Citations

Background: There are limited data on how sex influences the outcomes of acute myocardial infarction-cardiogenic shock (AMI-CS) in young adults. Methods: A retrospective cohort of AMI-CS admissions aged 18 to 55 years, during 2000 to 2017, was identified using the National Inpatient Sample. Use of coronary angiography, percutaneous coronary intervention, mechanical circulatory support and noncardiac interventions was identified. Outcomes of interest included in-hospital mortality, use of cardiac interventions, hospitalization costs, and length of stay. Results: A total 90 648 AMI-CS admissions ≤55 years of age were included, of which 26% were women. Higher rates of CS were noted in men (2.2% in 2000 to 4.8% in 2017) compared with women (2.6% in 2000 to 4.0% in 2017; P <0.001). Compared with men, women with AMI-CS were more frequently of Black race, from a lower socioeconomic status, with higher comorbidity, and admitted to rural and small hospitals (all P <0.001). Women had lower rates of ST-segment elevation presentation (73.0% versus 78.7%), acute noncardiac organ failure, cardiac arrest (34.3% versus 35.7%), and received less-frequent coronary angiography (78.3% versus 81.4%), early coronary angiography (49.2% versus 54.1%), percutaneous coronary intervention (59.2% versus 64.0%), and mechanical circulatory support (50.3% versus 59.2%; all P <0.001). Female sex was an independent predictor of in-hospital mortality (23.0% versus 21.7%; adjusted odds ratio, 1.11 [95% CI, 1.07–1.16]; P <0.001). Women had lower hospitalization costs ($156 372±$198 452 versus $167 669±$208 577; P <0.001) but comparable lengths of stay compared with men. Conclusions: In young AMI-CS admissions, women are treated less aggressively and experience higher in-hospital mortality than men.

Background: Abdominal aortic aneurysm (AAA) is an important cause of cardiovascular mortality; however, its genetic determinants remain incompletely defined. In total, 10 previously identified risk loci explain a small fraction of AAA heritability. Methods: We performed a genome-wide association study in the Million Veteran Program testing ≈18 million DNA sequence variants with AAA (7642 cases and 172 172 controls) in veterans of European ancestry with independent replication in up to 4972 cases and 99 858 controls. We then used mendelian randomization to examine the causal effects of blood pressure on AAA. We examined the association of AAA risk variants with aneurysms in the lower extremity, cerebral, and iliac arterial beds, and derived a genome-wide polygenic risk score (PRS) to identify a subset of the population at greater risk for disease. Results: Through a genome-wide association study, we identified 14 novel loci, bringing the total number of known significant AAA loci to 24. In our mendelian randomization analysis, we demonstrate that a genetic increase of 10 mm Hg in diastolic blood pressure (odds ratio, 1.43 [95% CI, 1.24–1.66]; P =1.6×10 −6 ), as opposed to systolic blood pressure (odds ratio, 1.06 [95% CI, 0.97–1.15]; P =0.2), likely has a causal relationship with AAA development. We observed that 19 of 24 AAA risk variants associate with aneurysms in at least 1 other vascular territory. A 29-variant PRS was strongly associated with AAA (odds ratio PRS , 1.26 [95% CI, 1.18–1.36]; P PRS =2.7×10 −11 per SD increase in PRS), independent of family history and smoking risk factors (odds ratio PRS+family history+smoking , 1.24 [95% CI, 1.14–1.35]; P PRS =1.27×10 −6 ). Using this PRS, we identified a subset of the population with AAA prevalence greater than that observed in screening trials informing current guidelines. Conclusions: We identify novel AAA genetic associations with therapeutic implications and identify a subset of the population at significantly increased genetic risk of AAA independent of family history. Our data suggest that extending current screening guidelines to include testing to identify those with high polygenic AAA risk, once the cost of genotyping becomes comparable with that of screening ultrasound, would significantly increase the yield of current screening at reasonable cost.

AbstractObjectivePsychotropic medication use in youth with eating disorders (EDs) is poorly understood despite high co‐occurrence of psychiatric disorders. This study examined characteristics associated with medication use in treatment‐seeking youth with EDs.MethodYouth up to age 18 reported on medication use when presenting to an academic medical center outpatient ED service in the United States. Data presented were collected between 1998–2015.ResultsThe sample (N = 604) was predominantly female (90.6%) with a mean age of 15.3 years (SD = 2.3). Approximately one‐third (30%, n = 173) were taking psychotropic medications (40%, n = 70, were taking multiple medications). Antidepressant use was most common (26%, n = 152), followed by atypical antipsychotics (8%, n = 43). Adjusting for co‐occurring psychiatric disorders, non‐Hispanic Whites who had received prior treatment (psychotherapy, hospitalization) were significantly more likely to be using medication. Longer illness duration and prior treatment were associated with greater antidepressant use. For atypical antipsychotics, prior hospitalization was associated with greater use.ConclusionsFindings confirm moderate psychotropic medication use among young patients with EDs despite a lack of clarity regarding optimally effective pharmacologic interventions in this population. Pharmacological trials examining the efficacy of medications for young patients with EDs are warranted to inform future prescribing practice.

AbstractObjectiveThe authors aimed to investigate the benefits and risks of catheter‐directed thrombolysis (CDT) in acute deep venous thrombosis (DVT).BackgroundThe role of CDT in the management of DVT is evolving. Data on CDT versus anticoagulation alone in acute DVT is sparse.MethodsWe performed a systematic review and meta‐analysis of published studies that compared CDT to anticoagulation alone in patients with acute DVT.ResultsWe included 11 studies (four randomized control trials [RCTs] and seven observational studies) with a total of 8,737 patients. During hospital stay, patients who received CDT had higher odds of major bleeding (2.5% vs. 1.6%; OR 1.46, 95% CI [1.07, 1.98], p = .02), blood transfusion (10.8% vs. 6.2%; OR 1.8, 95% CI [1.52, 2.13], p < .001), and thromboembolism (15.5% vs. 10%; OR 1.67, 95% CI [1.47, 1.91], p < .001) compared with anticoagulation alone. At 6‐month follow‐up, patients who received CDT had higher venous patency (71.1% vs. 37.7%; OR 5.49, 95% CI [2.63, 11.5], p < .001) and lower postthrombotic syndrome (PTS; 27% vs. 40.7%; OR 0.44, 95% CI [0.22, 0.86], p = .02). During a mean follow‐up duration of 30.5 ± 28 months, CDT group continued to have higher venous patency (79.6% vs. 71.8%; OR 3.79, 95% CI [1.54, 9.32], p = .004) and lower PTS (44.7% vs. 50.5%; OR 0.43, 95% CI [0.23, 0.78], p = .006), but no difference in thromboembolism.ConclusionCompared with anticoagulation alone, CDT for patients with acute DVT was associated with a higher risk of complications, but a higher rate of venous patency and lower risk of postthrombotic syndrome at 2.5 years follow‐up.

Abstract Background: The intrinsic immune response in triple negative breast cancer (TNBC) has both prognostic and predictive utility, and immune-related biomarkers are now actionable targets in TNBC. Current modalities for immune profiling are limited by lack of spatial context and precise quantitation. We used quantitative digital spatial profiling (DSP) to 1) characterize the immune architecture of tumoral and stromal regions in TNBC and 2) identify prognostic immune signatures. Methods: From the FinXX trial of adjuvant capecitabine therapy, tumor sections (FFPE) matched for patient characteristics, treatment arm and RFS-based outcome (N=44) were assessed with Nanostring GeoMxTM DSP. Briefly, with 3-plex immunofluorescence (pan-cytokeratin, CD45, CD68 with SYTO-13 dye for nuclei), spatially-defined CD45-enriched or CD68-enriched stromal segments and adjacent tumor segments (N=950) were selected for digital quantitation (NanoString nCounter) of 39 immune proteins (e.g. immune cell profiling proteins: CD3, CD4, CD8, CD11c, CD20, CD56, CD68, HLA-DR, PD-1, PD-L1, Granzyme B), immune drug targets (e.g. VISTA, STING, IDO1), and activation status-related proteins (e.g. ICOS, PD-L2, CD40, CD40L, CD44). Normalized, differentially-expressed (DE) proteins were evaluated, and weighted gene co-expression network analysis (WGCNA) was performed to identify modules of highly co-expressing immune proteins, and association with RFS as a categorical variable was determined. Results: 20 DE proteins in tumor segments were associated with RFS. Among them, those with the highest RFS-associated fold changes (FC) included CD20, CD40, CD56, HLA-DR, Granzyme B, and PD-L2 (FC): 2.1-4.4) (p &lt; 0.05). In contrast, only 4 DE proteins were associated with RFS in stromal segments (Granzyme B, IDO-1, PD-L1, and PD-L2 (FC: 1.5-3.3) (p &lt; 0.05). By WGCNA, 2 tumor-based immune modules [IM1 (lymphocyte infiltration) and IM2 (lymphocyte activation)] were identified based on their co-expression. The top three co-expressed proteins in IM1 were CD4, CD40, and CD45 (r &gt;0.9). The three top co-expressed proteins in IM2 were PD-L1, PD-L2, and Granzyme B (r &gt; 0.85). Together with CD56 expression, IM1 and IM2 comprised a set of 3 intratumoral immune features that associated with RFS. For recurring tumors, all 3 immune features clustered with low scores . Among non-recurrent tumors, two distinct, non-overlapping clusters with inverse characteristics were identified: high IM2, low IM1, low CD56 vs. low IM2, high IM1, and high CD56. Overall, across all 3 immune features, PDL2, CD40 and CD56 expression most strongly associated with RFS. Conclusion: With spatially-defined, precise quantification of immune proteins, we identified 3 immune features, including two distinct immune modules, IM1 and IM2 that correlate with durable RFS. These immune modules of highly co-expressing proteins were associated with RFS only when present in the tumor compartment but not tumor-adjacent, immune cell-rich stroma. Citation Format: Jodi M. Carter, Saranya Chumsri, Yaohua Ma, Xue Wang, Jennifer M. Kachergus, Douglas Hinerfeld, Heather Ann Brauer, Sarah Warren, Heikki Joensuu, Edith A. Perez, Aubrey Thompson. Quantitative digital spatial profiling reveals novel prognostic intratumoral immune signatures in triple-negative breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1004.

Background and Objectives: This study aimed to report the incidence of hospital-acquired dysmagnesemia and its association with in-hospital mortality in adult general hospitalized patients. Materials and Methods: We studied 26,020 adult hospitalized patients from 2009 to 2013 who had normal admission serum magnesium levels and at least two serum magnesium measurements during hospitalization. The normal range of serum magnesium was 1.7–2.3 mg/dL. We categorized in-hospital serum magnesium levels based on the occurrence of hospital-acquired hypomagnesemia and/or hypermagnesemia. We assessed the association between hospital-acquired dysmagnesemia and in-hospital mortality using multivariable logistic regression. Results: 28% of patients developed hospital-acquired dysmagnesemia. Fifteen per cent had hospital-acquired hypomagnesemia only, 10% had hospital-acquired hypermagnesemia only, and 3% had both hospital-acquired hypomagnesemia and hypermagnesemia. Compared with patients with persistently normal serum magnesium levels in hospital, those with hospital-acquired hypomagnesemia only (OR 1.77; p < 0.001), hospital-acquired hypermagnesemia only (OR 2.31; p < 0.001), and both hospital-acquired hypomagnesemia and hypermagnesemia (OR 2.14; p < 0.001) were significantly associated with higher in-hospital mortality. Conclusions: Hospital-acquired dysmagnesemia affected approximately one-fourth of hospitalized patients. Hospital-acquired hypomagnesemia and hypermagnesemia were significantly associated with increased in-hospital mortality.

Globally, diabetes mellitus is a leading cause of kidney disease, with a critical percent of patients approaching end-stage kidney disease. In the current era, sodium-glucose co-transporter 2 inhibitors (SGLT2i) have emerged as phenomenal agents in halting the progression of kidney disease. Positive effects of SGLT2i are centered on multiple mechanisms, including glycosuric effects, tubule—glomerular feedback, antioxidant, anti-fibrotic, natriuretic, and reduction in cortical hypoxia, alteration in energy metabolism. Concurrently, multiple kidney and cardiovascular outcome studies have reported remarkable advantages of SGLT2i including mortality benefits. Additionally, the superiority of combination therapies (SGLT2I along with metformin/DDP-4 Inhibitors) in treatment-naïve diabetic patients is further looked into with potential signal towards glycemic and blood pressure control. Reported promising results initiate a gateway for future research targeting kidney outcomes with combination therapies as an initial approach. In the current paper, we summarize leading cardiovascular and kidney outcome trials in patients with type 2 diabetes, the role of SGLT2i in non-diabetic proteinuric kidney disease, and the potential mechanisms of action of SGLT2i with special focus on combination therapy as an initial therapeutic approach in treatment-naïve diabetic patients.

Background: There is a paucity of contemporary data on the burden of intracranial hemorrhage (ICH) complicating acute myocardial infarction (AMI). This study sought to evaluate the temporal trends, predictors, and outcomes of ICH in AMI. Methods: The National Inpatient Sample (2000–2017) was used to identify adult (>18 years) AMI admissions with ICH. In-hospital mortality, hospitalization costs, length of stay, and measure of functional ability were the outcomes of interest. The discharge destination along with use of tracheostomy and percutaneous endoscopic gastrostomy were used to estimate functional burden. Results: Of a total 11,622,528 AMI admissions, 23,422 (0.2%) had concomitant ICH. Compared to those without, the ICH cohort was on average older, female, of non-White race, had greater comorbidities, and had higher rates of arrhythmias (all p < 0.001). Female sex, non-White race, ST-segment elevation AMI presentation, use of fibrinolytics, mechanical circulatory support, and invasive mechanical ventilation were identified as individual predictors of ICH. The AMI admissions with ICH received less frequent coronary angiography (46.9% vs. 63.8%), percutaneous coronary intervention (22.7% vs. 41.8%), and coronary artery bypass grafting (5.4% vs. 9.2%), as compared to those without (p < 0.001). ICH was associated with a significantly higher in-hospital mortality (41.4% vs. 6.1%; adjusted OR 5.65 (95% CI 5.47–5.84); p < 0.001), longer hospital length of stay, higher hospitalization costs, and greater use of percutaneous endoscopic gastrostomy (all p < 0.001). Among ICH survivors (N = 13, 689), 81.3% had a poor functional outcome at discharge. Conclusions: ICH causes a substantial burden in AMI due to associated higher in-hospital mortality and poor functional outcomes.

Background: The objective of this study was to describe inpatient prevalence, characteristics, outcomes, and resource use for acute salicylate intoxication hospitalizations in the United States. Methods: A total of 13,805 admissions with a primary diagnosis of salicylate intoxication from 2003 to 2014 in the National Inpatient Sample database were analyzed. Prognostic factors for in-hospital mortality were determined using multivariable logistic regression. Results: The overall inpatient prevalence of salicylate intoxication among hospitalized patients was 147.8 cases per 1,000,000 admissions in the United States. The average age was 34 ± 19 years. Of these, 35.0% were male and 65.4% used salicylate for suicidal attempts. Overall, 6% required renal replacement therapy. The most common complications of salicylate intoxication were electrolyte and acid-base disorders, including hypokalemia (25.4%), acidosis (19.1%), and alkalosis (11.1%). Kidney failure (9.3%) was the most common observed organ dysfunction. In-hospital mortality was 1.0%. Increased in-hospital mortality was associated with age ≥30, Asian/Pacific Islander race, diabetes mellitus, hyponatremia, ventricular arrhythmia, kidney failure, respiratory failure, and neurological failure, while decreased in-hospital mortality was associated with African American and Hispanic race. Conclusion: hospitalization for salicylate intoxication occurred in 148 per 1,000,000 admissions in the United States. Several factors were associated with in-hospital mortality.