Vojislav Parezanovic

4q34.1–q35.2 deletion in a boy with phenotype resembling 22q11.2 deletion syndrome

Small terminal or interstitial deletions involving bands 4q34 and 4q35 have been described in several patients with a relatively mild phenotype such as mild to moderate intellectual disability and minor dysmorphic features. We present a boy born from unrelated parents with a de novo 4q34.1–q35.2 deletion and clinical features resembling 22q11.2 deletion syndrome. To the best of our knowledge, this is the first reported patient with 4q34–q35 deletion and phenotype resembling 22q11.2 deletion syndrome without fifth finger anomalies as a specific feature of 4q- syndrome. G-banding karyotyping disclosed the deletion, which was further delineated by microarray comparative genomic hybridization. Fluorescence in situ hybridization and multiplex ligation-dependent probe amplification analyses did not reveal rearrangements of 22q11.2 region. MLPA confirmed the deletion within the 4q35.2 region. Conclusion: Given the considerable clinical overlaps between the 22q11.2 deletion syndrome and clinical manifestation of the patient described in this study, we propose that region 4q34.1–q35.2 should be considered as another region associated with phenotype resembling 22q11.2 deletion syndrome. We also propose that distal 4q deletions should be considered in the evaluation of patients with phenotypic manifestations resembling 22q11.2 deletion syndrome in whom no 22q11.2 microdeletion was detected, even in the absence of distinctive fifth finger anomalies. Additionally, we underline the importance of applying array CGH that enables simultaneous genome-wide detection and delineation of copy number changes (e.g., deletions and duplications).

Ruptured Hydatid Cyst of the Interventricular Septum with Acute Embolic Pulmonary Artery Complications

Hydatid cysts located in the interventricular septum are especially rare but with the high risk for intracavitary rupture. We report a patient with acute pulmonary embolism caused by an isolated, ruptured hydatid cyst on the right side of the interventricular septum. Early diagnosis was made by echocardiography and positive serology. Pulmonary artery embolism was confirmed by angiography and the patient was operated on. Embolectomy was performed by removing multiple fragments of ruptured endocyst from the left pulmonary artery, followed by surgical closure of a cyst cavity. Prompt diagnosis and an appropriate surgical treatment prevented a potentially fatal outcome.

Mycobacterium fortuitum Endocarditis Associated with Cardiac Surgery, Serbia

To the Editor: Mycobacterium fortuitum is a member of the group of rapidly growing nontuberculous mycobacteria. It is a well-known causative agent of skin and soft tissue infections, postsurgical wound infections, and other health care–associated infections (1). Only sporadic cases of endocarditis caused by this bacterium have been reported (2–4). We describe a cardiac surgery–related outbreak of endocarditis caused by M. fortuitum in 3 children. Over a 3-week period during 2009, eight children consecutively underwent surgery for correction of ventricular septal defect (VSD) by insertion of a bovine pericardial patch at the University Children’s Hospital in Belgrade, Serbia. None of them had previous cardiac surgery. The same patch, SJM Pericardial Patch with EnCap Technology (St. Jude Medical, St. Paul, MN, USA), was used as a source for smaller, tailored patches for all patients. Sterile scissors and forceps were used to tailor a piece of the patch needed for a corresponding VSD closure. During repeated performances of this procedure and between surgeries, the patch had been continuously stored in 2% propylene oxide (PO) provided by the manufacturer. Each tailored piece of the patch had been immersed into freshly prepared sterile saline for 6 min before defect patching. The postoperative course had been uneventful for all patients, and they were discharged 7 days after the procedure. However, 3 patients were readmitted to the hospital because of prolonged fever and increasing fatigue. Patients 1, 2, and 3 (Table) had been the fourth, sixth, and eighth patients undergoing VSD repair, respectively. Diagnosis of infective endocarditis in these patients was established by transthoracic echocardiography findings and blood cultures positive for acid-fast bacteria (Table). Acid-fast bacteria also were recovered from the patch and vegetation taken during reoperation in patient 3 (Table). The isolates were identified as M. fortuitum by the GenoType Mycobacterium CM assay (Hain Lifescience, Nehren, Germany) (5). Empiric treatment with vancomycin and ceftriaxone was switched to amikacin, ciprofloxacin, and imipenem. After 6 weeks of treatment, the patients were discharged, and all were asymptomatic 12 months later. Table Characteristics of patients in an outbreak of Mycobacterium fortuitum endocarditis, Serbia* The cultural characteristics and susceptibility patterns of all the isolates obtained were indistinguishable. To explore their possible clonal relatedness, we genotyped 3 M. fortuitum strains isolated from blood cultures (1 isolate per patient) and 2 M. fortuitum isolates recovered from samples taken during reoperation in 1 of the patients. The enterobacterial repetitive intergenic consensus PCR was used (6), and all isolates produced identical patterns. Nosocomially acquired M. fortuitum endocarditis has been reported but only sporadically in adults, and these cases usually were fatal (3,4,7). In contrast, we describe 3 related cases of M. fortuitum endocarditis in children who recovered. The relatedness of the cases is strongly supported by the following. First, epidemiologic links are obvious because the 3 patients underwent surgery in the same operating room, and the same patch was used in all of them. Second, M. fortuitum strains isolated from the 3 patients were phenotypically and genotypically identical. Repeated use of the same patch in multiple surgeries strongly suggests the contaminated patch was the source of M. fortuitum infection in the 3 patients. This possibility could not be corroborated by bacteriologic examination of the patch because the remaining unusable fragments had been discarded after the surgeries (i.e., ≈3 months before the outbreak became evident). Although contamination of the patch during manufacture is possible (8), it seems more reasonable to assume that the contamination occurred intraoperatively. The common factor in nosocomially acquired M. fortuitum infections is presumed to be exposure to a liquid contaminated with this organism (1,9). The patch was not exposed to solutions other than the PO in which it had been stored and the sterile saline used during the rinsing procedure. Because only a piece of the patch tailored for a particular patient was exposed to a saline freshly prepared for each surgery, contamination of the PO by M. fortuitum presumably led to contamination of the patch. Liquid PO is used as a chemical sterilant for bioprostheses intended for single use. However, multiple use of the same patch implied repeated exposure of the PO solution to the environment and prolonged storage at 4°C between surgeries. Because PO effectiveness is markedly reduced at temperatures <16°C (10), the specific circumstances could have compromised the sterilizing capacity of the PO solution and enabled contamination by ubiquitous M. fortuitum. We are well aware that the patch was intended for single use only and that application of the same patch in multiple patients is not a practice in industrialized countries. However, it is a practice in some resource-limited countries. The outbreak of M. fortuitum endocarditis we describe is a clear warning that such practice is associated with high risk and thus should be discontinued.

Echocardiographic evaluation of left ventricular outflow tract hemodynamics in healthy children with anomalous left ventricular band.

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Treatment of cyanotic heart diseases in children

Cyanotic heart diseases are relatively rare, but they are severe and heterogeneous congenital heart diseases, which require complex surgery. Development of different advanced surgical procedures, such as arterial switch operation (ASO), Fontan and its modifications, Norwood etc. operations, as well as better perioperative care significantly improved survival rate and quality of life of these children. The study group included 308 children treated for cyanotic heart disease in Yugoslavia, in the period January 2000 to July 2004. Some of them (239, 77.6%) were treated at the University Childrens Hospital in Belgrade, and others (69, 22.4%) in different institutions abroad. The age of the operated patients varied between 1 day and 19 years (median 12 months). The patients (pts) were divided into four groups, according to the disease and type of the operation. In the whole group of 308 patients treated due to cyanotic heart disease, there were 232 (75.3%) cases with open heart surgery and 76 (24.7%) with closed procedures. The mortality rate was significantly different between disease/operation groups, and age groups. Average mortality rates differed from 11.8% for palliative procedures to 12.5% for complete corrections. Mortality rate and achieved surgical results in treatment of children with cyanotic heart diseases were significantly worse than those published by leading cardiac surgery centers in the world. However, there is a clear tendency in introducing new surgical procedures, lowering the age at which the operation is done and decreasing the mortality rates.