Hematopoietic stem cell transplantation with reduced toxicity conditioning regimen in mitochondrial neurogastrointestinal encephalopathy syndrome.

BACKGROUND: Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive disorder due to mutations in the TYMP gene. Clinical findings are characterized by neurologic manifestations and severe gastrointestinal dysfunction. The syndrome is usually fatal, the most effective treatment appears to be hematopoietic stem cell transplantation (HSCT). PROCEDURE: In this retrospective study, we evaluated HSCT that was performed using a reduced toxicity myeloablative conditioning regimen in patients with MNGIE at our center. RESULTS: A total of six allogeneic transplant procedures were performed in four patients. Three patients had fully matched donors, and one patient had a haploidentical donor. Treosulfan-based myeloablative conditioning regimen was applied in five of six transplants. Bone marrow was used as a stem cell source. One patient is being followed up in the 4th year of posttransplant with full chimeric and without graft versus host disease (GVHD). One patient died of acute stage IV gastrointestinal system GVHD. Two patients underwent second transplantation due to engraftment failure, one of which was the patient who had a haploidentical transplant. CONCLUSIONS: Treosulfan-based regimen is well tolerated, although engraftment failure with this conditioning regimen can be a significant problem. We share our haploidentical transplant experience, which will be the first reported case in the literature.

The effectiveness of tools for monitoring hemophilic arthropathy.

INTRODUCTION: Hemophilic arthropathy is the most important cause of morbidity in patients with hemophilia. The earliest alterations that occur during the development of hemophilic arthropathy can be shown using magnetic resonance imaging (MRI). In addition, various tools have been developed to monitor joint health. AIM: : The purpose of this study was to determine the correlation between these tools when used to assess hemophilia patients. METHODS: This cross-sectional study enrolled 38 hemophilia patients between 2 and 18 years of age. Hemophilia Joint Health Score (HJHS) and radiologic scores (Pettersson and Arnold-Hilgartner) were used to evaluate the joints of the patients (n=236). Magnetic resonance imaging (MRI) was performed on 46 joints that were pathologic according to the HJHS. These joints were imaged bilaterally; therefore, 14 normal joints were imaged. In addition, the Functional Independence Score in Hemophilia (FISH) was used to evaluate the joints of 33 patients. RESULTS: The HJHS scores were correlated with the MRI and FISH scores. The annual bleeding rate was not correlated with any scores; however, the number of painful joints was correlated with the MRI scores. The radiologic scores were correlated weakly with progressive score and HJHS. CONCLUSION: The agreement between the HJHS scores and the MRI scores suggests that the HJHS may be used safely as a first-line tool. We recommend that the FISH should be used in the routine follow-up of hemophilia patients as a functional evaluation tool. Painful joints may be useful in deciding to apply MRI, whereas the bleeding frequency may not be useful.

Spontaneous epidural and subdural hematoma in a child with afibrinogenemia and postoperative management.

Congenital afibrinogenemia is a rare coagulation disorder that exhibits recessive inheritance. The prevalence of this disease is around 1 per 1 000 000, but it is increased in countries where consanguineous marriages are common. Umbilical cord bleeding during the neonatal period is generally the first manifestation of the disease, but a later age of onset is not uncommon. This disease may also be manifested by gastrointestinal, genitourinary, mucosal, muscular, articular, and intracranial bleeding during childhood. Intracranial hemorrhage is a rare condition, but it is the leading cause of death in patients with afibrinogenemia. In this report, we present the case of a 13-year-old female patient with afibrinogenemia who underwent an operation for spontaneous massive extradural and subdural hematoma.

A single center's experience with Candida parapsilosis related long-term central venous access device infections: the port removal decision and its outcomes.

Pediatric cancer patients have an increased risk of potentially life-threatening fungal infections such as Candida parapsilosis, associated with long-term CVADs. The Infectious Diseases Society of America (IDSA) guidelines on Candida catheter-related bloodstream infections recommend systemic antifungal therapy and catheter removal. In this study, we focused on our experience with antifungal failure due to totally implanted catheter-associated C. parapsilosis bloodstream infections. We investigated cases leading to port removal in pediatric malignancy patients and the associated patient outcomes. In the first phase of the study, a retrospective chart review was performed to collect patient information, including primary disease; time from hospitalization to port-related candidemia; antifungal drug choice; and the time at which port removal occurred. During the second phase, antifungal susceptibility tests for C. parapsilosis were performed in our microbiology laboratory. All patients had fevers and were neutropenic at the time of candidemia diagnosis. The mean duration between the first isolation of Candida parapsilosis from the port samples to the port removal was 9.75 ± 5.29 days for 11 patients. Patient fevers lasted for a mean time of 16.22 ± 6.51 days. The median recovery duration from fever after CVC removal was four days (range 2-12 days). The median duration for achieving negative blood cultures, following antifungal treatment was 18 days (range 10-27 days). Our data favored the removal of catheters in the presence of ongoing fever, as suggested by the guidelines, independent of the chosen antifungal treatment. Future studies with large samples are needed to evaluate the effects of catheter removal on mortality rates and patient outcomes.

Liposomal amphotericin B versus pentavalent antimony salts for visceral Leishmania in children.

The aim of this study was to investigate the efficacy of a 21-day schedule of liposomal amphotericin B compared to pentavalent antimony salts in the treatment of patients during a first episode of visceral leishmaniasis. In this study, 17 cases of visceral leishmaniasis admitted to Behçet Uz Children's Hospital between January 2005 and April 2012 were reviewed retrospectively. The study group was composed of 11 males (64.7%) and 6 females (35.3%). One group included 11 patients who were treated with pentavalent antimony salts, sodium stibogluconate or meglumine antimoniate, intramuscularly for 28 days. The second group was treated with amphotericin B intravenously at a dosage of 3 mg/kg on days 1-5, 10 and 21 (a cumulative dose of 21 mg/kg/day). While pentavalent antimony salts were found to increase biochemical and hematological findings, liposomal amphotericin B was responsible for rapid recovery in fever and shorter hospital stay. As a result, our study shows the advantages of both medications independent of their costs.

Arterial function and anatomy in obese children with cardiovascular risk factors.

BACKGROUND: Limited data are available related to the effects of cardiovascular risk factors on abdominal arterial stiffness using carotid and brachial artery indices. Therefore, we aimed to determine arterial changes in obese children and investigate any relation with cardiovascular risk factors. METHODS: Thirty-eight obese children (mean body mass index: 28.35 ± 4.65 kg/m(2) ) and 34 age- and sex-matched healthy subjects underwent ultrasound measurements of abdominal, carotid and brachial arteries. Aortic strain, pressure strain elastic modulus (Ep), pressure strain normalized by diastolic blood pressure (Ep*), carotid intima-media thickness, carotid artery compliance, brachial artery flow-mediated dilatation, and well-known cardiovascular risk factors were assessed in the obese children. RESULTS: Obese children had significantly higher Ep and Ep* parameters than the healthy controls (mean: 242.6 [107.1-666.6], 164.2 [110.6-231.5]; P < 0.001, and mean: 3.39 [1.76-7.5], 2.64 [1.46-4.2]; P < 0.001, respectively). Ep and Ep* were significantly correlated with the homeostasis model assessment of insulin resistance (r = 0.587, P = 0.001; r = 0.467, P = 0.004, respectively). Receiver-operator curve analysis of Ep for identification of children with cardiovascular risk factors showed that the area under the curve for hyperinsulinemia was 0.80 (P < 0.001) and for hypertriglyceridemia was 0.62 (P < 0.01). CONCLUSIONS: Abdominal arterial stiffness parameters as well as carotid intima-media thickness and brachial arterial flow-mediated dilatation assessment were similarly useful in identifying obese children with cardiovascular risk factors. Insulin resistance is related with the augmented rigidity of the aortic wall in obese children.

Higher expression of the novel gene upregulated gene 4 in two acute lymphoblastic leukemia patients with poor prednisolone response.

Elucidation of the molecular mechanisms of leukemogenesis is important for a better understanding of the prognosis of acute lymphoblastic leukemia (ALL). Studies have shown that the expression of upregulated gene 4 (URG4), which promotes cell growth and survival, is increased in different types of carcinomas including hepatocellular carcinoma, gastric cancer and osteosarcoma. Similarly, higher expression of URG4 and cyclin D1 gene might promote proliferation of the blast cells by causing escape from the G1 checkpoint and entry into the S phase. This study reports the high expression level of URG4 in 2 high-risk ALL patients for the first time in the literature. In conclusion, the higher expression of URG4 in our 2 patients suggests that URG4 might be involved in leukemogenesis. Future studies with a large number of high-risk ALL patients and cell culture studies are needed to demonstrate the exact role of URG4 in leukemogenesis.

Cardiovascular risk factors and noninvasive assessment of arterial structure and function in obese Turkish children.

Obesity is associated with a number of risk factors, such as hyperlipidemia, hyperinsulinemia, hypertension, and early atherosclerosis. Evidence indicates that atherosclerosis begins in childhood and progresses over decades. In this work, we examined the relationship between cardiovascular risk factors and ultrasonographic signs of subclinical atherosclerosis in 77 obese children and adolescents compared to 40 non-obese healthy peers. Carotis intima media thickness (cIMT), carotid artery compliance (CAC), brachial artery flow-mediated dilatation (FMD), and established cardiovascular risk factors were studied. In the obese patients, cIMT was significantly increased (0.57 mm vs 0.45 mm, p < 0.001) whereas CAC (1.84% vs 3.29%, p < 0.001) and FMD (9.67 % vs 14.81%, p < 0.001) were significantly decreased. In multiple linear regression analysis, a relation was observed between cIMT, CAC, brachial FMD on one hand, and body mass index (BMI) on the other. Among the lipid anomalies, only hypertriglyceridemia was found to be positively correlated with cIMT. Additionally, we found a significant association between waist circumference (WC) and FMD. These findings indicate that obesity in children is associated with arterial wall alterations and endothelial dysfunction. In hyperlipidemic situations, only hypertriglyceridemia was found to be positively correlated with cIMT. This finding has consistently indicated TG to be a risk factor for the development of atherosclerosis. To our knowledge this is the first study to determine the relation between FMD and WC, which is used as a parameter of obesity in childhood.