Three-dimensional cardiac magnetic resonance allows the identification of slow-conducting anatomical isthmuses in tetralogy of Fallot.

BACKGROUND AND AIMS: Patients with repaired tetralogy of Fallot remain at risk of life-threatening ventricular tachycardia related to slow-conducting anatomical isthmuses (SCAIs). Preventive ablation of SCAI identified by invasive electroanatomical mapping is increasingly performed. This study aimed to non-invasively identify SCAI using 3D late gadolinium enhancement cardiac magnetic resonance (3D-LGE-CMR). METHODS: Consecutive tetralogy of Fallot patients who underwent right ventricular electroanatomical mapping (RV-EAM) and 3D-LGE-CMR were included. High signal intensity threshold for abnormal myocardium was determined based on direct comparison of bipolar voltages and signal intensity by co-registration of RV-EAM with 3D-LGE-CMR. The diagnostic performance of 3D-LGE-CMR to non-invasively identify SCAI was determined, validated in a second cohort, and compared with the discriminative ability of proposed risk scores. RESULTS: The derivation cohort consisted of 48 (34 ± 16 years) and the validation cohort of 53 patients (36 ± 18 years). In the derivation cohort, 78 of 107 anatomical isthmuses (AIs) identified by EAM were normal-conducting AI, 22 were SCAI, and 7 blocked AI. High signal intensity threshold was 42% of the maximal signal intensity. The sensitivity and specificity of 3D-LGE-CMR for identifying SCAI or blocked AI were 100% and 90%, respectively. In the validation cohort, 85 of 124 AIs were normal-conducting AI, 36 were SCAI, and 3 blocked AI. The sensitivity and specificity of 3D-LGE-CMR were 95% and 91%, respectively. All risk scores showed an at best modest performance to identify SCAI (area under the curve ≤ .68). CONCLUSIONS: 3D late gadolinium enhancement cardiac magnetic resonance can identify SCAI with excellent accuracy and may refine non-invasive risk stratification and patient selection for invasive EAM in tetralogy of Fallot.

Early hybrid cardiac rehabilitation in congenital heart disease: the QUALIREHAB trial.

BACKGROUND AND AIMS: Cardiopulmonary fitness in congenital heart disease (CHD) decreases faster than in the general population resulting in impaired health-related quality of life (HRQoL). As the standard of care seems insufficient to encourage and maintain fitness, an early hybrid cardiac rehabilitation programme could improve HRQoL in CHD. METHODS: The QUALIREHAB multicentre, randomized, controlled trial evaluated and implemented a 12-week centre- and home-based hybrid cardiac rehabilitation programme, including multidisciplinary care and physical activity sessions. Adolescent and young adult CHD patients with impaired cardiopulmonary fitness were randomly assigned to either the intervention (i.e. cardiac rehabilitation) or the standard of care. The primary outcome was the change in HRQoL from baseline to 12-month follow-up in an intention-to-treat analysis. The secondary outcomes were the change in cardiovascular parameters, cardiopulmonary fitness, and mental health. RESULTS: The expected number of 142 patients was enroled in the study (mean age 17.4 ± 3.4 years, 52% female). Patients assigned to the intervention had a significant positive change in HRQoL total score [mean difference 3.8; 95% confidence interval (CI) 0.2; 7.3; P = .038; effect size 0.34], body mass index [mean difference -0.7 kg/m2 (95% CI -1.3; -0.1); P = .022; effect size 0.41], level of physical activity [mean difference 2.5 (95% CI 0.1; 5); P = .044; effect size 0.39], and disease knowledge [mean difference 2.7 (95% CI 0.8; 4.6); P = .007; effect size 0.51]. The per-protocol analysis confirmed these results with a higher magnitude of differences. Acceptability, safety, and short-time effect of the intervention were good to excellent. CONCLUSIONS: This early hybrid cardiac rehabilitation programme improved HRQoL, body mass index, physical activity, and disease knowledge, in youth with CHD, opening up the possibility for the QUALIREHAB programme to be rolled out to the adult population of CHD and non-congenital cardiac disease.

Amulet or Watchman Device for Percutaneous Left Atrial Appendage Closure: Primary Results of the SWISS-APERO Randomized Clinical Trial.

BACKGROUND: No study has so far compared Amulet with the new Watchman FLX in terms of residual left atrial appendage (LAA) patency or clinical outcomes in patients undergoing percutaneous LAA closure. METHODS: In the investigator-initiated SWISS APERO trial (Comparison of Amulet Versus Watchman/FLX Device in Patients Undergoing Left Atrial Appendage Closure), patients undergoing LAA closure were randomly assigned (1:1) open label to receive Amulet or Watchman 2.5 or FLX (Watchman) across 8 European centers. The primary end point was the composite of justified crossover to a nonrandomized device during LAA closure procedure or residual LAA patency detected by cardiac computed tomography angiography (CCTA) at 45 days. The secondary end points included procedural complications, device-related thrombus, peridevice leak at transesophageal echocardiography, and clinical outcomes at 45 days. RESULTS: Between June 2018 and May 2021, 221 patients were randomly assigned to Amulet (111 [50.2%]) or Watchman (110 [49.8%]), of whom 25 (22.7%) patients included before October 2019 received Watchman 2.5, and 85 (77.3%) patients received Watchman FLX. The primary end point was assessable in 205 (92.8%) patients and occurred in 71 (67.6%) patients receiving Amulet and 70 (70.0%) patients receiving Watchman, respectively (risk ratio, 0.97 [95% CI, 0.80-1.16]; P=0.713). A single justified crossover occurred in a patient with Amulet who fulfilled LAA patency criteria at 45-day CCTA. Major procedure-related complications occurred more frequently in the Amulet group (9.0% versus 2.7%; P=0.047) because of more frequent bleeding (7.2% versus 1.8%). At 45 days, the peridevice leak rate at transesophageal echocardiography was higher with Watchman than with Amulet (27.5% versus 13.7%, P=0.020), albeit none was major (ie, >5 mm), whereas device-related thrombus was detected in 1 (0.9%) patient with Amulet and 3 (3.0%) patients with Watchman at CCTA and in 2 (2.1%) and 5 (5.5%) patients at transesophageal echocardiography, respectively. Clinical outcomes at 45 days did not differ between the groups. CONCLUSIONS: Amulet was not associated with a lower rate of the composite of crossover or residual LAA patency compared with Watchman at 45-day CCTA. Amulet, however, was associated with lower peridevice leak rates at transesophageal echocardiography, higher procedural complications, and similar clinical outcomes at 45 days compared with Watchman. The clinical relevance of CCTA-detected LAA patency requires further investigation. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03399851.

Clinical Implications of CT-detected Hypoattenuation Thickening on Left Atrial Appendage Occlusion Devices.

Background At follow-up CT after left atrial appendage occlusion (LAAO), hypoattenuation thickening (HAT) on the atrial aspect of the device is a common finding but the clinical implications require further study. Purpose To assess the association of HAT grade at follow-up CT with clinical characteristics and outcomes in patients who underwent LAAO. Materials and Methods This prospective study included consecutive participants with atrial fibrillation and who were at high risk for stroke (CHA2DS2-VASc score ≥4) who underwent LAAO and were administered pacifier or nonpacifier devices at two French medical centers between January 2012 and November 2020. Postprocedure CT images were evaluated by two radiologists in consensus and device-specific interpretation algorithms were applied to classify HAT as low grade (low suspicion of thrombosis) or high grade (high suspicion of thrombosis). The association between HAT grade and clinical characteristics was assessed using multinomial logistic regression, and variables associated with risk of stroke were assessed using a Cox proportional hazard model. Results This study included 412 participants (mean age, 76 years ± 8 [SD]; 284 male participants) who underwent follow-up CT at a mean of 4.2 months ± 1.7 after LAAO. Low-grade and high-grade HAT were depicted in 98 of 412 (23.8%) and 21 of 412 (5.1%) participants, respectively. High-grade HAT was associated with higher odds of antithrombotic drug discontinuation during follow-up (odds ratio, 9.5; 95% CI: 3.1, 29.1; P < .001), whereas low-grade HAT was associated with lower odds of persisting left atrial appendage patency (odds ratio, 0.46; 95% CI: 0.27, 0.79; P = .005). During a median follow-up of 17 months (IQR, 11-41 months), stroke occurred in 24 of 412 (5.8%) participants. High-grade HAT was associated with stroke (hazard ratio, 4.6; 95% CI: 1.5, 14.0; P = .008) and low-grade HAT (P = .62) was not. Conclusion Low-grade HAT was a more common finding at CT performed after LAAO CT (24%) than was high-grade HAT (5%), but it was associated with more favorable outcomes than high-grade HAT, which was associated with higher stroke risk. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Choe in this issue.

Effect of sulfadoxine-pyrimethamine chemoprophylaxis in pregnant women on selection of the new P. falciparum dhps quintuple mutant carrying the I431V mutation.

BACKGROUND: A new mutation in the Plasmodium falciparum dihydropteroate synthetase gene (pfdhps), I431V, has been identified in several countries of Central and West Africa. This mutation is mostly found in association with four other SNPs on pfdhps (S436A, A437G, A581G and A613S), forming a quintuple mutant (vagKgs) and almost always associated with the Plasmodium falciparum dihydrofolate reductase gene (pfdhfr) CirnI (C50R, N51I, S108N) triple mutant. To date, nothing is known about the impact of this new pfdhps genotype on sulfadoxine-pyrimethamine (SP) resistance. OBJECTIVES: We sought to assess the prevalence of this pfdhps vagKgs quintuple mutant in two groups of pregnant women with malaria, one that took intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) and one that did not. METHODS: The pfdhfr and pfdhps genes from Plasmodium falciparum isolates collected in Yaoundé (Cameroon) from pregnant women with symptomatic malaria under IPTp-SP or not, were sequenced. RESULTS: Of 159 patients evaluated, 70 had already taken SP during pregnancy and 89 had never taken SP. Only the vagKgs allele was significantly overrepresented in the SP+ group (21.4% versus 3.4%; P < 0.001), whereas the ISgKAA mutant, widely distributed in this area and known to be less susceptible to SP, tended to be less abundant in this group (48.6% versus 64.0%; P = 0.0503). CONCLUSIONS: We found a strong overrepresentation of the CirnI/vagKgs haplotype in the IPTp-SP pregnant group, suggesting a high level of resistance of this mutant to SP. This could compromise not only the effectiveness of IPTp-SP but also the seasonal malaria chemoprevention of young children, now widely implemented.

Electrophysiological study prior to planned pulmonary valve replacement in patients with repaired tetralogy of Fallot.

AIM: Ventricular arrhythmias (VAs) are the most common cause of death in patients with repaired Tetralogy of Fallot (rTOF). However, risk stratifying remains challenging. We examined outcomes following programmed ventricular stimulation (PVS) with or without subsequent ablation in patients with rTOF planned for pulmonary valve replacement (PVR). METHODS: We included all consecutive patients with rTOF referred to our institution from 2010 to 2018 aged ≥18 years for PVR. Right ventricular (RV) voltage maps were acquired and PVS was performed from two different sites at baseline, and if non-inducible under isoproterenol. Catheter and/or surgical ablation was performed when patients were inducible or when slow conduction was present in anatomical isthmuses (AIs). Postablation PVS was undertaken to guide implantable cardioverter-defibrillator (ICD) implantation. RESULTS: Seventy-seven patients (36.2 ± 14.3 years old, 71% male) were included. Eighteen were inducible. In 28 patients (17 inducible, 11 non-inducible but with slow conduction) ablation was performed. Five had catheter ablation, surgical cryoablation in 9, both techniques in 14. ICDs were implanted in five patients. During a follow-up of 74 ± 40 months, no sudden cardiac death occurred. Three patients experienced sustained VAs, all were inducible during the initial EP study. Two of them had an ICD (low ejection fraction for one and important risk factor for arrhythmia for the second). No VAs were reported in the non-inducible group (p < .001). CONCLUSION: Preoperative EPS can help identifying patients with rTOF at risk for VAs, providing an opportunity for targeted ablation and may improve decision-making regarding ICD implantation.

Identification of Predictive Markers and Outcomes of Late-onset Pneumocystis jirovecii Pneumonia in Kidney Transplant Recipients.

BACKGROUND: In the era of prophylaxis, Pneumocystis pneumonia (PCP) has become a late-onset opportunistic infection requiring indications for prolonged prophylaxis to be defined. The primary objective of our study was therefore to evaluate risk factors associated with late-onset PCP. The secondary objective was to assess the impact of this infection on graft and patient survival. METHODS: We conducted a French case-control study in Bordeaux and Toulouse center by matching 1 case to 1-2 controls from the same center based on the transplant date and the type of induction treatment. RESULTS: Seventy cases and 134 controls were included. PCP occurred at a median of 3 years after transplantation. The total lymphocyte count and CD4+ and CD8+ T-lymphocyte values were lower in the cases than in their matched controls on the day of infection and annually up to 4 years earlier. The covariables independently associated with PCP were the total lymphocyte count 1 year before Pneumocystis, mTOR inhibitors used as maintenance immunosuppressive drugs, and the administration of corticosteroid boluses used in acute rejection. A total lymphocyte count threshold <1000/µL offered the best predictive value for infection occurrence. PCP was associated with high incidence of graft loss and patient death (30% and 17% respectively, 3 years after PCP). CONCLUSIONS: Pneumocystis pneumonia has dramatic consequences in kidney transplant recipients; a targeted prophylaxis based on simple criteria, such as chronic lymphopenia and/or history of corticosteroid boluses, could be useful to avoid life-threatening complications.

Efficacy of dihydroartemisinin/piperaquine in patients with non-complicated Plasmodium falciparum malaria in Yaoundé, Cameroon.

BACKGROUND: Dihydroartemisinin/piperaquine is increasingly used for the treatment of uncomplicated Plasmodium falciparum malaria in Africa. The efficacy of this combination in Cameroon is poorly documented, while resistance to dihydroartemisinin/piperaquine readily spreads in Southeast Asia. OBJECTIVES: This study evaluated the clinical efficacy of dihydroartemisinin/piperaquine in Cameroon, as well as the molecular profile and phenotypic susceptibility of collected isolates to dihydroartemisinin and piperaquine. PATIENTS AND METHODS: Dihydroartemisinin/piperaquine efficacy in 42 days was followed-up for 138 patients presenting non-complicated falciparum malaria. Piperaquine concentration was determined at day 7 for 124 patients. kelch13 gene polymorphisms (n = 150) and plasmepsin2 gene amplification (n = 148) were determined as molecular markers of resistance to dihydroartemisinin and piperaquine, respectively. Parasite susceptibility to dihydroartemisinin and piperaquine was determined using validated in vitro survival assays. RESULTS: The efficacy of dihydroartemisinin/piperaquine treatment was 100% after PCR correction. The reinfections were not associated with a variation of piperaquine concentration at day 7. Ninety-six percent (144/150) of the samples presented a WT allele of the kelch13 gene. Two percent (3/150) presented the non-synonymous mutation A578S, which is not associated with resistance to dihydroartemisinin. No duplication of the plasmepsin2 gene was observed (0/148). All the samples tested in vitro by survival assays (n = 87) were susceptible to dihydroartemisinin and piperaquine. CONCLUSIONS: Dihydroartemisinin/piperaquine has demonstrated excellent therapeutic efficacy with no evidence of emerging artemisinin or piperaquine resistance in Yaoundé, Cameroon. This observation suggests that dihydroartemisinin/piperaquine could be a sustainable therapeutic solution for P. falciparum malaria if implemented in areas previously free of artemisinin- and piperaquine-resistant parasites, unlike Southeast Asia.

Edge to edge repair using a MitraClip for severe tricuspid valve regurgitation after a Mustard operation.

A 48-year-old who underwent a Mustard operation in 1972 followed by a second cardiac intervention in 1996 for pulmonary venous baffle enlargement and residual baffle leak closure, complicated by recurrent atrial flutter, was admitted to our institution for severe systemic atrio-ventricular valve regurgitation (SAVVR) associated with severely impaired systemic right ventricular (RV) function. After careful preoperative anatomic assessment including three-dimensional transesophageal echocardiography (3DTEE) to define the clipping strategy and computed tomography to optimize the transvenous baffle puncture site, the intervention was performed under general anesthesia, fluoroscopic, and 3DTEE guidance. One XTR MitraClip was successfully implanted, achieving a significant reduction in regurgitation and immediate clinical improvement. The transbaffle puncture was closed using an 8 mm atrial septal defect (ASD) device without residual shunt or obstruction of the venous baffle. Post-operative clinical evaluation showed immediate improvement in the NYHA functional class (from III to II), but the patient presented with recurrent flutter at 1 week after the procedure, which was successfully treated by catheter ablation with another transbaffle approach next to the ASD device. Clinical improvement was maintained at 1- and 6-month follow-up with significant reduction in SAVVR, reduced systemic RV volumes and improved RV ejection fraction. This case demonstrates the feasibility of percutaneous treatment of systemic SAVV in patients with systemic RV after atrial redirection.

Characteristics and outcome according to underlying disease in non-AIDS patients with acute respiratory failure due to Pneumocystis pneumonia.

In the non-AIDS group, several underlying conditions and immune defects could lead to different PCP presentations. This study compared PCP presentation and outcome according to the underlying disease. A secondary analysis of a previously published prospective observational study including 544 PCP patients was done. Only non-AIDS patients were included. Underlying disease was defined as chronic lymphocytic leukemia (CLL), organ transplantation, solid cancer, allogeneic hematopoietic stem cell transplant (AHSCT), other hematological diseases, and immunosuppressive treatment. Clinical characteristics and outcomes were compared between groups. Multiple correspondent analyses compared clinical characteristics at diagnosis. Day 30 mortality was analyzed. Three hundred and twenty-one patients were included in the study. The underlying diseases were hematological malignancy (n = 75), AHSCT (n = 14), CLL (n = 19), solid organ transplant (n = 94), solid tumor (n = 39), and immunosuppressive treatment (n = 57). Compared with other underlying diseases, PCP related to CLL was closer to PCP related to AIDS presentation (long duration of symptoms before diagnosis, high level of dyspnea, and low oxygen saturation at diagnosis). Day 30 mortality was associated with underlying disease, oxygen flow, and shock at ICU admission. PCP presentations may vary according to the underlying reason for immunosuppression. Response to treatment and adjuvant steroid therapy should be analyzed regarding this result.

Epidemiological and clinical study of microsporidiosis in French kidney transplant recipients from 2005 to 2019: TRANS-SPORE registry.

INTRODUCTION: Microsporidiosis is an emerging opportunistic infection in renal transplantation (RT) recipients. We aimed to describe its clinical presentation and treatment. MATERIALS AND METHODS: We collected microsporidiosis cases identified in RT recipients between 2005 and 2019 in six French centers from the Crystal, Divat and Astre prospective databases. RESULTS: We report 68 RT recipients with intestinal microsporidiosis; the patients were predominantly male (61.8%), with a median age of 58 (46-69) years. Infection occurred at a median time of 3 (0.8-6.8) years posttransplant. Only Enterocytozoon bieneusi was found. Microsporidiosis manifested as diarrhea (98.5% of patients) with weight loss (72.1%) and acute renal injury (57.4%) without inflammatory biological parameters. The therapeutic approaches were no treatment (N = 9), reduction of the immunosuppressive regimen (∆IS) (N = 22), fumagillin alone (N = 9), fumagillin and ∆IS (N = 19), and albendazole or nitazoxanide and ∆IS (N = 9). Overall clinical remission was observed in 60 patients (88.2%). We observed no acute kidney rejection, renal transplant failure, or death within 6 months after microsporidiosis. CONCLUSION: E. bieneusi is an underestimated opportunistic pathogen in RT recipients, and infection with E. bieneusi leads to diarrhea with important dehydration and acute renal injury. The treatment is based on the reduction of the immunosuppressive regimen and the administration of fumagillin if available.

Microsporidiosis after liver transplantation: A French nationwide retrospective study.

BACKGROUND: Microsporidiosis has been largely reported in patients with acquired immunodeficiency syndrome, but emerged as a cause of persistent diarrhea in solid organ transplant patients. METHODS: Through the French Microsporidiosis Network and the Groupe français de recherche en greffe de foie, we collected all microsporidiosis cases identified in liver transplant patients between 1995 and 2020 in France. RESULTS: We identified 24 liver transplant recipients with microsporidiosis. Sex ratio was balanced and median age was 58.8 (3.5-83.5) years (there were 4 children). Microsporidiosis occurred at a median time of 3.9 (0.1-18.9) years post-transplant. Median duration of diarrhea before diagnosis was 22 days (12-45). Therapeutic care included immunosuppressive therapy changes in 20 patients, as follows: stop cyclosporine or tacrolimus (n = 2), dose reduction of cyclosporine or tacrolimus (n = 12), stop MMF (n = 5), and dose reduction of corticosteroids (n = 1). In addition, 15 patients received specific therapy against microsporidiosis: fumagillin (n = 11) or albendazole (n = 4). Median duration of treatment was 14 days (8-45 days). Finally, 7 patients had immunosuppressive treatment tapering only. Microsporidiosis was complicated by renal failure in 15 patients, requiring dialysis in one case. Two patients had infection relapse. No patient presented proven rejection within the 3 months after microsporidiosis. None of the patients died within the 3 months after microsporidiosis. CONCLUSIONS: Microsporidiosis is a very rare infection after liver transplantation but can induce severe dehydration and renal failure. Therefore, it must be systematically sought in any case of persistent diarrhea after first line screening of frequent infectious causes.

Vector flow mapping: A review from theory to practice.

BACKGROUND: The interest in intra-cardiac blood flow analysis is rapidly growing, and it has encouraged the development of different non-invasive imaging techniques. Among these, Vector Flow Mapping (VFM), combing Color-Doppler imaging and speckle tracking data, seems to be a promising approach, feasible in adult and children population. AIM OF THE REVIEW: The aim of this review is to give a historical perspective on the development of VFM method and a summary of the current algorithms and parameters potentially evaluable. Then, we will present the current state-of-the-art of VFM with an overview of clinical studies and applications of this technique.

Cardiovascular events in perimembranous ventricular septal defect with left ventricular volume overload: a French prospective cohort study (FRANCISCO).

The long-term prospective multi-centre nationwide (French) observational study FRANCISCO will provide new information on perimembranous ventricular septal defect with left ventricular overload but no pulmonary hypertension in children older than 1 year. Outcomes will be compared according to treatment strategy (watchful waiting, surgical closure, or percutaneous closure) and anatomic features of the defect. The results are expected to provide additional guidance about the optimal treatment of this specific population, which is unclear at present. BACKGROUND: The management of paediatric isolated perimembranous ventricular septal defect (pmVSD) with left ventricle (LV) volume overload but no pulmonary arterial hypertension (PAH) remains controversial. Three therapeutic approaches are considered: watchful waiting, surgical closure, and percutaneous closure. We aim to investigate the long-term outcomes of these patients according to anatomic pmVSD characteristics and treatment strategy. METHODS: The Filiale de Cardiologie Pediatrique et Congénitale (FCPC) designed the FRANCISCO registry, a long-term prospective nationwide multi-centre observational cohort study sponsored by the French Society of Cardiology, which enrolled, over 2 years (2018­2020), patients older than 1 year who had isolated pmVSD with LV volume overload. Prevalent complications related to pmVSD at baseline were exclusion criteria. Clinical, echocardiographic, and functional data will be collected at inclusion then after 1, 5, and 10 years. A core lab will analyse all baseline echocardiographic data to depict anatomical pmVSD features. The primary outcome is the 5-year incidence of cardiovascular events (infective endocarditis, sub-aortic stenosis, aortic regurgitation, right ventricular outflow tract stenosis, tricuspid regurgitation, PAH, arrhythmia, stroke, haemolysis, heart failure, or death from a cardiovascular event). We plan to enrol 200 patients, given the 10% estimated 5-year incidence of cardiovascular events with a 95% confidence interval of ±5%. Associations linking anatomical pmVSD features and treatment strategy to the incidence of complications will be assessed. CONCLUSIONS: The FRANSCICO study will provide the long-term incidence of complications in patients older than 1 year with pmVSD and LV volume overload. The results are expected to improve guidance for treatment decisions.

Comparison of Two Percutaneous Atrial Septal Defect Occluders for Device Healing and Nickel Release in a Chronic Porcine Model.

AIMS: To investigate the healing process and nickel release of the Hyperion occluder (Comed BV, Netherlands), as compared to the Amplatzer septal occluder (ASO) (St. Jude Medical Inc., St. Paul, MN, USA) in a chronic swine model. BACKGROUND: Some long-term complications occurring after percutaneous atrial septal defect (ASD) closure may be partially associated with an inappropriate healing of the device and increased nickel release. There is no direct comparative study of different occluders for healing and nickel release. METHODS: After percutaneous ASD creation, 12 pigs were implanted with 15 mm Hyperion (n = 6) and 15 mm ASO (n = 6) devices. After 1 month (n = 3 for each device) and 3 months (n = 3 for each device) of follow-up, device explantation was performed and healing was assessed using histopathological workup. Systemic and tissular nickel release was performed. RESULTS: Implantation was successful in 100% without complications. Device coverage was observed as early as 1 month after implantation and was almost complete after 3 months. A granulation tissue with a predominantly mononuclear inflammatory reaction was observed in contact with nitinol wires while an inflammatory reaction was seen in contact with textile fibers. We found no statistically significant difference between the 2 devices whether for histological grading scores or systemic nickel release, regardless to follow-up duration. CONCLUSIONS: In this preclinical study, we demonstrated that Amplatzer septal occluder and Hyperion occluder were not significantly different for device healing and nickel release processes.

Outcomes of solid organ transplant recipients with invasive aspergillosis and other mold infections.

OBJECTIVES: To characterize the clinical presentation and outcomes of invasive mold infections (IMI) in solid organ transplant (SOT) recipients. METHODS: Inclusion of all SOT recipients with IMI diagnosed between 2008 and 2016 at a referral center for SOT. Univariable analyses identified factors associated with death at one year, and logistic regression models retained independent predictors. RESULTS: Of the 1739 patients that received a SOT during this period, 68 developed IMI (invasive aspergillosis [IA] in 58). Cumulative incidence of IMI at 1 year ranged from 1.2% to 18.8% (kidney and heart transplantation, respectively). At baseline, compared with other IMI, the need for vasoactive drugs was more frequent in patients with IA. During follow-up, 35 patients (51%) were admitted to the ICU and required mechanical ventilation (n = 27), vasoactive drugs (n = 31), or renal replacement therapy (n = 31). The need for vasoactive drugs (OR 7.34; P = .003) and a positive direct examination (OR 10.1; P = .004) were independently associated with the risk of death at 1 year in patients with IA (n = 33; 57%) CONCLUSIONS: Characteristics of IMI at presentation varied according to the underlying transplanted organ and the mold species. Following IA, one-year mortality may be predicted by the need for hemodynamic support and initial fungal load.

SARS-CoV-2-related paediatric inflammatory multisystem syndrome, an epidemiological study, France, 1 March to 17 May 2020.

End of April 2020, French clinicians observed an increase in cases presenting with paediatric inflammatory multisystem syndrome (PIMS). Nationwide surveillance was set up and demonstrated temporospatial association with the coronavirus disease (COVID-19) epidemic for 156 reported cases as at 17 May: 108 were classified as confirmed (n = 79), probable (n = 16) or possible (n = 13) post-COVID-19 PIMS cases. A continuum of clinical features from Kawasaki-like disease to myocarditis was observed, requiring intensive care in 67% of cases.

Early necrotic skin lesions after a ABO-incompatible kidney transplantation: The threat of Cunninghamella Spp.

A 49-year-old man underwent ABO-incompatible kidney transplantation with a living donor. At day 33 post-transplantation, he presented with undiagnosed epilepsy with generalized tonic-clonic seizures. At day 44 post-transplantation, he developed left-sided pneumonia attributed to Aspergillus fumigatus and treatment with liposomal amphotericin B was initiated. At day 51 post-transplantation, necrotic skin lesions appeared. DNA sequencing in a fresh cutaneous biopsy finally identified Cunninghamella Spp., a member of the order Mucorales. Unfortunately, the necrotic lesions spread, and the patient died at day 60 post-transplantation. This case report highlights the infectious risk related to ABO-incompatible kidney transplantation and suggests a requirement for rapid identification of every skin lesion, even in the early phases of immunosuppression.

Quantitative PCR (qPCR) Detection of Mucorales DNA in Bronchoalveolar Lavage Fluid To Diagnose Pulmonary Mucormycosis.

Early diagnosis and treatment are essential to improving the outcome of mucormycosis. The aim of this retrospective study was to assess the contribution of quantitative PCR detection of Mucorales DNA in bronchoalveolar lavage fluids for early diagnosis of pulmonary mucormycosis. Bronchoalveolar lavage fluid samples (n = 450) from 374 patients with pneumonia and immunosuppressive conditions were analyzed using a combination of 3 quantitative PCR assays targeting the main genera involved in mucormycosis in France (Rhizomucor, Mucor/Rhizopus, and Lichtheimia). Among these 374 patients, 24 patients had at least one bronchoalveolar lavage fluid sample with a positive PCR; 23/24 patients had radiological criteria for invasive fungal infections according to consensual criteria; 10 patients had probable or proven mucormycosis, and 13 additional patients had other invasive fungal infections (4 probable aspergillosis, 1 proven fusariosis, and 8 possible invasive fungal infections). Only 2/24 patients with a positive PCR result on a bronchoalveolar lavage fluid sample had a positive Mucorales culture. PCR was also positive on serum in 17/24 patients. In most cases, a positive PCR result was first detected using sera (15/17). However, a positive PCR on bronchoalveolar lavage fluid was the earliest and/or the only biological test revealing mucormycosis in 4 patients with a final diagnosis of probable or proven mucormycosis, 3 patients with probable aspergillosis, and one patient with a possible invasive fungal infection. Mucorales PCR performed on bronchoalveolar lavage fluid could provide additional support for earlier administration of Mucorales-directed antifungal therapy, thus improving the outcome of lung mucormycosis cases.

Cost Effectiveness of Candida Polymerase Chain Reaction Detection and Empirical Antifungal Treatment among Patients with Suspected Fungal Peritonitis in the Intensive Care Unit.

BACKGROUND: Mortality from intra-abdominal candidiasis in intensive care units (ICUs) is high. It takes many days for peritoneal-fluid fungal culture to become positive, and the recommended empirical antifungal therapy involves excessive costs. Polymerase chain reaction (PCR) should produce results more rapidly than fungal culture. OBJECTIVES: To perform a cost-effectiveness analysis of the combination of several diagnostic and therapeutic strategies to manage Candida peritonitis in non-neutropenic adult patients in ICUs. METHODS: We constructed a decision tree model to evaluate the cost effectiveness. Cost and effectiveness were taken into account in a 1-year time horizon and from the French National Health Insurance perspective. Six strategies were compared: fluconazole or echinocandin as an empirical therapy, plus diagnosis by fungal culture or detection by PCR of all Candida species, or use of PCR to detect most fluconazole-resistant Candida species (i.e., Candida krusei and Candida glabrata). RESULTS: The use of fluconazole empirical treatment and PCR to detect all Candida species is more cost effective than using fluconazole empirical treatment without PCR (incremental cost-effectiveness ratio of €40,055/quality-adjusted life-year). Empirical treatment with echinocandin plus PCR to detect C. krusei and C. glabrata is the most effective strategy, but has an incremental cost-effectiveness ratio of €93,776/quality-adjusted life-year. If the cost of echinocandin decreases, then strategies involving PCR plus empirical echinocandin become more cost-effective. CONCLUSIONS: Detection by PCR of all Candida species and of most fluconazole-resistant Candida species could improve the cost-effectiveness of fluconazole and echinocandin given to non-neutropenic patients with suspected peritoneal candidiasis in ICUs.