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Single center studies using serial cerebral diffusion-weighted magnetic resonance imaging in patients having cardiac catheterization have suggested that cerebral microembolism might be responsible for silent cerebral infarct (SCI) as high as 15% to 22%. We evaluated in a multicenter trial the incidence of SCIs after cardiac catheterization and whether or not the choice of the arterial access site might impact this phenomenon. Patients were randomized to have cardiac catheterization either by Radial (n = 83) or Femoral (n = 77) arterial approaches by experimented operators. The main outcome measure was the occurrence of new cerebral infarct on serial diffusion-weighted magnetic resonance imaging. Patient and catheterization characteristics, including duration of catheterization, were similar in both groups. The risk of SCI did not differ significantly between the Femoral and Radial groups (incidence of 11.7% versus 17.5%; OR, 0.85; 95% CI, 0.62-1.16; P = .31). At multivariable analysis, the independent predictors of SCI were the patient's higher height and lower transvalvular gradient. The high rate of SCI after cardiac catheterization of patients with aortic stenosis was confirmed, but its occurrence was not affected by the selection of Radial and Femoral access.

Although rotational atherectomy (RA) and intravascular lithotripsy (IVL) have been proved to be effective for calcified de novo coronary lesions, their use in patients with in-stent restenosis (ISR) is still controversial. No comparison of these techniques in patients with ISR has been published so far. We sought to evaluate safety and feasibility of RA and IVL in patients with calcified ISR. Furthermore, we aimed to compare in-hospital and 1-year clinical outcomes between both groups. This is a retrospective single-center study evaluating patients with calcified ISR treated with RA (between 2012 and 2021) and IVL (between 2019 and 2021). Inhospital and 1-year clinical outcomes were compared between IVL and RA patients. In total, 28 patients with ISR who underwent RA were compared with 24 ISR subjects after IVL. The procedural success rate was 100% in both the groups. Quantitative coronary analysis demonstrated a similar degree of stenosis prior (66.4 ± 11.4 vs 68.8 ± 19.7, p = nonsignificant [NS]), and after the procedure (21.5 ± 20.5 vs 22.8 ± 12.1, p = NS) with no difference in acute luminal gain (1.34 ± 0.60 vs 1.38 ± 0.59, p = NS). There was one in-hospital major adverse cardiovascular event in the RA group. At 1-year follow-up, no difference was observed with respect to major adverse cardiovascular event rate (14.3% vs 16.7%, p = NS) and target vessel revascularization (7.1% vs 12.5%, p = NS). In conclusion, RA and IVL are safe and feasible techniques for calcified ISR yielding comparable results at 1-year follow-up. Further clinical studies are warranted to confirm our findings and shed more light on patient and lesion characteristics associated with the best outcomes.

Thrombus aspiration devices have been shown to improve reperfusion criteria and to reduce distal embolization in patients treated by percutaneous coronary interventions (PCI) in the acute phase of ST-elevation myocardial infarction (STEMI). There are, however, little data about their efficacy in the reduction of infarct size. We sought to assess in a prospective randomized trial the impact of thrombus aspiration on infarct size and severity and on left ventricular function in high-risk patients with a first STEMI. The primary end point was scintigraphic infarct size, and secondary end points were infarct severity and regional and global left ventricular function. Forty-four patients with completely occluded (Thrombolysis in Myocardial Infarction flow 0-1) proximal segments of infarct-related artery were randomly assigned to thrombus aspiration group with the Export catheter (n = 20) (Medtronic, Inc, Minneapolis, MN) or PCI-only group. A rest Tc-99-mibi gated single-photon emission computed tomographic and contrast-enhanced magnetic resonance imaging were performed 6 ± 2 days later. Infarct size was comparable in patients in the thrombus aspiration group and PCI-only group (30.6% ± 15.8% vs 28.5% ± 17.9% of the left ventricle, P = .7) as was infarct severity in infarct-related artery territory (55% ± 12% vs 55% ± 14%, P = .9). Transmurality score as assessed by magnetic resonance imaging was similar in both groups (2.03 ± 1.05 vs 2.16 ± 1.21, P = .7). There was no impact of thrombus aspiration on other secondary end points. In our study, thrombus aspiration with the Export catheter performed as adjunctive therapy in high-risk patients with total occlusion of the proximal part of major coronary arteries does not decrease infarct size or severity and has no effect on left ventricular regional and global function.

Bioprosthetic thromboses are rarely reported in post-transcatheter aortic valve implantation (TAVI). We describe herein the case of bioprosthetic valve thrombosis in an 82-year-old patient which resolved completely after anticoagulant therapy.

Background Left ventricular (LV) remodeling after myocardial infarction (MI) occurs frequently despite successful percutaneaous coronary intervention (PCI) but cannot be predicted by simple clinical parameters. Methods and Results This prospective study tested the value of rest and low-dose dobutamine (LDD) Tc-99m-mibi gated-SPECT for early prediction of LV remodeling in patients treated by PCI in the acute phase of a first MI. Infarct size, infarct severity, regional wall motion abnormality (RWMA), and wall thickening score (WTs) were assessed at rest and on LDD by SPECT 6 ± 2 days after MI in 40 patients. LV remodeling was defined as 20% increase at 6 months in LV end-diastolic volume assessed by MRI. Infarct severity at rest showed the best predictive values for left remodeling (PPV: 86%, NPV: 88%, accuracy: 88%; AUC: 0.750). Functional parameters at neither rest nor LDD study further improved predictive values of the SPECT imaging. Conclusions Infarct severity assessed by Tc-99m-sestamibi gated-SPECT performed in the subacute phase of a first STEMI predicts LV remodeling with high accuracy without incremental value nor of functional parameters nor of LDD. Therefore, our results suggest that LDD should not be used in this setting.

The purpose of this study was to assess the value of technetium 99m sestamibi gated single photon emission computed tomography (SPECT) in predicting the evolution of left ventricular volumes in patients treated successfully in the acute phase of a myocardial infarction (MI). Twenty-nine patients with acute MI and early percutaneous transluminal coronary angioplasty (PTCA) were included in this study. A rest Tc-99m sestamibi electrocardiography (ECG)-gated SPECT study was performed 21 ± 5 days after PTCA. The myocardial perfusion index was calculated by use of a semiautomatic sectorial analysis. All patients had contrast ventriculography performed during the acute phase and 6 months later. The patients were separated into two groups according to the absence (group I, n = 21) or presence (group II, n = 8) of end-systolic enlargement. The perfusion index in the infarct sectors was −2.29 ± 2.90 SD in group I and −6.40 ± 2.85 SD in group II ( P < .01). With a cutoff value of −2.46 SD, the sensitivity and specificity of Tc-99m sestamibi SPECT for the prediction of end-systolic volume enlargement were 100% and 62%, respectively. When the functional data from ECG-gated acquisitions were added, specificity increased to 86%. Despite successful PTCA in the acute phase of MI, an increase in end-systolic volume was observed at 6 months in 28% of patients. Tc-99m sestamibi ECG-gated SPECT performed 3 weeks after the acute phase could predict this enlargement with a high accuracy.

BackgroundEosinophilic granulomatosis with polyangiitis (EGPA) is often associated with glucocorticoid-dependent asthma and/or ear, nose and throat (ENT) manifestations. When immunosuppressants and/or mepolizumab are ineffective, dupilumab could be an option. We describe the safety and efficacy of off-label use of dupilumab in relapsing and/or refractory EGPA.Patients and methodsWe conducted an observational multicentre study of EGPA patients treated with dupilumab. Complete response was defined by Birmingham Vasculitis Activity Score (BVAS)=0 and prednisone dose ≤4 mg/day, and partial response by BVAS=0 and prednisone dose >4 mg/day. Eosinophilia was defined as an eosinophil count >500/mm3.ResultsFifty-one patients were included. The primary indication for dupilumab was disabling ENT symptoms in 92%. After a median follow-up of 13.1 months, 18 patients (35%) reported adverse events (AEs), including two serious AEs. Eosinophilia was reported in 34 patients (67%), with a peak of 2195/mm3 (IQR 1268–4501) occurring at 13 weeks (IQR 4–36) and was associated with relapse in 41%. Twenty-one patients (41%) achieved a complete response and 12 (24%) a partial response. Sixteen (31%) patients experienced an EGPA relapse while on dupilumab, which was associated with blood eosinophilia in 14/16 (88%) patients. The median eosinophil count at the start of dupilumab was significantly lower in relapsers than in non-relapsers, as was the median time between stopping anti-IL-5/IL-5R and switching to dupilumab.ConclusionThese results suggest that dupilumab may be effective in treating patients with EGPA-related ENT manifestations. However, EGPA flares occurred in one-third of patients and were preceded by eosinophilia in 88%, suggesting that caution is required.

BackgroundBenralizumab is effective in the treatment of eosinophilic asthma and is being investigated for the treatment of other eosinophil-associated diseases. Reports on the use of benralizumab for the treatment of eosinophilic granulomatosis with polyangiitis (EGPA) are limited to case reports and small case series.MethodsWe conducted a multicentre, retrospective study including EGPA patients treated with off-label benralizumab. The primary endpoint was the rate of complete response defined as no disease activity (Birmingham Vasculitis Activity Score=0) and a prednisone dose ≤4 mg/day. Partial response was defined as no disease activity and a prednisone dose ≥4 mg/day.ResultsSixty-eight patients were included, including 31 (46%) who had previously received mepolizumab. The use of benralizumab was warranted by uncontrolled asthma in 54 (81%), persistent ear, nose and throat (ENT) manifestations in 27 (40%) and persistent glucocorticoids (GCs) use in 48 (74%) patients. Median (IQR) follow-up after starting benralizumab was 23 (9–34) months. Thirty-three patients (49%) achieved a complete response, 24 (36%) achieved a partial response and 10 (15%) did not respond. Among the 57 patients who initially responded, 10 (18%) eventually required further line treatments. GCs were discontinued in 23 patients (38%). Prior mepolizumab use was associated with a higher rate of primary failure (26.7% vs 5.4%, p=0.034) and less frequent GCs discontinuation (14.8% vs 55.9%, p=0.001). Vasculitis flares occurred in 7 patients (11%) and were associated with histological evidence of vasculitis and/or antineutrophil cytoplasmic antibodies positivity at benralizumab initiation (p=0.004).ConclusionsBenralizumab appears to be an effective treatment for refractory asthma or ENT manifestations in EGPA and allows GC-sparing. However, its efficacy was lower after prior failure of mepolizumab.

Background:The treatment and prognosis of cryoglobulinemia vasculitis (CryoVas) depend on etiology. Rituximab (RTX) and corticosteroids (CS) are the first line treatment for mixed essential (ME) CryoVas and connective tissue disease (CTD)-related CryoVas. The prognosis and long term outcomes of these forms of CryoVas are as yet unknown.Objectives:The aim of this study was therefore to describe the risk of relapse and treatment-related morbidities in patients with ME and CTD-related CryoVas.Methods:A retrospective study was conducted of 63 patients in remission of ME or CDT-related CryoVas after RTX-CS therapy, with a median follow-up time of 58 months (interquartile range, 33–88 months).Results:Thirty-nine out of 63 patients (62%) had a relapse a median of 42 (23–65) months after the initial flare. The relapse incidence was 38% at 2 years and 46% at 3 years. The factors associated with relapse were purpura at the time of the qualifying flare (HR, 2.2; 95% confidence interval (CI), 1.1–4.4; p = 0.002) and prior history of CryoVas flares (HR, 1.9; 95% CI, 1.0–3.7; p = 0.04). Maintenance therapy was associated with a lower risk of relapse 6–24 months after the initial flare (HR, 0.27; 95% CI, 0.09–0.78; p = 0.02), but not thereafter (HR, 2.0; 95% CI, 0.7–5.7; p = 0.21). The most common form of maintenance therapy was 500 mg RTX every 6 months. The most frequent complication was infection, and maintenance RTX therapy was associated with a higher risk of severe infection (HR, 2,2; 95% CI, 0.9–5,6; p = 0.08).Conclusion:In this group of patients in RTX-CS remission of ME and CTD-related CryoVas, relapses were common and the risk of relapse was significantly associated with purpura during the qualifying flare and a prior history of relapse. Maintenance RTX was associated with a lower risk of relapse but was also associated with an increased risk of severe infection.REFERENCES:[1] Saadoun D, Sellam J, Ghillani-Dalbin P, Crecel R, Piette JC, Cacoub P. Increased Risks of Lymphoma and Death Among Patients With Non–Hepatitis C Virus–Related Mixed Cryoglobulinemia. Arch Intern Med. 2006 Oct 23;166(19):2101–8.[2] Cacoub P, Comarmond C, Domont F, Savey L, Saadoun D. Cryoglobulinemia Vasculitis. Am J Med. 2015 Sep 1;128(9):950–5.[3] Terrier B, Krastinova E, Marie I, Launay D, Lacraz A, Belenotti P, et al. Management of noninfectious mixed cryoglobulinemia vasculitis: data from 242 cases included in the CryoVas survey. Blood. 2012 Jun 21;119(25):5996–6004.[4] Terrier B, Carrat F, Krastinova E, Marie I, Launay D, Lacraz A, et al. Prognostic factors of survival in patients with non-infectious mixed cryoglobulinaemia vasculitis: data from 242 cases included in the CryoVas survey. Ann Rheum Dis. 2013 Mar 1;72(3):374–80.[5] Quartuccio L, Bortoluzzi A, Scirè CA, Marangoni A, Del Frate G, Treppo E, et al. Management of mixed cryoglobulinemia with rituximab: evidence and consensus-based recommendations from the Italian Study Group of Cryoglobulinemia (GISC). Clin Rheumatol. 2023 Feb 1;42(2):359–70.[6] Terrier B, Marie I, Launay D, Lacraz A, Belenotti P, de Saint-Martin L, et al. Predictors of early relapse in patients with non-infectious mixed cryoglobulinemia vasculitis: Results from the French nationwide CryoVas survey. Autoimmun Rev. 2014 Jun 1;13(6):630–4.[7] Foessel L, Besancenot JF, Blaison G, Magy-Bertrand N, Jaussaud R, Etienne Y, et al. Clinical Spectrum, Treatment, and Outcome of Patients with Type II Mixed Cryoglobulinemia without Evidence of Hepatitis C Infection. J Rheumatol. 2011 Apr 1;38(4):716–22.[8] Visentini M, Tinelli C, Colantuono S, Monti M, Ludovisi S, Gragnani L, et al. Efficacy of low-dose rituximab for the treatment of mixed cryoglobulinemia vasculitis: Phase II clinical trial and systematic review. Autoimmun Rev. 2015 Oct;14(10):889–96.[9] Colantuono S, Mitrevski M, Yang B, Tola J, Carlesimo M, De Sanctis GM, et al. Efficacy and safety of long-term treatment with low-dose rituximab for relapsing mixed cryoglobulinemia vasculitis. Clin Rheumatol. 2017 Mar 1;36(3):617–23.Acknowledgements:NIL.Disclosure of Interests:Claire POGGI: None declared, Eric Hachulla BOEHRINGER INGELHEIM, GSK, SANOFI,, JANSSEN-CILAG, Bayer HealthCare SAS, GSK, BRISTOL MYERS SQUIBB, IQVIA Operations France, United Therapeutics Corporation, NOVARTIS PHARMA SAS, CHUGAI PHARMA FRANCE, ASTRAZENECA, MSD, JANSSEN-CILAG, Bayer HealthCare SAS, GSK, BRISTOL MYERS SQUIBB,, GENZYME, SANOFI, RE-IMAGINE Health Agency, Otsuka Pharmaceutical France SAS, AXONAL, PFIZER SAS, LIVE! BY GL EVENTS, SHIRE France S.A., Cemka, ROCHE SAS, Galapagos SASU, PATIENTYS, Alexandre Karras Alnylam France SAS, BOEHRINGER INGELHEIM FRANCE, NOVARTIS PHARMA SAS, ASTRAZENECA, Otsuka Pharmaceutical France SAS, LABORATOIRE GLAXOSMITHKLINE, PFIZER SAS, Vertex Pharmaceuticals Incorporated, TRAVERE THERAPEUTICS, INC., Retrophin, Inc, Antoine BRIANTAIS BOEHRINGER INGELHEIM FRANCE,, ROCHE SAS, LABORATOIRE GLAXOSMITHKLINE, Genzyme, Camille Ravaiau: None declared, Pierre GOBERT Alexion Pharma France, MENARINI FRANCE, SANOFI AVENTIS FRANCE, Alban Deroux VIFOR FRANCE, EUSA Pharma (France) SAS, BOEHRINGER INGELHEIM FRANCE, LABORATOIRE GLAXOSMITHKLINE, SANOFI AVENTIS FRANCE, EXELTIS SANTE, Celltrion Healthcare France SAS, SWEDISH ORPHAN BIOVITRUM, Sarah Nicolas HD MEDICAL, MSD FRANCE, Hélène François SANOFI AVENTIS FRANCE,, Matthieu Groh SANOFI AVENTIS FRANCE, LABORATOIRE GLAXOSMITHKLINE, ASTRAZENECA, CSL BEHRING SA, CHUGAI PHARMA FRANCE, BRISTOL-MYERS SQUIBB, Jonathan London AMICUS THERAPEUTICS SAS, CORIN FRANCE, AMICUS THERAPEUTICS SAS, CORIN FRANCE, JANSSEN-CILAG, AbbVie, Julien Campagne SHIRE France S.A., SANOFI AVENTIS FRANCE,, BOEHRINGER INGELHEIM FRANCE,, VIFOR FRANCE SA, SANDOZ, Alnylam France SAS, AMGEN, Jean-Sébastien Allain LEO Pharma, LABORATOIRE GLAXOSMITHKLINE, Emmanuelle Dernis BRISTOL-MYERS SQUIBB, LILLY FRANCE, MSD France, JANSSEN-CILAG, Galapagos SASU, AbbVie, NORDIC PHARMA SAS, UCB Pharma SA, CHUGAI PHARMA FRANCE, FRESENIUS KABI FRANCE, MSD France, BRISTOL-MYERS SQUIBB,, NOVARTIS PHARMA SAS, AMGEN SAS, MEDAC SAS, RE-IMAGINE Health Agency, Cécile-Audrey Durel VIFOR FRANCE, NOVARTIS PHARMA SAS, Genzyme, NOVARTIS PHARMA SAS, Genzyme, Takeda France, SHIRE France S.A., BOEHRINGER INGELHEIM FRANCE, Thomas Le Gallou NOVARTIS PHARMA SAS, LABORATOIRE GLAXOSMITHKLINE, Alexandre Curie PFIZER SAS, LABORATOIRE GLAXOSMITHKLINE, SHIRE France S.A., Philippe Kerschen: None declared, Noémie Gensous Alnylam France SAS, SWEDISH ORPHAN BIOVITRUM, NOVARTIS PHARMA SAS, AMGEN SAS, ASTRAZENECA, AMGEN SAS, Anne-Hélène Reboux: None declared, Hélène Béhal: None declared, Benjamin Terrier VIFOR, ASTRAZENECA, GSK, ASTRAZENECA, LFB BIOMEDICAMENTS, BRISTOL-MYERS SQUIBB, PFIZER SAS, Lilly France SAS, GRIFOLS France, Oséus, Terumo BCT Europe SA, SANOFI-AVENTIS RECHERCHE & DEVELOPPEMENT, BOEHRINGER INGELHEIM FRANCE, FRESENIUS KABI FRANCE, SWEDISH ORPHAN BIOVITRUM, BRISTOL-MYERS SQUIBB, NOVARTIS PHARMA SAS, ROCHE SUISSE, JANSSEN-CILAG, MSD France, RE-IMAGINE Health Agency, LFB BIOMEDICAMENTS, Thomas Quéméneur VIFOR, LEO Pharma, ASTRAZENECA, VIFOR, OVERCOME,, VIFOR, SANOFI, GENZYME, GSK.

In pathogens, introgressions through secondary contacts between divergent populations from agricultural and nonagricultural disease reservoirs are expected to have crucial evolutionary and epidemiological implications. Despite the importance of this question for disease management, experimental demonstrations of these implications remain scarce. Recently, we identified a virulent population of the apple scab pathogen Venturia inaequalis that migrated from nonagricultural hosts to European domestic apple orchards. Here, we investigated the occurrence of gene flow between agricultural and nonagricultural populations sampled in two orchards, and thereafter its consequences on the pathogenicity of hybrids. Population genetic structure and demographic inferences based on the genotypes of 104 strains revealed a high amount of gene flow between the two populations in one orchard. In this site, mating between populations was made possible by the presence of a common host. Our results revealed an invasion of the virulent trait in the agricultural population; a main direction of introgression in hybrids from the agricultural to nonagricultural genetic backgrounds; and a population of hybrids with transgressive traits. We demonstrate a secondary contact with gene flow between divergent populations of pathogens. Our findings highlight evolutionary and epidemiological changes in pathogens and have concrete implications for sustainable disease management.