New insights into the haemo- and coelo-microbiota with antimicrobial activities from Echinodermata and Mollusca.

AIMS: The aim of this study was to investigate the diversity of bacteria with antimicrobial activity present in the coelomic fluid and haemolymph of wild and healthy echinodermata and mollusca. METHODS AND RESULTS: Collection expeditions of healthy marine molluscs and echinoderms were conducted in the Glenan archipelago in spring 2014. Members of the culturable microbiota present in the haemolymph, (haemo-microbiota) of Haliotis tuberculata (gastropoda, abalone) and Mytilus edulis (bivalvia, mussel), as well as in the coelomic fluid (coelo-microbiota) of Echinus esculentus (echinoidea, sea urchin) and Holothuria forskali (Holothuroidea, holothurian) were screened for antimicrobial activity, and further identified using 16S rRNA sequencing. Except for E. esculentus, culturable bacteria in the internal fluids of all studied organisms (mussel, abalone and holothurian) were more abundant than in seawater. The haemo- and coelo-microbiota with antimicrobial activity differed significantly between host species, in terms of abundance and diversity. Indeed, higher numbers were isolated from mussel than from abalone haemolymph. Moreover, in mussels and holothurians, bacteria with antimicrobial activities were predominantly Vibrio spp. (respectively 55 and 45%), while Pseudoalteromonas spp. were the most abundant (50%) in abalone haemolymph. Nevertheless, the activity spectra of these bacteria mainly included marine pathogens affiliated to the Vibrio genus. CONCLUSION: The haemo- and coelo-microbiota with antimicrobial activities were significantly related to their host species and differed in terms of abundance and diversity. These bacteria may play a key role in host homeostasis against pathogens. SIGNIFICANCE AND IMPACT OF THE STUDY: This study brings new knowledge on the diversity of bacteria present in the internal fluids of two marine molluscs and two echinoderms and their antimicrobial activities towards marine pathogens.

Direct thermo-optical tuning of silicon microresonators for the mid-infrared.

We use light from a visible laser diode to directly tune silicon-on-chip microresonators by thermo-optical effect. We show that this direct tuning is local, non invasive and has a much smaller time constant than global temperature tuning methods. Such an approach could prove to be highly effective for Kerr comb generation in microresonators pumped by quantum cascade lasers, which cannot be easily tuned to achieve comb generation and soliton-mode locked states.

Truncating mutations on myofibrillar myopathies causing genes as prevalent molecular explanations on patients with dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) is one of the leading causes of heart failure with high morbidity and mortality. More than 40 genes have been reported to cause DCM. To provide new insights into the pathophysiology of dilated cardiomyopathy, a next-generation sequencing (NGS) workflow based on a panel of 48 cardiomyopathies-causing genes was used to analyze a cohort of 222 DCM patients. Truncating variants were detected on 63 unrelated DCM cases (28.4%). Most of them were identified, as expected, on TTN (29 DCM probands), but truncating variants were also identified on myofibrillar myopathies causing genes in 17 DCM patients (7.7% of the DCM cohort): 10 variations on FLNC and 7 variations on BAG3 . This study confirms that truncating variants on myofibrillar myopathies causing genes are frequently associated with dilated cardiomyopathies and also suggest that FLNC mutations could be considered as a common cause of dilated cardiomyopathy. Molecular approaches that would allow to detect systematically truncating variants in FLNC and BAG3 into genetic testing should significantly increase test sensitivity, thereby allowing earlier diagnosis and therapeutic intervention for many patients with dilated cardiomyopathy.

Prevalence of drug-related problems associated with direct oral anticoagulants in hospitalized patients: a multicenter, cross-sectional study.

WHAT IS KNOWN AND OBJECTIVE: The complex dose regimens of the direct-acting oral anticoagulants (DOAC) make their appropriate prescribing highly challenging. Inappropriate prescribing of the DOAC remains poorly addressed. We studied the patterns of DOAC prescription and estimated the prevalence of drug-related problems (DRPs) associated with their use. METHODS: A cross-sectional study was conducted using data from medical records system of the Lyon teaching hospitals. DRPs, identified among patients who received a DOAC, between 1 January 2010 and 31 July 2013, were categorized according to the Pharmaceutical Care Network Europe Classification System. The prevalence of hospital stays with a DRP was estimated, and a subgroup analysis according to DOAC and their indication for use was provided. Clinical outcomes were not assessed. RESULTS: Of the 4154 hospital stays with at least one DOAC administration [3412 patients; median age (range): 71 years (14-98), 57% female], 70·8% were excluded from the analysis mainly due to missing information for renal function and/or patient weight. Of the 1188 hospital stays that were screened, 100 DRPs were identified (prevalence 8·4%; 95% CI, 6·8-10·0). The highest prevalence was found among patients who received rivaroxaban for atrial fibrillation (14·6%; 95% CI, 10·7-18·5). A too low drug dose was the most frequent DRP (n = 56; 4·7%), followed by a too high drug dose (n = 37; 3·1%), contraindication (n = 5; 0·4%), and pharmacokinetic problem requiring dose adjustment (n = 2; 0·2%). WHAT IS NEW AND CONCLUSION: Drug-related problems associated with the DOACs occur quite commonly among hospitalized patients. Although these DRPs were considered to be of minor severity, prescribing protocols to support better prescribing should be disseminated to reduce the risk to patients. Renal function and body weight data should be mandatory on prescriptions to allow cross-checking.

90Y-ibritumomab tiuxetan, fludarabine, busulfan and antithymocyte globulin reduced-intensity allogeneic transplant conditioning for patients with advanced and high-risk B-cell lymphomas.

BACKGROUND: Patients with advanced B-cell non-Hodgkin's lymphoma (NHL) refractory to initial chemotherapy or relapsing after autologous stem-cell transplantation have a poor prognosis. Allogeneic stem-cell transplantation after reduced-intensity conditioning (RIC) regimen can be a therapeutic option. However, the high incidence of relapse remains a challenging issue. We speculated that the incorporation of (90)Y-Ibritumomab tiuxetan into a fludarabine-based RIC regimen would improve the lymphoma control without overwhelming toxicity. Our aim was to evaluate the safety of (90)Y-Ibritumomab tiuxetan in association with such a regimen in a prospective multicenter phase II trial. PATIENTS AND METHODS: Thirty-one patients with advanced lymphoma from five distinct institutions were included between February 2008 and October 2010. Thirty patients in complete or partial response after failure of a median of 3 (range, 2-4) previous chemotherapy regimens including autologous transplant in 29 were evaluable for nonrelapse mortality (NRM) at day 100 post-transplant that was the primary end point. RESULTS: With a median follow-up of 32 months (range, 29-60 months), the 2-year event-free and overall survivals of the whole study group were both 80% [95 confidence interval (CI) 60.8% to 90.5%). The 100-day and 2-year post-transplant cumulative incidences of NRM were 3.3% (95% CI 0.2% to 14.9%) and 13.3% (95% CI 5.4% to 33.2%), respectively. The 2-year cumulative incidence of relapse was 6.7% (95% CI 1.7% to 25.4%). The cumulative incidences of grade II-IV and extensive chronic graft-versus-host disease were 27% and 14%, respectively. CONCLUSIONS: For chemosensitive advanced high-risk B-cell lymphoma, the addition of (90)Y-Ibritumomab tiuxetan to a RIC regimen based on fludarabine, busulfan and antithymocyte globulin followed by allogeneic transplant is safe and highly effective. clinicaltrials.gov: NCT00607854.

Arrhythmogenic cardiomyopathy as a myogenic disease: highlights from cardiomyocytes derived from human induced pluripotent stem cells.

Arrhythmogenic cardiomyopathy (ACM) is an inherited cardiomyopathy characterized by the replacement of myocardium by fibro-fatty infiltration and cardiomyocyte loss. ACM predisposes to a high risk for ventricular arrhythmias. ACM has initially been defined as a desmosomal disease because most of the known variants causing the disease concern genes encoding desmosomal proteins. Studying this pathology is complex, in particular because human samples are rare and, when available, reflect the most advanced stages of the disease. Usual cellular and animal models cannot reproduce all the hallmarks of human pathology. In the last decade, human-induced pluripotent stem cells (hiPSC) have been proposed as an innovative human cellular model. The differentiation of hiPSCs into cardiomyocytes (hiPSC-CM) is now well-controlled and widely used in many laboratories. This hiPSC-CM model recapitulates critical features of the pathology and enables a cardiomyocyte-centered comprehensive approach to the disease and the screening of anti-arrhythmic drugs (AAD) prescribed sometimes empirically to the patient. In this regard, this model provides unique opportunities to explore and develop new therapeutic approaches. The use of hiPSC-CMs will undoubtedly help the development of precision medicine to better cure patients suffering from ACM. This review aims to summarize the recent advances allowing the use of hiPSCs in the ACM context.

Visual and Hearing Sensitivity Affect Robot-Based Training for Children Diagnosed With Autism Spectrum Disorder.

In this paper, we investigate the impact of sensory sensitivity during robot-assisted training for children diagnosed with Autism Spectrum Disorder (ASD). Indeed, user-adaptation for robot-based therapies could help users to focus on the training, and thus improve the benefits of the interactions. Children diagnosed with ASD often suffer from sensory sensitivity, and can show hyper or hypo-reactivity to sensory events, such as reacting strongly or not at all to sounds, movements, or touch. Considering it during robot therapies may improve the overall interaction. In the present study, thirty-four children diagnosed with ASD underwent a joint attention training with the robot Cozmo. The eight session training was embedded in the standard therapy. The children were screened for their sensory sensitivity with the Sensory Profile Checklist Revised. Their social skills were screened before and after the training with the Early Social Communication Scale. We recorded their performance and the amount of feedback they were receiving from the therapist through animations of happy and sad emotions played on the robot. Our results showed that visual and hearing sensitivity influenced the improvements of the skill to initiate joint attention. Also, the therapists of individuals with a high sensitivity to hearing chose to play fewer animations of the robot during the training phase of the robot activity. The animations did not include sounds, but the robot was producing motor noise. These results are supporting the idea that sensory sensitivity of children diagnosed with ASD should be screened prior to engaging the children in robot-assisted therapy.

Valganciclovir prophylaxis for cytomegalovirus infection in thoracic transplant patients: retrospective study of efficacy, safety, and drug exposure.

Oral ganciclovir (GCV) was replaced by prodrug valganciclovir (vGCV) for cytomegalovirus (CMV) prophylaxis. We assessed retrospectively (2005-2007) vGCV effectiveness and safety during prophylaxis and 4 months after, in heart (HTx) and lung transplantation (LTx), including lung transplant for cystic fibrosis (CFTx). Patients with stable renal function received vGCV 900 mg daily during 3-6 and 8-12 months in HTx and LTx. Effectiveness was assessed by antigenemia (pp65Ag) and a GCV therapeutic drug monitoring to document exposure. A total of 32 patients (11 HTx, 7 LTx, and 14 CFTx) received vGCV for 106+/-67 days in HTx versus 270+/-85 days in LTx and CFTx. Doses were 700+/-225, 915+/-60, and 820+/-150 mg/24 h in HTx, LTx, and CFTx showing acceptable mean trough GCV 0.75+/-0.5 mg/L. Two of 9 cases of neutropenia were attributable to vGCV. Three CMV donor-positive/recipient-negative CFTx patients presented positive pp65Ag; 2 developed CMV disease (6%). We found that vGCV 900 mg, adapted to renal function, was effective and safe for long CMV prophylaxis together with efficient exposure in thoracic transplantation.

[How to improve the continuity of pharmacotherapy at hospital admission and discharge]. / Comment optimiser la continuité du traitement médicamenteux entre l'hôpital et le domicile?

The continuity of pharmacotherapy is of vital importance when patients move from one health care setting to another. Unfortunately, this continuity is not always guaranteed. The aim of this study is to propose solutions to enhance the continuity of pharmacotherapy at hospital admission and discharge. The study consists of a systematic review of the international literature and an analysis of seamless care initiatives in seven selected countries; a summary of Belgian data on problems as well as solutions with regard to continuity of care; a quantification of the extent of medication changes as a result of a hospital stay in Belgium; and a qualitative analysis of the perception of Belgian health care professionals (HCPs) on approaches to improve seamless care. The literature review yielded 15 papers of sufficient quality. However, this review did not generate definitive conclusions on the clinical impact and the cost-effectiveness of interventions aiming to enhance the continuity of pharmacotherapy. The most important initiatives that have been put in practice in foreign countries include the development and implementation of guidelines for HCPs; national information campaigns; education of HCPs; and the development of information technologies as to share patient and prescription data between settings of care. For Belgium, 66 seamless care initiatives were identified. The high number and variety of projects show the interest for this topic as well as the involvement of various HCPs from diverse settings in the development of solutions. Based on this research, and the solutions discussed in the focus groups, the following elements are proposed to enhance the continuity of pharmacotherapy: a national guideline governing the continuity of pharmacotherapy; a national campaign to sensitize HCPs and patients in this area; the availability of a comprehensive and up to date medication list for each patient; and electronic healthcare infrastructure that facilitates sharing of information.

Changes in action potentials and intracellular ionic homeostasis in a ventricular cell model related to a persistent sodium current in SCN5A mutations underlying LQT3.

In LQT3 patients, SCN5A mutations induce ultraslow inactivation of a small fraction of the hNav1.5 current, i.e. persistent Na+ current (IpNa). We explored the time course of effects of such a change on the intracellular ionic homeostasis in a model of guinea-pig cardiac ventricular cell [Pasek, M., Simurda, J., Orchard, C.H., Christé, G., 2007b. A model of the guinea-pig ventricular cardiomyocyte incorporating a transverse-axial tubular system. Prog. Biophys. Mol. Biol., this issue]. Sudden addition of IpNa prevented action potential (AP) repolarization when its conductance (gpNa) exceeded 0.12% of the maximal conductance of fast INa (gNa). With gpNa at 0.1% gNa, the AP duration at 90% repolarization (APD90) was initially lengthened to 2.6-fold that in control. Under regular stimulation at 1 Hz it shortened progressively to 1.37-fold control APD90, and intracellular [Na+]i increased by 6% with a time constant of 106 s. Further increasing gpNa to 0.2% gNa caused an immediate increase in APD90 to 5.7-fold that in control, which decreased to 2.2-fold that in control in 30s stimulation at 1 Hz. At this time diastolic [Na+]i and [Ca2+]i were, respectively, 34% and 52% higher than in control and spontaneous erratic SR Ca release occurred. In the presence of IpNa causing 46% lengthening of APD90, the model cell displayed arrhythmogenic behaviour when external [K+] was lowered to 5 mM from an initial value at 5.4 mM. By contrast, when K+ currents IKr and IKs were lowered in the model cell to produce the same lengthening of APD90, no proarrhythmic behaviour was observed, even when external [K+] was lowered to 2.5 mM.

Voriconazole pharmacokinetic variability in cystic fibrosis lung transplant patients.

BACKGROUND: Aspergillosis is a high-risk complication in cystic fibrosis (CF) lung transplant patients. Azole antifungal drugs inhibit CYP3A4, resulting in significant metabolic drug-drug interactions. Voriconazole (VRZ) was marketed without therapeutic drug monitoring (TDM) recommendations, consistent with favorable pharmacokinetics, but regular determinations of plasma VRZ concentration were introduced in our center to manage interactions with calcineurin inhibitors and to document the achievement of therapeutic levels. METHODS: VRZ TDM data analysis for trough concentration (C0) and peak concentration (C2) was carried out, using validated liquid chromatography assay with ultraviolet detection, for 35 CF lung transplant patients (mean age 25 years, mean weight 47 kg, balanced sex ratio) since 2003. Therapeutic range (C0: 1.5 +/- 0.5 - C2 : 4.0 +/- 1.0 mg/L) was expressed relative to pivotal pharmacokinetic trial data. RESULTS: The duration of VRZ treatment ranged from 9 days to 22 months. The recommended standard dose of VRZ (200 mg twice a day, following the loading dose) resulted in significant plasma concentrations (>0.5 mg/L) in 20% of CF lung transplant patients. Therapeutic concentrations were obtained using higher doses (average 570 +/- 160 mg/day, +43%, P<0.01). Despite adaptation, C0 remained <0.5 mg/L (11%), even when the drug was administered intravenously, highlighting the variability of VRZ pharmacokinetics, possibly enhanced by CYP2C19 polymorphism. The risk of inefficacy during periods of underdosage was overcome by treatment with antifungal drug combinations (caspofungin, n=10). The therapeutic index was limited by neurologic effects (14%) and hepatic abnormalities (30%). VRZ concentrations correlated significantly (P<0.01) with aspartate aminotransferase levels but not with bilirubin levels. VRZ acted as a metabolic inhibitor of tacrolimus (C0 to dose ratio 5.8 +/- 2.6, n=31/VRZ versus 1.7 +/- 0.9 alone, P<0.001). Large changes in azole concentration affected the magnitude of the drug-drug interactions and adjustment requirements. CONCLUSIONS: TDM is required because VRZ levels are often undetectable in treated CF lung transplant patients, supporting the use of antifungal drug combinations until achievement of VRZ C0 at a steady state between 1 and 2 mg/L. Plasma VRZ concentrations should be determined for the quantitative, individualized management of drug-drug interactions in lung transplant patients, in particular immunosuppressant such as tacrolimus, considering VRZ to be both a target and an inhibitor of CYP3A4.

Renal histopathological lesions after lung transplantation in patients with cystic fibrosis.

We have analyzed the evolution of renal status beyond the perioperative period in patients with cystic fibrosis (CF) undergoing lung transplantation and presented histological analysis of 15 patients biopsied for an episode of accelerated renal function loss (RFL). Episodes of accelerated RFL after the perioperative period occurred in 32.5% of patients and significantly raised the risk of end-stage renal disease (ESRD) (p < 0.001). The histologic lesions associated with these episodes differed according to the time of onset. Early onset (10 cases) was associated with tubulointerstitial lesions in the form of oxalate nephropathy (50%) and/or a pigmented tubulopathy (80%). This latter was correlated with treatment with antiviral agents (p = 0.002) and aminoside and glycopeptide antibiotics (p = 0.03) administered in the month preceding biopsy. Lesions in late episodes of accelerated RFL (5 cases) were principally vascular: arteriosclerosis and arteriolosclerosis (p = 0.007, p = 0.00002), correlated with diabetic glomerulosclerosis or focal segmental glomerulosclerosis in the absence of prominent diabetic changes. Specific calcineurin-inhibitor nephrotoxicity was present in 93.3% of biopsies associated with thrombotic microangiopathy in 46.7% of cases. The identification of specific etiologies of progressive kidney disease in patients with CF after lung transplantation should permit more effective post-transplant care of these patients.

Single-lung transplantation for cystic fibrosis and metachronus pneumonectomy: case reports.

Three patients with end-stage cystic fibrosis (CF) underwent single lung transplantation (SLT) with contralateral pneumonectomy. In the first case, contralateral pneumonectomy (CP) was performed before SLT. The patient is alive with no signs of infection or rejection. For the other 2 cases, CP was performed after SLT. One patient died 8 months later with septicemia; the other patient died after 10 days because of complicated bronchopleural fistula and infection of the pneumonectomy space. SLT can be a good option for some patients with CF. The outcome is good when CP is done before SLT. However, CP must be done simultaneously with SLTX.

[Recommendations for good practice, consensus, feed-back]. / Recommandations de bonne pratique, consensus et feed-back.

The author brings up the different phases in the development of the Recommendations for Good Practice by the Scientific Societies of General Practice in Belgium (Société Scientifique de Médecine Générale and Domus Medica) and by the Belgian Antibiotic Policy Coordination Committee (BAPCOC). Are also discussed the methodology of the consensus conferences organized by the National Sickness and Disability Insurance Institute and the process of the prescription feed-back campaigns to some groups of prescribers considered by the National Board of Quality Promotion.

[Long QT syndrome in children: analysis of the Lyon series]. / Syndrome du QT long congénital chez l'enfant. Analyse de la série lyonnaise.

Congenital long QT syndrome is a rare and serious disorder in children. In addition to the clinical and electrocardiographical diagnostic criteria, molecular biochemistry has identified six genes which are implicated in this pathology. Our study involved a retrospective analysis of 23 patients aged less than 21 with congenital long QT syndrome, followed up for an average of two years. Genotypes were obtained for all of the patients. There were unfortunately two deaths, one of which had a mutation in the SCN5A gene. The other patient had a double mutation of the SCN5A and KCNE2 genes. Symptomatic patients had QT and QTc intervals noticeably longer than the asymptomatic patients, although this difference was not shown to be significant. LQT3 patients as well as those with a double mutation were affected more severely because two of the three LQT3 patients and one of the two patients with a double mutation suffered a cardiac arrest. Three patients in our study showed no mutation. Nevertheless, two of them suffered a severe cardiac event. This confirms the limits of genetic diagnosis, which could be envisaged in all cases. All of the clinical and ECG data should be combined with the genetic analysis in order to confirm the diagnosis.

[Voriconazole photosensitivity: 7 cases]. / Photosensibilisation au voriconazole: 7 cas.

BACKGROUND: Voriconazole is a new second-generation fluconazole-derived triazole. With greater potency against susceptible species and a broader spectrum of activity than fluconazole, it is the treatment of choice for invasive pulmonary aspergillosis and other fungal infections (Fusarium, Scedosporium/Pseudalleschezria) is indicated in a visit Candida infections refractory to fluconazole. We describe 7 cases of photosensitivity during treatment with voriconazole in a setting of immunodepression. CASE REPORTS: The patients comprised 5 women and 2 men with a mean age of 38 years (17-67 years). Five had undergone pulmonary transplantation for mucoviscidosis, one had undergone kidney transplantation for lupus nephroangiosclerosis and one was on long-term systemic steroid treatment for Sjögren's syndrome. All patients had very severe immunosuppression and were receiving voriconazole for pulmonary aspergillosis (6 cases) or Scedosporium infection (1 case). Photosensitization appeared within 5 weeks to 14 months after the start of treatment, and in all cases followed exposure to sun, occasionally at low levels. In all cases, cutaneous lesions rapidly disappeared on discontinuation of treatment. DISCUSSION: There have been reports in the literature, although rare, of photosensitivity with voriconazole. Patients must be informed of the possibility of this adverse effect and sun protection must be recommended when voriconazole is prescribed, particularly during periods of intensive exposure.

Cost and co-morbidities associated with hypoglycemic inpatients in Belgium.

BACKGROUND AND OBJECTIVES: Little is known about the economic burden of hypoglycemia in Belgium, or its related co-morbidities. This study aimed at estimating the cost and length of stay associated with hypoglycemia-related hospitalizations in diabetic patients in Belgium and the association between hypoglycemia and in-hospital all-cause mortality, incidence of traumatic fractures, depression, and cardiovascular diseases (myocardial infarction or unstable angina), using retrospective data from 2011. METHODS: Patient data were retrieved from the IMS Hospital Disease Database, including longitudinal (per calendar year) information on diagnoses, procedures, and drugs prescribed in ∼20% of all Belgian hospital beds. The eligible population included all adult (<19 year) diabetic (both types) patients, further split between those with/without a history of hypoglycemia-related hospitalizations. Diabetes, hypoglycemia, and co-morbidities of interest were identified based on International Classification of Diseases and Related Health Problems Version 9 (ICD-9) diagnosis codes. All costs were extrapolated to 2014 using progression in hospitalization costs since 2001. RESULTS: A total of 43,410 diabetes-related hospitalizations were retrieved, corresponding to 30,710 distinct patients. The average hospitalization cost was €10,258 when hypoglycemia was documented (n = 2625), vs €7173 in other diabetic hospitalized patients (n = 40,785). When controlling for age and sex, a higher mortality risk (OR = 1.59; p-value <0.001), a higher incidence of traumatic fractures (OR = 1.25; p-value = 0.009), and a higher probability of depression-related hospitalizations (OR = 1.90; p-value <0.001) were observed in hypoglycemic patients. A similar risk of cardiovascular event was observed in both groups, but hypoglycemic patients were more at risk of experiencing multiple events. CONCLUSION: Hospitalizations for hypoglycemia are expensive and associated with an increased risk of depression and traumatic fractures as well as increased in-hospital mortality. Interventions that can help reduce the risk of hypoglycemia, and consequently the burden on hospitals and society, without compromising glycemic control, will help to further improve diabetes management.

Circumstances of death and gross and microscopic observations in a series of 200 cases of sudden death associated with arrhythmogenic right ventricular cardiomyopathy and/or dysplasia.

BACKGROUND: Sudden death is a possible consequence of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D). Prevalence of ARVC/D in unexpected sudden cardiac death (USCD), however, remains imprecise, as do circumstances of death and ARVC/D-associated gross and microscopic findings, especially His bundle anomalies. METHODS AND RESULTS: We reviewed 14 000 forensic autopsies required by judicial authorities from January 1980 to January 1999 in a 2 000 000-resident area. Age, gender, and circumstances of death were recorded. Hearts were examined macroscopically and microscopically. In this series, the ARVC/D group accounted for 200 consecutive cases (10.4%) of USCD, including 108 males and 92 females (average age 32.5 and 34.5 years, respectively). Nearly one third of deaths occurred during the fourth decade of life. Circumstances of death were various, but 75.6% occurred during everyday life events (at home, 63.1%; in the street, 6.6%; or at work, 6.1%); only 7 cases (3.5%) occurred during sports activity. Nineteen cases (9.5%) happened during the perioperative period. Adipose infiltration of the right ventricle was either isolated (20%) or associated with fibrosis (74.5%) and lymphocytes (5.5%). A total of 14.5% of cases had cardiac hypertrophy, assessed by an increase in heart weight and/or left ventricular wall thickness. In most cases, the His bundle and its branches were abnormal either because of infiltration of adipose tissue (8.1%), fibrosis (54.3%), or both (5.6%). CONCLUSIONS: In ARVC/D, both sexes are equally affected, and there is a peak of risk during the fourth decade. Death most frequently occurs during sedentary activity. His abnormalities and left ventricular hypertrophy may be associated with ARVC/D.