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

The impact of anorectal malformations on anorectal function and social integration in adulthood: report from a national database.

AIM: The impact of anorectal malformation (ARM) on bowel function and social, educational and occupational end-points was investigated in adult patients entered on a national database. METHOD: Data from a national database of adult patients operated on between 1962 and 1999 for ARM were analysed. The database Malformations Ano-rectales et Pelviennes rares (MAREP) was part of a common information system, CEMARA, on rare congenital disorders. A self-administered questionnaire regarding bowel function, academic qualifications, employment and family status was mailed to patients. The type of ARM, subsequent follow-up and management including surgical interventions were retrospectively retrieved from medical records. RESULTS: Of 210 adult patients on the registry since 2008, 68 were included in this study. Only three (8.5%) had had regular follow-up. All reported some disturbance in bowel function. The fertility rate of 1.5 children per woman did not differ from the general population. CONCLUSION: Anorectal malformation ARM often leads to suboptimal bowel function in adulthood. This has an impact on social integration

Variations in the detection of anorectal anomalies at birth amongst European cities

Aim: The diagnosis of anorectal malformations (ARM) is made at birth by perineal examination of the newborn, yet small series reported late diagnosis in almost 13%. No large series to date have looked into the magnitude of missed ARM cases in the neonatal period across Europe. This study aimed to define the rate of missed ARM at birth across four UK and EU centers. Methods: All ARM cases treated at two UK tertiary centers in the past 15 years were compared to two tertiary European centers. Demographic and relevant clinical data were collected. Late diagnosis was defined as any diagnosis made after discharge from the birth unit. Factors associated with late diagnosis were explored with descriptive statistics. Results: Across the four centers (117/1350, 8.7%) were sent home from the birth unit without recognizing the anorectal anomaly. Missed cases showed a slight female predominance (1.3:1), and the majority (113/117, 96.5%) were of the low anomaly with a fistula to the perineum. The rate of missed ARM cases was significantly higher in the UK centers combined (74/415, 17.8%) compared to those in the EU (43/935, 4.6%), (p<0.00001), and this was independent of individual center and year of birth. Conclusion: Significant variation exist between the UK and other European countries in the detection of ARM at birth. We recommend raising the awareness of accurate perineal examination at time of newborn physical examination. We feel this highlights an urgent need for a national initiative to assess and address the timely diagnosis of ARM in the UK

Malformations ano-rectales

Anorectal malformations (ARM) are the result of an abnormal development of the terminal part of the digestive tract interesting anus and/or rectum that occur early between the sixth and tenth week of embryonic development. They carry a malformation spectrum of severity depending on the level of disruption of the anorectal canal and of the associated caudal malformations (sacrum and spine). ARM are associated in over half the cases with other malformations that can be integrated in some cases in known syndromes. If surgical treatment to restore anatomy as normal as possible is indispensable, post-operative care is essential for these patients whose defecation mechanisms are altered, to reach if not continence, at least a socially acceptable cleanliness

Aplicación de células madres en caninos con enfermedad articular degenerativa; datos preliminares

Las células madre mesenquimales (CMM) son células no especializadas que pueden diferenciarse en varios linajes celulares con funciones específicas y poseen propiedades regenerativas. Las CMM de tejido adiposo (CMM-TA) crecen rápidamente y se obtienen de manera sencilla, por lo cual su utilización en las enfermedades degenerativas es prometedora. La enfermedad articular degenerativa (EAD) canina es una artropatía asociada a discapacidad y deterioro de la calidad de vida. El tratamiento médico busca mitigar el dolor, mejorar la amplitud de los movimientos articulares y retrasar la aparición de las lesiones degenerativas. La utilización de CMM-TA podría ser una terapia apropiada en la EDA debido a que previene la pérdida epitelial y la fibrosis, y mejora la angiogénesis. Su objetivo evaluar los beneficios del tratamiento a través de aplicación de CMM en caninos con EAD. Poner en marcha la técnica de obtención, depuración, clasificación y posterior aplicación en pacientes. Mejorar las condiciones clínicas de los pacientes estudiados

Immature Cryopreserved Ovary Restores Puberty and Fertility in Mice without Alteration of Epigenetic Marks

BACKGROUND: Progress in oncology could improve survival rate in children, but would probably lead to impaired fertility and puberty. In pre-pubertal girls, the only therapeutic option is the cryopreservation of one ovary. Three births have been reported after reimplantation of cryopreserved mature ovary. Conversely, reimplantation of ovary preserved before puberty (defined as immature ovary) has never been performed in humans. METHODOLOGY/PRINCIPAL FINDINGS: In order to analyze ovarian function, we performed transplantation using fresh or cryopreserved immature grafts in pre-pubertal or adult mice. Puberty as well as cyclic hormonal activity was restored. All follicle populations were present although a significant reduction in follicle density was observed with or without cryopreservation. Although fertility was restored, the graft is of limited life span. Because ex vivo ovary manipulation and cryopreservation procedure, the status of genomic imprinting was investigated. Methylation status of the H19 and Lit1 Imprinting Control Regions in kidney, muscle and tongue of offsprings from grafted mice does not show significant alteration when compared to those of unoperated mice. CONCLUSIONS/SIGNIFICANCE: These results demonstrate that immature ovarian grafting can restore spontaneous puberty and fertility. However, these data suggest that follicle depletion leads to premature ovarian failure. This study addresses the very important epigenetics issue, and provides valuable information to the study of ovarian transplantation suggesting that these procedures do not perturb normal epigenetics marks. These results are highly relevant to the reimplantation question of immature cortex in women

Cumulative effective dose from imaging in infants with esophageal atresia: How low can we go?

With the increasing life expectancy for patients with esophageal atresia (EA), and a known predisposition to certain cancers, cumulative radiation exposure from imaging is of increasing significance. This study describes the cumulative effective radiation dose (CED), during the first 6 months of life, estimated from radiologic procedures when dose reduction methods are used. Medical records of newborns with EA followed in our pediatric hospital in 2019–2020 were reviewed for demographics, EA subtype and hospitalization length of stay. Number and type of imaging studies, and radiation exposure were recorded in order to estimate CED in mSv. Twenty-one children were included. Each child underwent a median of 16 (IQR 13–39) imaging studies, which were primarily chest radiography (median of 12 (IQR 10–35)). The overall median CED per patient was 0.4 mSv (IQR 0.08–1.28), with the majority of radiation exposure resulting from plain radiography (median of 0.3 mSv (0.08–0.52)). Careful consideration should be given to the use of imaging in EA to minimize morbidity in these vulnerable infants. A low dose of radiation can be achieved by following these recommendations: proscription of systematic superfluous examinations, standardization and optimization of the imaging protocols, dosimetry monitoring and proper training of operators

Impaired synthesis and secretion of SopA in <i>Salmonella</i> Typhimurium <i>dam</i> mutants

DNA adenine methylation regulates virulence gene expression in certain bacteria, including Salmonella Typhimurium. The aim of this study was to investigate the involvement of DNA adenine methylase (Dam) methylation in the expression and secretion of the SPI-1 effector protein SopA. For this purpose, SopA–FLAG-tagged wild-type and dam strains of Salmonella Typhimurium were constructed. The expression and secretion of SopA were determined in bacterial culture and in intracellular bacteria recovered from infected HEp-2 epithelial cells. Bacterial culture supernatants and pellets were used to investigate secreted proteins and cell-associated proteins, respectively. Western blot and quantitative reverse transcriptase PCR analysis showed that the dam mutant expresses lower levels of SopA than the wild-type strain. Interestingly, the strain lacking Dam synthesizes SopA under nonpermissive conditions (28 °C). In addition, SopA secretion was drastically impaired in the dam mutant. In vivo experiments showed that the intracellular Salmonella dam mutant synthesizes SopA although in lower amounts than the wild-type strain. Taken together, our results suggest that Dam methylation modulates the expression and secretion of SopA in Salmonella Typhimurium