Clinical and ultrasonographic evaluation of the window of opportunity for retreatment with rituximab in rheumatoid arthritis patients from a multicentre real-life study.

OBJECTIVES: To determine a potential window of opportunity for retreatment with rituximab in patients with rheumatoid arthritis (RA) from a multicentre longitudinal real-life study based on tight monitoring with ultrasonography (US). METHODS: Thirty RA patients treated with rituximab were included. US parameters were collected at each time (8 visits) of the 18-month follow-up, notably the global score of power Doppler (PD) activity. Clinical relapse was defined as a DAS28 ESR of >3.2 after 6 months in responders while US relapse was defined as an increase of ≥20% of the global score of PD activity. The decision of retreatment was based exclusively on clinical findings. RESULTS: A total of 29 patients were analysed (mean (SD) age: 57.2 (12.2) years; female gender: 66%). The mean (SD) PD score decreased from 8.8 (5.2) at baseline to 4.9 (4.3) at 6 months (p <0.0001). A clinical response was observed at Month 4 or Month 6 for 93% of patients. A total of 19 patients had a first clinical relapse (with or without US relapse) after Month 6 (18 of them were retreated with rituximab). Among 10 patients without clinical relapse, 3 had US relapse (only one was retreated) and 7 had no US relapse (but 4 were retreated). CONCLUSIONS: This study highlights a great heterogeneity in terms of sequence of clinical relapse, US relapse and retreatment in RA patients receiving rituximab. Therefore, US monitoring does not seem to be relevant to determine the best time for retreatment with rituximab.

Role of protective stoma after primary anastomosis for generalized peritonitis due to perforated diverticulitis-DIVERTI 2 (a prospective multicenter randomized trial): rationale and design (nct04604730).

BACKGROUND: Traditionally, patients with peritonitis Hinchey III and IV due to perforated diverticulitis were treated with Hartmann's procedure. In the past decade, resection and primary anastomosis have gained popularity over Hartmann's procedure and recent guidelines recommend Hartmann's procedure in two situations only: critically ill patients and in selected patients with multiple comorbidity (at high risk of complications). The protective stoma (PS) is recommended after resection with primary anastomosis, however its interest has never been studied. The aim of this trial is to define the role of systematic PS after resection and primary anastomosis for peritonitis Hinchey III and IV due to perforated diverticulitis. METHODS/DESIGN: This DIVERTI 2 trial is a multicenter, randomized, controlled, superiority trial comparing resection and primary anastomosis with (control group) or without (experimental group) PS in patients with peritonitis Hinchey III and IV due to perforated diverticulitis. Primary endpoint is the overall 1 year morbidity according to the Clavien-Dindo classification of surgical complications. All complications occurring during hospitalization will be collected. Late complications occurring after hospitalization will be collected during follow-up. In order to obtain 80% power for a difference given by respective main probabilities of 67% and 47% in the protective stoma and no protective stoma groups respectively, with a two-sided type I error of 5%, 96 patients will have to be included in each group, hence 192 patients overall. Expecting a 5% rate of patients not assessable for the primary end point (lost to follow-up), 204 patients will be enrolled. Secondary endpoints are postoperative mortality, unplanned reinterventions, incisional surgical site infection (SSI), organ/space SSI, wound disruption, anastomotic leak, operating time, length of hospital stay, stoma at 1 year after initial surgery, quality of life, costs and quality-adjusted life years (QALYs). DISCUSSION: The DIVERTI 2 trial is a prospective, multicenter, randomized, study to define the best strategy between PS and no PS in resection and primary anastomosis for patients presenting with peritonitis due to perforated diverticulitis. TRIAL REGISTRATION: ClinicalTrial.gov: NCT04604730 date of registration October 27, 2020. https://clinicaltrials.gov/ct2/show/NCT04604730?recrs=a&cond=Diverticulitis&draw=2&rank=12 .

Caffeine use during pregnancy: prevalence of use and newborn consequences in a cohort of French pregnant women.

Many pregnant women, in the world, drink caffeine-containing beverages. Maternal caffeine consumption during pregnancy may have adverse effects on foetus but results are conflicting. Our goals were to estimate the prevalence of caffeine use in a cohort of French pregnant women using maternal self-reports and to evaluate the association between caffeine consumption during pregnancy and delivery and newborn characteristics. All pregnant women who gave birth in a large French urban area during a limited period of time were included (in total 724 mothers were included). Coffee, tea or cola consumption as well as pregnancy and neonate characteristics were analysed. The mean consumption of caffeine per day slightly decreased from the first to the third trimester of pregnancy: 587 caffeine users, with a consumption of caffeine of 59.2 ± 61.5 mg/day during the first trimester as compared to 577 consumers (54.3 ± 55.4 mg/day) during the third trimester, respectively. A significant decrease of neonates' birth length was observed when mothers were using at least 100 mg/day (or two cups) of caffeine during the second and third trimesters but this difference was no longer significant after adjustment on potential confounding factors such as tobacco use. The potential existence of other confounders (e.g. poorer dietary habits or other lifestyle variables) that might also be associated with reduced birth length, may not be excluded. Caffeine use during pregnancy was associated with reduced birth length but this effect was no longer significant after adjustment on potential confounding variables.

Assessment of anal sphincter distensibility following the STARR procedure: a pilot study.

Aim: The STARR (Stapled Trans-Anal Rectal Resection) procedure consists of a surgical correction of symptomatic rectocele refractory to medical treatment, involving anal dilatation. The aim of the study was to determine the impact of the STARR procedure on anal distensibility using EndoFLIP® device.Methods: All female patients with a minimal rectocele of 3 cm and with symptoms of obstructed defecation syndrome (ODS) refractory to medical treatment were included prospectively. Patients with previous anal incontinence were not included. Wexner, ODS and Kess scores were recorded. Endoanal ultrasounds and EndoFLIP® measurements were performed pre-surgery and 3 months following the STARR procedure. The distensibility index (DI) at 40 mL of inflation at rest was the primary study endpoint.Results: Seven patients (median age: 52.5, range: 44-62) were included between 2014 and 2017. The DI after surgery was the same as the pre-surgery DI. No patient developed symptoms of faecal incontinence or urge to defecate in the three months following the STARR procedure. All patients reported an improvement in their ODS and Kess scores three months after the STARR procedure. No anal sphincter defects were detected by endoanal ultrasound.Conclusion: Anal dilatation did not appear to alter anal distensibility in patients with a normal anal function before the STARR procedure.

Risk factors associated to tobacco and alcohol use in a large French cohort of pregnant women.

Tobacco and/or alcohol use during pregnancy is a major public health concern. The aim of our study was to identify risk factors associated to maternal alcohol and tobacco use assessed by maternal self-reports combined with biological measurements in meconium samples of cotinine and ethylglucuronide which reflect fetal exposure to tobacco and alcohol, respectively, during the 3rd trimester of pregnancy. We conducted a prospective study in three maternity hospitals in a large urban area during consecutive weeks (2010 and 2011). Maternal sociodemographic and clinical characteristics were assessed after delivery, using the French version of the Addiction Severity Index. Cotinine and ethylglucuronide were measured in meconium samples. Seven hundred and twenty-four women were included, and 645 meconium samples collected. Using multivariate analyses, we found that not being married or having a smoking partner predicts maternal tobacco use. In contrast, a decreased risk was associated with higher education level and wanted pregnancy. The risk for alcohol use increased when the mother had been in conflict with any relative or her partner for a long time throughout her life, as well as in case of previous treatment for any mental or emotional disorder. Using multivariate analyses and cotinine presence in meconium samples, the risks were similar except for marital status, which was not associated to cotinine presence. Community education and prevention programs should urgently be improved for all women of childbearing age with a special focus on those with past histories of mental or emotional disorders and addictive disorders. Smoking cessation should be recommended to both parents.

Autologous Myoblasts for the Treatment of Fecal Incontinence: Results of a Phase 2 Randomized Placebo-controlled Study (MIAS).

OBJECTIVE: The aim of this study was to evaluate the efficacy of intrasphincteric injections of autologous myoblasts (AMs) in fecal incontinence (FI) in a controlled study. SUMMARY OF BACKGROUND DATA: Adult stem cell therapy is expected to definitively cure FI by regenerating damaged sphincter. Preclinical data and results of open-label trials suggest that myoblast therapy may represent a noninvasive treatment option. METHODS: We conducted a phase 2 randomized, double-blind, placebo-controlled study of intrasphincteric injections of AM in 24 patients. The study compared outcome after AM (n = 12) or placebo (n = 12) injection using Cleveland Clinic Incontinence (CCI), score at 6 and 12 months. Patients in the placebo group were eligible to receive frozen AM after 1 year. RESULTS: At 6 months, the median CCI score significantly decreased from baseline in both the AM (9 vs 15, P = 0.02) and placebo (10 vs 15, P = 0.01) groups. Hence, no significant difference was found between the 2 groups (primary endpoint) at 6 months. At 12 months, the median CCI score continued to ameliorate in the AM group (6.5 vs 15, P = 0.006), while effect was lost in the placebo group (14 vs 15, P = 0.35). Consequently, there was a higher response rate at 12 months in the treated than the placebo arm (58% vs 8%, P = 0.03). After delayed frozen AM injection in the placebo group, the response rate was 60% (6/10) at 12 months. CONCLUSIONS: Intrasphincteric AM injections in FI patients have shown tolerance, safety, and clinical benefit at 12 months despite a transient placebo effect at 6 months.

First-line rituximab combined with short-term prednisone versus prednisone alone for the treatment of pemphigus (Ritux 3): a prospective, multicentre, parallel-group, open-label randomised trial.

BACKGROUND: High doses of corticosteroids are considered the standard treatment for pemphigus. Because long-term corticosteroid treatment can cause severe and even life-threatening side-effects in patients with this disease, we assessed whether first-line use of rituximab as adjuvant therapy could improve the proportion of patients achieving complete remission off-therapy, compared with corticosteroid treatment alone, while decreasing treatment side-effects of corticosteroids. METHODS: We did a prospective, multicentre, parallel-group, open-label, randomised trial in 25 dermatology hospital departments in France (Ritux 3). Eligible participants were patients with newly diagnosed pemphigus aged 18-80 years being treated for the first time (not at the time of a relapse). We randomly assigned participants (1:1) to receive either oral prednisone alone, 1·0 or 1·5 mg/kg per day tapered over 12 or 18 months (prednisone alone group), or 1000 mg of intravenous rituximab on days 0 and 14, and 500 mg at months 12 and 18, combined with a short-term prednisone regimen, 0·5 or 1·0 mg/kg per day tapered over 3 or 6 months (rituximab plus short-term prednisone group). Follow-up was for 3 years (study visits were scheduled weekly during the first month of the study, then monthly until month 24, then an additional visit at month 36). Treatment was assigned through central computer-generated randomisation, with stratification according to disease-severity (severe or moderate, based on Harman's criteria). The primary endpoint was the proportion of patients who achieved complete remission off-therapy at month 24 (intention-to-treat analysis). This study is registered with ClinicalTrials.gov, number NCT00784589. FINDINGS: Between May 10, 2010, and Dec 7, 2012, we enrolled 91 patients and randomly assigned 90 to treatment (90 were analysed; 1 patient withdrew consent before the random assignment). At month 24, 41 (89%) of 46 patients assigned to rituximab plus short-term prednisone were in complete remission off-therapy versus 15 (34%) of 44 assigned to prednisone alone (absolute difference 55 percentage points, 95% CI 38·4-71·7; p<0·0001. This difference corresponded to a relative risk of success of 2·61 (95% CI 1·71-3·99, p<0·0001), corresponding to 1·82 patients (95% CI 1·39-2·60) who would need to be treated with rituximab plus prednisone (rather than prednisone alone) for one additional success. No patient died during the study. More severe adverse events of grade 3-4 were reported in the prednisone-alone group (53 events in 29 patients; mean 1·20 [SD 1·25]) than in the rituximab plus prednisone group (27 events in 16 patients; mean 0·59 [1·15]; p=0·0021). The most common of these events in both groups were diabetes and endocrine disorder (11 [21%] with prednisone alone vs six [22%] with rituximab plus prednisone), myopathy (ten [19%] vs three [11%]), and bone disorders (five [9%] vs five [19%]). INTERPRETATION: Data from our trial suggest that first-line use of rituximab plus short-term prednisone for patients with pemphigus is more effective than using prednisone alone, with fewer adverse events. FUNDING: French Ministry of Health, French Society of Dermatology, Roche.

Copy number variations in DCC/18q and ERBB2/17q are associated with disease-free survival in microsatellite stable colon cancer.

We conducted a prospective study to assess the prognostic impact of selected copy number variations (CNVs) in Stage II-III microsatellite stable (MSS) colon cancer. A total of 401 patients were included from 01/2004 to 01/2009. The CNVs in 8 selected target genes, DCC/18q, EGFR/7p, TP53/17p, BLK/8p, MYC/8q, APC/5q, ERBB2/17q and STK6/20q, were detected using a quantitative multiplex polymerase chain reaction of short fluorescent fragment (QMPSF) method. The primary end-point was the impact of the CNVs on the 4-year disease-free survival (DFS). The recurrence rate at 4 years was 20.9%, corresponding to 14% Stage II patients versus 31% Stage III patients (p < 0.0001). The 4-year DFS was significantly decreased in patients with a loss at DCC/18q (p = 0.012) and a gain at ERBB2/17q (p = 0.041). The multivariate analysis demonstrated that Stage III, a loss at DCC/18q and a gain at ERBB2/17q were independent factors associated with DFS. A combination of DCC/18q and ERBB2/17q was also associated with relapse, with the hazard ratio increasing from 1 to 2.4 (95% confidence interval (CI), 1.5-4.1) and 3.1 (95% CI, 1.2-8.4) in the presence of 0, 1 or 2 alterations, respectively (p = 0.0013). CNVs in DCC/18q and ERBB2/17q are significantly associated with DFS in Stage II-III MSS colon cancer.

How do GP practices and patient characteristics influence the prescription of antidepressants? A cross-sectional study.

BACKGROUND: Under-prescription of antidepressants (ADs) among people meeting the criteria for major depressive episodes and excessive prescription in less symptomatic patients have been reported. The reasons influencing general practitioners' (GPs) prescription of ADs remain little explored. This study aimed at assessing the influence of GP and patient characteristics on AD prescription. METHODS: This cross-sectional study was based on a sample of 816 GPs working within the main health care insurance system in the Seine-Maritime district of France during 2010. Only GPs meeting the criteria for full-time GP practice were included. The ratio of AD prescription to overall prescription volume, a relative measure of AD prescription level, was calculated for each GP, using the defined daily dose (DDD) concept. Associations of this AD prescription ratio with GPs' age, gender, practice location, number of years of practice, number of days of sickness certificates prescribed, number of home visits and consultations, number and mean age of registered patients, mean patient income, and number of patients with a chronic condition were assessed using univariate and multivariate analysis. RESULTS: The high prescribers were middle-aged (40-59) urban GPs, with a moderate number of consultations and fewer low-income and chronic patients. GPs' workload (e.g., volume of prescribed drug reimbursement and number of consultations) had no influence on the AD prescription ratio. GPs with more patients with risk factors for depression prescribed fewer ADs, however, which could suggest the medications were under-prescribed among the at-risk population. CONCLUSIONS: Our study described a profile of the typical higher AD prescriber that did not include heavy workload. In future work, a more detailed assessment of all biopsychosocial components of the consultation and other influences on GP behavior such as prior training would be useful to explain AD prescription in GP's practice.

School-age outcomes following a randomized controlled trial of magnesium sulfate for neuroprotection of preterm infants.

In a French randomized trial, children at school-age demonstrated no evidence of harm from fetal exposure to MgSO4 before very preterm birth. Motor dysfunction/death, qualitative behavioral disorders, cognitive difficulties, school grade repetition, and education services were decreased in the children exposed to MgSO4, although the differences were not significant.

Low-Dose Remifentanil in Preterm Cesarean Section with General Anesthesia: A Randomized Controlled Trial.

BACKGROUND AND OBJECTIVE: The conventional technique of general anesthesia induction during a Cesarean section involves the use of opioids only after cord clamping. We hypothesized that the use of remifentanil before cord clamping might reduce the use of maternal supplemental anesthetic agents and improve the maternal hemodynamics status and neonatal adaptation of the preterm neonate. METHODS: A phase III, double-blind, randomized, placebo-controlled, hospital-based trial enrolled parturients undergoing a Cesarean section under general anesthesia before 37 weeks of gestation. Block randomization allocated pregnant women to remifentanil or placebo. The primary outcome was the rate of newborns with Apgar scores < 7 at 5 min. Secondary outcomes were maternal hemodynamic parameters, complications of anesthetic induction, use of adjuvant anesthetic agents, neonatal respiratory distress, umbilical cord pH, and lactate levels. RESULTS: A total of 52/55 participants were analyzed, comprising 27 women in the remifentanil group and 25 in the placebo group. Nine of 27 (33.3%) neonates had an Apgar score < 7 at 5 min in the remifentanil group versus 11/25 (44.0%) in the placebo group (p = 0.45, odds ratio = 0.66, 95 confidence interval 0.20-2.18). The blood cord gases, cognitive, behavior, sensory, sleeping, and feeding scores at 1 and 2 years of corrected age were not different. For the mothers, hemodynamic parameters, anesthesia duration, and the cumulative treatment dose until cord clamping did not differ between the groups. CONCLUSIONS: The use of a low dose of remifentanil before cord clamping for a Cesarean section appears to be safe both for the mother and the preterm newborn, but it does not improve maternal or neonatal outcomes. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT02029898.

Sustained Remission Without Corticosteroids Among Patients With Pemphigus Who Had Rituximab as First-Line Therapy: Follow-Up of the Ritux 3 Trial.

Importance: The Ritux 3 trial demonstrated the short-term efficacy and safety of first-line treatment with rituximab compared with a standard corticosteroid regimen in pemphigus. No data on the long-term follow-up of patients who received rituximab as first line are available. Objective: To assess the long-term efficacy and safety of the Ritux 3 treatment regimen. Design, Setting, and Participants: This 7-year follow-up study of the Ritux 3 trial included patients with pemphigus from 25 dermatology departments in France from January 1, 2010, to December 31, 2015. Exposure: Patients were initially randomized in the rituximab plus prednisone group or prednisone-alone group. Main outcomes and measures: The primary outcome was the 5- and 7-year disease-free survival (DFS) without corticosteroids, assessed by Kaplan-Meier curves. Secondary outcomes were occurrence of relapse, occurrence of severe adverse events (SAEs), and evolution of antidesmoglein (Dsg) antibody enzyme-linked immunosorbent assay values to predict long-term relapse. Results: Of the 90 patients in the Ritux 3 trial, 83 were evaluated at the end of follow-up study visit (44 in the rituximab plus prednisone group; 39 in the prednisone-alone group) with a median (IQR) follow-up of 87.3 (79.1-97.5) months. Forty-three patients (93%) from the rituximab plus prednisone and 17 patients (39%) from the prednisone-alone group had achieved complete remission without corticosteroids at any time during the follow-up. Patients from the rituximab group had much longer 5- and 7-year DFS without corticosteroids than patients from the prednisone-alone group (76.7% and 72.1% vs 35.3% and 35.3%, respectively; P < .001), and had about half the relapses (42.2% vs 83.7%; P < .001). Patients who received rituximab as second-line treatment had shorter DFS than patients treated as first line (P = .007). Fewer SAEs were reported in the rituximab plus prednisone group compared with the prednisone-alone group, 31 vs 58 respectively, corresponding to 0.67 and 1.32 SAEs per patient, respectively (P = .003). The combination of anti-Dsg1 values of 20 or more IU/mL and/or anti-Dsg3 values of 48 or more IU/mL yielded 0.83 positive predictive value and 0.94 negative predictive value to predict long-term relapse. Conclusions and Relevance: In this secondary analysis of the Ritux 3 trail, first-line treatment of patients with pemphigus with the Ritux 3 regimen was associated with long-term sustained complete remission without corticosteroid therapy without any additional maintenance infusion of rituximab.

Assessment of the rate of long-term complete remission off therapy in patients with pemphigus treated with different regimens including medium- and high-dose corticosteroids.

BACKGROUND: Few studies have evaluated pemphigus treatments according to the definitions of the consensus statement. Prognostic factors for complete remission off therapy (CRoffT) remain unknown. OBJECTIVE: We sought to assess the rate of CRoffT in patients with pemphigus treated with different regimens. METHODS: In all, 134 patients with pemphigus were included in a retrospective, multicenter study. Primary end point was the rate of CRoffT. Prognostic factors for CRoffT were determined using univariate and multivariate analyses. RESULTS: Eighty patients with pemphigus vulgaris, 47 with pemphigus foliaceus, and 7 with paraneoplastic pemphigus were included. Mean age was 60 ± 18 years. Patients were treated either with medium (≤0.5 mg/kg/d) (n = 32) or high (≥1 mg/kg/d) (n = 59) doses of prednisone, or without systemic corticosteroids (n = 43). Mean follow-up was 77 ± 64 months. In all, 68 patients (50.7%) achieved CRoffT (95% confidence interval 42.3%-59.2%) after a mean treatment duration of 36 ± 39 months, including 47 of 80 patients with pemphigus vulgaris (58.7%) and 21 of 47 with pemphigus foliaceus (44.7%). Main prognostic factors for CRoffT were initial mucosal involvement (hazard ratio 2.2; 95% confidence interval 1.05-4.58; P = .036) and younger age (<61 years) (hazard ratio 2.5; 95% confidence interval 1.18-5.12; P = .0167). The rate of long-lasting CRoffT was 44%, with a mean follow-up after treatment withdrawal of 59 ± 50 months. LIMITATIONS: This was a retrospective study. CONCLUSION: The rate of CRoffT was 51%. Patients with pemphigus vulgaris were more likely to achieve CRoffT than those with pemphigus foliaceus.

Efficacy of Methotrexate Alone vs Methotrexate Plus Low-Dose Prednisone in Patients With Alopecia Areata Totalis or Universalis: A 2-Step Double-Blind Randomized Clinical Trial.

Importance: Poor therapeutic results have been reported in patients with alopecia areata totalis (AT) or universalis (AU), the most severe and disabling types of alopecia areata (AA). Methotrexate, an inexpensive treatment, might be effective in AU and AT. Objective: To evaluate the efficacy and tolerance of methotrexate alone or combined with low-dose prednisone in patients with chronic and recalcitrant AT and AU. Design, Setting, and Participants: This academic, multicenter, double-blind, randomized clinical trial was conducted at 8 dermatology departments at university hospitals between March 2014 and December 2016 and included adult patients with AT or AU evolving for more than 6 months despite previous topical and systemic treatments. Data analysis was performed from October 2018 to June 2019. Interventions: Patients were randomized to receive methotrexate (25 mg/wk) or placebo for 6 months. Patients with greater than 25% hair regrowth (HR) at month 6 continued their treatment until month 12. Patients with less than 25% HR were rerandomized: methotrexate plus prednisone (20 mg/d for 3 months and 15 mg/d for 3 months) or methotrexate plus placebo of prednisone. Main Outcome and Measures: The primary end point assessed on photos by 4 international experts was complete or almost complete HR (Severity of Alopecia Tool [SALT] score <10) at month 12, while receiving methotrexate alone from the start of the study. Main secondary end points were the rate of major (greater than 50%) HR, quality of life, and treatment tolerance. Results: A total of 89 patients (50 female, 39 male; mean [SD] age, 38.6 [14.3] years) with AT (n = 1) or AU (n = 88) were randomized: methotrexate (n = 45) or placebo (n = 44). At month 12, complete or almost complete HR (SALT score <10) was observed in 1 patient and no patient who received methotrexate alone or placebo, respectively, in 7 of 35 (20.0%; 95% CI, 8.4%-37.0%) patients who received methotrexate (for 6 or 12 months) plus prednisone, including 5 of 16 (31.2%; 95% CI, 11.0%-58.7%) who received methotrexate for 12 months and prednisone for 6 months. A greater improvement in quality of life was observed in patients who achieved a complete response compared with nonresponder patients. Two patients in the methotrexate group discontinued the study because of fatigue and nausea, which were observed in 7 (6.9%) and 14 (13.7%) patients receiving methotrexate, respectively. No severe treatment adverse effect was observed. Conclusions and Relevance: In this randomized clinical trial, while methotrexate alone mainly allowed partial HR in patients with chronic AT or AU, its combination with low-dose prednisone allowed complete HR in up to 31% of patients. These results seem to be of the same order of magnitude as those recently reported with JAK inhibitors, with a much lower cost. Trial Registration: ClinicalTrials.gov Identifier: NCT02037191.

Evaluation of a Supervised Adapted Physical Activity Program Associated or Not with Oral Supplementation with Arginine and Leucine in Subjects with Obesity and Metabolic Syndrome: A Randomized Controlled Trial.

Background: In patients with obesity and metabolic syndrome (MetS), lifestyle interventions combining diet, in particular, and physical exercise are recommended as the first line treatment. Previous studies have suggested that leucine or arginine supplementation may have beneficial effects on the body composition or insulin sensitivity and endothelial function, respectively. We thus conducted a randomized controlled study to evaluate the effects of a supervised adapted physical activity program associated or not with oral supplementation with leucine and arginine in MetS-complicated patients with obesity. Methods: Seventy-nine patients with obesity and MetS were randomized in four groups: patients receiving arginine and leucine supplementation (ALs group, n = 20), patients on a supervised adapted physical activity program (APA group, n = 20), patients combining ALs and APA (ALs+APA group, n = 20), and a control group (n = 19). After the baseline evaluation (m0), patients received ALs and/or followed the APA program for 6 months (m6). Body composition, MetS parameters, lipid and glucose metabolism markers, inflammatory markers, and a cardiopulmonary exercise test (CPET) were assessed at m0, m6, and after a 3-month wash-out period (m9). Results: After 6 months of intervention, we did not observe variable changes in body weight, body composition, lipid and glucose metabolism markers, inflammatory parameters, or quality of life scores between the four groups. However, during the CPET, the maximal power (Pmax and Ppeak), power, and O2 consumption at the ventilatory threshold (P(VT) and O2(VT)) were improved in the APA and ALs+APA groups (p < 0.05), as well as the forced vital capacity (FVC). Between m6 and m9, a gain in fat mass was only observed in patients in the APA and ALs+APA groups. Conclusion: In our randomized controlled trial, arginine and leucine supplementation failed to improve MetS in patients with obesity, as did the supervised adapted physical activity program and the combination of both. Only the cardiorespiratory parameters were improved by exercise training.

Is abnormal 25 g fructose breath test a predictor of symptomatic response to a low fructose diet in irritable bowel syndrome?

BACKGROUND: Fructose malabsorption may trigger gastrointestinal symptoms in irritable bowel syndrome patients and a low fructose diet seems to improve digestive symptoms. AIM: The aim of our study was to determine whether fructose malabsorption detected by a 25g fructose breath test could be a predictor of the efficacy of a low fructose diet. METHODS: 88 patients (73 women, median age, 45.5 years, range 18-69) with irritable bowel syndrome according to Rome III criteria were included in this prospective, controlled study. All 88 patients had a 25 g fructose breath test; 37 had a positive test result defining fructose malabsorption. All 88 patients followed a low fructose diet for 2 weeks, blinded to their test results. Patients filled self validated-questionnaires before and at the end of the dietary period. The main outcome measurement was the Irritable Bowel Syndrome-Symptom Severity Score. RESULTS: Irritable Bowel Syndrome-Symptom Severity Score significantly decreased in fructose absorbers and fructose malabsorbers after a low fructose diet (-68.0 [-137; 0] versus -73.5 [-173; -11.5]) with no difference according to fructose breath test result (adjusted P = 0.984). CONCLUSION: A positive 25 g fructose breath test is not a predictor of the efficacy of a low fructose diet in irritable bowel syndrome. REGISTERED CLINICAL TRIAL: www.clinicaltrials.gov (NCT02188680).

Is there a timing for sensitivity to acute cerebral ischemia in migraine patients?

BACKGROUND: Migraine may be a factor of increased cerebral sensitivity to ischemia. Previous studies were conducted within 6 to 72 after stroke onset. We aimed to determine if an accelerated infarct growth exists in migraine patients within the first 4.5 h. METHOD: A retrospective case-control study was conducted where all patients admitted for acute stroke started <4.5 h before and who underwent perfusion CT were assessed. The hypoperfusion and necrosis volumes on initial CT perfusion were analyzed, as well as the final infarct volume on MRI performed within 72 h after admission. A no-mismatch pattern was defined as a ratio necrosis/hypoperfusion volume > 83%. RESULTS: 24 patients with personal history of migraine were identified, 8 of them with aura. The control cohort included 51 patients. No difference was found between groups in terms of demographics, initial severity or outcome or presumed cause of stroke. Mean time to CT scan was 125 min in migraine patients and 127 min in the control group. A no-mismatch pattern was equally found in migraine patients and controls, even after adjustment for age, sex and presence of proximal occlusion (p = .22). The final infarct volume was also similar in both groups. CONCLUSIONS: Migraine patients did not display more no-mismatch pattern than controls within the 4.5 h of stroke onset. This deviates from previous studies and may be due to our earlier time from stroke onset to CT scan. A history of migraine may lead to malignant progression of ischemia but occurring only after several hours.

Factors Associated With Short-term Relapse in Patients With Pemphigus Who Receive Rituximab as First-line Therapy: A Post Hoc Analysis of a Randomized Clinical Trial.

Importance: Rituximab and short-term corticosteroid therapy are the criterion standard treatments for patients with newly diagnosed moderate to severe pemphigus. Objective: To examine factors associated with short-term relapse in patients with pemphigus treated with rituximab. Design, Setting, and Participants: This post hoc analysis of a randomized clinical trial (Comparison Between Rituximab Treatment and Oral Corticosteroid Treatment in Patients With Pemphigus [RITUX 3]) conducted from January 1, 2010, to December 31, 2015, included patients from 20 dermatology departments of tertiary care centers in France from the RITUX 3 trial and 3 newly diagnosed patients treated according to the trial protocol. Data analysis was performed from February 1 to June 30, 2019. Exposure: Patients randomly assigned to the rituximab group in the RITUX 3 trial and the 3 additional patients were treated with 1000 mg of intravenous rituximab on days 0 and 14 and 500 mg at months 12 and 18 combined with a short-term prednisone regimen. Main Outcomes and Measures: Baseline (pretreatment) clinical and biological characteristics (Pemphigus Disease Area Index [PDAI] score, ranging from 0-250 points, with higher values indicating more severe disease) and changes in anti-desmoglein (DSG) 1 and anti-DSG3 values as measured by enzyme-linked immunosorbent assay during the 3 months after rituximab treatment were compared between patients with disease relapse and those who maintained clinical remission during the first 12 months after treatment. The positive and negative predictive values of these factors were calculated. Results: Among 47 patients (mean [SD] age, 54.3 [17.0] years; 17 [36%] male and 30 [64%] female) included in the study, the mean (SD) baseline PDAI score for patients with relapsing disease was higher than that of the patients with nonrelapsing disease (54 [33] vs 28 [24]; P = .03). At month 3, 7 of 11 patients with relapsing disease (64%) vs 7 of 36 patients with nonrelapsing disease (19%) had persistent anti-DSG1 antibody values of 20 IU/mL or higher and/or anti-DSG3 antibody values of 130 IU/mL or higher (P = .01). A PDAI score of 45 or higher defining severe pemphigus and/or persistent anti-DSG1 antibody values of 20 IU/mL or higher and/or anti-DSG3 antibody values of 130 IU/mL or higher at month 3 provided a positive predictive value of 50% (95% CI, 27%-73%) and a negative predictive value of 94% (95% CI, 73%-100%) for the occurrence of relapse after rituximab. Conclusions and Relevance: The findings suggest that initial PDAI score and changes in anti-DSG antibody values after the initial cycle of rituximab might help differentiate a subgroup of patients with high risk of relapse who might benefit from maintenance rituximab infusion at month 6 from a subgroup of patients with low risk of relapse who do not need early maintenance therapy. Trial Registration: NCT00784589.