Acute pulmonary thromboembolism during mitral valve repair

Perioperative pulmonary thromboembolism during cardiac surgery is extremely rare. We report a 55-year-old male, who developed acute pulmonary thromboembolism during mitral valve repair. Intra-operative trans oesophageal echocardiography failed to demonstrate thromboembolus in the pulmonary arteries but it showed the secondary signs of acute pulmonary artery obstruction. Thromboembolectomy was done after high index of suspicion on clinical grounds was found and the patient recovered. The diagnostic accuracy and sensitivity of transoesophageal echocardiography in circumstances with altered haemodynamics is questionable and has not been investigated. Therefore, indirect evidence of pulmonary artery obstruction on echocardiography may have a predictive value and failure to demonstrate pulmonary thromboembolism by this tool should not exclude the possibility of it especially when it is highly suspected.     

Systematic Analysis of CCNO Variants in a Defined Population: Implications for Clinical Phenotype and Differential Diagnosis

Reduced generation of multiple motile cilia (RGMC) is a novel chronic destructive airway disease within the group of mucociliary clearance disorders with only few cases reported. Mutations in two genes, CCNO and MCIDAS, have been identified as a cause of this disease, both leading to a greatly reduced number of cilia and causing impaired mucociliary clearance. This study was designed to identify the prevalence of CCNO mutations in Israel and further delineate the clinical characteristics of RGMC. We analyzed 170 families with mucociliary clearance disorders originating from Israel for mutations in CCNO and identified two novel mutations (c.165delC, p.Gly56Alafs*38; c.638T>C, p.Leu213Pro) and two known mutations in 15 individuals from 10 families (6% prevalence). Pathogenicity of the missense mutation (c.638T>C, p.Leu213Pro) was demonstrated by functional analyses in Xenopus. Combining these 15 patients with the previously reported CCNO case reports revealed rapid deterioration in lung function, an increased prevalence of hydrocephalus (10%) as well as increased female infertility (22%). Consistent with these findings, we demonstrate that CCNO expression is present in murine ependyma and fallopian tubes. CCNO is mutated more frequently than expected from the rare previous clinical case reports, leads to severe clinical manifestations, and should therefore be considered an important differential diagnosis of mucociliary clearance disorders.     

A novel repair for patients with atrioventricular septal defect requiring reoperation for left atrioventricular valve regurgitation.

OBJECTIVE: Left atrioventricular valve regurgitation (LAVVR) is the most frequent indication for reoperation following atrioventricular septal defect (AVSD) repair. We estimate from our experience that within 10 years of initial repair, 14% of patients undergoing repair of atrioventricular septal defect (AVSD) require reoperation for this complication. We have developed a novel leaflet augmentation technique for LAVVR which may avoid failure of conventional repair and/or the need for valve replacement. METHOD: The novel technique consists of insertion of a glutaraldehyde-treated autologous pericardial patch to augment the bridging leaflets of the atrioventricular valve. We describe the outcome of eight patients in whom this technique was used and compared them to 68 other patients with AVSD undergoing reoperation for LAVVR by either conventional repair (n=54) or valve replacement (n=14). RESULTS: There were no early deaths or major complications following patch repair. The mean follow-up is 2.3 years (range 1-8.5 years) during which there were no late deaths. Two patients underwent reintervention at 3.5 and 5 years after patch repair for LAVVR and were successfully rerepaired. Mild residual LAVVR was seen at last echocardiography in six patients and mild to moderate in two. These results compare favorably with the 68 patients who underwent conventional surgery. The 3-year freedom from reoperation was 86% for both repair groups. Dysplastic valve tissue appears to be a major risk factor for failure of conventional repair or for valve replacement. Failure of conventional valve repair led to valve replacement in six of seven patients. CONCLUSIONS: For patients with late LAVVR after AVSD repair, pericardial leaflet augmentation is durable and may avoid failure of conventional repair or valve replacement in patients with dysplastic valves.     

Exclusion of the candidate genes ACE and Bcl-2 for six families with nephronophthisis not linked to the NPH1 locus.

BACKGROUND: Nephronophthisis (NPH) is an autosomal recessively transmitted kidney disease, characterized by cyst formation at the cortico-medullary junction, and a sclerosing tubulointerstitial nephropathy. Juvenile nephronophthisis (NPH1) is the most common genetic cause of renal failure in children and maps to chromosome 2q12-q13. The responsible gene NPHP1 has been identified and encodes for nephrocystin. Not all families with NPH demonstrate linkage to that locus. METHODS: We studied six families with NPH without linkage to the NPH1 locus. In order to attempt identification of a new causative gene, the candidate genes ACE (angiotensin converting enzyme) and Bcl-2 (B cell leukaemia/lymphoma 2 gene) originating from mouse models, were examined. For the six families highly polymorphic microsatellites covering the whole candidate gene regions were haplotyped and linkage analysis was performed. RESULTS: Haplotype analyses of all families examined were incompatible with linkage of the disease status to ACE or Bcl-2. Linkage analysis excluded both candidate gene regions with a LOD-score of < -2. CONCLUSIONS: This study excluded the candidate genes ACE and Bcl-2 for NPH. Additional linkage studies need to be performed in order to identify further genes responsible for nephronophthisis.     

Role of intraoperative transesophageal echocardiography in pediatric cardiac surgery

Background

Intraoperative transesophageal echocardiography (TEE) has a major role in detecting residual lesions during and/or after pediatric cardiac surgery.

Methods

All pediatric patients who underwent cardiac surgery between July 2001 and December 2008 were reviewed. The records of surgical procedure, intraoperative TEE, and predischarge transthoracic echocardiograms were reviewed to determine minor and major residual cardiac lesions after surgical repair.

Results

During the study period, a total of 2268 pediatric cardiac patients were operated in our center. Mean age was 21 months (from 1 day to 14 years). Of these patients, 1016 (48%) had preoperative TEE and 1036 (46%) were evaluated by intraoperative echocardiography (TEE or epicardial study). We identified variations between TEE and preoperative transthoracic echocardiography in 14 patients (1.3%). Only one surgical procedure was cancelled after atrial septal defect exclusion. The other 13 patients had minor variation from their surgical plan. Major residual lesions requiring surgical revision were detected in 41 patients (3.9%), with the following primary diagnoses: tetralogy of Fallot in 12 patients (29%), atrioventricular septal defect in seven patients (17%), ventricular septal defect in seven patients (17%), double outlet right ventricle in two patients (5%), Shone complex in two patients (5%), subaortic stenosis in two patients (5%), mitral regurgitation in two patients (5%), pulmonary atresia in two patients (5%), and five patients (12%) with other diagnoses.

Conclusion

Intraoperative TEE has a major impact in pediatric cardiac surgery to detect significant residual lesions. Preoperative TEE has a limited role in case of a high quality preoperative transthoracic echocardiography. We recommend routine use of intraoperative TEE during and/or after intracardiac repair in children.     

Association between Helicobacter. <Emphasis Type="Italic">pylori</Emphasis> and coronary artery disease

The high prevalence of both Helicobacter.pylori infection and coronary atherosclerosis in our country prompted us to assess the probable association between both conditions. This cross-sectional study recruited 153 patients scheduled to undergo coronary artery angiography. Patients were divided into two groups on the basis of coronary angiography results. Sixty-nine patients had coronary atherosclerosis and the 84 remaining patients were normal. Characteristics and pre-angiographic serum levels of triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein, and Helicobacter.pylori IgG antibody were assessed in the patients and compared between the groups. Helicobacter.pylori infection occurred in 88 (57.51%) patients: 40 (58%) in the atherosclerotic group and 48 (57.1%) in the control group with no significant differences (P=0.918). Our multivariable analysis revealed that Helicobacter.pylori infection was not an independent predictive factor for coronary artery disease (P =0.915). Also, the prevalence of atherosclerosis risk factors with respect to the seropositive and seronegative Helicobacter.pylori infection was assessed in the case group, which showed no significant difference. Furthermore, the prevalence of seropositive Helicobacter.pylori infection in terms of the number of diseased coronary vessels was evaluated, this demonstrated no significant association between the number of the diseased vessels and Helicobacter.pylori infection. This study demonstrated that Helicobacter.pylori infection was not an independent predictive factor of atherosclerosis.     

Analysis of BRAF V600E mutation in 1,320 nervous system tumors reveals high mutation frequencies in pleomorphic xanthoastrocytoma, ganglioglioma and extra-cerebellar pilocytic astrocytoma

Missense mutations of the V600E type constitute the vast majority of tumor-associated somatic alterations in the v-RAF murine sarcoma viral oncogene homolog B1 (BRAF) gene. Initially described in melanoma, colon and papillary thyroid carcinoma, these alterations have also been observed in primary nervous system tumors albeit at a low frequency. We analyzed exon 15 of BRAF spanning the V600 locus by direct sequencing in 1,320 adult and pediatric tumors of the nervous system including various types of glial, embryonal, neuronal and glioneuronal, meningeal, adenohypophyseal/sellar, and peripheral nervous system tumors. A total of 96 BRAF mutations were detected; 93 of the V600E type and 3 cases with a three base pair insertion between codons 599 and 600. The highest frequencies of BRAF (V600E) mutations were found in WHO grade II pleomorphic xanthoastrocytomas (42/64; 66%) and pleomorphic xanthoastrocytomas with anaplasia (15/23; 65%), as well as WHO grade I gangliogliomas (14/77; 18%), WHO grade III anaplastic gangliogliomas (3/6) and pilocytic astrocytomas (9/97; 9%). In pilocytic astrocytomas BRAF (V600E) mutation was strongly associated with extra-cerebellar location (p?=?0.009) and was most frequent in diencephalic tumors (4/12; 33%). Glioblastomas and other gliomas were characterized by a low frequency or absence of mutations. No mutations were detected in non-glial tumors, including embryonal tumors, meningiomas, nerve sheath tumors and pituitary adenomas. The high mutation frequencies in pleomorphic xanthoastrocytomas, gangliogliomas and extra-cerebellar pilocytic astrocytomas implicate BRAF (V600E) mutation as a valuable diagnostic marker for these rare tumor entities. Future clinical trials should address whether BRAF (V600E) mutant brain tumor patients will benefit from BRAF (V600E)-directed targeted therapies.