Sandhyavenu, Harigopal

Abstract Background Anal squamous cell carcinoma is a rare cancer with increased occurrence of multiple cancers before and after the anal squamous cell carcinoma diagnosis. However, there are limited data on this aspect. This multi-institutional analysis aimed to define the occurrence of malignancies before and after anal squamous cell carcinoma, time trends, and impact on survival and to identify prognostic factors. Methods Initial primary malignancy was defined as a malignancy occurring before the anal squamous cell carcinoma. Second primary malignancy was defined as a distinct primary cancer that developed after anal squamous cell carcinoma diagnosis. Retrospective multi-institutional chart review was done. Progression-free survival (PFS), overall survival, and prognostic factors were evaluated. Results A total of 647 patients with anal squamous cell carcinoma treated with curative intent were analyzed. Median age was 61.2 years with 72% as females. Of these, 150 (23.3%) patients had multiple malignancies with initial primary malignancy in 16% and second primary malignancy in 8%. Patients without prior cancer had better 5-year PFS (81.2% vs 67.2%, P = .011) and overall survival (81% vs 69%, P = .008) compared with those with prior cancer. Second primary malignancies had a statistically significant adverse impact on PFS (hazard ratio [HR] = 4.22) and overall survival (HR = 3.56). Females had better 5-year PFS (82% vs 70%, P = .016) as compared with males. The median time interval for developing anal squamous cell carcinoma (as second primary malignancy) after initial primary malignancy was 9.32 years. Conclusions Anal squamous cell carcinoma patients have an increased risk of multiple malignancies. These patients who have prior cancers have inferior outcomes. Second primary malignancy is a poor prognostic factor in patients with anal cancer. Second primary malignancy can develop years after treatment of primary anal squamous cell carcinoma.

Background Optimal duration and choice of antiplatelet therapy in patients with acute coronary syndrome undergoing percutaneous coronary intervention remain controversial. Methods and Results Digital databases (PubMed, Cochrane, and Embase) were queried to select all randomized controlled trials on a post–percutaneous coronary intervention population with acute coronary syndrome. Dual‐antiplatelet therapy (DAPT) with aspirin and clopidogrel for 12 months was compared with 4 major strategies: high‐potency, high‐ to low‐potency, low‐dose, and short‐duration DAPT. A network meta‐analysis was performed to compare the safety and efficacy of different antiplatelet strategies. This study was the second updated manuscript under the International Prospective Register of Systematic Review registration (CRD42021286552). Thirty‐two randomized controlled trials comprising 103 459 (51 750 experimental, 51 709 control) patients were included. Compared with DAPT with aspirin and clopidogrel for 12 months, high‐ to low‐potency DAPT (risk ratio [RR], 0.69 [95% CI, 0.52–0.92]) and aspirin+prasugrel containing DAPT for 12 months (RR, 0.84 [95% CI, 0.72–0.98]) had a significantly lower, whereas DAPT for 1 month followed by clopidogrel only (RR, 1.59 [95% CI, 1.06–2.39]) had a higher, incidence of major adverse cardiovascular events at 1 year (median follow‐up). Prasugrel (RR, 1.35 [95% CI, 1.09–1.66]) and ticagrelor (RR, 1.38 [95% CI, 1.17–1.62]) containing DAPT for 12 months had significantly higher rates, whereas high‐ to low‐potency DAPT (RR, 0.85 [95% CI, 0.63–1.15]) had no significant risk of major bleeding. Conclusions Aspirin and ticagrelor for 3 months, followed by aspirin and clopidogrel for the remaining duration, can be considered the optimal strategy for treating post–percutaneous coronary intervention patients with acute coronary syndrome because of a significantly reduced risk of major adverse cardiovascular events without increasing the risk of bleeding.

Introduction: Severe hypertriglyceridemia (SHTG), defined as plasma triglyceride (TG) level ≥ 500 mg/dl, is a risk factor for cardiovascular disease. In the NHANES dataset (2001 - 2006), the prevalence of SHTG was 1.7%. However, the prevalence of primary SHTG in the community is unknown. We conducted a community-based study to estimate the prevalence of primary SHTG, in Olmsted County, Minnesota. Methods: We used the Rochester Epidemiology Project (REP) records linkage system to identify individuals with TG ≥ 500 mg/dl between 1998-2015. Index date was defined as the first documentation of TG ≥500 mg/dl during the study period. We excluded individuals with mixed hyperlipidemia (TG ≥500 mg/dl and non-high density lipoprotein (HDL) cholesterol ≥190 mg/dl). HTG was defined as secondary in the presence of hypothyroidism, biliary obstruction, nephrotic syndrome, uncontrolled diabetes, pregnancy, liver disease, renal failure, BMI ≥35 and medication use (isotretinoin, tetracyclines, anti-retrovirals). Primary HTG was defined as absence of an identifiable secondary etiology. Characteristics of the primary SHTG individuals were ascertained from the electronic health record. Results: SHTG was identified in 3802 individuals of whom 2511 had mixed hyperlipidemia, 743 had a secondary cause for SHTG and the remaining 548 had primary SHTG. Using the 2015 population census of 151,436 for Olmsted County, the prevalence of SHTG was 2.5%, of secondary SHTG was 0.49% and of primary SHTG was 0.36%. Only half of the primary SHTG group had a diagnosis of dyslipidemia in the electronic health record and 44.3% were on lipid-lowering therapy on index date. Characteristics of individuals with primary SHTG are summarized in Table 1. Conclusions: These data highlight that primary SHTG is relatively common (≈1 in 300, similar to the prevalence of familial hypercholesterolemia), underdiagnosed and undertreated.

Introduction: Obesity is associated with a higher burden of atrial fibrillation (AF) and related complications. Hypothesis: Bariatric surgery in patients with AF is associated with a reduction in mortality and long-term complications at 1 year. Methods: Patients with AF who underwent bariatric surgery were identified by analyzing the nationwide readmission database and incorporating the validated ICD-10 CM codes from October 2015 to December 2019. We performed the propensity score matching to adjust the confounders and cox proportional hazard regression to generate hazard ratios. Moreover, we generated Kaplan Meier curves for time-to-event analysis. The primary endpoint was all-cause mortality at 1 year, whereas secondary endpoints were ischemic stroke, major bleeding, and AF readmission at 1 year. Results: Out of 892488 obese patients with AF, 18766 underwent bariatric surgery. After propensity score matching, 18764 patients were identified in each group. At 1-year, patients undergoing bariatric surgery had a significant reduction in mortality (2.18% vs. 2.73%, HR: 0.91, 95% CI: 0.85-0.96, p=0.001). Additionally, risk of ischemic stroke was also reduced (1.98% vs. 2.29%, HR: 0.91, 95% CI: 0.86-0.97, p=0.01), whereas no difference was noted in AF readmissions (4.02% vs. 3.34%, HR: 0.97, 95% CI: 0.92-1.04, p=0.49) and risk of major bleeding was increased (5.74% vs. 3.42%, HR: 1.17, 95% CI: 1.10-1.25, p<0.0001) at 1 year in AF patients with bariatric surgery. (Figure 1) Conclusions: Bariatric surgery in patients with AF was associated with a reduction in 1-year mortality and ischemic stroke. However, the risk of major bleeding was noted to be increased and no difference was noted in AF readmission at 1 year.

Background Hypertriglyceridemia is associated with increased risk of coronary heart disease but the association is often attributed to concomitant metabolic abnormalities. We investigated the epidemiology of primary isolated hypertriglyceridemia (PIH) and associated cardiovascular risk in a population‐based setting. Methods and Results We identified adults with at least one triglyceride level ≥500 mg/dL between 1998 and 2015 in Olmsted County, Minnesota. We also identified age‐ and sex‐matched controls with triglyceride levels <150 mg/dL. There were 3329 individuals with elevated triglyceride levels; after excluding those with concomitant hypercholesterolemia, a secondary cause of high triglycerides, age <18 years or an incomplete record, 517 patients (49.4±14.0 years, 72.0% men) had PIH (triglyceride 627.6±183.6 mg/dL). The age‐ and sex‐adjusted prevalence of PIH in adults was 0.80% (0.72–0.87); the diagnosis was recorded in 60%, 46% were on a lipid‐lowering medication for primary prevention and a triglyceride level <150 mg/dL was achieved in 24.1%. The association of PIH with coronary heart disease was attenuated but remained significant after adjustment for demographic, socioeconomic, and conventional cardiovascular risk factors (hazard ratio [HR], 1.53; 95% CI, 1.06‐2.20; P = 0.022). There was no statistically significant association between PIH and cerebrovascular disease (HR, 1.06; 95% CI, 0.65‐1.73, P = 0.813), peripheral artery disease (HR, 1.27; 95% CI, 0.43‐3.75; P = 0.668), or the composite end point of all 3 (HR, 1.28; 95% CI, 0.92‐1.80; P =0.148) in adjusted models. Conclusions PIH was associated with incident coronary heart disease events (although there was attenuation after adjustment for conventional risk factors), supporting a causal role for triglycerides in coronary heart disease. The condition is relatively prevalent but awareness and control are low.

Background There are limited data on the use of venoarterial extracorporeal membrane oxygenation ( VA ‐ ECMO ) or cardiopulmonary bypass ( CPB ) to provide hemodynamic support periprocedurally during transcatheter aortic valve replacement. This study sought to evaluate patients receiving transcatheter aortic valve replacement with concomitant use of CPB / VA ‐ ECMO . Methods and Results We systematically reviewed the published literature from 2000 to 2018 for studies evaluating adult patients requiring CPB / VA ‐ ECMO periprocedurally during transcatheter aortic valve replacement. Studies reporting short‐term and long‐term mortality were included. Given the significant methodological and statistical differences between published studies, meta‐analysis of the association of CPB / VA ‐ ECMO with mortality was not performed. Of the 537 studies identified, 9 studies representing 5191 patients met our inclusion criteria. Median ages were between 75 and 87 years with 33% to 75% male patients. Where reported, the Edwards SAPIEN ™ transcatheter heart valve was the most frequently used. A total of 203 (3.9%) patients received periprocedural hemodynamic support with CPB / VA ‐ ECMO . Common indications for CPB / VA ‐ ECMO included left ventricular or aortic annular rupture, rapid hemodynamic deterioration, aortic regurgitation, cardiac arrest, and left main coronary artery obstruction. The use of CPB / VA ‐ ECMO was predominantly an emergent strategy and was used for durations of 1 to 2 hours. Short‐term mortality (in‐hospital and 30‐day) was 29.8%, and 1‐year mortality was 52.4%. Major complications such as bleeding, vascular injury, tamponade, stroke, and renal failure were noted in 10% to 50% of patients. Conclusions CPB / VA ‐ ECMO was used in 4% in the early experience of patients undergoing transcatheter aortic valve replacement, most commonly for periprocedural complications. There are limited data on preprocedural planned use of VA ‐ ECMO , and the characteristics of this population remain poorly defined.