Activating mutations in genes related to TCR signaling in angioimmunoblastic and other follicular helper T-cell-derived lymphomas.

Angioimmunoblastic T-cell lymphoma (AITL) and other lymphomas derived from follicular T-helper cells (TFH) represent a large proportion of peripheral T-cell lymphomas (PTCLs) with poorly understood pathogenesis and unfavorable treatment results. We investigated a series of 85 patients with AITL (n = 72) or other TFH-derived PTCL (n = 13) by targeted deep sequencing of a gene panel enriched in T-cell receptor (TCR) signaling elements. RHOA mutations were identified in 51 of 85 cases (60%) consisting of the highly recurrent dominant negative G17V variant in most cases and a novel K18N in 3 cases, the latter showing activating properties in in vitro assays. Moreover, half of the patients carried virtually mutually exclusive mutations in other TCR-related genes, most frequently in PLCG1 (14.1%), CD28 (9.4%, exclusively in AITL), PI3K elements (7%), CTNNB1 (6%), and GTF2I (6%). Using in vitro assays in transfected cells, we demonstrated that 9 of 10 PLCG1 and 3 of 3 CARD11 variants induced MALT1 protease activity and increased transcription from NFAT or NF-κB response element reporters, respectively. Collectively, the vast majority of variants in TCR-related genes could be classified as gain-of-function. Accordingly, the samples with mutations in TCR-related genes other than RHOA had transcriptomic profiles enriched in signatures reflecting higher T-cell activation. Although no correlation with presenting clinical features nor significant impact on survival was observed, the presence of TCR-related mutations correlated with early disease progression. Thus, targeting of TCR-related events may hold promise for the treatment of TFH-derived lymphomas

By-pass gastrique de révision : une opportunité chirurgicale sûre ? : résultats d'une étude cas-témoins

Objectives: to evaluate the safety and efficacy of revisional RYGB after AGB or SG compared with primary RYGB, in regards to early and late morbidity, weight, and resolution of obesity related comorbidities. Methods: the group of patients undergoing revisional RYGB was matched in a 1:1 ratio with control patient who underwent a primary RYGB, based on age, gender, ASA score, preoperative body mass index (BMI), and diabetes mellitus. Demographics, anthropometrics, pre-operative work-up and perioperative data were retrieved. Results: 115 patients (16 males and 99 females) with a mean age of 45.5 +/- 1.5 years underwent revisional RYBG following either LAGB in 82 patients (71.3%) or LSG in 33 patients (28.7%). There was no conversion and no mortality in either group. Revisional RYBG was associated with similar early (16.5 v 15.6%, ns) and late (42.6% vs 32.2%, ns) morbidity rates with a mean follow-up of 25.3 +/- 16.6 months compared to primary LRYGB. Revisional RYGB group had significantly less weight loss (mean %EWL 67.4 +/- 20.7 vs 72.7 +/- 22.9, p=0.023; and mean %EBMI 68.1 +/- 22 vs 78.3 +/- 25.7; p = 0.01) at the time of at one year. Improvement of comorbidities including hypertension (62.5 vs 70.5%; p>0.05), diabetes (73.7 vs 79%; p>0.05), and OSAS (100 vs 97%; p>0.05) was similar. Conclusion: this large case-matched study suggests that conversion of SG or AGB to RYGB is feasible with early and late comparable morbidity in accredited center, even weight results might be inferior.Objectifs : évaluer l’efficacité et la sécurité des by-pass gastriques de révision (BPGR) après anneau gastrique ajustable (AGA) ou sleeve gastrectomy (SG) comparés aux by-pass gastriques de première intention (BPGP), en s’intéressant aux morbidités précoces et tardives, le poids, la résolution des comorbidités liées à l’obésité. Méthodes : le groupe de by-pass de révision a été apparié à un ratio de 1 :1 avec un groupe contrôle à qui il a été réalisé un bypass gastrique en première intention. Les critères d’appariement étaient l’âge, le sexe, le score ASA, l’IMC préopératoire et le diabète. Les données démographiques, anthropométriques, pré-opératoires et péri opératoires ont été enregistrées. Résultats : 115 patients (16 hommes et 99 femmes) d’âge moyen de 45.5 +/- 1.5 ans ont eu un by-pass gastrique après soit un AGA pour 82 patients (71.3%) soit une SG pour 33 patients (28.7%). Il n’y avait aucune conversion ni mortalité dans les deux groupes. BPGR et BPGP présentaient les mêmes taux de morbidité précoce et tardive, respectivement (16.5 vs 15.6%, ns) et (42.6 vs 32.2%, ns) avec un suivi moyen de 25.3 +/- 16.6 mois. A un an, le groupe BPGR avait une perte d’excès de poids (PEP) significativement moins importante que BPGP (%PEP 67.4 +/- 20.7 vs 72.7 +/- 22.9%, p= 0.023) ; de même pour la perte d’excès d’IMC (PEIMC) (%PEIMC 68.1 +/- 22 vs 78.3 +/- 25.7% ; p = 0.01). L’amélioration des comorbidités, incluant l’hypertension artérielle (62.5 vs 70.5% ; p>0.05), le diabète (73.7 vs 79% ; p>0.05), et le syndrome d’apnée du sommeil (100 vs 97% ; p>0.05) était similaire. Conclusion : cette étude cas témoin suggère que la conversion de SG ou AGA en by-pass gastrique par coelioscopie est faisable avec une morbidité précoce et tardive comparable aux BPG de première intention en centre référente. Cependant, l’efficacité sur le poids semble inférieure

Comparison of sleeve gastrectomy and Roux-en-Y gastric bypass after failure of gastric banding: a two-center study with a propensity score-matched analysis (August, 10.1007/s00464-020-07809-9, 2020)

International audienc

Comparison of sleeve gastrectomy and Roux-en-Y gastric bypass after failure of gastric banding: a two-center study with a propensity score-matched analysis

International audienceBackground Few studies on series comparing sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) after failure of gastric banding (GB) are available. The objective of this study was to compare the short- and medium-term outcomes of SG and RYGB after GB. Materials and methods Between January 2006 and December 2017, patients undergoing SG (n = 186) or RYGB (n = 107) for failure of primary GB were included in this two-center study. Propensity-score matching was performed based on preoperative factors with a 2:1 ratio. Primary endpoint was the weight loss at 2 years between the SG and RYGB groups. Secondary endpoints were overall mortality and morbidity, reoperation, correction of comorbidities and the rate of adverse events at 2 years follow-up. Results In our propensity score matching analysis, operative time was significantly less in the SG group (95 min vs. 179 min;p < 0.001). Post-operative complications were lower in the SG group (9.5% vs. 35.4%;p = 0.003). At 2 years follow-up, the mean EWL was similar as same as comorbidities. There was a significant difference in favor of SG concerning the rate of adverse events at 2 years follow-up (p < 0.001). Conclusion Revision of GB by SG or RYGB is feasible, with a higher rate of early post-operative complications for RYGB. Weight loss at 2 years follow-up is similar; however, RYGB appears to result in a higher rate of adverse events than SG

Revisional Roux-en-Y Gastric Bypass: a Safe Surgical Opportunity? Results of a Case-Matched Study

International audienceOBJECTIVE:To evaluate the safety and efficacy of revisional Roux-en-Y gastric bypass (RYGB) after adjustable gastric banding (AGB) or sleeve gastrectomy (SG) compared with primary RYGB, in regard to early and late morbidity, weight, and resolution of obesity-related comorbidities.METHODS:The group of patients undergoing revisional RYGB was matched in a 1:1 ratio with control patient who underwent a primary RYGB, based on age, gender, American Society of Anesthesiologist (ASA) score, preoperative body mass index (BMI), and diabetes mellitus. Demographics, anthropometrics, preoperative work-up, and perioperative data were retrieved.RESULTS:One hundred fifteen patients (16 males and 99 females) with a mean age of 45.5 ± 1.5 years underwent revisional RYGB following either LAGB in 82 patients (71.3%) or laparoscopic sleeve gastrectomy (LSG) in 33 patients (28.7%). There was no conversion and no mortality in either group. Revisional RYGB was associated with similar early (16.5 vs 15.6%, ns) and late (42.6% vs 32.2%, ns) morbidity rates with a mean follow-up of 25.3 ± 16.6 months compared to primary laparoscopic Roux-en-Y gastric bypass. The revisional RYGB group had significantly less weight loss (mean %EWL 67.4 ± 20.7 vs 72.7 ± 22.9, p = 0.023 and mean %EBMI 68.1 ± 22 vs 78.3 ± 25.7, p = 0.01) at the time of 1 year. Improvement of comorbidities including hypertension (62.5 vs 70.5%; p > 0.05), diabetes (73.7 vs 79%; p > 0.05), and obstructive sleep apnea syndrome (100 vs 97%; p > 0.05) was similar.CONCLUSION:This large case-matched study suggests that conversion of SG or AGB to RYGB is feasible with early and late comparable morbidity in an accredited center; even weight results might be inferior

Effect of Tocilizumab vs Usual Care in Adults Hospitalized With COVID-19 and Moderate or Severe Pneumonia

International audienceImportance Severe pneumonia with hyperinflammation and elevated interleukin-6 is a common presentation of coronavirus disease 2019 (COVID-19).Objective To determine whether tocilizumab (TCZ) improves outcomes of patients hospitalized with moderate-to-severe COVID-19 pneumonia.Design, Setting, and Particpants This cohort-embedded, investigator-initiated, multicenter, open-label, bayesian randomized clinical trial investigating patients with COVID-19 and moderate or severe pneumonia requiring at least 3 L/min of oxygen but without ventilation or admission to the intensive care unit was conducted between March 31, 2020, to April 18, 2020, with follow-up through 28 days. Patients were recruited from 9 university hospitals in France. Analyses were performed on an intention-to-treat basis with no correction for multiplicity for secondary outcomes.Interventions Patients were randomly assigned to receive TCZ, 8 mg/kg, intravenously plus usual care on day 1 and on day 3 if clinically indicated (TCZ group) or to receive usual care alone (UC group). Usual care included antibiotic agents, antiviral agents, corticosteroids, vasopressor support, and anticoagulants.Main Outcomes and Measures Primary outcomes were scores higher than 5 on the World Health Organization 10-point Clinical Progression Scale (WHO-CPS) on day 4 and survival without need of ventilation (including noninvasive ventilation) at day 14. Secondary outcomes were clinical status assessed with the WHO-CPS scores at day 7 and day 14, overall survival, time to discharge, time to oxygen supply independency, biological factors such as C-reactive protein level, and adverse events.Results Of 131 patients, 64 patients were randomly assigned to the TCZ group and 67 to UC group; 1 patient in the TCZ group withdrew consent and was not included in the analysis. Of the 130 patients, 42 were women (32%), and median (interquartile range) age was 64 (57.1-74.3) years. In the TCZ group, 12 patients had a WHO-CPS score greater than 5 at day 4 vs 19 in the UC group (median posterior absolute risk difference [ARD] −9.0%; 90% credible interval [CrI], −21.0 to 3.1), with a posterior probability of negative ARD of 89.0% not achieving the 95% predefined efficacy threshold. At day 14, 12% (95% CI −28% to 4%) fewer patients needed noninvasive ventilation (NIV) or mechanical ventilation (MV) or died in the TCZ group than in the UC group (24% vs 36%, median posterior hazard ratio [HR] 0.58; 90% CrI, 0.33-1.00), with a posterior probability of HR less than 1 of 95.0%, achieving the predefined efficacy threshold. The HR for MV or death was 0.58 (90% CrI, 0.30 to 1.09). At day 28, 7 patients had died in the TCZ group and 8 in the UC group (adjusted HR, 0.92; 95% CI 0.33-2.53). Serious adverse events occurred in 20 (32%) patients in the TCZ group and 29 (43%) in the UC group (P = .21).Conclusions and Relevance In this randomized clinical trial of patients with COVID-19 and pneumonia requiring oxygen support but not admitted to the intensive care unit, TCZ did not reduce WHO-CPS scores lower than 5 at day 4 but might have reduced the risk of NIV, MV, or death by day 14. No difference on day 28 mortality was found. Further studies are necessary for confirming these preliminary results.Trial Registration ClinicalTrials.gov Identifier: NCT0433180