Profil clinique et anatomopathologique des cancers de l’ovaire à Yaounde, Cameroun.

Le but de cette étude rétrospective et descriptive était de déterminer les aspects cliniques et anatomopathologiques des cancers de l’ovaire recensés entre le 1er juillet 2003 et le 31 décembre 2008 à l’Hôpital Gynéco-Obstétrique et Pédiatrique de Yaoundé au Cameroun. Nous avons retenu 30 cas avec un âge moyen de 48,50 ± 13,06 ans. Les cancers de l’ovaire représentaient 10,75 % des 279 cancers génitaux diagnostiqués au cours de la même période. Deux tiers des patientes avaient plus de 50 ans, et les grandes multipares constituaient 43,33% de l’échantillon. On notait une faible représentativité des patientes nullipares (10 %). Des douleurs pelviennes associées étaient présentes dans 56,67% de cas. La majorité des tumeurs (93,33%) avaient une origine épithéliale. Les stades cliniques FIGO II et III réunis représentaient trois quarts de l’échantillon. La classification selon le TNM montrait des stades avancés (pT3 et pT4 réunis) chez 40 % de la population. En conclusion, les cancers ovariens au Cameroun montrent une variété histomorphologique, les types épithéliaux étant plus fréquents. Les cancers sont souvent découverts à des stades avancés. Le rôle protecteur de la multiparité n’est pas relevé par cette étude. Des actions devraient être menées pour favoriser un diagnostic précoce et une prise en charge adéquate de la maladie. Des études à plus grande échelle doivent être menées, les résultats pouvant être d’une plus grande utilité aux politiques de santé.MOTS CLES: Cancers - Ovaire - Histopathologie- Epidémiologie - Cameroun

Intermittent PI3Kδ inhibition sustains anti-tumour immunity and curbs irAEs

Phosphoinositide 3-kinase δ (PI3Kδ) has a key role in lymphocytes, and inhibitors that target this PI3K have been approved for treatment of B cell malignancies1-3. Although studies in mouse models of solid tumours have demonstrated that PI3Kδ inhibitors (PI3Kδi) can induce anti-tumour immunity4,5, its effect on solid tumours in humans remains unclear. Here we assessed the effects of the PI3Kδi AMG319 in human patients with head and neck cancer in a neoadjuvant, double-blind, placebo-controlled randomized phase II trial (EudraCT no. 2014-004388-20). PI3Kδ inhibition decreased the number of tumour-infiltrating regulatory T (Treg) cells and enhanced the cytotoxic potential of tumour-infiltrating T cells. At the tested doses of AMG319, immune-related adverse events (irAEs) required treatment to be discontinued in 12 out of 21 of patients treated with AMG319, suggestive of systemic effects on Treg cells. Accordingly, in mouse models, PI3Kδi decreased the number of Treg cells systemically and caused colitis. Single-cell RNA-sequencing analysis revealed a PI3Kδi-driven loss of tissue-resident colonic ST2 Treg cells, accompanied by expansion of pathogenic T helper 17 (TH17) and type 17 CD8+ T (TC17) cells, which probably contributed to toxicity; this points towards a specific mode of action for the emergence of irAEs. A modified treatment regimen with intermittent dosing of PI3Kδi in mouse models led to a significant decrease in tumour growth without inducing pathogenic T cells in colonic tissue, indicating that alternative dosing regimens might limit toxicity

COVID-19 infection in adult patients with hematological malignancies: a European Hematology Association Survey (EPICOVIDEHA)

Background: Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. Methods: The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020. Results: The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (March–May 2020) and the second wave (October–December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value < 0.0001). In the multivariable analysis, age, active malignancy, chronic cardiac disease, liver disease, renal impairment, smoking history, and ICU stay correlated with mortality. Acute myeloid leukemia was a higher mortality risk than lymphoproliferative diseases. Conclusions: This survey confirms that COVID-19 patients with HM are at high risk of lethal complications. However, improved COVID-19 prevention has reduced mortality despite an increase in the number of reported cases.EPICOVIDEHA has received funds from Optics COMMITTM (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by GILEAD Science, United States (Project 2020-8223)

Intermittent PI3Ko inhibition sustains anti-tumor immunity and curbs irAEs

YesPhosphoinositide 3-kinase δ (PI3Kδ) has a key role in lymphocytes, and inhibitors that target this PI3K have been approved for treatment of B cell malignancies1–3. Although studies in mouse models of solid tumours have demonstrated that PI3Kδ inhibitors (PI3Kδi) can induce anti-tumour immunity4,5, its effect on solid tumours in humans remains unclear. Here we assessed the effects of the PI3Kδi AMG319 in human patients with head and neck cancer in a neoadjuvant, double-blind, placebo-controlled randomized phase II trial (EudraCT no. 2014-004388-20). PI3Kδ inhibition decreased the number of tumour-infiltrating regulatory T (Treg) cells and enhanced the cytotoxic potential of tumour-infiltrating T cells. At the tested doses of AMG319, immune-related adverse events (irAEs) required treatment to be discontinued in 12 out of 21 of patients treated with AMG319, suggestive of systemic effects on Treg cells. Accordingly, in mouse models, PI3Kδi decreased the number of Treg cells systemically and caused colitis. Single-cell RNA-sequencing analysis revealed a PI3Kδi-driven loss of tissue-resident colonic ST2 Treg cells, accompanied by expansion of pathogenic T helper 17 (TH17) and type 17 CD8+ T (TC17) cells, which probably contributed to toxicity; this points towards a specific mode of action for the emergence of irAEs. A modified treatment regimen with intermittent dosing of PI3Kδi in mouse models led to a significant decrease in tumour growth without inducing pathogenic T cells in colonic tissue, indicating that alternative dosing regimens might limit toxicity

Available Fail-Safe Systems

Continuity of service and cost-effectiveness are adding new challenges to life critical systems over and above the underlying safety concerns. The introduction of redundant components is a necessary condition for increasing the overall system availability with respect to physical component failures. Here we consider redundancy by means of replicating fail-safe components in a distributed real-time system for railway applications. In such a system, some functions cannot tolerate even a brief service interruption. These functions have to be replicated using active redundancy, and their outputs must be consolidated with the goal that the failure of one component has no effect on the delivered service. We formally investigate conditions for preserving safety properties of fail-safe components when replicating them using active redundancy. We focus our analysis on duplex computers with two fail-safe units. Given some safety constraints, we show that inconsistency of replicated units can lea..

Effect of the aqueous extract of dry fruits of Piper guineense on the reproductive function of adult male rats

OBJECTIVE: To study the effect of the aqueous extract of Piper guineense (Piperaceae) on male reproductive function in Wistar rats. MATERIALS AND METHODS: Male rats, 3 months old, weighing 180-210 g were administered (by gastric intubation) the aqueous extract of dry fruits of Piper guineense at two doses, 122.5 and 245 mg/kg for 8 days and 122.5 mg/kg for 55 days. The control group received distilled water for the same duration. Animals were sacrificed and the blood, testes, epididymis, seminal vesicles and prostate were collected for biochemical analyses. RESULTS: There was a significant increase in the level of testosterone in the serum and testes, cholesterol in the testes, α-glucosidase in the epididymis and fructose in the seminal vesicles after 8 days of treatment, while with 55 days of treatment, the levels of cholesterol in the testes increased by 75%, while the levels of α-glucosidase in the epididymis and the seminal vesicle fructose decreased by 24 and 21% respectively. On the other hand, there was a 20% reduction of fertility in the P. guineense-treated rats after 55 days of treatment. CONCLUSION: The aqueous extract of P. guineense at both doses (122.5 and 245 mg/kg) had a positive impact on the male reproductive function since it stimulated the secretions of the testes, epididymis and seminal vesicles. The use of P. guineense could negatively influence male fertility