Citations

PURPOSE BRCA carriers face high risks of developing both breast and ovarian/fallopian tube cancers (hereafter referred to as ovarian ). Among BRCA carriers with ovarian cancer, it is not clear whether the risk of breast cancer is sufficiently high that risk-reducing mastectomy should be offered. This study aimed to assess the risk of breast cancer BRCA carriers after a diagnosis of ovarian cancer. METHODS We included women with a pathogenic/likely pathogenic variant in BRCA1 or BRCA2 , a diagnosis of ovarian cancer, and no other cancer history and no risk-reducing bilateral mastectomy. Women were followed for incident breast cancer from the date of ovarian cancer diagnosis or the date of baseline questionnaire, whichever came last. The 5-, 10-, and 15-year cumulative risks of breast cancer were compared for women with ovarian cancer and an age-matched set of control women without ovarian cancer. RESULTS A total of 960 participants with ovarian cancer were identified (814 BRCA1 and 146 BRCA2 carriers). After a mean follow-up of 4.9 years, 41 women (4.3%) developed breast cancer, at a mean age at diagnosis of 57.5 years (range, 39-74). Actuarial cumulative breast cancer risks after ovarian cancer were 4.4%, 8.9%, and 11.5% at 5, 10, and 15 years, respectively. Only three breast cancer–related deaths occurred. Among 741 age-matched BRCA carriers without ovarian cancer, actuarial cumulative risks of breast cancer were 20.9%, 38.6%, and 47.2% at 5, 10, and 15 years, respectively. The hazard ratio for breast cancer, after an ovarian cancer diagnosis, compared with no ovarian cancer, was 0.18 ([95% CI, 0.12 to 0.27]; P < .0001). CONCLUSION After ovarian cancer, BRCA carriers have a relatively low risk of breast cancer. Risk-reducing mastectomy should not be recommended routinely, but might be considered for long-term survivors. Magnetic resonance imaging surveillance and/or mammography is a realistic alternative.

Abstract Background The functional significance of the left ventricular (LV) hypercontractile phenotype (HP) in hypertrophic cardiomyopathy (HCM) remains unclear. Purpose To assess the systemic and coronary hemodynamic correlates of HP in HCM. Methods We enrolled 1533 HCM patients (age 51 ± 15 years, 965 males, 63%) with ejection fraction (EF) ≥50%, referred for rest transthoracic echocardiography (TTE) in 27 laboratories from 13 countries. Two-dimensional volumetric TTE assessment included LV outflow tract gradient (LVOTG), end-diastolic volume (EDV), end-systolic volume (ESV), EF, and LV force (systolic blood pressure + LVOTG/ESV, mmHg/mL). Coronary flow velocity in the mid-distal left anterior descending (LAD) coronary artery was assessed in 325 patients. HP was defined as the highest quartile of the force (&gt; 7.32 mmHg/ml). Results Force was moderately related to EF (r = 0.48, p &lt; 0.0001) and weakly to LVOTG (r = 0.36, p &lt; 0.0001). Compared to non-HP patients, HP showed higher heart rate (72 ± 14 vs 67 ± 14 beats per minute, p &lt;0.0001), lower stroke volume (50 ± 22 vs 67 ± 22 ml, p &lt; 0.0001), larger left atrial volume index (44 ± 16 vs 40 ± 16 ml/m2, p = 0.011) and higher coronary flow velocity in the LAD (n = 325, 41 ± 12 vs 37 ± 14 cm/s, p = 0.021), see Figure. Abnormal B-lines (≥ 2) were present in 11 of the 39 HP compared to 39 of the 271 non-HP patients (28% vs 14 %, p = 0.05). E/e’ ratio was higher in HP (n = 59) vs. non-HP (n = 571) patients (11 ± 5.4 vs 9.6 ± 4.2, p = 0.018). Conclusion In patients with HCM, preserved EF, and no history of coronary artery disease, HP identified by resting TTE with supernormal LV force was associated with an unfavorable systemic hemodynamic and coronary flow profile. Compared to non-HP HCM patients, the HP was characterized by reduced stroke volume, impaired diastolic function, and increased resting coronary flow velocity. HP may reflect inefficient myocardial mechanics, with disproportionate energy expenditure mirrored by higher resting coronary flow despite reduced stroke volume generation, ultimately contributing to adverse remodeling and worse prognosisNon-HP vs HP LAVI and coronary LAD flow

Abstract The Association for Diagnostics & Laboratory Medicine (ADLM) aims to improve health by providing education to laboratory scientists worldwide. Different regions of the world face unique challenges shaped by their national and regional contexts. However, the needs of clinical laboratories worldwide remain largely understudied. To address this gap, we conducted a comprehensive needs assessment survey among laboratory professionals in the Latin American region. The survey was distributed to over 2708 individuals across Latin American countries and yielded 148 responses. Most respondents were from urban areas (74%) and worked in private hospital laboratories (45%), with microbiology (25%) and chemistry (23%) identified as the most common specialties. Key findings include continuing education as the top challenge, identified by 59% of respondents, with a predominant preference for virtual learning formats (83%), though not exclusively; 50% also identified a preference for in-person learning. Other challenges, such as staff shortages, lack of equipment and funding, were selected by 30% to 36% of respondents, whereas regulatory oversight and quality management were less frequently identified as priorities. To contextualize the survey findings, we conducted interviews with laboratory professionals in the region. Common themes included resource and technology constraints, uneven implementation of quality standards, and the need for collaboration between government and professional organizations to bridge gaps in practice. This assessment highlights the need for targeted educational interventions to address the distinct challenges faced by Latin American laboratories. Addressing these gaps in continued education, fostering collaboration, and engaging stakeholders in the region offer a roadmap to strengthening laboratory services and health outcomes.

Abstract Background The presence of the significant left ventricular outflow tract gradient (LVOTG) changes clinical symptoms, prognosis and treatment in hypertrophic cardiomyopathy enabling the classification into its obstructive (HOCM) and non-obstructive form (non-HOCM). However, the more detailed functional characteristics and comparison of these forms remains poorly known. Purpose To compare the demographic, clinical and echocardiographic features between non-HOCM (defined as LVOTG &lt; 30 mmHg) and HOCM patients enrolled into multi-centred study in years 1996-2024 as well as to analyse their long –term prognosis in relation to registered LVOTG. Methods We enrolled 1533 HCM patients (age 51 ± 15 years, 965 males, 63%) with ejection fraction (EF) ≥50%, referred for rest transthoracic echocardiography (TTE) in 27 centers, nevertheless quantitative assessment of LVOTG was available in 1252 patients. Survival analysis was performed in a subset of 1200 patients with follow-up information. Beyond standard TTE, the number of B-lines, the maximal diastolic velocity of coronary flow in left anterior descending artery (LAD) as well as left ventricular force defined as the ratio of systolic blood pressure plus LVOTG divided by left ventricular end-systolic volume was assessed with specification of hypercontractile phenotype (HP) as the highest force quartile. Additionally age and sex matched control group was included. Results Compared to non-HOCM patients, HOCM showed a bit higher body mass index (27 ± 4 vs 26 ± 4 kg/m2, p = 0.001), were often burdened with diabetes and hypertension, presented more advanced NYHA class and higher risk of SCD, see Table. In the echocardiographic assessment HOCM presented lower end-systolic left ventricular volume (LV ESV: 27 ± 14 vs 29 ± 13 ml, p = 0.014) although maintained equal stroke volume and even higher ejection fraction (EF: 69 ± 8% vs 67 ± 7%, p &lt; 0.001), cardiac output (CO: 4.3 ± 1.7 vs 4.0 ± 1.4 l/min, p &lt; 0.001) and force in comparison to counterparts without LVOTG. This high-contractility performance was however sustained at the cost of larger left atrium volume index (LAVI: 49 ± 19 vs 40 ± 15 ml/m2, p &lt; 0.001), higher coronary flow velocity (43 ± 12 vs 27 ± 13 cm/s, p &lt; 0.001) as well as more frequent B-lines in the lung assessment. During a median follow-up of 87 months (interquartile range 45 – 143 months), 131 all-cause deaths occurred and not only patients with HOCM but also those with HP showed the worse long-term survival, see Figure. Conclusion HOCM remains the form of HCM burdened with more overt clinical symptoms, signs and prognosis. On the other hand LVOTG seems to be important but not always necessary element of this presentation, which seems to be related even more tightly to general hypercontractility phenotype reflected by higher force and resting coronary flow.Table.Non-HOCM vs HOCM comparison Figure.Force and LVOTG prognostic value