NVH Medicinal (France)

To compare our experience with N-butyl cyanoacrylate glue as the primary embolic agent versus other embolic agents for transcatheter arterial embolization (TAE) in refractory peptic ulcer bleeding and to identify factors associated with early rebleeding and 30-day mortality. Retrospective study of 148 consecutive patients comparing the clinical success rate in 78 patients managed with Glubran®2 N-butyl cyanoacrylate metacryloxysulfolane (NBCA-MS) alone or with other agents and 70 with other embolic agents only (coils, microspheres, ethylene-vinyl alcohol copolymer, or gelatin sponge) at a university center in 2008-2019. Univariate and multivariate logistic regression analyses were done to identify prognostic factors. The technical success rate was 95.3% and the primary clinical success was 64.5%. The early rebleeding and day-30 mortality rates were 35.4% and 21.3%, respectively. Rebleeding was significantly less common with than without Glubran®2 (OR, 0.47; 95% CI, 0.22-0.99; p =.047) and significantly more common with coils used alone (OR, 20.4; 95% CI, 10.13-50.14; p =.024). The only other factor independently associated with early rebleeding was having two or more comorbidities (OR, 20.14; 95% CI, 10.01-40.52; p =.047). Day-30 mortality was similar in the two treatment groups. A lower initial hemoglobin level was significantly associated with higher day-30 mortality (OR, 10.38; 95% CI, 10.10-10.74; p =.006). Fluoroscopy time was significantly shorter with Glubran®2 (20.8 ± 11.5min vs. 35.5 ± 23.4min, p = .002). Both groups (Glubran®2 vs. other agents) had similar rates of overall complications (10.7% vs. 9.1%, respectively, p = .786). Glubran®2 NBCA-MS as the primary agent allowed for faster and better clinical success compared to other embolic agents when used for TAE to safely stop refractory peptic ulcer bleeding. • Choice of embolic agent for arterial embolization of refractory peptic ulcer bleeding is still debated. We compared our experience with N-butyl cyanoacrylate (NBCA) glue vs. other embolic agents. • The use of Glubran®2 NBCA glue in the endovascular management of refractory peptic ulcer bleeding was significantly faster and more effective, and at least as safe compared to other embolic agents. • NBCA glue offers several advantages compared to other embolic agents and provides rapid hemostasis when used for arterial embolization to treat refractory peptic ulcer bleeding. It should be the first-line therapy.

Hepatic arterial infusion (HAI) of chemotherapy could be used in patients with liver-only metastatic colorectal cancer (mCRC) to fight against chemoresistance. We previously reported the efficacy of raltitrexed plus oxaliplatin (HAI) in a retrospective series. We performed a randomized two-stage phase-II study to evaluate the efficacy of HAI of the combination of raltitrexed and oxaliplatin in refractory mCRC with only liver metastases in comparison with standard of care. Eligible patients had unresectable mCRC and were refractory or intolerant to fluoropyrimidine, irinotecan, oxaliplatin, anti-VEGF therapy, and anti-EGFR therapy (for tumors with wild-type KRAS). Patients were randomized between HAI raltitrexed (3mg/m2 over 1h) followed by oxaliplatin (130mg/m2 over 2h) every 3weeks and standard of care in a 2:1 ratio. A total of 57 patients (38 in the experimental arm and 19 in the standard of care arm) were to be included. The main objective was to demonstrate 6-month PFS of 45% by intention-to-treat analysis in the experimental arm, compared to theoretical PFS of 20%, with a unilateral alpha risk of 5% and beta risk of 10%. After inclusion of 27 patients, the trial was terminated due to insufficient accrual. In the experimental arm, 11 and 4 patients experienced grade 3 and 4 toxicities, respectively. The most frequent grade 3-4 toxicities were neutropenia, liver toxicity, and abdominal pain. Median progression-free survival was 6.7months (95% Confidence Interval; 3.9-7.2) in the HAI group and 2.2months (95% CI 1.2-4.3) with standard of care [HR 0.32 (95% CI 0.14-0.76), p = 0.01]. Median overall survival did not differ between the two groups, at 11.2 months (95% CI 4.8-17.6) for the HAI group and 11.9months (95% CI 2.8-14.3) for standard of care [HR 0.86 (95% CI 0.36-2.04), p = 0.73]. Although stopped prematurely, this randomized trial provides evidence for the benefit and safety of HAI of a combination of raltitrexed and oxaliplatin in liver-only mCRC with chemoresistant disease.

Splenic macrophages play a key role in immune thrombocytopenia (ITP) pathogenesis by clearing opsonized platelets. Fcγ receptors (FcγR) participate in this phenomenon, but their expression on splenic macrophages and their modulation by treatment have scarcely been studied in human ITP. We aimed to compare the phenotype and function of splenic macrophages between six controls and 24 ITP patients and between ITP patients according to the treatments they received prior to splenectomy. CD86, human leucocyte antigen D-related (HLA-DR) and FcγR expression were measured by flow cytometry on splenic macrophages. The major FcγR polymorphisms were determined and splenic macrophage function was assessed by a phagocytosis assay. The expression of the activation markers CD86 and HLA-DR was higher on splenic macrophages during ITP compared to controls. While the expression of FcγR was not different between ITP and controls, the phagocytic function of splenic macrophages was reduced in ITP patients treated with intravenous immunoglobulin (IVIg) within the 2weeks prior to splenectomy. The FCGR3A (158V/F) polymorphism, known to increase the affinity of FcγRIII to IgG, was over-represented in ITP patients. Thus, these are the first results arguing for the fact that the therapeutic use of IVIg during human chronic ITP does not modulate FcγR expression on splenic macrophages but decreases their phagocytic capabilities.

BackgroundThe PCSK9 antibody alirocumab (75 mg every 2 weeks; Q2W) as monotherapy reduced low‐density lipoprotein‐cholesterol (LDL‐C) levels by 47%. Because the option of a monthly dosing regimen is convenient, ODYSSEY CHOICE II evaluated alirocumab 150 mg Q4W in patients with inadequately controlled hypercholesterolemia and not on statin (majority with statin‐associated muscle symptoms), receiving treatment with fenofibrate, ezetimibe, or diet alone.Methods and ResultsPatients were randomly assigned to placebo, alirocumab 150 mg Q4W or 75 mg Q2W (calibrator arm), with dose adjustment to 150 mg Q2W at week (W) 12 if W8 predefined LDL‐C target levels were not met. The primary efficacy endpoint was LDL‐C percentage change from baseline to W24. Mean baseline LDL‐C levels were 163.9 mg/dL (alirocumab 150 mg Q4W, n=59), 154.5 mg/dL (alirocumab 75 mg Q2W, n=116), and 158.5 mg/dL (placebo, n=58). In the alirocumab 150 mg Q4W and 75 mg Q2W groups (49.1% and 36.0% of patients received dose adjustment, respectively), least‐squares mean LDL‐C changes from baseline to W24 were −51.7% and −53.5%, respectively (placebo [+4.7%]; both groups P<0.0001 versus placebo). In total, 63.9% and 70.3% of alirocumab‐treated patients achieved their LDL‐C targets at W24. Treatment‐emergent adverse events occurred in 77.6% (alirocumab 150 mg Q4W), 73.0% (alirocumab 75 mg Q2W), and 63.8% (placebo) of patients, with injection‐site reactions among the most common treatment‐emergent adverse events.ConclusionsAlirocumab 150 mg Q4W can be considered in patients not on statin with inadequately controlled hypercholesterolemia as a convenient option for lowering LDL‐C.Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT02023879.

Converging sources of evidence point to a role for inflammation in the development of depression, fatigue and cognitive dysfunction. More precisely, the tryptophan (TRP) catabolism is thought to play a major role in inflammation-induced depression. Mastocytosis is a rare disease in which chronic symptoms, including depression, are related to mast cell accumulation and activation. Our objectives were to study the correlations between neuropsychiatric features and the TRP catabolism pathway in mastocytosis in order to demonstrate mast cells' potential involvement in inflammation-induced depression. Fifty-four patients with mastocytosis and a mean age of 50.1 years were enrolled in the study and compared healthy age-matched controls. Depression and stress were evaluated with the Beck Depression Inventory revised and the Perceived Stress Scale. All patients had measurements of TRP, serotonin (5-HT), kynurenine (KYN), indoleamine 2,3-dioxygenase 1 (IDO1) activity (ratio KYN/TRP), kynurenic acid (KA) and quinolinic acid (QA). Patients displayed significantly lower levels of TRP and 5-HT without hypoalbuminemia or malabsorption, higher IDO1 activity, and higher levels of KA and QA, with an imbalance towards the latter. High perceived stress and high depression scores were associated with low TRP and high IDO1 activity. In conclusion, TRP metabolism is altered in mastocytosis and correlates with perceived stress and depression, demonstrating mast cells' involvement in inflammation pathways linked to depression.

Frailty is a geriatric syndrome associated with high risk for falls, disability, hospitalization, and mortality. The aim of this study is to assess the prevalence of frailty to the Fried's criteria in primary care and its evolution and the outcome of the patients at 1 year. Descriptive prospective study of patients over 75 years coming consult three general practitioners, evaluated initially and at 1 year. Frailty was defined by the presence of three criteria including weight loss, weakness (grip strength), self-reported exhaustion, low physical activity and slow walking speed. Of the 55 patients re-evaluated, 10.9% of patients were frail, 56.4% pre-frail and 32.7% were robust. Robust who become frail during the initial assessment, had a lower IADL score (p = 0.004) and a lower grip strength (p = 0.0311) than those who remained robust. Fried tool is difficult to implement in primary care. Grip strength and IADL are interesting for a simple screening tool in general practice to allow early treatment and delay progression to addiction.