Influence of prenatal urinary incontinence and mode of delivery in postnatal urinary incontinence: A systematic review and meta-analysis.

BACKGROUND: It is likely that the pathophysiology of urinary incontinence (UI) differs between women who are incontinent before the first delivery and those whose incontinence occurs after. In this systematic review, we aimed to assess the association between the mode of delivery and the risk of postpartum UI in primiparous women with and without prenatal UI. METHODS: We searched MEDLINE, Cochrane, Web of Science, Embase and CINHAL databases. Prospective studies including primiparous women during their pregnancy with a comparison of the rate of postpartum UI in women who underwent cesarean delivery or vaginal delivery according to continence status before delivery were included. The Risk Ratio (RR) was calculated with a 95% confidence interval (95% CI) using the total number of events and patients extracted from the individual studies. A subgroup comparison analysed the potential influence of women's prenatal continence status. Heterogeneity was estimated using I² statistics. RESULTS: The risk of postpartum UI was significantly higher after vaginal delivery than after cesarean section (RR 1.80, 95% CI 1.48- 2.18). According to the subgroup test, the postpartum UI risk following a vaginal delivery, compared to cesarean section, was significantly higher in the subgroup of continent women during pregnancy (RR 2.57, 95% CI 2.17-3.04) than in the subgroup of incontinent pregnant women (1.56, 95% CI 1.27-1.92). CONCLUSIONS: The effect of a cesarean section in preventing postpartum UI appears controversial, particularly in women with prenatal UI.

[Induced abortions for maternal indications: Retrospective study in Western Normandy between 2010 and 2019]. / Interruptions médicales de grossesse pour indications maternelles : analyse rétrospective en Normandie Occidentale (2010­2019).

INTRODUCTION: Termination of pregnancy for maternal reasons (MTOP) are authorized in France without limit of term when "the continuation of the pregnancy puts in serious danger the health of the woman". The literature on the subject is rare and we wanted to make an inventory in our region. METHODS: Retrospective observational study between 2010 and 2019 at the multidisciplinary center for prenatal diagnosis in Western Normandy. RESULTS: Thirty-one cases of MTOP were included (2.5% of all TOP). At the CHU de Caen, they represented one in 1200 births. Twenty-three percent of MTOP had a psychosocial or psychiatric indication (average term=22 SA) and 29% an obstetric indication due to severe preeclampsia (23 SA). Finally, 48% were linked to a non-obstetric somatic disorder including 46% pre-existing pathologies (average term=11 SA), most often cardiological or nephrological and 54% diagnosed during pregnancy (17 SA) dominated by neoplasias. They were more often (68%) performed in the second trimester. Vaginal births were more frequent (74% against 26% of endouterine aspirations). CONCLUSION: Strict medical contraindications to pregnancy are exceptional. Recourse to the medical termination of pregnancy within the framework of a preexisting pathology must remain rare, by systematizing of the preconception consultation.

[Pomalidomide for multiple myeloma]. / Le pomalidomide dans le myélome multiple.

Once characterized by a very poor outcome, multiple myeloma (MM) now has a significantly prolonged survival, with major improvements allowed by the use of "novel agents": proteasome inhibitors (first-in-class bortezomib) and immunomodulatory compounds (IMiDs; first-in-class thalidomide and lenalidomide). However, the vast majority - if not all - of patients with MM ultimately end up being refractory to all existing drugs, including these efficient novel agents. There is a clear unmet medical need in this situation, which warrants the development of the next generation of proteasome inhibitors and IMiDs, as well as new drug classes. This review focuses on pomalidomide, the next generation IMiD, recently approved by the US FDA and the EMA for patients with relapsed or refractory MM who have received at least two prior therapies, including lenalidomide and bortezomib, and have demonstrated disease progression on their last therapy.

11 Beta-hydroxysteroid dehydrogenase type 1 is induced in human monocytes upon differentiation to macrophages.

11beta-hydroxysteroid dehydrogenases (11beta-HSD) perform prereceptor metabolism of glucocorticoids through interconversion of the active glucocorticoid, cortisol, with inactive cortisone. Although the immunosuppressive and anti-inflammatory activities of glucocorticoids are well documented, the expression of 11beta-HSD enzymes in immune cells is not well understood. Here we demonstrate that 11beta-HSD1, which converts cortisone to cortisol, is expressed only upon differentiation of human monocytes to macrophages. 11beta-HSD1 expression is concomitant with the emergence of peroxisome proliferator activating receptor gamma, which was used as a surrogate marker of monocyte differentiation. The type 2 enzyme, 11beta-HSD2, which converts cortisol to cortisone, was not detectable in either monocytes or cultured macrophages. Incubation of monocytes with IL-4 or IL-13 induced 11beta-HSD1 activity by up to 10-fold. IFN-gamma, a known functional antagonist of IL-4 and IL-13, suppressed the induction of 11beta-HSD1 by these cytokines. THP-1 cells, a human macrophage-like cell line, expressed 11beta-HSD1 and low levels of 11beta-HSD2. The expression of 11beta-HSD1 in these cells is up-regulated 4-fold by LPS. In summary, we have shown strong expression of 11beta-HSD1 in cultured human macrophages and THP-1 cells. The presence of the enzyme in these cells suggests that it may play a role in regulating the immune function of these cells.

Activation of peroxisome proliferator-activated receptor gamma does not inhibit IL-6 or TNF-alpha responses of macrophages to lipopolysaccharide in vitro or in vivo.

We have investigated the potential use of peroxisome proliferator-activated receptor gamma (PPARgamma) agonists as anti-inflammatory agents in cell-based assays and in a mouse model of endotoxemia. Human peripheral blood monocytes were treated with LPS or PMA and a variety of PPARgamma agonists. Although 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2) at micromolar concentrations significantly inhibited the production of TNF-alpha and IL-6, four other high affinity PPARgamma ligands failed to affect cytokine production. Similar results were obtained when the monocytes were allowed to differentiate in culture into macrophages that expressed significantly higher levels of PPARgamma or when the murine macrophage cell line RAW 264.7 was used. Furthermore, saturating concentrations of a potent PPARgamma ligand not only failed to block cytokine production, but also were unable to block the inhibitory activity of 15d-PGJ2. Thus, activation of PPARgamma does not appear to inhibit the production of cytokines by either monocytes or macrophages, and the inhibitory effect observed with 15d-PGJ2 is most likely mediated by a PPARgamma-independent mechanism. To examine the anti-inflammatory activity of PPARgamma agonists in vivo, db/db mice were treated with a potent thiazolidinedione that lowered their elevated blood glucose and triglyceride levels as expected. When thiazolidinedione-treated mice were challenged with LPS, they displayed no suppression of cytokine production. Rather, their blood levels of TNF-alpha and IL-6 were elevated beyond the levels observed in control db/db mice challenged with LPS. Comparable results were obtained with the corresponding lean mice. Our data suggest that compounds capable of activating PPARgamma in leukocytes will not be useful for the treatment of acute inflammation.