Shamim, Urooj

e13162 Background: BRCA1/2 mutations impair homologous recombination repair, forcing cancer cells to rely on alternative DNA repair pathways, such as those mediated by poly(ADP-ribose) polymerase (PARP). PARP inhibitors (PARPis), like iniparib, olaparib, talazoparib, niraparib, and veliparib, exploit this dependency, inducing lethality in cells of BRCA-mutated, HER2-negative breast cancers (BRCAm, HER2-BC). Only 2 PARPis, talazoparib and olaparib, are FDA-approved for BRCAm, HER2-BC. However, the treatment with the highest efficacy remains unclear. We conducted a network meta-analysis (NMA) of randomised controlled trials (RCTs) to compare the efficacy of PARPis in treating BRCAm, HER2-BC. Methods: We systematically searched PubMed, Cochrane CENTRAL, SCOPUS, and ClinicalTrials.gov (up to December 2024) for randomized controlled trials (RCTs) following PRISMA-NMA guidelines. Primary outcome was overall survival(OS), with hazard ratios (HRs) and 95% confidence intervals (CIs). Secondary outcome was progression-free survival (PFS). Survival times were converted to HRs under the assumption of exponential distribution. Standard of care (SOC) was defined as taxane/anthracycline-based regimens with additional platinum-based chemotherapy. Physician's choice chemotherapy (PCT) included capecitabine, eribulin, gemcitabine, or vinorelbine. A frequentist approach with random-effects modeling was used to pool estimates, and P-scores ranked treatment efficacy. Heterogeneity and inconsistency were assessed using τ², I², and Q-statistics. Analyses were conducted in R version 4.4.1. Results: 8 studies including 4432 participants incorporating 8 pairwise comparisons and 7 treatments were analyzed for OS. Compared to SOC (reference), HRs of OS were significantly reduced with talazoparib+SOC (HR = 0.49, 95% CI: 0.32–0.74; P = 0.64), olaparib+SOC (HR = 0.46, 95% CI: 0.36–0.59; P = 0.69), niraparib+SOC (HR = 0.44, 95% CI: 0.26–0.76; P = 0.76), and veliparib+SOC (HR = 0.38, 95% CI: 0.29–0.48; P = 0.91). No heterogeneity or inconsistency was detected (τ² = 0; I² = 0; Q = 1.27, p = 0.53). For PFS, iniparib/gemcitabine, talazoparib, olaparib, and niraparib showed significant reduction in HR with increasing order of P-scores, in combination with SOC. Conclusions: Veliparib combined with SOC showed the highest OS improvement, while niraparib ranked highest for PFS, followed by talazoparib and olaparib. Further trials are needed to confirm these findings and refine treatment strategies for BRCAm, HER2-BC.

Introduction: Thoracic aortic aneurysms (TAA) are a significant health concern, with the true prevalence likely underestimated due to undiagnosed cases. Outcomes in TAA are influenced by factors like age, sex, and comorbidities such as hypertension. This study examines mortality trends and disparities associated with TAA in US adults. Methodology: This study analyzed death certificates from 1999 to 2020 using the CDC WONDER Database to identify TAA-related deaths in individuals aged 25 and older using ICD-10 codes I71.1 and I71.2. Age-adjusted mortality rates (AAMRs) per 1 000 000 and annual percent changes (APCs) were calculated and stratified by year, sex, age group, race/ethnicity, region, and urbanization status. Results: Between 1999 and 2020, 47 136 TAA-related deaths were reported among US adults. The AAMR decreased from 16.2 to 8.2 per 1 000 000, with a significant decline from 1999 to 2013 (APC: −5.00; 95% CI: −5.54 to −4.54; P<0.001). Older adults had the highest AAMRs at 44.6 per 1 000 000. Men had higher AAMRs than women (11.2 vs. 9). AAMRs were highest among non-Hispanic (NH) Black (11), followed by NH White (10.3), NH Asian or Pacific Islander (9.5), NH American Indian or Alaska Native (7.8), and Hispanic (5.2) populations. Nonmetropolitan areas had higher AAMRs than metropolitan areas (11 vs. 9.8). Conclusions: The analysis showed a significant decline in TAA mortality since 1999, with recent stabilization. However, disparities persist, with higher AAMRs among men, older adults, NH Black adults, and nonmetropolitan residents, highlighting the need for targeted and equitable interventions.

Background: Hypertensive heart disease (HHD) poses a growing public health concern. Global data reveal a concerning rise in HHD prevalence, deaths, and disability-adjusted life years (DALYs) between 1990 and 2019. The Framingham Study highlights that hypertension is linked to approximately one-quarter of heart failure cases. This association is even stronger among older adults, in whom hypertension is responsible for up to 68% of heart failure cases. Methods: This study analyzed death certificates within the CDC WONDER database for patients in the United States from 1999 to 2020. We identified deaths among individuals aged 25 years and older caused by HHD and CHF using the International Classification of Diseases, Tenth Revision (ICD-10) code I11.0. Age-adjusted mortality rates (AAMRs) per 1,000,000 individuals and annual percent change (APC) were computed and categorized based on year, gender, race/ethnicity, and urbanization status. Results: Between 1999 and 2020, a total of 302,270 deaths were reported in patients due to HHD with CHF. Overall, AAMR increased from 37.3 to 134.9 per 1,000,000 population between 1999 and 2020, with a significant decrease from 1999 to 2004 (APC: -7.91; 95% CI: -20.16 to -1.04), followed by a significant increase from 2004 to 2007 (APC: 42.47; 95% CI: 21.27 to 55.62), a slight decrease from 2007 to 2014 (APC: -0.9; 95% CI: -9.38 to 2.39), and finally a steep increase from 2014 to 2020 (APC: 14.22; 95% CI: 10.87 to 20.84). Gender-based analysis revealed that men had slightly higher AAMRs than women (Men: 63.1; 95% CI: 62.8 to 63.5 vs. Women: 60.7; 95% CI: 60.5 to 61). Moreover, AAMRs were highest among non-Hispanic African Americans (109.6; 95% CI: 108.6 to 110.6), followed by non-Hispanic American Indian or Alaska Natives (66.6; 95% CI: 63.1 to 70.1), non-Hispanic Whites (58.5; 95% CI: 58.2 to 58.7), Hispanics (53.7; 95% CI: 52.9 to 54.5), and non-Hispanic Asian or Pacific Islanders (39; 95% CI: 38–39.9). In addition, non-metropolitan areas had higher AAMRs than metropolitan areas (non-metropolitan: 65.7; 95% CI: 65.2 to 66.3 vs. metropolitan: 62.1; 95% CI: 61.8 to 62.3) (Figure 1). Conclusions: Despite an initial decline, mortality from combined HHD and CHF has risen significantly since 1999. Notably, mortality was most pronounced among men, non-Hispanic African Americans, and individuals residing in non-metropolitan areas.

Background: Acute Kidney Injury (AKI) is a multifactorial complication following repair of Stanford Type A aortic dissection (TAAD) with an alarmingly high incidence, varying from 20 to 77%. Postoperative AKI following life-threatening disease tends to be much more complex. However, the exact role of postprocedural AKI in the prognosis of patients undergoing TAAD repair has not been elucidated. Aims: This meta-analysis aimed to evaluate the prognostic significance of postprocedural AKI in patients undergoing TAAD repair. Methods: A literature search was conducted using PubMed, EMBASE, and SCOPUS databases. The primary endpoint was 30-day mortality with several secondary endpoints. Risk ratios (RR) with 95% confidence intervals (CIs) were pooled using Review Manager software. Statistical significance was set at p <0.05. Random-effects meta-analyses were performed for all outcomes. Results: Our analysis included 21 studies comprising 10396 patients. Patients with AKI exhibited a significantly higher risk of 30-day mortality (RR=3.98; 95% CI: 3.04-5.22; p<0.00001; I 2 =57%), stroke (RR= 2.05; 95% CI: 1.68-2.50; p<0.00001; I 2 =32%), dialysis requirement (RR= 32.9; 95% CI: 10.39-104.24; p<0.00001; I 2 =90%) (Figure 1), cardiovascular complications (RR= 2.85; 95% CI: 1.65-4.92; p<0.0002; I 2 =85%), sepsis (RR= 4.92; 95% CI: 2.62-9.24; p<0.00001; I 2 =64%), and re-exploration for bleeding (RR=2.46; 95%CI: 1.79-3.39; p<0.00001; I 2 =58%) compared to those without AKI (Figure 2). Conclusion: Patients with AKI demonstrated a significantly increased risk of mortality, stroke, need for dialysis, sepsis, postoperative cardiovascular complications, and re-exploration for bleeding. Further prospective studies are required to better understand the prevention strategies and long-term effects on prognosis of AKI post-repair for TAAD.

Acute kidney injury (AKI) frequently complicates the repair of Stanford type A aortic dissection (TAAD). This systematic review, meta-analysis, and meta-regression analysis aimed to elucidate the prognostic impact of AKI in these patients. A literature search in PubMed, EMBASE, and Google Scholar identified relevant studies on the predictors and outcomes of AKI following TAAD repair. The primary endpoint was 30-day mortality; secondary endpoints included stroke, dialysis/continuous renal replacement therapy (CRRT), and other complications. Random-effects meta-analyses were used, with significance set at P < 0.05. Twenty-one studies (10 396 patients) were analyzed. AKI was associated with higher risks of 30-day mortality (risk ratio = 3.98), stroke (risk ratio = 2.05), dialysis/CRRT (risk ratio = 32.91), cardiovascular (risk ratio = 2.85) and respiratory complications (risk ratio = 2.13), sepsis (risk ratio = 4.92), and re-exploration for bleeding (risk ratio = 2.46). No significant differences were noted in sternal wound infection, tracheostomy, paraplegia, or hepatic failure. AKI significantly increases mortality, morbidity, hospital, and ICU stay duration in TAAD repair patients.