knee Score (OKS) 6 months postoperatively. After adjustment for age, sex, American Society of Anaesthesiologists (ASA) grade, indication for operation, year of primary TKR, and fixation type, patients with high BMI were more likely to undergo revision surgery within 10 years compared to those with "normal" BMI (obese class II hazard ratio (HR) 1.21, 95% CI: 1.10, 1.32 (p < 0.001) and obese class III HR 1.13, 95% CI: 1.02, 1.26 (p = 0.026)). All BMI classes had revision estimates within the recognised 10-year benchmark of 5%. Overweight and obese class I patients had lower mortality than patients with "normal" BMI (HR 0.76, 95% CI: 0.65, 0.90 (p = 0.001) and HR 0.69, 95% CI: 0.58, 0.82 (p < 0.001)). All BMI categories saw absolute increases in OKS after 6 months (range 18-20 points). The relative improvement in OKS was lower in overweight and obese patients than those with "normal" BMI, but the difference was below the minimal detectable change (MDC; 4 points). The main limitations were missing BMI particularly in the early years of data collection and a potential selection bias effect of surgeons selecting the fitter patients with raised BMI for surgery. CONCLUSIONS: Given revision estimates in all BMI groups below the recognised threshold, no evidence of increased mortality, and difference in change in OKS below the MDC, this large national registry shows no evidence of poorer outcomes in patients with high BMI. This study does not support rationing of TKR based on increased BMI.

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.

Outcomes of Idiopathic Pulmonary Fibrosis Improve with Obesity: A Rural Appalachian Experience.

OBJECTIVES: Obesity can be an independent predictor of fibrosis in tissues, including the liver, heart, and skin. We evaluated a rural Appalachian cohort of idiopathic pulmonary fibrosis (IPF) for its relation to obesity. METHODS: Using American Thoracic Society 2018 diagnostic guidelines, an IPF cohort was systematically identified at an Appalachian academic medical center (2015-2019). The cohort was categorized in subgroups of body mass index (BMI) <30 or BMI ≥30 kg/m2. Demographics, clinical variables, and treatment details were collected retrospectively and evaluated for their associations with obesity. RESULTS: In our IPF cohort (N = 138), a usual interstitial pneumonia pattern was less prevalent in the obese group (n = 49) relative to the nonobese group (69% vs 85%, respectively). The obese group was younger (mean age 73.27 ± 9.12 vs 77.97 ± 9.59 years) and had a higher prevalence of hypertension (90% vs 72%), hyperlipidemia (83% vs 68%), diabetes mellitus (47% vs 25%), sleep-disordered breathing (47% vs 25%), chronic pain disorders (28% vs 15%), and deep vein thrombosis (19% vs 7%). An increased proportion of obese-IPF patients was seen at a tertiary or an interstitial lung disease center, with more surgical lung biopsies performed and incident diagnosis (ie, within 6 months of presentation) assigned. Only a minority of patients underwent lung transplantation (3.6%), all of them from the obese-IPF subgroup. Approximately 30% of the total IPF cohort died, with a lower mortality observed in the obese group (35% vs 20%, P = 0.017). An increasing BMI predicted a better survival in the total IPF cohort (BMI 25-29.9, 20-24.9, and <20 had mortality rates of 20%, 47%, and 75%, respectively; P < 0.001). CONCLUSIONS: Our study represents a first known effort to develop an IPF cohort in a rural Appalachian region. Although they shared an increased burden of comorbidities, the obese subgroup showed less advanced fibrosis with a lower mortality rate relative to nonobese subgroup, suggesting a potential "obesity paradox" in IPF. The study findings significantly advance our understanding of challenges posed by IPF in a rural population that also suffers from an alarming rate of obesity. We highlight the need for the multidisciplinary management of these patients and prospective studies to better define this complex relation.

Future life expectancy in Europe taking into account the impact of smoking, obesity, and alcohol.

Introduction: In Europe, women can expect to live on average 82 years and men 75 years. Forecasting how life expectancy will develop in the future is essential for society. Most forecasts rely on a mechanical extrapolation of past mortality trends, which leads to unreliable outcomes because of temporal fluctuations in the past trends due to lifestyle 'epidemics'. Methods: We project life expectancy for 18 European countries by taking into account the impact of smoking, obesity, and alcohol on mortality, and the mortality experiences of forerunner populations. Results: We project that life expectancy in these 18 countries will increase from, on average, 83.4 years for women and 78.3 years for men in 2014 to 92.8 years for women and 90.5 years for men in 2065. Compared to others (Lee-Carter, Eurostat, United Nations), we project higher future life expectancy values and more realistic differences between countries and sexes. Conclusions: Our results imply longer individual lifespans, and more elderly in society. Funding: Netherlands Organisation for Scientific Research (NWO) (grant no. 452-13-001).

On average, in Europe, men can currently expect to live till the age of 75 and women until they are 82. But what will their lifespans be in the next decades? Reliable answers to this question are essential to help governments plan for future health care and social security costs. While medical improvements are likely to further extend lifespans, lifestyle factors can result in temporal distortions of this trend. Yet, most estimates of future life expectancy fail to consider changing lifestyles, as they only use past mortality trends in their calculations. This can make these projections unreliable: for example, increases in smoking rates among Northern and Western European men led to stagnating male life expectancies in the 1950s and 1960s, but these picked up again after smoking declined. The same pattern is showing for women, except it is lagging as they took up smoking later than men. Based simply on the extrapolation of past mortality trends, current projection models fail to consider the past and predicted modifications of life expectancy trends prompted by changing rates of health behaviours ­ such as increases followed by (anticipated) declines in alcohol consumption and obesity rates, similar to what was observed with smoking. To produce a more reliable forecast, Janssen et al. incorporated trends in smoking, obesity, and alcohol use into life expectancy projections for 18 European countries. The predictions suggest that life expectancy for women in these countries will increase from 83.4 years in 2014 to 92.8 years in 2065. For men, it will also go up, from 78.3 to 90.5 years. In the future, this integrative approach may help to track the effects of health-behaviour related prevention policies on life expectancy, and allow scientists to account for changes caused by the COVID-19 pandemic. In the meantime, these estimates are higher than those obtained using more traditional methods; they suggest that communities should start to adjust to the possibility of longer individual lifespans, and of larger numbers of elderly people in society.

Non-communicable diseases deaths attributable to high body mass index in Chile.

We estimated the proportion and number of deaths from non-communicable diseases (NCD) attributable to high body mass index (BMI) in Chile in 2018. We used data from 5927 adults from a 2016-2017 Chilean National Health Survey to describe the distribution of BMI. We obtained the number of deaths from NCD from the Ministry of Health. Relative risks (RR) and 95% confidence intervals per 5 units higher BMI for cardiovascular disease, cancer, and respiratory disease were retrieved from the Global BMI Mortality Collaboration meta-analyses. The prevalences of overweight and obesity were 38.9% and 39.1%, respectively. We estimated that reducing population-wide BMI to a theoretical minimum risk exposure level (mean BMI: 22.0 kg/m2; standard deviation: 1) could prevent approximately 21,977 deaths per year (95%CI 13,981-29,928). These deaths represented about 31.6% of major NCD deaths (20.1-43.1) and 20.4% of all deaths (12.9-27.7) that occurred in 2018. Most of these preventable deaths were from cardiovascular diseases (11,474 deaths; 95% CI 7302-15,621), followed by cancer (5597 deaths; 95% CI 3560-7622) and respiratory disease (4906 deaths; 95% CI 3119-6684). A substantial burden of NCD deaths was attributable to high BMI in Chile. Policies and population-wide interventions are needed to reduce the burden of NCD due to high BMI in Chile.

Reference Equation for the Six-Minute Walk Test in Brazilian Patients with Obesity

Abstract Background: Obesity has repercussions on functional capacity (FC). The six-minute walk test (6MWT) is a useful tool for assessing submaximal FC, and the distance reached at 6 minutes of walking (D6MW) is a relevant prognostic marker. Objective: This paper aims to establish a reference equation for the distance predicted in 6MWT in obese Brazilian subjects. Methods: This study included 460 patients (306 women), with a body mass index (BMI) > 30 kg/m2, 71% (328) of whom presented a grade III obesity (BMI ≥ 40 Kg/m²) and were evaluated with 6MWT. Heart rate, blood pressure, oxygen saturation and Borg scale perception of effort were recorded before and after the 6MWT. For statistical analysis, Kolmogorov-Smirnov tests, an unpaired T-Test, Pearson's correlation, and multiple linear regression were used, together with a significance level set at p<0.05. Results: Gender, age, and BMI were significantly correlated with D6MW and were identified by multiple linear regression as the best predictors of the D6MW. Together, they explain 48.7% of the D6MW variance for obese Brazilian subjects. Based on these findings, an equation was proposed - D6MW = 930.138 + (27.130 x Genderfemales = 0; males = 1) − (5.550 x BMI kg/m2) − (4.442 x Age years). When the average of the D6MW obtained with the above equation was compared to the average calculated with the equations described in medical literature for healthy and obese individuals, the latter tended to overestimate the D6MW. Conclusion: The proposed reference equation exhibited better assessment of FC in obese Brazilian patients, providing proper subsidies for the follow up ofinterventions in this population..

The impact of race, comorbid conditions and obesity on survival endpoints in women with high grade endometrial carcinoma.

OBJECTIVE: To estimate overall survival, disease-specific survival, and progression-free survival among high grade endometrial carcinoma cases and to determine factors impacting survival for non-Hispanic white and non-Hispanic black women. METHODS: We identified high grade endometrial carcinoma cases among non-Hispanic white and non-Hispanic black women from ongoing institutional studies, and determined eligibility through medical record and pathologic review. We estimated effects of demographic and clinical variables on survival outcomes using Kaplan Meier methods and Cox proportional hazards modelling. RESULTS: Non-Hispanic Black women with BMI <25.0 had poorest overall survival compared to non-Hispanic white women with BMI <25.0 (HR 3.03; 95% CI [1.35, 6.81]), followed by non-Hispanic black women with BMI 25.0+ (HR 2.43; 95% CI [1.28, 4.60]). A similar pattern emerged for disease-specific survival. Non-Hispanic black women also had poorer progression-free survival than non-Hispanic white women (HR 1.40; 95% CI [1.01, 1.93]). Other significant factors impacting survival outcomes included receipt of National Cancer Center Network (NCCN) guideline-concordant treatment (GCT), earlier stage at diagnosis, and fewer comorbid conditions. CONCLUSIONS: BMI and race interact and modify the association with high grade endometrial carcinoma survival. Other potentially modifiable factors, such as reducing comorbidities and increasing access to GCT will potentially improve survival after diagnosis of high grade endometrial carcinomas. A better understanding of the molecular drivers of these high grade carcinomas may lead to targeted therapies that reduce morbidity and mortality associated with these aggressive tumors.