Heterozygous loss of Rbm24 in the adult mouse heart increases sarcomere slack length but does not affect function.

RNA-binding proteins are key regulators of post-transcriptional processes such as alternative splicing and mRNA stabilization. Rbm24 acts as a regulator of alternative splicing in heart and skeletal muscle, and is essential for sarcomere assembly. Homozygous inactivation of Rbm24 in mice disrupts cardiac development and results in embryonic lethality around E12.5. In the present study, we generated somatic Rbm24 knockout (KO) mice and investigated the effects of reduced levels of Rbm24 in the adult heart. Due to the embryonic lethality of Rbm24 KO mice, we examined cardiac structure and function in adult Rbm24 heterozygotes (HETs). Rbm24 protein expression was 40% downregulated in HET hearts compared to WT hearts. Force measurements on isolated membrane-permeabilized myocytes showed increased sarcomere slack length and lower myofilament passive stiffness in adult Rbm24 HET compared to wildtype cardiomyocytes. As a result of the differences in sarcomere slack length, the relations between force development and sarcomere length differed between WT and Rbm24 HET hearts. No differences in sarcomere structure and titin isoform composition were observed. Likewise, in vivo cardiac function and myocardial structure was unaltered in Rbm24 HET mice compared to WT, at baseline and upon pressure overload after transverse aortic constriction. In conclusion, we generated a somatic Rbm24 KO model and recapitulated the previously reported embryonic phenotype. In adult Rbm24 HET cardiomyocytes we observed increased sarcomere slack length, but no difference in sarcomere structure and cardiac function.

[Heart transplantation, indications and results at the University Hospital of Liege]. / La transplantation cardiaque : indications actuelles et résultats de l'expérience liégeoise.

Heart transplantation remains undoubtedly the most effective treatment for end-stage heart failure, whatever its cause. Last decade has witnessed significant improvements in terms of morbidity and mortality following heart transplant. The 5-year survival rate is now beyond 70 %. However, the shortage of potential donors limits its use and requires strict criteria before listing a candidate for heart transplantation. Herein, we present a review of current indications and results of the heart transplantation program at the University hospital of Liège.

La transplantation cardiaque demeure, à ce jour sans conteste, le traitement de choix de l'insuffisance cardiaque terminale, quelle qu'en soit l'origine. La dernière décennie a été marquée par une amélioration significative des résultats de la transplantation cardiaque tant en termes de mortalité que de morbidité. La survie globale à 5 ans dépasse maintenant 70 %. Cependant, la pénurie d'organes limite malheureusement son emploi et impose des critères de sélection rigoureux des potentiels candidats. Une revue des indications actuelles ainsi qu'un aperçu des résultats de la transplantation cardiaque au CHU de Liège sont présentés.

[Minimally invasive aortic valve surgery. Experience of the academic hospital of Liege and review of the literature]. / Chirurgie «mini-invasive¼ de la valvule aortique. Expérience du CHU de Liège et revue de la littérature.

Minimally invasive aortic valve surgery aims at reducing surgical invasiveness whilst preserving the high efficacy of surgical aortic valve replacement. As such it increases the value of the overall procedure. The surgical experience at the ULg is reported and replaced in the context of the pertinent related litterature.

La réalisation de la chirurgie de la valve aortique par une voie d'abord réduite atténue le traumatisme chirurgical subi par le patient, mais doit garantir un geste de qualité équivalente. Au travers de la présentation d'une histoire clinique inscrite dans la routine, nous rapportons l'expérience du service dans ce domaine et nous la confrontons aux données de la littérature. L'approche mini-invasive apporte des avantages supplémentaires par rapport à la chirurgie conventionnelle et s'inscrit dans l'évolution actuelle des procédures interventionnelles.

Small sample sizes in high-throughput miRNA screens: A common pitfall for the identification of miRNA biomarkers.

Since the discovery of microRNAs (miRNAs), circulating miRNAs have been proposed as biomarkers for disease. Consequently, many groups have tried to identify circulating miRNA biomarkers for various types of diseases including cardiovascular disease and cancer. However, the replicability of these experiments has been disappointingly low. In order to identify circulating miRNA candidate biomarkers, in general, first an unbiased high-throughput screen is performed in which a large number of miRNAs is detected and quantified in the circulation. Because these are costly experiments, many of such studies have been performed using a low number of study subjects (small sample size). Due to lack of power in small sample size experiments, true effects are often missed and many of the detected effects are wrong. Therefore, it is important to have a good estimate of the appropriate sample size for a miRNA high-throughput screen. In this review, we discuss the effects of small sample sizes in high-throughput screens for circulating miRNAs. Using data from a miRNA high-throughput experiment on isolated monocytes, we illustrate that the implementation of power calculations in a high-throughput miRNA discovery experiment will avoid unnecessarily large and expensive experiments, while still having enough power to be able to detect clinically important differences.

[Budd-Chiari syndrome: a case report and review of the literature]. / LE CAS CLINIQUE DU MOIS. Le syndrome de Budd-Chiari. Revue de la literature.

We report the history of a 20-year-old woman admitted for thrombosis of the sus-hepatic veins and of the inferior vena cava (IVC) with extension of the thrombus into the right atrium. The etiological research was negative and a diagnosis of idiopathic Budd-Chiari syndrome was retained. In view of the absence of vein repermeabilisation under adequate anticoagulant therapy, a venous thrombectomiy was performed under cardiopulmonary bypass, which improved the hepatic venous drainage. Budd-Chiari syndrome is a very serious disorder. Its treatment implies a step by step procedure. An effective anticoagulation must first be established. The complications of portal hypertension then require attention. For a symptomatic patient, one should assess the possibility of restoring the venous permeability, improving the hepatic drainage and decompressing the liver by radiological interventional or surgical procedures. Finally, an hepatic transplantation should be considered in case of treatment ineffectiveness, of fulminant hepatic failure, or of an evolution towards cirrhosis.

Artificial insemination with donor sperm (AID): heterogeneity in sperm banking facilities in a single country (Belgium).

Due to the high inflow of foreign patients seeking cross-border reproductive care in Belgium and the increased number of lesbian couples and single women who call for artificial insemination with donor sperm (AID), Belgian sperm banks nowadays face a shortage in donor sperm. However, since there is no central registration system for sperm donors in Belgium, no figures are currently available supporting this statement. Therefore a study was performed to obtain a detailed overview of the sperm banking facilities in Belgium. Questionnaires were sent to all Belgian centres for assisted reproduction with laboratory facilities (n = 18) to report on their sperm banking methods. The results showed that 82% of the centres rely partially or completely on foreign donor sperm. Moreover, four of the thirteen centres that have their own sperm bank use imported donor sperm in > 95% AID cycles. Our results show that in 63% of the Belgian AID cycles imported Danish donor sperm is being used. Donor recruitment is mainly performed through the centre's website (61%) or by distributing flyers in the centre (46%) and 9 to 180 potential donors have been recruited per centre in 2013. Eventually, 15 to 50% of these candidate donors were accepted. Different criteria for donor acceptance are handled by the centres: donor age limits range from 18-25 to 36-46 years old, and thresholds for sperm normality differ considerably. We can conclude that a wide variation in methods associated with sperm banking is observed in Belgian centres.

Surgical treatment of cardiovascular complications in patients with Marfan syndrome: a report of two cases and literature review.

Cardiovascular disease is the main cause of morbidity and mortality in patients with Marfan syndrome. The most life threatening complication is aortic root aneurysms leading to aortic dissection or rupture. It can be prevented by regular aortic follow-up and prophylactic aortic surgery. Modern aortic surgery has led to a substantial increase in the life expectancy of these patients. We report two cases of Marfan syndrome with cardiovascular complications. Their management is discussed according to the most recent literature.

[Structured differential diagnosis of a transient impairment of consciousness]. / La vignette diagnostique de l'étudiant. Diagnostic différentiel structuré d'une perte brève de conscience.

Transient impairment of consciousness frequently prompts the patient to consult a neurologist or a cardiologist. Detailed medical history and physical examination allow to distinguish fainting from epileptic seizure, metabolic or psychogenic events. We report the history of an 83-year-old woman who presented a transient loss of consciousness.The vascular, investigation demonstrated a subocclusive stenosis of one of the internal carotid arteries. We shall consider the differential diagnosis of transient impairment of consciousness and discuss the relationship between fainting and carotid artery disease.

Cryopreservation of human sperm: efficacy and use of a new nitrogen-free controlled rate freezer versus liquid nitrogen vapour freezing.

Preservation of spermatozoa is an important aspect of assisted reproductive medicine. The aim of this study was to investigate the efficacy and use of a recently developed liquid nitrogen and cryogen-free controlled rate freezer and this compared with the classical liquid nitrogen vapour freezing method for the cryopreservation of human spermatozoa. Ten patients entering the IVF programme donated semen samples for the study. Samples were analysed according to the World Health Organization guidelines. No significant difference in total sperm motility after freeze-thawing between the new technique and classical technique was demonstrated. The advantage of the new freezing technique is that it uses no liquid nitrogen during the freezing process, hence being safer to use and clean room compatible. Investment costs are higher for the apparatus but running costs are only 1% in comparison with classical liquid nitrogen freezing. In conclusion, post-thaw motility of samples frozen with the classical liquid nitrogen vapour technique was comparable with samples frozen with the new nitrogen-free freezing technique. This latter technique can thus be a very useful asset to the sperm cryopreservation laboratory.

[Endoleak, a specific complication of the endovascular treatment of aortic aneurysms]. / Le cas clinique du mois. Les endofuites, une complication spécifique du traitement endovasculaire des pathologies aortiques.

Endoleaks represent the most common complication of endovascular aortic aneurysm repair. With the increasing use of endovascular techniques for aortic aneurysm repair, the prevalence of endoleaks has risen. While maintaining pressurization of the aneurysm sac, endoleaks expose to persistent risks of an evolution towards rupture. Long-term surveillance with imaging studies is necessary to reduce the incidence of these specific complications that may require intervention. The objective of this article is to draw the attention to the possible occurrence of these complications and to report the elements of diagnosis and treatment.

Relationship between hyaluronic acid binding assay and outcome in ART: a pilot study.

The sperm-hyaluronan binding assay (HBA) is a diagnostic kit for assessing sperm maturity, function and fertility. The aim of this prospective cohort pilot study was to evaluate the relationship between HBA and WHO sperm parameters (motility, concentration and detailed morphology) and possible influence of sperm processing on hyaluronic acid binding. A cohort of 68 patients undergoing a first combo in vitro fertilisation/intracytoplasmic sperm injection treatment after failure of three or more intrauterine insemination cycles were included in the study. Outcome measures studied were fertilisation rate, embryo quality, ongoing pregnancy rate and cumulative pregnancy rate. HBA outcome improved after sperm preparation and culture, but was not correlated to detailed sperm morphology, concentration or motility. HBA did not provide additional information for identifying patients with poor or absent fertilisation, although the latter had more immature sperm cells and cells with cytoplasmic retention present in their semen. HBA outcome in the neat sample was significantly correlated with embryo quality, with miscarriage rates and ongoing pregnancy rates in the fresh cycles, but not with the cumulative ongoing pregnancy rate. No threshold value for HBA and outcome in combo IVF/ICSI treatment could be established. The clinical value for HBA in addition to routine semen analysis for this patient population seems limited.

Endovascular aneurysm repair (EVAR): does it fulfil all its promises?

In the trend of the endovascular revolution for occlusive arterial disease, management of aneurysmal disease has known an analogous change in the nineties. Elective endo-aneurysmal stentgrafting (EVAR or endovascular aneurysm repair) is nowadays of widespread application in contemporary practice all over the world, sometimes by over-enthusiast proponents. There is a burden of recent publications on that topic. Critical analysis of relevant data reveal compelling evidence that elective EVAR is a safe procedure with a threefold reduced 30-day morbidity-mortality, when compared to conventional open aneurysm repair. EVAR also deemed efficace in terms of AAA rupture prevention. At the other hand, mid-term follow-up revealed that EVAR does not endure at the long-term in any late survival benefit, compared to open AAA repair. The major concern and drawback of EVAR is its higher cost and the need for indefinite, life-long surveillance, with a 20% reintervention rate (almost catheter-based endovascularly) at 5-year follow-up. In this review-paper, short-term gains of EVAR are balanced against the inherent disadvantages and long-term losses. According best available evidence, EVAR should not longer be the first choice for high-risk patients, judged unfit for open aneurysm repair. There also exist doubt on the use of EVAR in young fit patients with an anticipated long life expectancy. In approximately half of the AAA patients, EVAR can be considered as the appropriate treatment option.

[Aortic pseudo-aneurysm after coarctation repair]. / Pseudo-anévrysme de l'isthme aortique après correction chirurgicale de la coarctation aortique.

Aortic pseudo-aneurysm is a well-known late complication after surgical repair of aortic coarctation. We report two cases of pseudo-aneurysm of the aortic isthmus evidenced after previous surgical repair of congenital aortic coarctation. These clinical observations give us the opportunity to underline the importance of a specific lifelong medical follow-up for patients who have undergone such surgery.

Open surgery for abdominal aortic aneurysm or aorto-iliac occlusive disease--clinical and ultrasonographic long-term results.

OBJECTIVE: To determine postoperative and long-term outcome and assess the relevance of abdominal ultrasound (US) after surgery for abdominal aortic aneurysm (AAA) or aortoiliac occlusive disease (AIOD). METHODS: Records of 1704 consecutive patients having graft implantation from 1988 to 2000, either for AAA (n = 1144) or for AIOD (n = 560), were reviewed. In 2006, follow-up was 9180 patients-years for the AAA group and 5450 patients-years for the AIOD group. Among 1006 alive patients, 377 were invited randomly for US and clinical examination. RESULTS: Hospital death occurred in 99 patients (8.6%) of the AAA group (53% in ruptured and 2% in elective AAA), and in 18 patients of the AIOD group (3.2%). There were 581 late deaths, including eight due to prosthesis infection, one to pseudo-aneurysm rupture, and one to graft thrombosis (0.6% graft-related mortality). Prosthesis thrombosis occurred in 32 patients (26 in AIOD group, p < 0.001), and graft infection in 26 (17 in AAA group, p < 0.01). Pseudoaneurysms developed in 90 patients (68 in AIOD group, p < 0.001), including eight at the proximal aortic, one at the distal aortic, two at the iliac and 79 at the femoral anastomosis. In the AAA group only, surgery was required for a new thoraco-abdominal and pararenal aneurysm in eight and four patients, respectively, while US evidenced a 26-35 and a 36-50 mm supraanastomotic aortic dilatation in 65 (32%) and in 14 (7%) patients, at a mean follow-up of 10.5 and 9.3 years, respectively. CONCLUSION: Long-term results are good after open surgery for AAA or AIOD. Prosthesis infection and anastomotic pseudo-aneurysm are the main causes of graft-related mortality and morbidity, respectively. Because of high incidence of asymptomatic supraanastomotic aortic dilatation, all patients with a history of AAA repair should have regular abdominal US.

Cerebral subarachnoid blood migration consecutive to a lumbar haematoma after spinal anaesthesia.

We report the case of a woman who received spinal anaesthesia for peripheral vascular surgery of the lower limbs and subsequently developed a spinal subarachnoid haematoma. Interestingly, low back pain was the only symptom of this spinal subarachnoid haemorrhage. During the following days, blood migrated from the spinal haematoma towards the cerebral subarachnoid spaces. The patient presented with stupor, nausea and vomiting that resolved within 2 weeks with conservative treatment.

[Isolated spontaneous dissection of the superior mesenteric artery: a case report]. / Dissection isolée de l'artère mésentérique supérieure: à propos d'un cas.

We report the case of a 38-year-old man admitted at the emergency department for abdominal pain of abrupt onset. Computed tomographic examination revealed a spontaneous isolated dissection of the superior mesenteric artery and an anevrysm of the coeliac artery caused by the arcuate ligament. Outcome was favorable under conservative medical treatment and a three months follow-up was uneventful. This observation offers the opportunity to present recent insights concerning this pathology.