Response to immune checkpoint blockade is increased in obesity-related cancers, but the mechanisms remain unclear. In a recent issue of Nature, Bader et al. report that obesity in mice induces macrophage PD-1 upregulation to promote tumor growth while potentiating immunotherapy responses.

OBJECTIVE: Numerous studies have indicated that increased obesity in patients with established peripheral artery disease (PAD) is inversely associated with disease prognosis, a phenomenon coined as the \"obesity paradox\". A major cause of criticism in studies investigating the obesity paradox is the use of body mass index (BMI) as a surrogate marker in defining and quantifying the degree or severity of obesity. We conducted a retrospective review to verify whether the obesity paradox persists in patients with PAD when using body surface area (BSA) as an alternative anthropometric measure.
METHODS: Patients undergoing surgery (open or endovascular) for PAD between January 2009 and March 2020 were identified from the Vascular Quality Initiative (VQI) national database. The association between BSA/BMI and risk of post-operative complications was evaluated using logistic regression and restricted cubic spline analysis, both of which adjusted for demographic and comorbid risk predictors. When analyzing BSA and BMI as categorical variables, patients were grouped according to BSA quintiles and the World Health Organization (WHO) BMI categories.
RESULTS: A total of 130,428 patients were included based on our eligibility criteria, of which 85,394 (65.5%) were men. Patients were typically hypertensive (87.8%), diabetic (50.4%), and overweight (63.0% over 25 kg/m2). Patients with a high BMI or BSA typically presented at a younger age and with greater pre-operative administration of drugs (statin, ACE-inhibitor, anticoagulant, and beta blocker). Our results indicate that BSA and BMI are inversely associated with post-operative risk of all-cause morbidity, mortality, and cardiac complications. This finding was displayed when analyzing BMI/BSA as a continuous variable, or when indexing patients into BMI/BSA groups.
CONCLUSIONS: Our data suggests that the obesity paradox persists in patients with PAD when using either BMI or BSA as anthropometric measures. Future studies with a prospective design and utilizing newer anthropometric indices should be conducted to fully verify the presence of this phenomenon.

The triglyceride-glucose (TyG) index, proven to be a crucial insulin resistance biomarker (better than the Homeostasis Model Assessment for Insulin Resistance), is simple and non-invasive. Recently, indisputable evidence has shown that the TyG index is strongly associated with cardiovascular disease [CVD, including atherosclerosis, heart failure (HF), and hypertension] prognosis and mortality. Nevertheless, the value of the TyG index in HF patients treated with sodium-glucose cotransporter 2 inhibitors (SGLT2is) has not been systematically evaluated. Therefore, in this review, we summarized the value of the TyG index and its related parameters as markers of CVD, especially HF. Furthermore, we addressed the use of SGLT2is and GLP-1 receptor antagonists in HF patients. Finally, we summarized the mechanism of the \"obesity paradox.\"

BACKGROUND: This study investigates the obesity paradox, where obesity is linked to lower mortality in certain patient groups, focusing on its impact on long-term mortality in chronic critically ill (CCI) patients.
METHODS: We retrospectively analyzed CCI patients from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database\'s Intensive Care Unit, categorizing them into six groups based on Body Mass Index (BMI). Using stepwise multivariable Cox regression and restricted cubic spline models, we examined the association between BMI and 90 day mortality, accounting for confounding variables through subgroup analyses.
RESULTS: The study included 1996 CCI patients, revealing a 90 day mortality of 34.12%. Overweight and obese patients exhibited significantly lower mortality compared to normal-weight individuals. Adjusted analysis showed lower mortality risks in overweight and obese groups (HRs 0.60 to 0.72, p < 0.001). The cubic spline model indicated a negative correlation between BMI and 90 day mortality, with subgroup analyses highlighting interactions with age.
CONCLUSIONS: Our findings confirm the obesity paradox in CCI patients, especially among the elderly (65-85 years) and very elderly (≥ 85 years). The results suggest a beneficial association of higher BMI in older CCI patients, though caution is advised for those under 45.

BACKGROUND: Obesity paradox in cardiovascular risk prediction has gained increasing attention in recent years. We aimed to investigate the impact of BMI on mortality following transcatheter aortic valve replacement (TAVR).
METHODS: We performed a multi-center retrospective analysis of patients with severe aortic stenosis undergoing TAVR. Patients were categorized into: Underweight (BMI < 18.5), normal weight (18.5 ≤ BMI < 25), overweight (25 ≤ BMI < 30) and obese (BMI ≥ 30). Multivariate cox-proportional hazard model was used to compare all-cause mortality.
RESULTS: Total of 6688 patients included (175 underweight, 2252 normal weight, 2368 overweight and 1893 with obesity). Mean age of patients was 81 ± 8 years with 55% males. Patients with obesity had higher prevalence of comorbidities but a lower overall STS score. Mortality at 30-days post-TAVR was lower in the obese population compared to underweight, normal weight, and overweight patients (1.6% vs. 6.9%, 3.6%, and 2.8%, respectively, p < 0.001). Similarly, 3-year mortality was lowest in patients with obesity (17.1% vs. 28.9%, 24.5% and 18.6%, respectively, p < 0.001). On multivariate analysis, long term all-cause mortality at 3-years remained significantly lower in patients with obesity compared to underweight (HR 1.74, 95% CI: 1.30-2.40, p < 0.001) and normal weight (HR: 1.41, 95% CI:1.21-1.63, p < 0.001) but not in overweight patients (HR: 1.10, 95% CI:0.94-1.28, p = 0.240).
CONCLUSIONS: In conclusion, patients with obesity have improved short and long term mortality following TAVR with an observed progressive increase in mortality with lower BMI ranges.

Obesity, characterized by its complexity and heterogeneity, has emerged as a significant public health concern. Its association with increased incidence and mortality of cardiovascular diseases stems not only from its complications and comorbidities but also from the endocrine effects of adipose tissue. Abdominal aortic aneurysm (AAA), a chronic inflammatory condition, has been closely linked to obesity. Intriguingly, mild obesity appears to confer a protective effect against AAA mortality, whereas severe obesity and being underweight do not, giving rise to the concept of the \"obesity paradox\". This review aims to provide an overview of obesity and its paradoxical relationship with AAA, elucidate its underlying mechanisms, and discuss the importance of preoperative weight loss in severely obese patients with AAA.

OBJECTIVE: Patients with obesity have an overall higher cardiovascular risk, at the same time obesity could be associated with a better outcome in a certain subgroup of patients, a phenomenon known as the obesity paradox. Data are scarce in candidates for cardiac resynchronization therapy (CRT). We aimed to investigate the association between body mass index (BMI) and all-cause mortality in patients eligible for CRT.
METHODS: Altogether 1,585 patients underwent cardiac resynchronization therapy between 2000-2020 and were categorized based on their BMI, 459 (29%) patients with normal weight (BMI < 25 kg/m2), 641 (40%) patients with overweight (BMI 25- < 30 kg/m2) and 485 (31%) with obesity (BMI ≥ 30 kg/m2). The primary endpoint was all-cause mortality, heart transplantation, and left ventricular assist device implantation. We assessed periprocedural complications and 6-month echocardiographic response.
RESULTS: Normal-weight patients were older compared to patients with overweight or obesity (70 years vs. 69 years vs. 68 years; P ‹0.001), respectively. Sex distribution, ischaemic aetiology, and CRT-D implantation rates were similar in the three patient groups. Diabetes mellitus (BMI < 25 kg/m2 26% vs. BMI 25- < 30 kg/m2 37% vs. BMI ≥ 30 kg/m2 48%; P ‹0.001) and hypertension (BMI < 25 kg/m2 71% vs. BMI 25- < 30 kg/m2 74% vs. BMI ≥ 30 kg/m2 82%; P ‹0.001) were more frequent in patients with overweight and obesity. During the mean follow-up time of 5.1 years, 973 (61%) reached the primary endpoint, 66% in the BMI < 25 kg/m2 group, 61% in the BMI 25- < 30 kg/m2 group and 58% in the BMI ≥ 30 kg/m2 group (log-rank P‹0.05). Patients with obesity showed mortality benefit over normal-weight patients (HR 0.78; 95%CI 0.66-0.92; P = 0.003). The obesity paradox was present in patients free from diabetes, atrial fibrillation, and ischemic events. Periprocedural complication rates did not differ in the three groups (BMI < 25 kg/m2 25% vs. BMI 25- < 30 kg/m2 28% vs. BMI ≥ 30 kg/m2 26%; P = 0.48). Left ventricular ejection fraction improved significantly in all patient groups (BMI < 25 kg/m2 median ∆ $$ \\Delta $$ -LVEF 7% vs. BMI 25- < 30 kg/m2 median ∆ $$ \\Delta $$ -LVEF 7.5% vs. BMI ≥ 30 kg/m2 median ∆ $$ \\Delta $$ -LVEF 6%; P < 0.0001) with a similar proportion of developing reverse remodeling (BMI < 25 kg/m2 58% vs. BMI 25- < 30 kg/m2 61% vs. BMI ≥ 30 kg/m2 57%; P = 0.48); P = 0.75).
CONCLUSIONS: The obesity paradox was present in our HF cohort at long-term, patients underwent CRT implantation with obesity and free of comorbidities showed mortality benefit compared to normal weight patients. Patients with obesity showed similar echocardiographic response and safety outcomes compared to normal weight patients.

UNASSIGNED: Sepsis is a significant contributor to both intensive care unit (ICU) admissions and mortality among patients in ICU, with a rising prevalence of obesity. There is a lack of extensive research on the correlation between TyGI and findings in patients with sepsis, especially in obese patients.
UNASSIGNED: This study used a retrospective cohort design and included patients with sepsis (≥18 years) from the Medical Information Mart for Intensive Care IV database. The association between TyGI and outcome was examined using multivariable logistic regression analysis.
UNASSIGNED: 8,840 patients with sepsis were included in the analysis. The in-ICU mortality rate was 9.7%. Non-survivors exhibited significantly greater TyGI levels than survivors [9.19(8.76-9.71) vs. 9.10(8.67-9.54), p < 0.001]. The adjusted multivariate regression model showed that elevated TyGI values were linked to a greater likelihood of death in ICU (odds ratio [OR] range 1.072-1.793, p < 0.001) and hospital (OR range 1.068-1.445, p = 0.005). Restricted Cubic Spline analysis revealed a nonlinear association between TyGI and in-ICU and in-hospital mortality risks within specified ranges. Subgroup analysis revealed interaction effects in the general obesity, abdominal obesity, and impaired fasting glucose subgroups (p = 0.014, 0.016, and < 0.001, respectively).
UNASSIGNED: TyGI was associated with an increased sepsis-related short-term mortality risk and adverse outcomes after ICU admission.

BACKGROUND: The \"obesity paradox\" claims that although obesity is a risk factor for atrial fibrillation, obese patients have lower inpatient mortality when admitted due to atrial fibrillation. This study aims to analyze if the obesity paradox still holds true after weight loss from bariatric surgery.  Methods: This study analyzed discharge data from the National Inpatient Sample, 2016-2020. Patients admitted due to atrial fibrillation or atrial flutter, with or without obesity, and with or without a past medical history of bariatric surgery were identified using ICD-10-CM and ICD-10-PCS codes. The primary outcome was mortality. Secondary outcomes included length of stay, resource utilization, necessity for endotracheal intubation, and necessity for cardioversion. STATA v.13 was used for univariate and multivariate analysis (StataCorp LLC, Texas, USA).
RESULTS: Among 2,292,194 patients who had a primary diagnosis of atrial fibrillation or atrial flutter, 494,830 were obese and 25,940 had bariatric surgery. Mortality was not significantly different in post-bariatric surgery patients when compared to the general population (OR 0.76; 95% [CI 0.482-1.2; p=0.24]). Mortality was significantly lower in obese patients when compared to the general population (OR 0.646; 95% [CI 0.583-0.717; p<0.001]). Therefore, post-bariatric surgery patients had a higher mortality than obese patients when compared to the general population. Obese patients spent more days in the hospital (regression 0.219; 95% [CI 0.19-0.248, p<0.001]), had higher resource utilization (regression 3491.995; 95% [CI 2870.085-4113.905, p<0.001]), more cardioversions (OR 1.434; 95% [CI 1.404-1.465; p<0.001]), and no difference in endotracheal intubation rate (OR 1.02; 95% [CI 0.92-1.127; p=0.724]) when compared to the general population. Post-bariatric patients had no difference in length of stay (regression -0.053; 95% [CI -0.137-0.031; p=0.218]) and resource utilization (regression 577.297; 95% [CI -1069.801-2224.396; p=0.492]), fewer endotracheal intubations (OR 0.583; 95% [CI 0.343-0.99; p=0.046]), and more cardioversions (OR 1.223; 95% [CI 1.134-1.32; p<0.001]) when compared to the general population.
CONCLUSIONS: Compared to the general population, post-bariatric patients had higher inpatient mortality than obese patients when admitted due to atrial fibrillation or atrial flutter. This research reinforces the presence of the obesity paradox following bariatric surgery with respect to mortality.

UNASSIGNED: The relationship between adiposity and sepsis has received increasing attention. This study aims to explore the causal relationship between life course adiposity and the sepsis incidence.
UNASSIGNED: Mendelian randomization (MR) method was employed in this study. Instrumental variants were obtained from genome-wide association studies for life course adiposity, including birth weight, childhood body mass index (BMI), childhood obesity, adult BMI, waist circumference, visceral adiposity, and body fat percentage. A meta-analysis of genome-wide association studies for sepsis including 10,154 cases and 454,764 controls was used in this study. MR analyses were performed using inverse variance weighted, MR Egger regression, weighted median, weighted mode, and simple mode. Instrumental variables were identified as significant single nucleotide polymorphisms at the genome-wide significance level (P < 5×10-8). The sensitivity analysis was conducted to assess the reliability of the MR estimates.
UNASSIGNED: Analysis using the MR analysis of inverse variance weighted method revealed that genetic predisposition to increased childhood BMI (OR = 1.29, P = 0.003), childhood obesity (OR = 1.07, P = 0.034), adult BMI (OR = 1.38, P < 0.001), adult waist circumference (OR = 1.01, P = 0.028), and adult visceral adiposity (OR = 1.53, P < 0.001) predicted a higher risk of sepsis. Sensitivity analysis did not identify any bias in the MR results.
UNASSIGNED: The results demonstrated that adiposity in childhood and adults had causal effects on sepsis incidence. However, more well-designed studies are still needed to validate their association.