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.

[Single procedure treatment of complex nephrolithiasis: about a modern series of anatrophic nephrolithotomy]. / Traitement en un temps de la lithiase rénale complexe : à propos d'une série moderne de néphrotomies bivalves.

PURPOSE: Advances in endourology have significantly reduced indications of open surgery in the treatment of staghorn calculi. However, in our experience, open surgery is still the treatment of choice in some cases. This study presents the results of a series of selected patients and discusses the results in terms of efficacy and morbidity. MATERIALS: A cohort of 26 patients underwent anatrophic nephrolithotomy by lombotomy to treat a complex staghorn calculus. RESULTS: The mean stone size was 68,5mm, 70% were complete staghorn calculi. The operative time was 100minutes. Blood loss was 225mL, with a postoperative transfusion rate of 15.4%. The hospital stay was 8.4 days. The stone free rate following the procedure was 92%. The creatinine clearance (MDRD) at 3 months was improved from 5.9mL/min/m(2) on average over the entire series. CONCLUSION: There are clearly still indications for open surgery in staghorn stones management, with good results in this contemporary series on both stone removal and nephronic preservation. Yet, it appears that this technique is no longer taught. LEVEL OF EVIDENCE: 5.

Molecular diagnosis of known recessive ataxias by homozygosity mapping with SNP arrays.

The diagnosis of rare inherited diseases is becoming more and more complex as an increasing number of clinical conditions appear to be genetically heterogeneous. Multigenic inheritance also applies to the autosomal recessive progressive cerebellar ataxias (ARCAs), for which 14 genes have been identified and more are expected to be discovered. We used homozygosity mapping as a guide for identification of the defective locus in patients with ARCA born from consanguineous parents. Patients from 97 families were analyzed with GeneChip Mapping 10K or 50K SNP Affymetrix microarrays. We identified six families homozygous for regions containing the autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) gene, two families homozygous for the ataxia-telangiectasia gene (ATM), two families homozygous for the ataxia with oculomotor apraxia type 1 (AOA1) gene, and one family homozygous for the AOA type 2 (AOA2) gene. Upon direct gene testing, we were able to identify a disease-related mutation in all families but one of the two kindred homozygous at the ATM locus. Although linkage analyses pointed to a single locus on chromosome 11q22.1-q23.1 for this family, clinical features, normal levels of serum alpha-foetoprotein as well as absence of mutations in the ATM gene rather suggest the existence of an additional ARCA-related gene in that interval. While the use of homozygosity mapping was very effective at pointing to the correct gene, it also suggests that the majority of patients harbor mutations either in the genes of the rare forms of ARCA or in genes yet to be identified.

Delineation of the clinical phenotype associated with OPHN1 mutations based on the clinical and neuropsychological evaluation of three families.

Recent reports have demonstrated that mutations in the OPHN1 gene were responsible for a syndromic rather than non-specific mental retardation. Abnormalities of the posterior fossa with cerebellar hypoplasia have been demonstrated in all male patients reported to date. We report here a new family with X-linked mental retardation due to mutation in OPHN1 and present unpublished data about two families previously reported, concerning the facial and psychological phenotype of affected males and carrier females. Our study confirms that cerebellar hypoplasia is a hallmark of this syndrome. In addition, affected males display facial similarities that can help the diagnosis. Most carrier females have mild mental retardation and subtle facial changes.

[Monitoring of multiple trauma in an emergency hospital unit]. / Le monitorage des polytraumatisés en situation d'urgence hospitalière.

In the monitoring of multiple trauma patients in the emergency hospital setting the use of monitors should be graduated. However, the use and interpretation of data from these monitors is becoming increasingly complex and can lead to errors and responses which may not be adopted. Clinical nomination and observation have their limits and the anaesthetist is faced with the added difficulties of interpretation of data from monitors and is pitfalls. The management of the patient is based on this human-machine relationship, which provides the basis for the therapeutic attitude and the treatment which ensues. Basic monitoring comprises a pulse oximeter, a capnograph, an ECG and a blood pressure monitor, 52% of incidents are detected by these instruments; 27% by SpO2, 24% by capnography. The pertinence is 82% for the oximeter when used alone and 55% for the capnography alone, although when the two are used together this increases to 88%. If the blood pressure monitor is added the pertinence increases to 93%, and to 95% if the FiO2 is monitored. The use of monitors of levels of haemoglobin or haematocrit must take into account the important variations in volaemia. The displayed values have a poor predictive value. The second level of monitoring comprises the use of a pulmonary artery catheter. The errors in measurement and interpretation are reviewed and finally, we consider the possible use of FOE transoesophageal echocardiography in the multiple trauma patient.

[Reconstruction with free jejunal graft after pharyngo-esophageal resection for cancer: functional results and survival]. / Reconstruction par greffon jéjunal libre après exérèse pharyngo-oesophagienne pour cancer: résultats fonctionnels et survie.

57 patients with cancer of the hypopharynx underwent 59 pharyngo-esophageal reconstructions with a free jejunal graft after total removal of a tumor combined with resection of the circumferential tissues. 18 patients had been previously irradiated. Median resumption of oral intake was 16 days; 40 out of 50 patients (98%) followed for more than 2 years regained normal eating habits. The cumulative 5-year survival rate was 44%. The free jejunal graft should be advocated as a safe and reliable procedure for hypopharyngeal cancer.

[Deaths due to smallpox vaccination in France 1968-1977 (author's transl)]. / Etude des décès imputés à la vaccination antivariolique en France, de 1968 à 1977.

Between 1968 and 1977 there were 4 113 109 primary smallpox vaccinations in France. There were 30 deaths but no deaths occurred after re-vaccination. The mortality can be analysed as follows: -- proven or probable cases: 1.5 death/million vaccinations; -- proven, probable or possible cases 2.9/million vaccinations; -- proven, probable, possible or doubtful 7.3 cases/million vaccinations. The risk of death is 3 to 4 times greater under the age of one year and an overall death rate of 6/million vaccinations in reasonably accurate.