Higher neutrophil counts and NLR are independently associated with sICH and worse outcome at 3 months. The identification of mediators of this effect could provide new targets for neuroprotection in patients treated by rtPA.

PPARs (peroxisome-proliferator-activated receptors) are ligand-activated transcriptional factor receptors belonging to the so-called nuclear receptor family. The three isoforms of PPAR (alpha, beta/delta and gamma) are involved in regulation of lipid or glucose metabolism. Beyond metabolic effects, PPARalpha and PPARgamma activation also induces anti-inflammatory and antioxidant effects in different organs. These pleiotropic effects explain why PPARalpha or PPARgamma activation has been tested as a neuroprotective agent in cerebral ischaemia. Fibrates and other non-fibrate PPARalpha activators as well as thiazolidinediones and other non-thiazolidinedione PPARgamma agonists have been demonstrated to induce both preventive and acute neuroprotection. This neuroprotective effect involves both cerebral and vascular mechanisms. PPAR activation induces a decrease in neuronal death by prevention of oxidative or inflammatory mechanisms implicated in cerebral injury. PPARalpha activation induces also a vascular protection as demonstrated by prevention of post-ischaemic endothelial dysfunction. These vascular effects result from a decrease in oxidative stress and prevention of adhesion proteins, such as vascular cell adhesion molecule 1 or intercellular cell-adhesion molecule 1. Moreover, PPAR activation might be able to induce neurorepair and endothelium regeneration. Beyond neuroprotection in cerebral ischaemia, PPARs are also pertinent pharmacological targets to induce neuroprotection in chronic neurodegenerative diseases.

These data confirm a strong signal for an increased risk of bullous pemphigoid during DPP-IV inhibitor exposure. This adverse drug reaction is observed for each DPP-IV inhibitor, suggesting a class effect. The signal was higher with vildagliptin than with the other DPP-IV inhibitors.

BackgroundTreatment for bacterial vaginosis in pregnant women to reduce risk of spontaneous very preterm birth and late miscarriage remains controversial. We conducted a randomized control trial to determine whether bacterial vaginosis treatment could decrease spontaneous very preterm births and late miscarriages. MethodsThe PREMEVA trial was a multicenter randomized control double-blinded trial performed in 40 French centers. A total of 84,530 pregnant women were screened for bacterial vaginosis before 14 weeks of gestation. Women with bacterial vaginosis in the first trimester of pregnancy were randomly assigned to three similarly sized parallel arms: one four-day course of 600 mg oral clindamycin daily, three four-day courses of 600 mg daily a month apart or placebo. The primary outcome was a composite of late miscarriage (16-21 weeks) or spontaneous very preterm delivery (22-32 weeks) according to clindamycin treatment or placebo. Secondary outcomes included spontaneous preterm delivery before 37 weeks (22-36 weeks). FindingsBetween 04/01/2006 and 06/30/2011, 84,530 pregnant women were screened before 14 weeks of gestation, 5630 (6•7%) had bacterial vaginosis and 2869 were randomized. The primary outcome did not differ significantly between the groups (1•2% in the clindamycin group and 1.0% in the placebo group, relative risk, 1.10; 95% confidence interval [CI], 0•53 to 2•32), nor in the rate of spontaneous preterm delivery before 37 weeks (4•8% and 4•1%, respectively; relative risk, 1•17; 95% CI, 0•81 to 1•69). Side effects were more common in the clindamycin group (3•0% vs 1•3%, p=0•003) but not severe. InterpretationSystematic screening and subsequent treatment for bacterial vaginosis in low-risk pregnant women does not decrease late miscarriage, spontaneous very preterm birth, or spontaneous preterm birth.

The hospitalised patients in a cardiological hospital (Lille, France) over an 18-month period were subjected to a prospective high-intensity adverse drug reaction (ADR) monitoring in order to assess the additional financial resource utilisation associated with ADRs and analyse the distribution of excess of cost according to ADR nature and therapeutic classes. Over 18 months, among the 16,916 hospitalised patients, 371 verified ADRs detected by self-report stimulated by a special unit of nurses and pharmacologists occurred in 336 patients with an overall ADR rate of 2.2%. This rate increased with age. The most common reactions were cutaneous events (24%), cardiovascular events (21%), metabolic disorders (12%), coagulation disorders (10%) and nervous system impairment (10%). The most common drug classes involved were cardiovascular agents (36%), contrast media (20%), drugs affecting blood clotting (13%) and anti-infectives (14%). Increased ADR-induced costs result especially from prolongation of length of stay and cost increase was evaluated at Euro 4150 per ADR. Among the 371 ADRs, 134 ADRs, which were significantly more severe, induced a prolongation of length of stay. Renal insufficiency and cardiovascular events were significantly over-represented in this sub-group. The most common ADR-inducing drugs associated with a prolongation of length of stay are cardiovascular agents and drugs affecting blood clotting. In contrast, cutaneous ADRs were significantly over-represented in the group of ADRs without prolongation of length of stay. The severity and substantial costs of ADRs in hospital justify investments to prevent these events. Nevertheless, only a portion of ADRs induces cost increases, suggesting that prevention efforts should focus on this limited category of ADRs.

These cases emphasize the need for regular monitoring of renal function during zoledronic acid treatment, with particular attention to patients with preexisting impaired renal function.

We used data prospectively collected in a registry of consecutive patients treated with intravenous r-tPA for cerebral ischemia in the stroke center of the Lille University Hospital, from September 30, 2003 to February 4, 2015. The general organization, 4,5 eligibility criteria for thrombolysis, 2,6,7 clinical assessment, 8-10 imaging procedures, and treatment administration 7 have been previously described. 4,5 Patients from this cohort were included in previous studies of our group including one in which the occurrence of OLAE was reported 11 and in a case report. 12Background and Purpose-Orolingual angioedema (OLAE) is a life-threatening complication of intravenous thrombolysis. Our objective was to compare outcomes of patients with and without OLAE. Methods-We prospectively included consecutive patients who received intravenous thrombolysis for cerebral ischemia at Lille University Hospital. We examined tongue and lips every 15 minutes during thrombolysis and ≤30 minutes after. We evaluated the 3-month outcome with the modified Rankin scale (mRS) and compared outcomes of patients with and without OLAE. Results-Of 923 consecutive patients, 20 (2.2%) developed OLAE. None of them needed oro-tracheal intubation. They were more likely to be under angiotensin-converting enzyme inhibitors (adjusted odds ratio [adjOR], 3.9; 95% confidence interval [CI], 1.6-9.7; P=0.005) to have total insular infarcts (OR, 5.0; 95% CI, 1.5-16.5; P=0.004) and tended to develop more symptomatic intracerebral hemorrhages. Results concerning angiotensin-converting enzyme inhibitors were not modified after adjustment for propensity scores (OR, 4.4; 95% CI, 1.6-11.9; P=0.004) or matched analysis based on propensity scores (OR, 3.4; 95% CI, P=0.010). Patients with OLAE did not significantly differ at 3 months for the proportion of patients with mRS score of 0 to 1 (adjOR, 0.9; 95% CI, 0.3-2.1), mRS score of 0 to 2 (adjOR, 0.8; 95% CI, 0.1-1.8), and death (adjOR, 1.1; 95% CI, 0.3-3.8). Conclusions-OLAE occurs in 1 of 50 patients who receive intravenous thrombolysis, 1 of 10 in case of total insular infarct, and 1 of 6 if they are under angiotensin-converting enzyme inhibitors. Their long-term outcome does not differ from that of other patients.

ObjectiveIn acute cerebral ischemia, circulating neutrophil count and neutrophil-to-lymphocyte ratio (NLR) are positively associated with stroke severity and worse outcomes. Mediators of this effect are unknown. We aimed to investigate (1) the relationship between plasma matrix metalloproteinase-9 (MMP-9) and myeloperoxidase (MPO) concentrations with stroke severity and outcome and (2) MMP-9 and MPO release after ex vivo stimulation of neutrophils by recombinant tissue plasminogen activator (rtPA).MethodsWe analyzed data collected in 255 patients with supratentorial cerebral infarcts recruited within 48 hours of symptoms onset irrespective of rtPA treatment. The endpoints were excellent outcome (modified Rankin Scale score 0–1), symptomatic intracerebral hemorrhage (European Cooperative Acute Stroke Study–II definition), and death at 3 months. The role of rtPA treatment on peripheral neutrophil degranulation was investigated in 18 patients within 4.5 hours and after 72 hours.ResultsNeutrophil counts, NLR, and MPO plasma concentrations, but not MMP-9, were positively correlated with stroke severity. Higher neutrophil counts and NLR were independently associated with worse outcomes and higher mortality rates at month 3. Higher MPO plasma concentrations, but not MMP-9, were associated with worse outcome. Neutrophil-derived MMP-9, after ex vivo rtPA stimulation, but not MPO, were higher after 72 hours in patients treated by IV rtPA but not associated with hemorrhagic transformation.ConclusionsNeutrophil counts, NLR, and MPO plasma concentrations are associated with worse outcome in patients with acute cerebral ischemia, in contrast to MMP-9. Further investigations are needed to deepen our knowledge on MPO’s role in the deleterious effect of neutrophils because it could represent a potential therapeutic target.