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AbstractObservational studies indicate that pleural effusion has an association with risk and the clinical prognosis of COVID‐19 disease; however, the available literature on this area is inconsistent. The objective of this systematic review and meta‐analysis is to evaluate the correlation between COVID‐19 disease and pleural effusion. A rigorous literature search was conducted using multiple databases. All eligible observational studies were included from around the globe. The pooled prevalence and associated 95% confidence interval (CI) were calculated using the random effect model. Mantel–Haenszel odds ratios were produced to report overall effect size using random effect models for severity and mortality outcomes. Funnel plots, Egger regression tests, and Begg–Mazumdar's rank correlation test were used to appraise publication bias. Data from 23 studies including 6234 COVID‐19 patients was obtained. The overall prevalence of pleural effusion in COVID‐19 patients was 9.55% (95% CI,I2 = 92%). Our findings also indicated that the presence of pleural effusions associated with increased risk of severity of disease(OR = 5.08, 95% CI 3.14–8.22,I2 = 77.4%) and mortality due to illness(OR = 4.53, 95% CI 2.16–9.49,I2 = 66%) compared with patients without pleural effusion. Sensitivity analyses illustrated a similar effect size while decreasing the heterogeneity. No significant publication bias was evident in the meta‐analysis. The presence of pleural effusion can assist as a prognostic factor to evaluate the risk of worse outcomes in COVID‐19 patients hence, it is recommended that hospitalized COVID‐19 patients with pleural effusion should be managed on an early basis.

Background and aim First pass effect (FPE) is defined as achieving a complete recanalization with a single thrombectomy device pass. Although clinically desired, FPE is reached in less than 30% of thrombectomy procedures. Multiple device passes are often necessary to achieve successful or complete recanalization. We performed a systematic review and meta-analysis to determine the recanalization rate after each pass of mechanical thrombectomy and its association with good neurological outcome. Methods A literature search was performed for studies reporting the number of device passes required for either successful (mTICI 2b or higher) or complete (mTICI 2c or higher) recanalization. Using random-effect meta-analysis, we evaluated the likelihood of recanalization and good neurological outcome (measured with the modified Rankin Score <2 at 90 days) after each device pass. Results Thirteen studies comprising 4197 patients were included. Among cases with failed first pass, 24% of them achieved final complete recanalization and 45% of them achieved final successful recanalization. Independently to the total number of previously failed attempts, the likelihood of achieving successful recanalization was 30% per pass, and the likelihood to achieve complete recanalization was about 20% per pass. The likelihood of good neurological outcome in patients with final successful recanalization decreased after each device pass: 55% after the first pass, 48% after the second pass, 42% after the third pass, 36% after the fourth pass, and 26% for 5 passes or more. Conclusion Each pass is associated with a stable likelihood of recanalization but a decreased likelihood of good neurological outcome.

Background: Reduced left atrial (LA) compliance (LAC) contributes to pulmonary venous hypertension in heart failure with preserved ejection fraction (HFpEF); however the underlying mechanisms are poorly defined. We hypothesized that microvascular inflammation with rarefaction and impaired nitric oxide (NO) signaling, LA titin hypophosphorylation and fibrosis may each contribute to reduced LAC in HFpEF. Methods: Invasive LA pressure-volume (PV) analyses (open-chest; pericardiotomy; admittance catheter) were performed in 9 aged dogs with experimental hypertension (bilateral renal wrap + DOCA; HFpEF) compared to 13 sham-operated young adult dogs (control). LAC was measured at end-LA reservoir during acute preload reduction (cava occlusion). LA tissue and LA microvascular function were analyzed. Results: Compared to controls, the curvilinear end-LA reservoir PV relationship ( Fig A ) was shifted upward/leftward in HFpEF (LA diastolic stiffness constant 0.08 vs 0.16 mmHg/mL in controls, p=0.005). LA microvascular density (MVD; CD31 stain) tended to be lower in HFpEF than controls (2154±578 vs 2650±523 vessels/mm 2 , p=0.07) and LA MVD negatively correlated with the LA diastolic stiffness constant (r=-0.66, p=0.006). LA microvessels from HFpEF dogs showed impaired endothelium-dependent shear stress-mediated dilation compared to controls, consistent with impaired NO signaling ( Fig B ). Titin isoform expression was similar between groups, but isoform N2B (stiffer) was (p=0.03) and N2BA (compliant) tended to be (p=0.09) hypophosphorylated in HFpEF LA appendage (LAA) tissue. Fibrosis (Picrosirius Red) was similar between groups in the LA free wall and LAA, but increased in areas adjacent to the pulmonary veins in HFpEF (27±12% vs controls 15±8%, p=0.01). Conclusion: In experimental HFpEF, LAC was reduced in association with evidence of LA microvascular rarefaction and impaired NO signaling, titin hypophosphorylation and regional increases in LA fibrosis.

Background: Galectin-3 (Gal-3) may promote cardiac and renal fibrosis in heart failure (HF). Plasma Gal-3 levels predict outcome in HF but are tightly correlated with renal function. The source of Gal-3 in human HF, chronic kidney disease (CKD) or cardio-renal failure (HF+CKD) is unclear. Objective: To assess Gal-3 presence and location in human heart or kidney tissue from patients with HF, CKD or HF+CKD. Methods: Plasma Gal-3 levels and LV tissue explanted at time of cardiac transplant in systolic HF (n=15) and autopsy renal sections from patients with normal kidneys (n=4), CKD (n=17) or CKD+HF (n=14) were examined (H&E, Masson’s trichrome and CD-68 and Gal-3 immunohistochemistry). In the systolic HF patients, we quantified the number of Gal-3+/CD-68+ cells per HPF in LV tissue and assessed the correlation with plasma Gal-3 levels. In autopsy renal tissue, we derived a Composite Gal-3 Score (CG3S) incorporating the % of Gal-3+ tubules per HPF, % of Gal-3+ cells/tubule per HPF, and intensity of Gal-3 staining and assessed the correlation of the CG3S with ante-mortem estimated glomerular filtration rate(eGFR). Renal macrophage Gal-3 staining was also assessed. Results: In systolic HF LV tissue, Gal-3 was present in macrophages rather than myocytes but Gal-3+/CD-68+ cells per HPF was not correlated with plasma Gal-3 levels (p> 0.9) which correlated inversely with eGFR (r = -0.89 for log Gal-3 vs eGFR, p<0.0001). In the kidney, Gal-3 was not present in macrophages but was localized to renal tubular cells (Figure). The CG3S increased exponentially as eGFR decreased (r = - 0.88 for log CG3S versus eGFR; p<0.0001) and this relationship was not different (p=0.44) in patients with or without HF (Figure). The log CG3S correlated with the degree of fibrosis (tubulointerstitial scarring) in the kidney (r=0.88; p<0.0001). Conclusion: Collectively, these data suggest that plasma Gal-3 is predominantly of renal tubular epithelial origin in human HF, CKD, and CKD+HF.

Background: The Acute Decompensated Heart Failure National Registry (ADHERE) Classification and Regression Tree (CART) algorithm is an accepted method to assess a heart failure (HF) patient’s risk of inpatient mortality based on the patient’s systolic blood pressure (≥115 vs. <115 mmHg), blood urea nitrogen (BUN; ≥43 vs. <43 mg/dL), and creatinine (≥2.75 vs. <2.75 mg/dL) at the time of admission. Whether the ADHERE CART algorithm identifies risk of longer term poor outcomes and is predictive in patients with systolic (EF < 50%) or diastolic (EF ≥ 50%) HF in the community is unclear. Methods: We identified all hospitalizations for a primary diagnosis of HF occurring between 2000-2013 in a community-based cohort living within 40 miles of Rochester, MN. Outcomes including length of stay, in-hospital mortality, 30 and 90 day post-discharge mortality and readmission for any cause at 30 and 90 days were compared across the ADHERE CART risk groups using logistic regression for the entire cohort and separately for systolic (EF < 50%) and diastolic (EF ≥ 50%) HF. Results: See Table. We examined 5,918 heart failure hospitalizations among 3,628 individual patients. Distribution of hospitalizations across the risk categories is shown in table. Length of stay, in-hospital mortality, 30 and 90 day mortality and 30 and 90 day readmission rates all increased with increasing ADHERE risk categories. Similar results were obtained separately for systolic and diastolic HF. Conclusion: The ADHERE CART algorithm is simple, uses data universally available on admission, and identifies groups that differ substantially in their post-discharge adverse outcomes regardless of HF type (systolic vs diastolic) in the community. The ADHERE CART algorithm may inform clinical decision regarding advanced HF treatments, end-of-life planning and care transition services in patients hospitalized for HF in the community.

6549 Background: Representation and outcomes of women, older adults, and racial minorities in ICI trials has not been previously described. Methods: MEDLINE and Embase were searched to identify ICI RCTs. Data for trial characteristics, proportion of trials reporting race, age and sex as well as the proportion of patients by race, age and sex enrolled in ICI trials was collected. Descriptive statistics were reported for trials reporting minority representation and proportion of included patients by race, age and sex. Disparities in representation were calculated using enrollment incidence disparity (EID) and enrollment incidence ratios (EIR) by comparing trial enrollment against U.S. population-based estimates acquired from the SEER 18 incidence database. The relationship of EID to key trial characteristics were compared using standard parametric and non-parametric statistical tests. Trends in EIR were analyzed using the Joinpoint Regression Analysis software. Results: 108 ICI trials from 2009 to 2020 with 48,360 patients were included in this analysis. All RCTs reported sex (101/101). 78 trials reported race (72%), of which only 41 trials (38%) reported data on all 5 U.S. racial categories (Black, White, Asian, Pacific Islander and Native American). Participation of Black patients was reported in 66 trials (61%), White participants in 78 trials (72%), Asians in 69 trials (64%), Native Americans and Pacific Islanders in 41 trials (38%), and Hispanics in 24 trials (22%). Age categories were inconsistently defined, and 80 trials (74%) reported the proportion of patient by age categories. Subgroup analyses of clinical outcomes by race, age and sex were reported in 17 (22%), 62 (79%) and 57 (73%) trials respectively. Women (trial proportion [TP]: 32%; EIR: 0.77), patients aged ≥ 65 years (TP: 42%; EIR: 0.74), Black participants (TP: 1.8%; EIR: 0.17) and Hispanic participants (TP: 5.9%; EIR: 0.67) were largely underrepresented, and Asians were overrepresented (TP: 15.9%; EIR: 2.64). Black patients were underrepresented across all cancer types. Similarly, women, older adults ( > 65 years of age) and Hispanic patients were consistently underrepresented across cancer types with few exceptions. Representation of older adults increased significantly from 2010-2020 (APC: 2.72), while representation of Black patients decreased significantly from 2009-2020 (APC: -23.37). Black patients were found to be significantly underrepresented in phase III trials (p = 0.0005), trials with OS as the primary endpoint (p = 0.004), and PD1 inhibitor trials (p = 0.002). Hispanics were significantly underrepresented in PD1 inhibitor trials (p = 0.003). Conclusions: There is both suboptimal reporting about participation and underrepresentation of women, racial minorities (particularly Black patients) and older adults in ICI trials as compared to their cancer incidence.

5001 Background: Tak is an oral selective nonsteroidal 17, 20-lyase inhibitor that blocks the synthesis of gonadal and adrenal androgens. We evaluated the clinical benefit of Tak with ADT in pts with newly diagnosed mHSPC. Methods: Pts with mHSPC with a Zubrod performance status (PS) of 0-2 and a PSA of ≥ 2 ng/ml were randomized 1:1 to ADT+Tak (300 mg twice daily) or ADT+Bic (50 mg daily). Stratification factors included PS (0-1 vs ≥2), extent of disease (minimal vs extensive), and receipt of ADT prior to registration (yes vs no). The primary endpoint was overall survival (OS). Secondary endpoints were progression free survival (PFS; based on PSA, imaging or clinical progression), PSA at 7 months (≤0.2 vs 0.2 < PSA; ≤-4 vs. > 4 ng/ml) and adverse event (AE) profile. With 2.75 yrs to accrue 1,186 eligible pts and 3 additional yrs of follow-up, we would have 90% power to determine a 33% improvement in OS from 54 to 72 mos (1-sided α = 0.025). A final analysis was pre-specified after 523 deaths using a 1-sided α = 0.022 to account for interim analyses. Results: Between 3/2013 and 7/2017, 1,313 pts were randomized and 1,279 were included in the intention-to-treat (ITT) analysis (32 pts were ineligible and 2 pts withdrew consent). Median age was 68 yrs and 10% of subjects were Black. Median PSA was 30 ng/mL (range 2-6710) and 49% of pts had extensive disease. After a median follow-up of 4.9 yrs, PFS and PSA response were significantly improved with Tak over Bic but no significant improvement in OS was observed (Table). More grade 3/4 AEs occurred in Tak vs. Bic arms (43% vs. 14%), and included hypertension (20% vs. 5%) and fatigue (5% vs. 2%). Five pts in Tak and 1 pt in the Bic arm had grade 5 AE. Conclusions: Despite clinically meaningful improvement in various outcome measures with Tak+ADT over Bic+ADT in this representative population of mHSPC, the improvement in OS did not meet the pre-specified criteria for statistical significance. The median OS of 70 mos in the control arm (standard ADT) was higher than that reported in contemporary phase 3 trials in this setting, and 16 mos higher than originally estimated. This trial sets a new landmark for survival estimates when pts with mHSPC have access to multiple approved subsequent life-prolonging therapies. Funding: NIH/NCI/NCTN grants U10CA180888, U10CA180819, U10CA180820; U10CA180821; and in part by Millennium Pharmaceuticals, Inc. (Takeda Pharmaceutical Company LTD) Clinical trial information: NCT01809691. [Table: see text]