Can 17 hydroxyprogesterone caproate (17P) decrease preterm deliveries in patients with a history of PMC or pPROM?

BackgroundA history of spontaneous preterm birth (sPTB) is a significant risk factor for recurrence. Intra-muscular-7α-hydroxyprogesterone caproate (17P) has been the preventive treatment of choice until the recent "Prolong study" that reported no benefit.ObjectiveTo determine the benefit of (17P) treatment in preventing reoccurrence of sPTB, by evaluating two presenting symptoms of the first sPTB: premature contractions (PMC) and preterm premature rupture of membranes (pPROM).Study designThis retrospective study included 342 women with a previous singleton sPTB followed by a subsequent pregnancy. sPTB were either due to PMC (n = 145) or pPROM (n = 197). During the subsequent pregnancy, 90 (26.3%) patients received 250 mg 17P IM. Each presenting symptom-PMC or pPROM-was evaluated within itself comparing treated vs. untreated groups. Data were analyzed using t-test, Chi-square and Fisher's exact test. Logistic regression analysis was also performed.ResultsPatients treated with 17P in the subsequent pregnancy had delivered earlier in the previous pregnancy (33.4w vs. 35.3w in the PMC group, and 34.1w vs. 35.7w in the pPROM group, pConclusions17P might delay preterm delivery in patients with a previous sPTB on an individual level (prolongation of the pregnancy for each patient compared to her previous delivery). Therefore, our results imply that 17P can decrease potential premature delivery complications for patients with a previous sPTB due to PMC or pPROM

The effect of steepness of temporal resource gradients on spatial root allocation

Plants are able to discriminately allocate greater biomass to organs that grow under higher resource levels. Recent evidence demonstrates that split-root plants also discriminately allocate more resources to roots that grow under dynamically improving nutrient levels, even when their other roots grow in richer patches. Here, we further tested whether, besides their responsiveness to the direction of resource gradients, plants are also sensitive to the steepness of environmental trajectories. Split-root Pisum sativum plants were grown so that one of their roots developed under constantly-high nutrient levels and the other root was subjected to dynamically improving nutrient levels of variable steepness. As expected, plants usually allocated a greater proportion of their biomass to roots that developed under constantly high resource availability; however, when given a choice, they allocated greater biomass to roots that initially experienced relatively low but steeply improving nutrient availabilities than to roots that developed under continuously-high nutrient availability. Such discrimination was not observed when the roots in the poor patch experienced only gentler improvements in nutrient availability. The results are compatible with the notion that responsiveness to the direction and steepness of environmental gradients could assist annual plants to increase their performance by anticipating resource availabilities foreseeable before the end of the growing season. The results exemplify the ability of plants to integrate and utilize environmental information and execute adaptive behaviors which, until recently, were attributed only to animals with central nervous systems

COVID-19 in Patients with Inflammatory Bowel Disease: The Israeli Experience

Background: Crohn’s disease (CD) and ulcerative colitis (UC) are chronic, immune-mediated inflammatory bowel diseases (IBD) affecting millions of people worldwide. IBD therapies, designed for continuous immune suppression, often render patients more susceptible to infections. The effect of the immune suppression on the risk of coronavirus disease-19 (COVID-19) is not fully determined yet. Objective: To describe COVID-19 characteristics and outcomes and to evaluate the association between IBD phenotypes, infection outcomes and immunomodulatory therapies. Methods: In this multi-center study, we prospectively followed IBD patients with proven COVID-19. De-identified data from medical charts were collected including age, gender, IBD type, IBD clinical activity, IBD treatments, comorbidities, symptoms and outcomes of COVID-19. A multivariable regression model was used to examine the effect of immunosuppressant drugs on the risk of infection by COVID-19 and the outcomes. Results: Of 144 IBD patients, 104 (72%) were CD and 40 (28%) were UC. Mean age was 32.2 ± 12.6 years. No mortalities were reported. In total, 94 patients (65.3%) received biologic therapy. Of them, 51 (54%) at escalated doses, 10 (11%) in combination with immunomodulators and 9 (10%) with concomitant corticosteroids. Disease location, behavior and activity did not correlate with the severity of COVID-19. Biologics as monotherapy or with immunomodulators or corticosteroids were not associated with more severe infection. On the contrary, patients receiving biologics had significantly milder infection course (p = 0.001) and were less likely to be hospitalized (p = 0.001). Treatment was postponed in 34.7% of patients until recovery from COVID-19, without consequent exacerbation. Conclusion: We did not witness aggravated COVID-19 outcomes in patients with IBD. Patients treated with biologics had a favorable outcome

Anti-TNFα Treatment Impairs Long-Term Immune Responses to COVID-19 mRNA Vaccine in Patients with Inflammatory Bowel Diseases

Patients with inflammatory bowel disease (IBD) treated with anti-tumor-necrosis factor-alpha (TNFα) exhibited lower serologic responses one-month following the second dose of the COVID-19 BNT162b2 vaccine compared to those not treated with anti-TNFα (non-anti-TNFα) or to healthy controls (HCs). We comprehensively analyzed long-term humoral responses, including anti-spike (S) antibodies, serum inhibition, neutralization, cross-reactivity and circulating B cell six months post BNT162b2, in patients with IBD stratified by therapy compared to HCs. Subjects enrolled in a prospective, controlled, multi-center Israeli study received two BNT162b2 doses. Anti-S levels, functional activity, specific B cells, antigen cross-reactivity, anti-nucleocapsid levels, adverse events and IBD disease score were detected longitudinally. In total, 240 subjects, 151 with IBD (94 not treated with anti-TNFα and 57 treated with anti-TNFα) and 89 HCs participated. Six months after vaccination, patients with IBD treated with anti-TNFα had significantly impaired BNT162b2 responses, specifically, more seronegativity, decreased specific circulating B cells and cross-reactivity compared to patients untreated with anti-TNFα. Importantly, all seronegative subjects were patients with IBD; of those, >90% were treated with anti-TNFα. Finally, IBD activity was unaffected by BNT162b2. Altogether these data support the earlier booster dose administration in these patients