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 prognostic impact on prognosis of young patients harboring a pathogenic variant (PV) in the BRCA1 and/or BRCA2 genes. PATIENTS AND METHODS: This international, multicenter, retrospective cohort study included young patients (aged ≤40 years) diagnosed with invasive breast cancer and harboring germline PVs 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 receptor expression (positive versus negative), and then according to breast cancer subtype [luminal A-like versus luminal B-like versus triple-negative versus human epidermal growth factor receptor 2 (HER2)-positive breast cancer]. RESULTS: From 78 centers worldwide, 4709 BRCA carriers were included, of whom 2143 (45.5%) had hormone receptor-positive and 2566 (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% versus 9.6%, P < 0.001), while the rate of second primary breast cancer was lower (9.1% versus 14.7%, P < 0.001) compared to patients with hormone receptor-negative disease. The 8-year DFS was 65.8% and 63.4% in patients with hormone receptor-positive and negative disease, respectively. The hazard ratio of hormone receptor-positive versus negative disease changed over time for DFS, BCSS, and OS (P < 0.05 for interaction 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-year DFS: 60.8% in luminal A-like versus 63.5% in triple-negative versus 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 versus negative disease warrant 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.

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

Terapias emergentes en artritis reumatoide / Emergent therapies for rheumatoid arthritis

The use of biological agents such as etanercept, infliximab, adalimumab and anakinra has been recently approved for the treatment of rheumatoid arthritis. All are effective controlling signs and symptoms and inhibiting disease progression. To overcome the problems generated by their high costs and possible participation in reactivating latent infections, other therapeutic tools are being developed. Gene therapy using expression vectors carrying genes coding for specific proteins, may interfere in key points involved in the pathogenesis of the disease. Intra-articular administration of cDNA coding for soluble TNF receptors, IL-1, or IL-1Ra decreases signs of the disease in animal models. Vectors, expressing inhibitors of signal transduction pathways involving to NF-kB and JAK-STAT-3, are effective in modulating joint inflammation in mice. The use of antigen-pulsed antigen presenting cells or dendritic cells (DC) bound to apoptosis-inducing molecules, specifically eliminates autoreactive T cells. Other novel approach attempts the development of T regulatory-inducing tolerogenic DC-based vaccines that inhibit autoreactive T cells, through the secretion of suppressing cytokines or by other mechanisms to be elucidated. Oral tolerance induction to auto-antigens is also a successful experimental strategy under study. Current research aims to control peripheral tolerance in rheumatoid arthritis patients.

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.

[A case of polymyositis in autoimmune thyroiditis with hyperthyroidism]. / Su un caso di polimiosite in corso di tiroidite autoimmune con ipertiroidismo.

A young woman, during an autoimmune thyroiditis with hyperthyroidism, suffered from progressive proximal weakness at her four limbs. The diagnosis of a concomitant polymyositis was indicated by a marked increase of plasma CPK, myopathic findings at EMG and a clearcut picture of inflammatory alterations at muscle biopsy. Steroid therapy brought a full recovery of both thyroid and muscular symptoms. In the following months, the patient suffered from a second episode of thyroiditis and subsequently from another poussée of polymyositis. The possible pathogenesis underlying the unusual association of an autoimmune thyroiditis with a polymyositis is discussed.

[Histologic findings in laser radiation of myocardial pericrater in dogs]. / Hallazgos histológicos en la irradiación por laser sobre el miocardio canino pericrater.

Laser beam constitutes a potential therapy in modern cardiology. Although its myocardial effects are known, they have been insufficiently evaluated at the surviving myocytes zone surrounding the evaporated crater. In order to assess myocyte cellular and organelar damage, we studied 8 isolated canine hearts radiated with different intensities by a CO2He laser beam 2.4, 3.5, 5, 15, 25, 30 and 40 Watts, varying the exposition time from 1 to 6 sec. Color photographs from the post-radiated lesions on front and depth were obtained. Their volumes were measured applying the cylinder and the cut out-conus formulas according to the shape of the lesions and then the involved tissues were embedded in paraffin for histological studies. Previously, samples of the lesions were fixed in glutaraldehyde for ultrastructural studies. Volumes of the craters were from 0.0004 to 19.57 mm3. Three layers were observed: a) a carbonized internal lining which measured x 15 microns in thickness; b) a coagulation necrotic zone ("gruyere cheese-like"), 70 microns thickness; c) finally more peripherally, a layer consisting of myocytes with patchy homogeneous cytoplasm, and scare positivity for the Barbeito López Trichome Stain (a positive technique in cases of myocardial damage). Ultrastructurally, crater peripherical cells showed cytosol and mitochondrial edema without membrane disruptions. These findings suggest that myocytes surrounding the laser beam crater, show reversible lesions. Therefore laser beam apperrs a safe procedure to be used in myocardium.

Tracheal obstruction presenting as new-onset wheezing.

Two cases of recent-onset dyspnea and wheezing initially treated with bronchodilator therapy for presumed reactive airway disease are presented. Plain-film chest radiographs subsequently demonstrated mediastinal masses causing extrinsic tracheal compression. The first patient had inoperable poorly differentiated squamous cell carcinoma resistant to radiotherapy. The second patient underwent resection of a substernal multinodular goiter with complete resolution of symptoms. The physician should always entertain the diagnosis of upper airway obstruction in all adult patients with new-onset wheezing. New-onset adult wheezing of uncertain etiology should prompt the physician to refer the patient for pulmonary function testing with flow-volume loops.

Análisis de los componentes equipo y catéteres para la fulguración endocavitaria / Analysis of equipment and catheters for endocavitarian fulguration

Se analizan 25 catéteres, 5 Cordis, 15 USCI y 5 Elecath bi, tri, y tetrapolares con mediddas de 5, 6 y 7F. Se midieron la resistencia eléctrica, las posibles conexiones para evitar fallas de aislación y las pérdidas de energia del sistema. Se diseñaron prolongadores y un relevador temporizador que permite aislar el registrador ene le momento de la descarga y obtener en forma casi inmediata el registro post-choque sin cambiar ninguna conexión. En los 5 catéteres Elecath bipolar la resistencia varió entre 10,4 y 13 Ohms, 3 explotaron y 2 tuvieron fallas de aislación; en un caso producida al repetir el choque. Los catéteres Cordis tuvieron resistencias entre 18,7 y 21 Ohms, y de los 15 catéteres USCI, 7 fueron aptos para fulguración con resistencias entre 2 y 3,1 Ohms; explotaron 6: 4 tetra y 2 bipolares y 2 tuvieron fallas de aislación 1 bi y 1 tetrapolar. Sólo el 28% de los catéteres fueron aptos y éstos fueron los de menor resistencia; se analizaron 11 defibriladores observándose que para una descarga de 200 Joules la energia almacenada se puede obtener desde 60 microfaradios y 2600 voltios hasta 6 microfaradios y 8200 voltios, siendo estas altas tensiones más peligrosas pues requieren mayor aislación. Es importante una adecuada interconexión para evitar pérdidas de energía. Los fulguradores que operan con tensiones relativamente bajas evitan el deterioro de los catéteres. El control previo al procedimiento previene fallas y complicaciones

[Double clone in cells of pleural effusion caused by metastasis of oat cell carcinoma of the lung]. / Doppio clono in cellule di versamento pleurico da metastasi di microditoma del polmone

The Authors report a chromosome study carried out on pleural effusion cells from metastases of oat cell carcinoma. They observed a double cell clone: the former, with 44 chromosomes, with various alterations of the karyotype and a big acrocentric "marker", the latter, with 45 chromosomes with various alterations of the karyotype and a big submetacentric "marker". From these observations the Authors draw some interpretative considerations.