Citations

Abstract Background Breast cancer is etiologically heterogeneous, but which risk factors differ in their associations across tumor subtypes remains unclear. We conducted a large, pooled analysis to evaluate independent, dose-response associations between breast cancer risk factors and quantitative tumor features. Methods Analyses of 15,731 invasive breast cancers from 24 studies evaluated associations (p-trend) between reproductive and hormonal factors, body mass index (BMI), alcohol, smoking, and family history in relation to quantitative immunohistochemistry measures on tissue microarrays (ER, PR, HER2, KI67, TP53) and tumor grade. Analyses in a subset of 10 population-based studies estimated subtype-specific odds ratios (ORs) comparing cases to controls. A Bayesian False Discovery Probability (BFDP) <0.2 was used to identify associations with strong statistical evidence. Results Nulliparity and later age at menopause were associated with higher ER-positivity (p-trend=0.021 and 0.001, respectively), with corresponding OR[ER+] (95% CI) = 1.49 (1.16-1.90) for nulliparous vs. parous and 1.07 (1.03-1.11) per 5 years. Current combined menopausal hormone therapy (MHT) use was associated with lower grade (p-trend<0.001), with OR [grade1] = 3.37 (2.69-4.21) for current vs. never users. Higher BMI was associated with lower ER-positivity and higher grade in premenopausal women (p-trend<0.001 and <0.001), with OR[ER+] = 0.80 (0.74-0.87) and OR[grade1] = 0.75 (0.63-0.88) per 5 units, and with higher PR-positivity and higher grade in postmenopausal women (p-trend<0.001 and <0.001), with OR[PR+] = 1.08 (1.03-1.14) and OR[grade 3] = 1.10 (1.04-1.17) per 5 units. Conclusion This pooled analysis of 15,731 cases showed that nulliparity, age at menopause, MHT, and BMI have independent, dose-response associations with ER, PR, and grade, clarifying patterns of etiologic heterogeneity. Associations with HER2, KI67 and TP53, or other risk factors did not meet our threshold for strong evidence.

Summary Achalasia is a motility condition defined by failure of relaxation of the lower esophageal sphincter and loss of peristalsis in the distal esophagus. Per-oral endoscopic myotomy (POEM) is a technique to reduce lower esophageal sphincter pressure. We performed a systematic review and meta-analysis to assess the association between POEM and the clinical outcomes. We performed a systematic review and a meta-analysis (CRD420251052240). Literature search was done on PubMed and Embase (up to 8 June 2025). Original studies involving achalasia patients who underwent esophageal POEM with impedance planimetry using 8-cm balloon at 30 or 40 mL filling volumes with 325 catheter only (not the 322-N catheter) were included. The outcomes of interest were the clinical response groups (responders’ Eckardt score [ES] < 3 and non-responders’ ES > 3), reflux esophagitis, cross-sectional area (CSA), distensibility index (DI), and diameter. Nineteen studies with 1215 patients were included. The responders (ES < 3) showed a statistically significantly greater increase in DI due to POEM (post-op minus pre-op) (mean difference [MD] = 1.92 mm2/mmHg [0.32, 3.53], P = 0.02) as well as a higher postoperative DI (MD = 1.87 mm2/mmHg [0.04, 3.70], P = 0.05) (40 mL). Reflux esophagitis group had statistically significantly higher CSA and diameter values (CSA MD = 15.68 mm2 [6.91, 24.24], P = 0.0005) (diameter MD = 0.96 mm [0.58, 1.33], P < 0.00001) but no statistically significant difference for DI as compared to the non-reflux esophagitis group (DI MD = 0.19 mm2/mmHg [−0.51, 0.89], P = 0.59). In achalasia patients undergoing esophageal POEM, a greater interval increase in the DI as well as a higher post-procedural DI absolute value predicts a favorable clinical response. Higher postoperative CSA and diameter were linked to reflux esophagitis.

We report the rare coexistence of extensive coronary-cameral fistulas (CCFs) with aneurysmal dilatation of coronary arteries and an incidental left ventricular papillary fibroelastoma (PFE) in a female in her early 70s who presented with chest pain and lower extremity oedema. Multimodality imaging, including transoesophageal echocardiography, cardiac CT and coronary angiography, confirmed the diagnosis. The PFE was surgically resected to prevent embolic complications, while the CCFs were managed conservatively due to their haemodynamic insignificance. This case demonstrates that even extensive CCFs may be haemodynamically insignificant, while a small PFE can pose a significant embolic threat, justifying disparate management strategies guided by multimodality imaging and haemodynamic assessment.

Background: Breast cancer polygenic risk scores (PRS) and traditional risk models (e.g., the Gail model [Gail]) are known to contribute largely independent information, but it is unclear how the overlap varies by ancestry, age, disease type (invasive breast cancer, DCIS), and risk threshold. Methods: In a retrospective case–control study, we evaluated risk prediction performance in 180,398 women (161,849 of European ancestry; 18,549 of Asian ancestry). Odds ratios (ORs) from logistic regression models and the area under the receiver operating characteristic curve (AUC) were estimated. Results: PRS for invasive disease showed a stronger association in younger (<50 years) women (OR = 2.51, AUC = 0.622) than in women ≥ 50 years (OR = 2.06, AUC = 0.653) of European ancestry. PRS performance in Asians was lower (OR range = 1.62–1.64, AUC = 0.551–0.600). Gail performance was modest across groups and poor in younger Asian women (OR = 0.94–0.99, AUC = 0.523–0.533). Age interactions were observed for both PRS (p < 0.001) and Gail (p < 0.001) in Europeans, whereas in Asians, age interaction was observed only for Gail (invasive: p < 0.001; DCIS: p = 0.002). PRS identified more high-risk individuals than Gail in Asian populations, especially ≥50 years, while Gail identified more in Europeans. Overlap between PRS, Gail, and family history was limited at higher thresholds. Calibration analysis, comparing empirical and model-based ROC curves, showed divergence for both PRS and Gail (p < 0.001), which indicates miscalibration. In Europeans, family history and prior biopsies drove Gail discrimination. In younger Asians, age at first live birth was influential. Conclusions: PRS adds value to risk stratification beyond traditional tools, especially in younger women and Asian ancestry populations.

Background: Despite obesity being a major cardiovascular risk factor, studies in heart failure populations have reported an inverse association between body mass index and mortality—a phenomenon termed the "obesity paradox." However, the consistency and shape of this relationship across different HF phenotypes and clinical subgroups remain unclear. This meta-analysis aimed to quantify the dose-response relationship between BMI and mortality in HF patients and assess potential variations across subgroups. Hypothesis: Higher BMI is associated with reduced mortality in patients with heart failure, and that this relationship varies across clinical subgroups and U-shaped relationship. Methods: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A search strategy was developed, and studies were extracted from Cochrane and PubMed databases through December 2023. The main outcomes were all-cause mortality, cardiovascular deaths, and heart failure hospitalizations. Data were summarized as hazard ratios with 95% confidence intervals, and a spline model was used to assess non-linear relationships, with 21.7 kg/m2 as the reference point in the dose-response curve. PROSPERO: CRD42023455124 Results: Thirty-three studies (457,124 person-years) showed that each 5 kg/m2 increase in BMI was significantly associated with a 6% reduction in all-cause mortality (HR 0.94; 95% CI 0.92–0.96). Significant reductions were observed in acute decompensated heart failure (7%), HFpEF (9%), HFrEF (8%), diabetes (9%), males (9%), and females (8%). Cardiovascular mortality declined by 5% per 5 kg/m2 increase. Non-linear analysis revealed a significant U-shaped relationship, with lowest all-cause mortality between BMI 21.7 and 39 kg/m2. Subgroup analysis showed significant non-linear all-cause mortality reductions in acute decompensated heart failure (23.5–26 kg/m2), HFpEF (21.7–31 kg/m2), HFrEF (21.7–43 kg/m2), females (24–25.5 kg/m2), diabetes (21.7–36 kg/m2), and non-diabetics (21.7–33 kg/m2). Conclusion: Higher BMI is significantly associated with lower all-cause and cardiovascular mortality in patients with heart failure, supporting the presence of an obesity paradox. This protective effect was consistent across clinical subgroups, including HFpEF, HFrEF, males, females, and individuals with diabetes. The BMI paradox was evident in patients with acute decompensated heart failure, HFpEF, HFrEF, females, and both with and without diabetes.

ABSTRACT Background Patients with hypertrophic obstructive cardiomyopathy (HOCM) were excluded from all major trials for transcatheter aortic valve replacement (TAVR). “Suicide left ventricle” occurring after TAVR is postulated to occur as a result of chronic pressure overload from fixed obstruction that is acutely relieved after the valve deployment resulting in worsening left ventricular outflow tract obstruction. Aims The aim of this study was to determine the clinical and readmission outcomes in HOCM patients undergoing TAVR. Methods Data was extracted from the National Inpatient and National Readmission 2016−2020 Databases. We performed multivariable Logistic regression analysis to determine the odds of in‐hospital mortality and other relevant clinical outcomes in patients undergoing TAVR with and without comorbid HOCM. Multivariable Cox regression analysis was used to assess 30‐day hospital readmission in HOCM patients undergoing TAVR. Results We identified 296,670 patients who underwent TAVR, of whom 534 (0.2%) had comorbid HOCM. The patients undergoing TAVR with comorbid HOCM had more than threefold higher risk of in‐hospital mortality (adjusted odds ratio: 3.47, 95% CI 1.37–8.81, p = 0.009) when compared to patients without HOCM. Additionally, patients undergoing TAVR with comorbid HOCM had a higher risk of atrioventricular blocks, cardiogenic shock, acute kidney injury, and the need for intubation. There was no difference in readmission outcomes post‐TAVR among patients with and without HOCM. Conclusion Our analysis of a large, real‐world cohort of patients undergoing TAVR showed that patients with HOCM have a significantly higher risk of in‐hospital mortality and procedural complications when compared to patients without HOCM.

ABSTRACTBackgroundTricuspid regurgitation (TR) is a common occurrence in patients with heart failure (HF), and its role in disease progression has gained attention in recent years. Although TR can worsen clinical outcomes in HF patients, the impact of gender, racial, and socioeconomic factors remains largely unexplored. With growing evidence supporting the role of percutaneous interventions for the treatment of significant TR, understanding these disparities is more crucial than ever.MethodsData were extracted from the National Inpatient and National Readmission 2016–2020 Databases. We used ICD‐10 code I50 to identify the patients primarily admitted for HF and subdivided the cohort into two groups based on the presence or absence of TR. We performed multivariable logistic regression analysis to determine odds of the in‐hospital mortality and multivariable Cox regression analysis to assess the 30‐ and 90‐day hospital readmission in HF patients with and without TR. All the analyses were adjusted for age, gender, insurance status, Charlson comorbidity index, and hospital characteristics. STATA 16 software was used for analysis.ResultsThere was no difference in the in‐hospital mortality among HF patients with and without TR (OR: 1.04, 95% CI 0.94–1.16, p = 0.442) except in certain subgroups of HF patients. HF patients with TR were 6% more likely to have HF‐specific readmission in 30 days (HR: 1.06, 95% CI 1.00–1.13, p = 0.044) and 9% more likely to have HF‐specific readmission in 90 days (HR: 1.09, 95% CI 1.03–1.15, p = 0.002). Subgroup analysis revealed significant gender, racial, and socioeconomic disparities in the in‐hospital mortality and the readmission outcomes of HF patients with TR compared to those without TR.ConclusionIn our population‐based survey analysis, we observed significant gender, racial, and socioeconomic disparities in the clinical outcomes of HF patients with TR compared to those without TR.

Gastroesophageal reflux disease (GERD) is a prevalent condition impacting physical and mental health, characterized by symptoms like heartburn and acid regurgitation. GERD affects 18.1–27.8% of North Americans, rising to ~ 50% under less strict criteria. Effective management of GERD is critical to improving patients’ quality of life. Traditional treatments range from lifestyle modifications and pharmacological interventions to surgical approaches like laparoscopic anti-reflux surgery (LARS). Patients with erosive esophagitis receive a near 70–80% rate of “complete” symptom relief by 4 weeks using PPIs, in contrast to patients with non-erosive reflux disease (NERD), who demonstrate an intermediate response on the order of 50–60%. However, the invasiveness and associated side effects of surgical options have spurred the development of endoscopic techniques, including anti-reflux mucosectomy (ARMS) and transoral incisionless fundoplication (TIF). This review evaluates ARMS and TIF as therapeutic interventions for GERD, focusing on their risks, benefits, outcomes, and complications. ARMS is noted for shorter procedure times and fewer complications, particularly dysphagia and bleeding, making it an efficient choice for symptom control. TIF, while associated with a higher recurrence and reoperation rate, demonstrates superior long-term efficacy in medication reduction and sustained quality-of-life improvements, especially in patients without prior anti-reflux surgeries. Emerging advancements in endoscopic technologies, such as improved suturing techniques and refinements in mucosal resection, hold promise for reducing recurrence rates and enhancing procedural durability. The choice between ARMS and TIF should be tailored to individual patient needs, taking into account GERD severity, comorbidities, and surgical history. Both procedures exemplify significant advancements in minimally invasive GERD management, and ongoing innovations in endoscopic technologies are expected to further refine their safety and effectiveness. This comparative analysis provides insights into optimizing treatment selection and underscores the importance of personalized care in managing GERD.