Impact of Hormone Receptor Status and Tumor Subtypes of Breast Cancer in Young BRCA Carriers.

BACKGROUND: Hormone receptor expression is a known positive prognostic and predictive factor in breast cancer; however, limited evidence exists on its impact on prognosis of young patients harboring BRCA pathogenic variant (PV). PATIENTS AND METHODS: This international, multicenter, retrospective cohort study included young patients (≤40 years) diagnosed with invasive breast cancer and harboring germline PV in BRCA genes. We investigated the impact of hormone receptor status on clinical behavior and outcomes of breast cancer. Outcomes of interest (disease-free survival [DFS], breast cancer specific survival [BCSS] and overall survival [OS]) were first investigated according to hormone receptors expression (positive vs. negative), and then according to breast cancer subtype (luminal A-like vs. luminal B-like vs. triple-negative vs. HER2-positive breast cancer). RESULTS: From 78 centers worldwide, 4,709 BRCA carriers were included, of whom 2,143 (45.5%) had hormone receptor-positive and 2,566 (54.5%) hormone receptor-negative breast cancer. Median follow-up was 7.9 years. The rate of distant recurrences was higher in patients with hormone receptor-positive disease (13.1% vs. 9.6%, p<0.001), while the rate of second primary breast cancer was lower (9.1% vs. 14.7%, p<0.001) compared to patients with hormone receptor-negative disease. The 8-years DFS was 65.8% and 63.4% in patients with hormone receptor-positive and negative disease, respectively. The hazard ratio of hormone receptor-positive vs. negative disease changed over time for DFS, BCSS, and OS (p<0.05 for interactions of hormone receptor status and survival time). Patients with luminal A-like breast cancer had the worst long-term prognosis in terms of DFS compared to all the other subgroups (8-years DFS: 60.8% in luminal A-like vs. 63.5% in triple-negative vs. 65.5% in HER2-positive and 69.7% in luminal B-like subtype). CONCLUSIONS: In young BRCA carriers, differences in recurrence pattern and second primary breast cancer among hormone receptor-positive vs. negative disease warrants consideration in counseling patients on treatment, follow-up, and risk-reducing surgery.

Personalized embryo transfer guided by endometrial receptivity analysis: a systematic review with meta-analysis.

STUDY QUESTION: Does a personalized embryo transfer (pET) guided by tests for endometrial receptivity (TER) increase the effectiveness of ART procedures? SUMMARY ANSWER: The use of TER-guided pET is not supported by current published evidence in women without repeated implantation failure (RIF), while in women with RIF more research is needed to assess a potential benefit. WHAT IS KNOWN ALREADY: Implantation rates are still far from ideal, especially in some patients that have RIF with good-quality embryos. As a potential solution, a wide range of diverse TER use different sets of genes to identify displacements of the window of implantation to adjust the individual length of progesterone exposure in a pET. STUDY DESIGN, SIZE, DURATION: A systematic review with meta-analysis was performed. Search terms included endometrial receptivity analysis, ERA, personalized embryo transfer. CENTRAL, PubMed, Embase, reference lists, clinical trials registers, and conference proceedings (search date October 2022) were searched, with no language restrictions. PARTICIPANTS/MATERIALS, SETTING, METHODS: Randomized controlled trials (RCTs) and cohort studies comparing a pET guided by TER vs standard embryo transfer (sET) in different subgroups that undergo ART were identified. We also investigated pET in non-receptive-TER vs sET in receptive-TER, and pET in a specific population vs sET in a general population. Risk of bias (RoB) was assessed with the Cochrane tool and ROBINS-I. Only those with low/moderate RoB underwent meta-analysis. The GRADE approach was used to evaluate the certainty of evidence (CoE). MAIN RESULTS AND THE ROLE OF CHANCE: We screened 2136 studies and included 35 (85% used ERA and 15% used other TER). Two studies were RCTs comparing endometrial receptivity analysis (ERA)-guided pET vs sET in women with no history of RIF. In women without RIF, no important differences (moderate-CoE) were found in live birth rates and clinical pregnancy rates (CPR). We also performed a meta-analysis of four cohort studies that were adjusted for confounding. In agreement with the RCTs, no benefits were found in women without RIF. However, in women with RIF, low CoE suggests that pET might improve the CPR (OR 2.50, 95% CI 1.42-4.40). LIMITATIONS, REASONS FOR CAUTION: We found few studies with low RoB. Only two RCTs in women without RIF were published, and none in women with RIF. Furthermore, the heterogeneity observed in populations, interventions, co-interventions, outcomes, comparisons, and procedures limited the pooling of many of the included studies. WIDER IMPLICATIONS OF THE FINDINGS: In the population of women without RIF, in agreement with previously published reviews, pET did not prove to be more effective than sET and, therefore, it precludes the routine use of this strategy in this population until more evidence is available. However, more research is advisable in women with RIF as low-certainty evidence from observational studies adjusted for confounders suggests that the CPR might be higher with pET guided by TER in this population. Although this review presents the best available evidence, it is still insufficient to change current policies. STUDY FUNDING/COMPETING INTEREST(S): No specific funding was obtained for this study. There are no conflicts of interest to declare. REGISTRATION NUMBER: PROSPERO CRD42022299827.

A synopsis of global frontiers in fertility preservation.

Since 2007, the Oncofertility Consortium Annual Conference has brought together a diverse network of individuals from a wide range of backgrounds and professional levels to disseminate emerging basic and clinical research findings in fertility preservation. This network also developed enduring educational materials to accelerate the pace and quality of field-wide scientific communication. Between 2007 and 2019, the Oncofertility Consortium Annual Conference was held as an in-person event in Chicago, IL. The conference attracted approximately 250 attendees each year representing 20 countries around the world. In 2020, however, the COVID-19 pandemic disrupted this paradigm and precluded an in-person meeting. Nevertheless, there remained an undeniable demand for the oncofertility community to convene. To maintain the momentum of the field, the Oncofertility Consortium hosted a day-long virtual meeting on March 5, 2021, with the theme of "Oncofertility Around the Globe" to highlight the diversity of clinical care and translational research that is ongoing around the world in this discipline. This virtual meeting was hosted using the vFairs ® conference platform and allowed over 700 people to participate, many of whom were first-time conference attendees. The agenda featured concurrent sessions from presenters in six continents which provided attendees a complete overview of the field and furthered our mission to create a global community of oncofertility practice. This paper provides a synopsis of talks delivered at this event and highlights the new advances and frontiers in the fields of oncofertility and fertility preservation around the globe from clinical practice and patient-centered efforts to translational research.

Mycobacterium fortuitum presenting as an asymptomatic enlarging pulmonary nodule.

A case of Mycobacterium fortuitum presenting as an asymptomatic enlarging pulmonary nodule is described. This case is unusual because the patient was female, did not have underlying pulmonary disease, was not immunocompromised, had no evidence of dissemination, and had no history of aspiration or diabetes mellitus. The patient underwent thoractomy for resection of the pulmonary nodule, which led to the diagnosis. She recovered fully and is doing well without chemotherapy.

Adult respiratory distress syndrome as a complication of postanginal sepsis.

Adult respiratory distress syndrome (ARDS) was described in 1971 by Petty and Ashbaugh. Since that time it has been reported in association with many disease entities. We report a case in which a patient with postanginal sepsis, also known as Lemierre's syndrome, had development of ARDS.

Effects of insufficient sleep on blood pressure in hypertensive patients: a 24-h study.

The influence of acute sleep deprivation during the first part of the night on 24-h blood pressure monitoring (ABPM) was studied in 36 never-treated mild to moderate hypertensive patients. According to a crossover design, they were randomized to have either sleep deprivation or a full night's sleep 1 week apart, during which they were monitored with ABPM. Urine samples for analysis of nocturnal urinary excretion of norepinephrine were collected. During the sleep-deprivation day, both mean 24-h blood pressure and mean 24-h heart rate were higher in comparison with those recorded during the routine workday, the difference being more pronounced during the nighttime (P < .01). Urinary excretion of norepinephrine showed a significant increase at night during sleep deprivation (P < .05). Blood pressure and heart rate significantly increased in the morning after a sleep-insufficient night (P < .05). These data suggest that lack of sleep in hypertensive patients may increase sympathetic nervous activity during the night and the following morning, leading to increased blood pressure and heart rate. This situation might represent an increased risk for both target organ damage and acute cardiovascular diseases.

Electrophysiologic-structural correlations in chagasic aneurysms causing malignant arrhythmias.

We studied the structure and ultrastructure of three chagasic aneurysms, the excision of which abolished malignant arrhythmias. Chronic recurrent ventricular tachycardia often occurs in patients with chagasic aneurysms, and ventricular mapping indicates that these arrhythmias originate in regions adjacent to those aneurysms. In our patients, ventricular tachycardia had been refractory to medical treatment. During surgery, epicardial and endocardial mapping showed abnormal potentials. Sutures were placed in the areas of resection, their sizes approximating those of earliest activation so that these sites could be identified. The myocardium showed chronic inflammatory reaction, myocytolysis and fibrosis. The presence of "islets" was common (normal, "early" damaged or "established" necrotic myocytes surrounded by fibrous tissue). The "early" lesions were predominant at the previously identified areas of arrhythmogenic activity. The ultrastructural studies showed hypertrophy of myocytes and partial or complete loss of myofibrils, swelling of mitochondria and disruption of mitochondrial cristae, accumulation of lipofuscin granules, and intracellular oedema. A most striking alteration was the thickening of the basement membranes of myocytes and vascular endothelial and smooth muscle cells. The interlaced fronts of respectively healthy (fast conducting) and "early" damaged (slow conducting) myocytes seen in serial sectioning produced an ideal configuration for reentry circuits. The final proof that the arrhythmias originated in these endocardial regions was their abolition by resection of the aneurysm.

Pulmonary artery catheterization in exacerbations of COPD requiring mechanical ventilation: a cost-effectiveness analysis.

UNLABELLED: The cost-effectiveness of pulmonary artery catheterization (PAC) has been questioned in many clinical situations. We sought to assess the cost-effectiveness of PAC in patients with an acute exacerbation of chronic obstructive pulmonary disease (COPD) requiring mechanical ventilation. METHODS: We constructed a decision analysis model and calculated the incremental cost/quality-adjusted life-year (QALY) saved for hypothetical patients, comparing a PAC strategy to one of no PAC. Sensitivity analyses were performed to test the stability of conclusions over wide ranges of values. RESULTS: The incremental cost/QALY saved in the cost-effectiveness analysis using baseline data is $77,407 when catheterization-driven therapeutic changes result in a 5% improvement in survival. Cost-effectiveness is sensitive to variations in post-hospital life expectancy, quality of life, and the probability of favorable therapeutic changes resulting from the use of catheterization data. CONCLUSIONS: Pulmonary artery catheterization in COPD exacerbation requiring mechanical ventilation is expensive compared to accepted medical interventions for other conditions, unless changes in therapy prompted by catheterization increase hospital survival to a level 8.7% above baseline. Randomized, controlled trials are needed to investigate the economic impact of PAC and its effect on morbidity and mortality of critically ill patients.

[Atrioventricular node catheter ablation with condenser discharge and radiofrequency]. / Ablación del nódulo atrioventricular con descarga de condensadores y radiofrecuencia.

The AV junction ablation was useful to treat patients with drug-refractory supraventricular arrhythmias. The purpose of this study was to determine short and long-term success and complications of the atrioventricular nodal catheter ablation and to compare direct current and radiofrequency energy. Forty patients underwent AV nodal ablation with direct current energy (Group I) and forty patients with radiofrequency (Group II). They were followed up for a mean of 76 +/- 49 and 28 +/- 20 months, respectively. Persistent complete AV block was successfully induced during the first ablation session in 45% of 40 patients who underwent DC energy, while in 50% it was modulated. All patients in the radiofrequency group had complete AV block. The rate of recurrence of AV conduction was 7.5% and 2.5% respectively. Immediate complications did not occur after either procedure. One patient died suddenly in each group during follow-up. AV nodal ablation with radiofrequency energy appears to be as efficacious and safe as direct current energy.

Evaluation of emerging biomarkers in cardiovascular risk stratification of hypertensive patients: a 2-year study.

OBJECTIVE: To evaluate if there is a correlation between some new emerging biomarkers, such as lipoprotein(a) (Lp[a]), apo(a) isoform phenotyping, soluble advanced glycation end products (sRAGE), soluble CD40 ligand (sCD40L), serum myeloperoxidase (MPO), and cardiovascular risk stratification. RESEARCH DESIGN AND METHODS: Three hundred patients were enrolled in this open-label, case-control design trial: 156 hypertensive patients and 144 healthy subjects as control group. Hypertensive patients were treated according to the latest ESH/ESC guidelines, until the desirable goal of systolic blood pressure (SBP)<140 mmHg, and diastolic blood pressure (DBP)<90 mmHg was reached. We evaluated at baseline and after 6, 12, 18, and 24 months: SBP, DBP, lipid profile, Lp(a), apo(a) isoform phenotyping, sRAGE, sCD40L, and MPO. RESULTS: Hypertensive patients presented higher levels of blood pressure, Lp(a), sCD40L, and MPO and lower levels of sRAGE compared with controls. We observed a decrease of blood pressure, Lp(a), sCD40L, and MPO and an increase of sRAGE after anti-hypertensive treatment. Moreover we observed moderate, but statistically significant, correlations between blood pressure decrease and Lp(a), MPO, and sCD40L decrease and between blood pressure decrease and sRAGE increase. There was also a modest, positive correlation between low molecular weight apo(a) isoforms and hypertension. A limitation of this study is that we cannot exclude a role for lifestyle measures. Furthermore the studied markers seem to improve with blood pressure lowering treatment, but we do not have enough statistical power to definitely state which drug used has a specific action on the various variables measured. CONCLUSION: Lp(a), sRAGE, MPO, sCD40L, and low molecular weight apo(a) isoforms are associated with hypertension and may represent an increased cardiovascular risk. Longer studies are needed to see if these parameters can be also used to predict specific complications linked to hypertension.

Recuento de folículos antrales como predictor de la respuesta ovárica / Antral follicle counts as a predictor of ovarian response

Objetivo: Evaluar la relación entre el número de folículos antrales en condiciones basales y la cantidad de ovocitos recuperados luego del tratamiento de estimulación ovárica, y establecer el rol del recuento de folículos antrales mediante ecografía como predictor de la respuesta ovárica. Como propósito secundario, se examinó la correlación del recuento de folículos antrales con la edad de las pacientes y el éxito del tratamiento. Materiales y métodos: Entre enero y marzo de 2015 se estudió retrospectivamente a 40 candidatas a punción aspiración folicular, que se habían realizado una ecografía transvaginal con recuento de folículos antrales antes de la estimulación. Se tomaron en cuenta solo los folículos que medían entre 3 y 8 mm. Todas las pacientes recibieron estimulación hormonal y monitoreo ecográfico y hormonal en sangre hasta la punción aspiración de folículos. Resultados: Se observó una importante correlación inversa entre la edad de las pacientes y el recuento de los folículos antrales y una correlación inversa muy marcada entre la edad y la recuperación de ovocitos. También se constató una muy importante correlación positiva entre el recuento de folículos antrales y la cantidad de ovocitos recuperados en la aspiración transvaginal. El número reducido de pacientes limitó el análisis del éxito del tratamiento. Conclusión: El recuento de folículos antrales permite predecir la respuesta ovárica y la cantidad de ovocitos recuperados mediante punción folicular. Debido a su bajo costo, alto rendimiento diagnóstico y fácil acceso y realización, el recuento ovárico folicular mediante ecografía debería ser considerado la prueba de reserva ovárica de primera elección

Objective:To evalúate the relationship between the number of antral follicles under basal conditions and the number of oocytes retrieved after ovarían stimulation treatment, to establish the role of antral count follicles by ultrasonography as a predictor of ovarían response. Secondary objective: to assess the correlation of antral follicle count with the age of patients and the success of treatment. Materials and methods: This is a retrospective cohort study, between January and March 2015, assessing 40 women undergoing transvaginal ultrasonography guided follicular aspiration. Trans-vaginal ultrasonography follicle count was performed prior to antral follicles stimulation, (follicles measuring between 3 and 8 mm were taken into account), they also received hormonal stimulation, ultrasonography and hormonal monitoring blood until the follicle aspiration. Results: A strong inverse correlation between patient age and antral follicle count and a very strong inverse correlation between age and oocyte retrieval was observed. A very strong positive correlation between the antral follicle count and the number of oocytes retrieved in the transvaginal aspiration was also observed. The small number of patients limited the analysis linked to the success of treatment. Conclusion: The antral follicle count had significant associations with ovarían response and the number of oocytes retrieved. The antral follicles count by ultrasonography should be considerad the first choice of test of ovarían reserve because of its low cost, good performance and accessibility