Objectives
As sex between men is a major route of human immunodeficiency virus (HIV) infection in most western countries, restrictive deferral rules for blood donation have largely been implemented ...regarding men having sex with men (MSM). Here, we sought here to assign unreported HIV risk factors in blood donors (BDs) and reevaluated the MSM‐associated fraction of HIV transfusion residual risk (%RRMSM).
Methods
We applied a genetic distance‐based approach to infer an HIV transmission network for 384 HIV sequences from French BDs and 1337 HIV sequences from individuals with known risk factors (ANRS PRIMO primary HIV infection cohort). We validated the possibility of assigning a risk factor according to clustering using assortative mixing. Finally, we recalculated the %RRMSM.
Results
A total of 81 of 284 (28.5%) male and 5 of 100 (5%) female BDs belonged to a cluster; 72 (88.9%) of the 81 male BDs belonged to MSM clusters. After cluster correction, 8 of 67 (11.9%), 4 of 21 (19.0%), and 19 of 88 (21.6%) HIV‐positive (HIV+) male BDs with heterosexual, other, or unknown risk factors could be reclassified as MSM, accounting for 10.9% of the total HIV+ male BDs. Overall, 139 of 284 HIV+ male donors (48.9%) could be considered MSM between 2000 and 2016 in France. Between 2005 and 2016, the %RRMSM increase varied from 0 to 19%, without differing significantly from the %RRMSM before reclassification.
Conclusion
Network inference can be used to complement declaration data on risk factors for HIV infection in BDs. This approach, complementary to behavioral studies, is a valuable tool to evaluate the effect of changes in deferral criteria on BD compliance.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Genetic causes of many familial arrhythmia syndromes remain elusive. In this study, whole‐exome sequencing (WES) was carried out on patients from three different families that presented with ...life‐threatening arrhythmias and high risk of sudden cardiac death (SCD). Two French Canadian probands carried identical homozygous rare variant in TECRL gene (p.Arg196Gln), which encodes the trans‐2,3‐enoyl‐CoA reductase‐like protein. Both patients had cardiac arrest, stress‐induced atrial and ventricular tachycardia, and QT prolongation on adrenergic stimulation. A third patient from a consanguineous Sudanese family diagnosed with catecholaminergic polymorphic ventricular tachycardia (CPVT) had a homozygous splice site mutation (c.331+1G>A) in TECRL. Analysis of intracellular calcium (Ca2+i) dynamics in human induced pluripotent stem cell‐derived cardiomyocytes (hiPSC‐CMs) generated from this individual (TECRLHom‐hiPSCs), his heterozygous but clinically asymptomatic father (TECRLHet‐hiPSCs), and a healthy individual (CTRL‐hiPSCs) from the same Sudanese family, revealed smaller Ca2+i transient amplitudes as well as elevated diastolic Ca2+i in TECRLHom‐hiPSC‐CMs compared with CTRL‐hiPSC‐CMs. The Ca2+i transient also rose markedly slower and contained lower sarcoplasmic reticulum (SR) calcium stores, evidenced by the decreased magnitude of caffeine‐induced Ca2+i transients. In addition, the decay phase of the Ca2+i transient was slower in TECRLHom‐hiPSC‐CMs due to decreased SERCA and NCX activities. Furthermore, TECRLHom‐hiPSC‐CMs showed prolonged action potentials (APs) compared with CTRL‐hiPSC‐CMs. TECRL knockdown in control human embryonic stem cell‐derived CMs (hESC‐CMs) also resulted in significantly longer APs. Moreover, stimulation by noradrenaline (NA) significantly increased the propensity for triggered activity based on delayed afterdepolarizations (DADs) in TECRLHom‐hiPSC‐CMs and treatment with flecainide, a class Ic antiarrhythmic drug, significantly reduced the triggered activity in these cells. In summary, we report that mutations in TECRL are associated with inherited arrhythmias characterized by clinical features of both LQTS and CPVT. Patient‐specific hiPSC‐CMs recapitulated salient features of the clinical phenotype and provide a platform for drug screening evidenced by initial identification of flecainide as a potential therapeutic. These findings have implications for diagnosis and treatment of inherited cardiac arrhythmias.
Synopsis
Mutations in the novel TECRL gene were identified in patients with malignant exercise‐induced arrhythmias. Increased triggered electrical activity upon stimulation in patient‐specific hiPSC‐CMs was rescued by the antiarrhythmic drug flecainide.
Trans‐2,3‐enoyl‐CoA reductase‐like (TECRL) is preferentially expressed in the heart.
Mutations in TECRL cause lethal arrhythmias in humans.
Cardiac defects in TECRL patients are characterized by overlapping features of long QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia (CPVT).
Cardiomyocytes differentiated from patient‐specific human induced pluripotent stem cells (hiPSCs) recapitulate the electrical abnormalities observed in TECRL patients.
Mutations in the novel TECRL gene were identified in patients with malignant exercise‐induced arrhythmias. Increased triggered electrical activity upon stimulation in patient‐specific hiPSC‐CMs was rescued by the antiarrhythmic drug flecainide.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Atrial arrhythmias are the most common complication encountered in the growing and aging population with congenital heart disease.
This study sought to assess the types and patterns of atrial ...arrhythmias, associated factors, and age-related trends.
A multicenter cohort study enrolled 482 patients with congenital heart disease and atrial arrhythmias, age 32.0 ± 18.0 years, 45.2% female, from 12 North American centers. Qualifying arrhythmias were classified by a blinded adjudicating committee.
The most common presenting arrhythmia was intra-atrial re-entrant tachycardia (IART) (61.6%), followed by atrial fibrillation (28.8%), and focal atrial tachycardia (9.5%). The proportion of arrhythmias due to IART increased with congenital heart disease complexity from 47.2% to 62.1% to 67.0% in patients with simple, moderate, and complex defects, respectively (p = 0.0013). Atrial fibrillation increased with age to surpass IART as the most common arrhythmia in those ≥50 years of age (51.2% vs. 44.2%; p < 0.0001). Older age (odds ratio OR: 1.024 per year; 95% confidence interval CI: 1.010 to 1.039; p = 0.001) and hypertension (OR: 2.00; 95% CI: 1.08 to 3.71; p = 0.029) were independently associated with atrial fibrillation. During a mean follow-up of 11.3 ± 9.4 years, the predominant arrhythmia pattern was paroxysmal in 62.3%, persistent in 28.2%, and permanent in 9.5%. Permanent atrial arrhythmias increased with age from 3.1% to 22.6% in patients <20 years to ≥50 years, respectively (p < 0.0001).
IART is the most common presenting atrial arrhythmia in patients with congenital heart disease, with a predominantly paroxysmal pattern. However, atrial fibrillation increases in prevalence and atrial arrhythmias progressively become permanent as the population ages.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
While the coronavirus disease 2019 (COVID-19) pandemic has peaked in many countries already, the current challenge is to assess population immunity on a large scale. Many serological tests are ...available and require urgent independent validation. Here, we report performance characteristics of Orient Gene Biotech COVID-19 IgG/IgM Rapid Test Cassette (OG) and compare it to Abbott SARS-CoV-2 IgG immunoassay (ASIA). Patients (
= 102) with a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcriptase PCR (RT-PCR) were tested. The patients were asymptomatic (
= 2) or had mild (
= 37) or severe symptoms requiring hospitalization in a medical unit (
= 35) or intensive care unit (
= 28). Specificity was evaluated for 42 patients with previous viral and parasitic diseases as well as a high level of rheumatic factor. The sensitivity of OG was 95.8% (95% confidence interval CI95%, 89.6 to 98.8) for samples collected ≥10 days after the onset of symptoms, which was equivalent to the sensitivity of ASIA of 90.5% (CI95%, 82.8 to 95.6). OG uncovered six false-negative results of ASIA, of which two had only IgM with OG. Specificity was 100% (CI95%, 93.4 to 100) with both tests on samples, including patients infected with endemic coronavirus. Overall, OG performance characteristics indicate that the test is suitable for routine use in clinical laboratories, and its performance is equivalent to that of immunoassay. Testing OG on a larger asymptomatic population may be needed to confirm these results.
HIV-1 diagnosis in babies born to seropositive mothers is one of the challenges of HIV epidemics in children. A simple, rapid protocol was developed for quantifying HIV-1 DNA in whole blood samples ...and was used in the ANRS French pediatric cohort in conditions of prevention of mother-to-child transmission. A quantitative HIV-1 DNA protocol (LTR real-time PCR) requiring small blood volumes was developed. First, analytical reproducibility was evaluated on 172 samples. Results obtained on blood cell pellets and Ficoll-Hypaque separated mononuclear cells were compared in 48 adult HIV-1 samples. Second, the protocol was applied to HIV-1 diagnosis in infants in parallel with plasma HIV-RNA quantitation. This prospective study was performed in children born between May 2005 and April 2007 included in the ANRS cohort. The assay showed good reproducibility. The 95% detection cut-off value was 6 copies/PCR, that is, 40 copies/10⁶ leukocytes. HIV-DNA levels in whole blood were highly correlated with those obtained after Ficoll-Hypaque separation (r = 0.900, P < 0.0001). A total of 3,002 specimens from 1,135 infants were tested. The specificity of HIV-DNA and HIV-RNA assays was 100%. HIV-1 infection was diagnosed in nine infants before age 60 days. HIV-DNA levels were low, underlining the need for sensitive assays when highly active antiretroviral therapy (HAART) has been given. The performances of this HIV-DNA assay showed that it is adapted to early diagnosis in children. The results were equivalent to those of HIV-RNA assay. HIV-DNA may be used even in masked primary infection in newborns whose mothers have received HAART. J. Med. Virol. 81:217-223, 2009.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Eisenmenger syndrome is the most severe and extreme phenotype of pulmonary arterial hypertension associated with congenital heart disease. A large nonrestrictive systemic left-to-right shunt triggers ...the development of pulmonary vascular disease, progressive pulmonary arterial hypertension, and increasing pulmonary vascular resistance at the systemic level, which ultimately results in shunt reversal. Herein, we review the changing epidemiological patterns and pathophysiology of Eisenmenger syndrome. Multiorgan disease is an integral manifestation of Eisenmenger syndrome and includes involvement of the cardiac, hematological, neurological, respiratory, gastrointestinal, urinary, immunological, musculoskeletal, and endocrinological systems. Standardized practical guidelines for the assessment, management, risk stratification, and follow-up of this very fragile and vulnerable population are discussed. Multidisciplinary care is the best clinical practice. An approach to the prevention and management of a broad spectrum of complications is provided. Relevant therapeutic questions are discussed, including anticoagulation, noncardiac surgery, physical activity, transplantation, and advanced-care planning (palliative care). Advanced pulmonary arterial hypertension therapies are indicated in patients with Eisenmenger syndrome and World Health Organization functional class II or higher symptoms to improve functional capacity, quality of life, and—less well documented—survival. Specific recommendations regarding monotherapy or combination therapy are provided according to functional class and clinical response. The ultimate challenge for all care providers remains early detection and management of intracardiac and extracardiac shunts, considering that Eisenmenger syndrome is a preventable condition.
Le syndrome d'Eisenmenger est le phénotype le plus sévère et extrême de l'hypertension artérielle pulmonaire associée aux cardiopathies congénitales. Un important shunt gauche-droit systémique non restrictif engendre une maladie vasculaire pulmonaire, l'apparition d'une hypertension artérielle pulmonaire et la majoration des résistances vasculaires pulmonaires; les pressions pulmonaires atteignent un seuil systémique à l'origine du renversement du shunt. Cet article discute des bases physiopathologiques et du changement épidémiologique du syndrome d'Eisenmenger. L'atteinte multiviscérale est caractéristique du syndrome d'Eisenmenger impliquant le système cardio-vasculaire, hématologique, neurologique, respiratoire, gastro-intestinal, urinaire, immunologique, musculo-squelettique et endocrinien. Nous proposons des lignes directrices pratiques pour l’évaluation, la prise en charge, la stratification des risques et le suivi de cette population fragile et vulnérable. Les pratiques cliniques exemplaires recommandent des soins multidisciplinaires. Nous présentons aussi une approche pour la prévention et la prise en charge d'un grand éventail de complications et nous abordons des questions thérapeutiques pertinentes, notamment l'anticoagulothérapie, la chirurgie non cardiaque, l'activité physique, la greffe et la planification préalable des soins (soins palliatifs). Les traitements spécifiques de l'hypertension artérielle pulmonaire sont indiqués chez les patients atteints de syndrome d'Eisenmenger avec une classe fonctionnelle de II ou plus de l'Organisation mondiale de la Santé afin d'améliorer la capacité fonctionnelle, la qualité de vie, et bien que moins documentée la survie. Enfin, nous formulons des recommandations spécifiques concernant le recours à la monothérapie ou à l'association thérapeutique selon la classe fonctionnelle et la réponse clinique. Le diagnostic précoce et la prise en charge optimale des shunts intracardiaques et extracardiaques sont les défis ultimes des équipes traitantes médicales pour prévenir le syndrome d'Eisenmenger.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The Fontan procedure is the palliative procedure of choice for patients with single ventricle physiology. Pulmonary vascular disease (PVD) is an important contributor to Fontan circulatory failure.
...We review the pathophysiology of PVD in patients with Fontan palliation and share our initial experience with optical coherence tomography (OCT) in supplementing standard hemodynamics in characterizing Fontan-associated PVD. In the absence of a sub-pulmonary ventricle, low pulmonary vascular resistance (PVR; ≤2 WU/m
) is required to sustain optimal pulmonary blood flow. PVD is associated with adverse pulmonary artery (PA) remodeling resulting from the non-pulsatile low-shear low-flow circulation. Predisposing factors to PVD include impaired PA growth, endothelial dysfunction, hypercoagulable state, and increased ventricular end-diastolic pressure. OCT parameters that show promise in characterizing Fontan-associated PVD include the PA intima-to-media ratio and wall area ratio (i.e. difference between the whole-vessel area and the luminal area divided by the whole-vessel area).
OCT carries potential in characterizing PVD in patients with Fontan palliation. PA remodeling is marked by intimal hyperplasia, with medial regression. Further studies are required to determine the role of OCT in informing management decisions and assessing therapeutic responses.
SARS-CoV-2 is a coronavirus causing a globalized outbreak called COVID-19. SARS-CoV-2 transmission is associated with inhalation of contaminated respiratory droplets and could causes severe ...complications. Until today several “waves” of infections have been observed despite implementation of strict health policies. Decisions for such sanitary measures are based on population health monitoring. Unfortunately, for COVID-19, a significant proportion of individuals are asymptomatic but play a role in the virus transmission.
To overcome these limitations, several strategies were developed including genome quantification in wastewater that could allow monitoring of the health status of population, since shedding of SARS-CoV-2 in patient stool is frequent. Wastewater-based epidemiology (WBE) was established and several countries implemented this approach to allow COVID-19 outbreak monitoring. In France, the OBEPINE project performed a quantitative analysis of SARS-CoV-2 in raw wastewater samples collected from major wastewater treatment plants (WWTP) since March 2020.
In the greater Paris area 1101 samples (507 for five WWTP and 594 for sewer) were collected. This 16 months monitoring allows us to observe the outbreak dynamics. Comparison of WBE indicators with health data lead to several important observation; the good level of correlation with incidence rates, the average 3 days lead time, and the sensitivity (WBE change when incidence is > to 7/100000 inhabitants). We also compared the local monitoring (city level) with the regional monitoring, to help cluster identification.
Moreover, variants of concern (VOC) emerged due to the selection pressure. We developed a specific RT-qPCR method targeting the deletion H69-V70 in the spike protein, using this deletion as a proxy of the B.1.1.7 presence in the wastewater. With this data we demonstrate the predominant role played by this strain in the third wave.
All these results allow a better description and understanding of the pandemic and highlight the role of such WBE indicators.
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•Genome quantification of pathogens in wastewater allow monitoring of the health status of population.•Bi weekly sampling allows description of WBE indicators lag with incidence and sensibility at the regional or local level.•RT qPCR tools, targeting specific mutations allow dynamic monitoring of VOC in wastewater and population.•Variant monitoring in Wastewater demonstrates the important role played by some strains in the third wave.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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