The challenge of measuring quality of life in children with Hirschsprung's disease or anorectal malformation

PURPOSE: The aim of the present study was to assess, after adaptation to French, the only specific quality of life (QoL) instrument for children with Hirschsprung\u27s disease or anorectal malformation, the Hirschsprung\u27s disease/Anorectal Malformation Quality of Life questionnaire (HAQL), in order to get a standardized QoL evaluation instrument that could further be used to help health care improvement. METHODS: The study was conducted in three teaching hospitals, including the French reference center for anorectal and pelvic malformations. After adaptation to French, QoL questionnaires were sent to the children and proxies. The questionnaire was mailed to 280 families. Psychometrics properties of the questionnaires (validity and reliability) were analysed from 120 proxy and 96 child questionnaires. RESULTS: The HAQL with the original structure was not acceptable. Exploratory steps led to a clinically pertinent structure that had acceptable fit and good validity and reliability properties. The final structure pools physical symptoms (continence, discomfort) and psychosocial dimensions (general well-being, social and emotional functioning) of QoL. CONCLUSION: The final structure, despite the disadvantage of being a new structure, allows assessment of QoL in this population and has the advantage of being shorter and validated on the clinical postoperative questionnaire from the Krickenbeck international consensus

Tolerance and efficacy of preventive gastrostomy feeding in pediatric oncology

BackgroundMalnutrition in pediatric oncology remains underestimated, although having a negative impact on outcome. Enteral nutrition (EN) using percutaneous endoscopic gastrostomy (PEG) may prevent or reverse malnutrition consequences. We aimed to evaluate both efficacy and safety of early EN during tumors treatment in children. Procedures Medical records of pediatric patients having a PEG tube inserted between 1995 and 2009 were retrospectively reviewed. We compared type and incidence of complications in Group 1, including 74 patients suffering from cancer, and control Group 2, including 57 patients with neurological impairment. Efficacy of EN was evaluated through nutritional parameters [Z-scores weight for height (W/H) and height for age (H/A)], post-operative complications and relapse rates. Statistical significance was set for P < 0.05. Results PEG tolerance was similar in both groups, as shown by comparable complication rates (62% vs. 76%, NS). EN allowed improvement or stabilization of Z-score W/H in 76% of oncologic patients. The final height loss was lower (−0.5 vs. −1.2 SD of Z-scores H/A) when EN was started at the beginning of the oncologic treatment. In bone tumors, EN prevented weight loss during chemotherapy, and tended to lessen surgical complications, relapses and deaths. Conclusions Early gastrostomy feeding represents a relatively safe way to prevent malnutrition in children with cancer, and might play a role in bone tumors oncological outcome. Further prospective studies are needed to confirm these results and assess the impact of EN and PEG on quality of life

Factors influencing immune response after in vivo retrovirus-mediated gene transfer to the liver.

BACKGROUND: Highly efficient retrovirus-mediated gene transfer into hepatocytes in vivo triggers an immune response directed against transduced hepatocytes. This effect may be due either to spreading of retroviral vectors in the blood stream with subsequent infection of antigen presenting cells (APCs) or to cross-presentation of the transgene product present as a contaminant in the viral stock. In order to decrease immune response, we evaluated the effect of asanguineous perfusion of the liver as well as purification of the viral stock on long-term transduction of hepatocytes using the nls-lacZ marker gene. METHODS: Animals were divided in four groups. In group 1, the viral supernatant was perfused in the regenerating liver after complete vascular exclusion of the organ. In group 2, using the same strategy, animals received retroviral supernatant that was passed through a beta-galactosidase affinity column to reduce beta-galactosidase contamination. In two control groups (respectively groups 3 and 4) the corresponding viral supernatants were delivered via peripheral injection. RESULTS: In group 1, 23.1% of animals had no immune response 2 months after gene delivery vs. 33.4% in group 2, 4.3% in control group 3, and 0% in control group 4. Statistical analysis of the results demonstrated that only the difference between groups 2 and 3 was statistically significant. This indicated that both asanguineous perfusion together with passage through an affinity column were required to decrease significantly immune response. CONCLUSIONS: Our present results suggest that both supernatant contamination and viral spreading contribute to immune response after retrovirus-mediated gene delivery to the liver

Laparoscopic adjustable gastric banding in adolescents: Results at two years including psychosocial aspects

BACKGROUND/PURPOSE: Obesity now affects 3%-4% of the pediatric population and contributes to the increase in cardiac mortality in adulthood. Bariatric surgery is the best treatment for weight loss and the obesity-associated comorbidities in adults. We report here our experience of laparoscopic adjustable gastric banding (LAGB) in adolescents. METHODS: The medical charts of the first 16 patients operated on in our center were reviewed. Data were compiled concerning weight loss, physical and biological comorbidities, health-related quality of life (QOL) and surgical complications before surgery and during 24months of follow-up. RESULTS: The maximal pre-operative median body mass index was 43.0kg·m(-2), decreasing to 33.0kg·m(-2) at 2years post-LAGB, which corresponded to a 49.2% excess body weight loss (p<0.001). Most comorbidities (glucose intolerance, hypertension and sleep apnea) resolved within the first year post-LAGB and QOL was improved on the PedsQL™ scales. No severe surgical complications were noted, with only three re-interventions for device failure (2) or band removal (1). CONCLUSION: LAGB is well tolerated in adolescents and shows a beneficial impact on weight loss and obesity-related comorbidities. Associated with global management, it may have a positive impact on patients\u27 QOL and social and psychological status

Uncertainties in power computations in a turbocharger test bench

A specific study of the uncertainties of turbine power output measured in turbocharger test benches is presented using the law of uncertainty propagation and the influence of the different terms that contribute to it is shown. Then, non-linear mixed integer mathematical programming algorithms used with the turbine power uncertainty expression become an essential tool to overcome the problem of selection new sensors to improve an existing test rig or to contribute to a new one. A method of optimisation is presented for two different scenarios: first, where the maximum cost is a constraint; second where the maximum uncertainty is a constraint and the total cost is minimised. When using a large transducers database, computational efforts may be reduced by solving the relaxed non-integer problem by means of sequential quadratic programming and then probing the ceilings and floors of the parameters to get an optimum approximation with low costs. A comparison between the linear uncertainty propagation model and Monte Carlo simulations is also presented, only showing benefits of the later method when computing high order statistical moments of the turbine power output probability distribution.This work has been partially supported by the Spanish Ministerio de Ciencia e Innovacion through Grant No. DPI2010-20891-C02-02 and by the Spanish Ministerio de Economia y Competitividad through Grant No. TRA2012-36954.Olmeda González, PC.; Tiseira Izaguirre, AO.; Dolz Ruiz, V.; García-Cuevas González, LM. (2015). Uncertainties in power computations in a turbocharger test bench. Measurement. 59:363-371. https://doi.org/10.1016/j.measurement.2014.09.055S3633715

Outcome of alimentary tract duplications operated on by minimally invasive surgery: a retrospective multicenter study by the GECI (Groupe d'Etude en Coeliochirurgie Infantile).

BACKGROUND: Alimentary tract duplications (ATD) are a rare cause of intestinal obstruction in childhood. There are many case reports but few series about laparoscopy or thoracoscopy for ATD. The aim of our study was to report the outcome of minimally invasive surgery (MIS) for ATD. METHODS: This was a retrospective multicenter study from the GECI (Groupe d\u27Etude en Coeliochirurgie Infantile). We reviewed the charts of 114 patients operated on by MIS for ATD from 1994 to 2009. RESULTS: Sixty-two patients (54 %) had a prenatal diagnosis. Forty-nine patients (43 %) were symptomatic before surgery: 33 of those patients (63 %) with postnatal diagnosis compared to 16 (25 %) with prenatal diagnosis (P < 0.01). In this last group, the median age at onset of symptoms was 16 days (range = 0-972). One hundred and two patients had laparoscopy (esophageal to rectal duplications) and 12 patients had thoracoscopy for esophageal duplications. The mean operative time was 90 min (range = 82-98). There were 32 (28 %) resection anastomoses, 55 (48 %) enucleations, and 27 (24 %) unroofings. The conversion rate was 32 %, and in a multivariate analysis, it was significantly higher, up to 41 % for patients weighing <10 kg (P < 0.01). Ten patients (8 %) had unintentional perioperative opening of the digestive tract during the dissection. Eight patients had nine postoperative complications, including six small bowel obstructions. The median length of hospital stay was 4 days (range = 1-21) without conversion and 6 days (range = 1-27) with conversion (P = 0.01). The median follow-up was 3 months (range = 1-120). Eighteen of the 27 patients who underwent partial surgery had an ultrasound examination during follow-up. Five (18 %) of them had macroscopic residue. CONCLUSION: This study showed that MIS for ATD is feasible with a low rate of complications. Patients with prenatal diagnosis should have prompt surgery to prevent symptoms, despite a high rate of conversion in small infants

A comparison of surgical devices for grade II and III hemorrhoidal disease. Results from the LigaLongo Trial comparing transanal Doppler-guided hemorrhoidal artery ligation with mucopexy and circular stapled hemorrhoidopexy

PURPOSE: Little is presently known on the impact of device type for Doppler-guided hemorrhoidal artery ligation/mucopexy (DGHAL) or circular stapled hemorrhoidopexy (CSH) when a surgical treatment is considered for hemorrhoidal disease (HD). In this study, we aimed to compare the outcome in terms of adverse events and recurrence rate, of patients included in the multicenter LigaLongo RCT ( ClinicalTrials.gov NCT01240772) according to the type of devices used. METHODS: In the DGHAL arm (N = 193), the procedure was done with transanal hemorrhoidal dearterialization (THD)™ (THD, Correggio, Italy) (104 patients) and with HAL-RAR™ (Agency for Medical Innovations (AMI) GmbH, Feldkirch, Austria) (89 patients). In the CSH arm (N = 184), procedure for prolapse and hemorrhoids (PPH)-03™ (Ethicon Endo-Surgery, Cincinnati OH) and hemorrhoidopexy and prolapse (HEM)™ (Covidien, Inc.) staplers were used in respectively 106 and 78 cases. Surgery-related morbidity at 90 postoperative days (POD) based on the Clavien-Dindo procedure-related complication score and clinical outcome in terms of recurrence and reoperation rate at 12 postoperative months (POM) was collected. RESULTS: Three hundred and seventy-seven patients were randomized according to HD grade. In the DGHAL arm, the number of ligations and mucopexies was higher in the AMI group (p < 0.0001); at 90 POD, the overall morbidity was similar between the two groups. In the CSH arm, donut sizes were similar; at 90 POD, the PPH group had a higher risk of postoperative grade 1 morbidity (anal urgency or incontinence) compared to the HEM group (p = 0.003). At 12 POM, no statistical difference was found between the two groups of each arm in terms of grade III recurrence or reoperation. CONCLUSION: Postoperative morbidity and outcome at 1 year were similar regardless of the type of devices used. These findings suggest that device type has little impact on HD treatment results. TRIAL REGISTRATION: clinicaltrials.gov -Identifier NCT01240772

Esophageal atresia: data from a national cohort

PURPOSE: A prospective national register was established in 2008 to record all new cases of live-birth newborns with esophageal atresia (EA). This epidemiological survey was recommended as part of a national rare diseases plan. METHODS: All 38 national centers treating EA participated by completing for each patient at first discharge a questionnaire validated by a national committee of experts. Data were centralized by the national reference center for esophageal anomalies. Quantitative and qualitative analyses were performed, with P-values of less than 0.05 considered statistically significant. Results of the 2008-2009 data collection are presented in this report. RESULTS: Three hundred seven new living cases of EA were recorded between January 1, 2008, and December 31, 2009. The male/female sex ratio was 1.3, and the live-birth prevalence of EA was 1.8 per 10,000 births. Major characteristics were comparable to those reported in the literature. Survival was 95%, and no correlation with caseload was noted. CONCLUSIONS: Epidemiologic surveys of congenital anomalies such as EA, which is a rare disease, provide valuable data for public health authorities and fulfill one important mission of reference centers. When compared with previous epidemiological data, this national population-based registry suggests that the incidence of EA remains stable

Lentiviral Vectors That Express UGT1A1 in Liver and Contain Mir-142 Target Sequences Normalize Hyperbilirubinemia in Gunn Rats

Background & AimsCrigler–Najjar type 1 (CN-I) is an inherited liver disease caused by an absence of bilirubin–uridine 5′-diphosphate–glucuronosyltransferase (UGT1A1) activity. It results in life-threatening levels of unconjugated bilirubin, and therapeutic options are limited. We used adult Gunn rats (an animal model of the disease) to evaluate the efficiency of lentiviral-based gene therapy to express UGT1A1 in liver. Methods Gunn rats were given intraportal injections of VSVG-pseudotyped lentiviral vectors that encode UGT1A1 under the control of a liver-specific transthyretin promoter (mTTR.hUGT1A1); this vector does not contain target sequences for miR-142, a microRNA that is expressed specifically in hematopoietic cells. Rats were also injected with the vector mTTR.hUGT1A1.142T, which contains 4 copies of the miR-142 target sequences; its messenger RNA should be degraded in antigen-presenting cells. Bilirubinemia was monitored, and the presence of transduced hepatocytes was analyzed by quantitative polymerase chain reaction. Vector expression was tested in vitro in rat hematopoietic cells. Results In Gunn rats, bilirubin levels normalized 2 weeks after administration of mTTR.hUGT1A1. However, hyperbilirubinemia resumed 8 weeks after vector administration, concomitant with the induction of an immune response. In contrast, in rats injected with mTTR-UGT1A1.142T, bilirubin levels normalized for up to 6 months and transduced cells were not eliminated. Conclusions Lentiviral vectors that express UGT1A1 reduce hyperbilirubinemia in immunocompetent Gunn rats for at least 6 months. The immune response against virally expressed UGT1A1 can be circumvented by inclusion of miR-142 target sequences, which reduce vector expression in antigen-presenting cells. This lentiviral-based gene therapy approach might be developed to treat patients with CN-I