Design of the Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor Versus Placebo in Patients With Congenital Systemic Right Ventricle Heart Failure (PARACYS-RV) Trial.

The presence of a systemic right ventricle (sRV) with biventricular physiology (biV) is associated with increased patient morbidity and mortality. To date, no pharmacologic therapy for heart failure has been proven effective for patients with systolic dysfunction of the sRV-biV. We designed a randomized, double-blind, placebo-controlled crossover trial to compare sacubitril/valsartan treatment to placebo in adults (aged ≥ 18 years) with moderate-to-severe sRV-biV dysfunction and New York Heart Association functional class II to III symptoms. Two primary efficacy endpoints are assessed in the trial: exercise capacity (submaximal exercise duration) and neurohormonal activation (N-terminal prohormone brain natriuretic peptide). Secondary objectives include assessing a change in the Kansas City Cardiomyopathy Questionnaire score and evaluating the safety and tolerance of sacubitril/valsartan. A 6-week open run-in phase identifies the maximum tolerated dose of sacubitril/valsartan, up to 97 mg/103 mg twice daily. After a 2-week washout period, patients are randomized 1:1 to sacubitril/valsartan treatment vs placebo for a 24-week phase, followed by another 2-week washout period and subsequent crossover to the alternative treatment arm for an additional 24-week phase. Data to assess primary and secondary endpoints are collected at baseline and at the end of each phase. A total of 48 patients is required to provide > 80% power to detect a 30% difference in distance walked and in N-terminal prohormone brain natriuretic peptide levels with sacubitril/valsartan treatment vs placebo, each with a 2-sided P-value of 0.025. In summary, the Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor vs Placebo in Patients With Congenital Systemic Right Ventricular Heart Failure Trial (PARACYS-RV) should determine the role of sacubitril/valsartan in treating heart failure in patients with sRV-biV and carries the potential to alter management of this patient population.

La présence d'un ventricule droit systémique (VDs) avec physiologie biventriculaire (PbiV) est associée à une morbidité et une mortalité accrues chez les patients. À ce jour, aucune pharmacothérapie de l'insuffisance cardiaque ne s'est révélée efficace chez les patients atteints d'une dysfonction systolique du VDs-PbiV. Nous avons conçu un essai croisé, à répartition aléatoire et à double insu, contrôlé par placebo pour comparer la bithérapie sacubitril-valsartan au placebo chez les adultes (≥ 18 ans) ayant une dysfonction modérée ou sévère du VDs-PbiV et des symptômes de la classe fonctionnelle II à III de la New York Heart Association. Deux paramètres d'évaluation principaux de l'efficacité sont définis pour l'essai : tolérance à l'effort (durée d'effort sous-maximal) et activation neurohormonale (propeptide natriurétique de type B N-Terminal [NT-proBNP]). La mesure d'une variation du score au questionnaire sur la cardiomyopathie de Kansas City de même que l'évaluation de l'innocuité et de la tolérance de la bithérapie sacubitril-valsartan sont des objectifs secondaires. Une phase préparatoire de six semaines en mode ouvert permet d'établir la dose maximale tolérée de sacubitril-valsartan, jusqu'à concurrence de 97 mg/103 mg deux fois par jour. Après une période de repos thérapeutique de deux semaines, les patients sont affectés au hasard, dans un rapport 1:1, à la bithérapie sacubitril-valsartan ou au placebo pendant une phase de traitement de 24 semaines, suivie d'une autre période de repos thérapeutique de deux semaines et d'un passage subséquent à l'autre groupe de traitement pendant une phase additionnelle de 24 semaines. Les données sur les paramètres d'évaluation principaux et secondaires sont recueillies au début de l'essai et à la fin de chaque phase. Il faut un total de 48 patients afin d'obtenir une puissance supérieure à 80 % pour détecter une différence de 30 % entre la bithérapie sacubitril-valsartan et le placebo quant à la distance parcourue à la marche et aux taux de NT-proBNP, la valeur p bilatérale étant de 0,025 pour les deux valeurs. En résumé, l'essai PARACYS-RV (Prospective Comparison ofAngiotensinReceptor-Neprilysin Inhibitor vs Placebo in Patients WithCongenital SystemicRightVentricular Heart Failure) doit déterminer le rôle de la bithérapie sacubitril-valsartan dans le traitement de l'insuffisance cardiaque chez les patients ayant un VDs-PbiV et pourrait modifier la prise en charge de cette population de patients.

Stress-buffering effect of social support on immunity and infectious risk during chemotherapy for breast cancer.

OBJECTIVE: This study investigated the stress-buffering effect of social support on immune function and infectious risk in women with breast cancer, during and after chemotherapy. METHOD: Data were collected from 50 women with breast cancer before and after their chemotherapy, as well as three months later. Stress was measured by daily hassles related to cancer and social support by marital status (MS) and perceived support from friends (Ps-fr). Blood was collected to measure innate immune markers (i.e., T cells, NK cells and neutrophils). Infections were evaluated using a semi-structured interview. Moderation, mediation and moderated mediation models were computed to test the hypotheses. RESULTS: Higher stress at baseline was found to significantly predict a higher occurrence of infections during chemotherapy, but not three months later. The relationship between stress and infections was not significantly explained by any of the immune markers. The interaction between stress and social support was tested using MS alone and combined with Ps-fr. A protective effect of social support on the deleterious effect of stress on infectious risk was found. Single patients reporting lower Ps-fr showed the strongest association between stress and infections, while the weakest association was found in patients in a committed relationship with a higher level of Ps-fr. CONCLUSIONS: Women experiencing more stress before the beginning of chemotherapy would appear to be at a higher risk of developing infections during their treatment. Results of this study also suggest that this effect could be buffered by the presence of a romantic partner and by higher Ps-fr.

Disruptions of the pulp-dentin complex in an investigated case of pink secondary retained molar.

A pink retained left mandibular first molar without carious lesions was diagnosed in a healthy 12-year-old girl presenting normal clinical tests. An orthopantomogram failed to detect other retained teeth. Both periapical radiography and computed tomography showed the absence of a periodontal ligament space in the bifurcation area and the presence of radiolucency or calcifications in the pulp cavity. The coronal part of the removed tooth was subjected to histological and immunohistochemical analysis using anti-PCNA (proliferation marker) and anti-p53 (apoptosis marker) antibodies. Root surfaces were observed by scanning electron microscopy. The pink color of the molar reflected the extension of resorptive tissue into the clinical crown and the underlining proliferation of pulp vessels. Ankylosis observed in the bifurcation area was also detected in the coronal part of the pulp. Whereas odontoblasts secreted tertiary dentin despite no evidence for a carious lesion, only osteocytes in the newly formed bone were apoptotic and the root surfaces were free of resorption lacunae. The etiopathology of the lesion in this case indicated a pulp origin, suggesting that new therapies targeting this tissue should be developed.

Visceral/epicardial adiposity in nonobese and apparently healthy young adults: association with the cardiometabolic profile.

OBJECTIVE: We investigate associations of regional adipose tissues with cardiometabolic profile of nonobese and apparently healthy young adults. METHODS: Four hundred twenty-five nonobese and apparently healthy individuals were assessed for blood pressure and fasting lipid profile, blood glucose and adiponectin. Subcutaneous abdominal adipose tissue (SAT) and ectopic fat depots (visceral abdominal adipose tissue [VAT], epicardial adipose tissue [EAT] and hepatic fat fraction [HFF]) were quantified by magnetic resonance imaging. RESULTS: According to anthropometric measurements, blood pressure and blood markers, the population (18-35 years, 54% women) had a low cardiometabolic risk. Compared to women, men had more VAT, EAT and HFF, but less SAT. Regional adipose tissues were positively correlated with each other. VAT and EAT carried significant correlations with all markers of cardiometabolic risk, while SAT and HFF correlated variably with these markers. While taking into account age and gender, SAT, VAT and EAT were associated with most cardiometabolic markers, while HFF was only associated with total cholesterol/high-density lipoprotein ratio (TC/HDL-C) and triglycerides (TG). When comparing SAT, VAT and EAT head-to-head, VAT was the only adipose tissue location maintaining significant association with most markers of cardiometabolic risk. Greater VAT (≥50th percentile) was associated with a worse cardiometabolic profile, whether individuals were overweight or normal weight. CONCLUSION: Even in nonobese and apparently healthy young women and men, accumulation of ectopic visceral adiposity in general, and of VAT in particular, is associated with a worse cardiometabolic profile whether individuals were overweight or normal weight.