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1.
Med Educ ; 56(6): 660-669, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35263461

RESUMEN

INTRODUCTION: Multisource feedback (MSF), also called 360-degree assessment, is one form of assessment used in postgraduate training. However, there is an ongoing discussion on its value, because the factors that influence the impact of MSF and the main impact of MSF are not fully understood. In this study, we investigated both the influencing factors and the impact of MSF on residency training. METHODS: We conducted a qualitative case study within the boundaries of the residency training for paediatricians and paediatric surgeons at a University Hospital. We collected data from seven focus group interviews with stakeholders of MSF (residents, raters and supervisors). By performing a reflexive thematic analysis, we extracted the influencing factors and the impact of MSF. RESULTS: We found seven influencing factors: MSF is facilitated by the announcement of a clear goal of MSF, the training of raters on the MSF instrument, a longitudinal approach of observation, timing not too early and not too late during the rotation, narrative comments as part of the ratings, the residents' self-assessment and a supervisor from the same department. We found three themes on the impact of MSF: MSF supports the professional development of residents, enhances interprofessional teamwork and increases the raters' commitment to the training of residents. CONCLUSION: This study illuminates the influencing factors and impact of MSF on residency training. We offer novel recommendations on the continuity of observation, the timing during rotations and the role of the supervisor. Moreover, by discussing our results through the lens of identity formation theory, this work advances our conceptual understanding of MSF. We propose identity formation theory as a framework for future research on MSF to leverage the potential of MSF in residency training.


Asunto(s)
Internado y Residencia , Niño , Competencia Clínica , Educación de Postgrado en Medicina , Retroalimentación , Humanos , Investigación Cualitativa
2.
BMC Pediatr ; 22(1): 455, 2022 07 28.
Artículo en Inglés | MEDLINE | ID: mdl-35902844

RESUMEN

BACKGROUND: Surgical site infections (SSIs) in children represent a common and serious postoperative complication. Surgical skin preparation is an essential preventive measure in every surgical procedure. The most commonly used antiseptic agents for surgical skin preparation are chlorhexidine gluconate and iodophors in alcohol-based solutions. In adult patients the use of chlorhexidine-containing antiseptic solutions for preoperative skin preparation has been advocated to reduce SSI rates. Our objective was to conduct a systematic literature review on use of antiseptic agents for surgical skin preparation in children less than 16 years of age. METHODS: A systematic review of MEDLINE, EMBASE, CINAHL and CENTRAL was performed using both MeSH and free text terms and using the relevant Cochrane filter to identify full text randomized trials (RCTs) and comparative observational studies. Interventions of interest were the choice of main agent in antiseptic solutions (chlorhexidine/povidone-iodine/alcohol) compared with each other or with other antiseptic agents. Primary outcome was the reported rate of surgical site infections. RESULTS: In total 8 studies were included in the review; 2 RCTs and 6 observational studies. Observational studies generally did not primarily investigate the association of different antiseptics with subsequent SSI. The identified randomised controlled trials included only 61 children in total, and were of low quality. Consequently, we did not conduct a formal meta-analysis. Since the publication of a comprehensive systematic review of perioperative measures for the prevention of SSI in 2016, no randomized controlled trials comparing antiseptic agents for surgical skin preparation in paediatric surgery have been conducted. CONCLUSION: Robust evidence on the optimal skin antisepsis to reduce SSIs in children is lacking. Direct extrapolation of effects from trials involving adults is not appropriate as physiologic characteristics and risk factors for SSIs differ between adults and children. It is therefore essential to conduct high quality RCT investigating interventions to identify optimal measures to reduce SSI rates in children. TRIAL REGISTRATION: Prospero registration ( CRD42020166193 ).


Asunto(s)
Antiinfecciosos Locales , Clorhexidina , Adulto , Antiinfecciosos Locales/uso terapéutico , Niño , Clorhexidina/uso terapéutico , Humanos , Povidona Yodada , Cuidados Preoperatorios/métodos , Infección de la Herida Quirúrgica/prevención & control
3.
BMC Med Educ ; 20(1): 357, 2020 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-33046060

RESUMEN

BACKGROUND: In medical settings, multisource feedback (MSF) is a recognised method of formative assessment. It collects feedback on a doctor's performance from several perspectives in the form of questionnaires. Yet, no validated MSF questionnaire has been publicly available in German. Thus, we aimed to develop a German MSF questionnaire based on the CanMEDS roles and to investigate the evidence of its validity. METHODS: We developed a competency-based MSF questionnaire in German, informed by the literature and expert input. Four sources of validity evidence were investigated: (i) Content was examined based on MSF literature, blueprints of competency, and expert-team discussions. (ii) The response process was supported by analysis of a think-aloud study, narrative comments, "unable to comment" ratings and evaluation data. (iii) The internal structure was assessed by exploratory factor analysis, and inter-rater reliability by generalisability analysis. Data were collected during two runs of MSF, in which 47 residents were evaluated once (first run) or several times (second and third run) on 81 occasions of MSF. (iv) To investigate consequences, we analysed the residents' learning goals and the progress as reported via MSF. RESULTS: Our resulting MSF questionnaire (MSF-RG) consists of 15 items and one global rating, which are each rated on a scale and accompanied by a field for narrative comments and cover a construct of a physician's competence. Additionally, there are five open questions for further suggestions. Investigation of validity evidence revealed that: (i) The expert group agreed that the content comprehensively addresses clinical competence; (ii) The response processes indicated that the questions are understood as intended and supported the acceptance and usability; (iii) For the second run, factor analysis showed a one-factor solution, a Cronbach's alpha of 0.951 and an inter-rater reliability of 0.797 with 12 raters; (iv) There are indications that residents benefitted, considering their individual learning goals and based on their ratings reported via MSF itself. CONCLUSIONS: To support residency training with multisource feedback, we developed a German MSF questionnaire (MSF-RG), which is supported by four sources of validity evidence. This MSF questionnaire may be useful to implement MSF in residency training in German-speaking regions.


Asunto(s)
Internado y Residencia , Lenguaje , Competencia Clínica , Retroalimentación , Humanos , Reproducibilidad de los Resultados , Encuestas y Cuestionarios
4.
J Pediatr Gastroenterol Nutr ; 66(2): e28-e35, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-29095348

RESUMEN

OBJECTIVES: Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer used in many polyvinylchloride medical devices and is washed out easily. Thereby critically ill infants can become exposed to DEHP concentrations significantly exceeding the recommended threshold. We suspect DEHP to play an important role in the development of intestinal failure-associated liver disease. The aim of this study was therefore to determine the direct influence of DEHP on different liver cell types. METHODS: HepG2, human upcyte hepatocytes, primary murine hepatocytes, LX-2, human upcyte hepatic stellate cells, and liver organoids were cultured with DEHP (0.5-500 µmol/L) and parameters including cytotoxicity, cell-cell interactions, and expression of metabolizing enzymes were investigated. RESULTS: DEHP modulated the expression of xenobiotic metabolizing enzymes, reduced the formation of bile canaliculi and cell polarity, and inhibited Cyp-activity in hepatocytes. DEHP had a toxic effect on LX-2 and induced the fibrogenic activation of hepatic stellate cells. The mode of action of DEHP was different in monolayer cultures compared to 3D-liver organoids, which were more sensitive to DEHP. CONCLUSIONS: This study suggests that DEHP modulates expression and activity of drug-detoxifying liver enzymes in humans at a clinically relevant concentration. Furthermore, it may contribute to the development of cholestasis and fibrosis. These findings strongly support the opinion, that there is a significant potential for serious adverse effects of DEHP derived from medical devices on human health, especially in very young infants with immature livers.


Asunto(s)
Colestasis/inducido químicamente , Dietilhexil Ftalato/farmacología , Hígado/efectos de los fármacos , Animales , Técnicas de Cultivo de Célula , Dietilhexil Ftalato/efectos adversos , Técnica del Anticuerpo Fluorescente , Humanos , Inmunohistoquímica , Hígado/citología , Hígado/patología , Ratones , Reacción en Cadena en Tiempo Real de la Polimerasa
5.
J Pediatr Orthop ; 36(4): 410-5, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25851687

RESUMEN

INTRODUCTION: Acute compartment syndrome (ACS) can lead to irreversible damage if fasciotomy is not performed in a timely manner. Needle manometry is a tool to confirm suspected ACS. The threshold for compartment pressures that can be tolerated has been debated. The aim of this study is to assess the normal compartment pressures in noninjured forearms of children. Further, we sought to quantify the maximum tolerable compartment pressures in fractured forearms of children, thus establishing a baseline and providing guidance in evidence-based decision making to evaluate children with suspected ACS. METHODS: This prospective study included children up to the age of 16 years with forearm fractures that needed reduction with or without osteosynthesis. Between June 2009 and March 2013, 41 children were included. Mean age was 9.25 years (range, 4 to 15.4 y). We used needle manometry to measure the pressures in the superficial and deep volar as well as in the dorsal compartments (DCs) on both the forearms. The mean pressures between compartments in healthy versus injured arms were analyzed using a 1-sided, paired t test. RESULTS: On the injured side, the mean compartment pressure was 19.12 mm Hg (range, 3 to 49 mm Hg) in the deep volar compartment, 15.56 mm Hg (range, 5 to 37 mmHg) in the DC, and 14.8 mm Hg (range, 2 to 35 mm Hg) in the superficial volar compartment. On the noninjured side, the mean compartment pressure was 12.9 mm Hg (range, 6 to 31 mm Hg) in the DC, 10.22 mm Hg (range, 3 to 22 mm Hg) in the deep volar compartment, and 9.66 mm Hg (range, 3 to 21 mm Hg) in the superficial volar compartment. We measured an absolute compartment pressure of >30 mm Hg in 15 patients on the fractured side. Three of them had an absolute compartment pressure of >45 mm Hg. Only 1 had ACS. This patient underwent fasciotomy and was excluded for further analysis. On follow-up (mean, 24.84 mo), no patient was found to have any sequelae of ACS. DISCUSSION: This is the first study to report normal compartment pressure measurements in noninjured forearms and in fractured forearms without clinical suspicion of ACS in children.The mean compartment pressure measured in the deep volar compartment (DVC) in healthy children was 10.22 mm Hg (range, 3 to 22 mm Hg) and therefore slightly higher than in adults. Some children with fractures tolerated absolute compartment pressures >30 mm Hg without clinical signs of ACS. Fasciotomy in children under close observation could eventually be delayed despite surpassing the accepted pressure limits for adults. LEVEL OF EVIDENCE: Level I-prognostic.


Asunto(s)
Síndromes Compartimentales/fisiopatología , Traumatismos del Antebrazo/fisiopatología , Antebrazo , Fracturas Óseas/fisiopatología , Manometría , Presión , Adolescente , Estudios de Casos y Controles , Moldes Quirúrgicos , Niño , Preescolar , Reducción Cerrada , Síndromes Compartimentales/etiología , Síndromes Compartimentales/terapia , Fasciotomía , Femenino , Traumatismos del Antebrazo/complicaciones , Traumatismos del Antebrazo/terapia , Fijación Interna de Fracturas , Fracturas Óseas/complicaciones , Fracturas Óseas/terapia , Humanos , Masculino , Manipulación Ortopédica , Estudios Prospectivos , Valores de Referencia
6.
Pediatr Radiol ; 45(5): 767-70, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25287358

RESUMEN

Conjoined twins are a rare developmental anomaly with a reported prevalence of 1.47 per 100,000 births. We present an uncommon case of a parasitic ischiopagus tetrapus with a parasitic ischiopagus partial twin joined to the complete fetus at the level of the ischium diagnosed in utero by fetal MRI. The correct prenatal diagnosis led to birth by caesarean section. Prenatal MRI findings are presented and corroborated by postnatal imaging delineating the full extent and associated anomalies of this rare malformation. Differential diagnosis of duplicated lower extremities is discussed.


Asunto(s)
Anomalías Múltiples/diagnóstico , Anomalías Múltiples/cirugía , Imagen por Resonancia Magnética , Diagnóstico Prenatal , Gemelos Siameses/cirugía , Anomalías Urogenitales/diagnóstico , Adulto , Cesárea , Diagnóstico Diferencial , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Isquion/diagnóstico por imagen , Isquion/patología , Isquion/cirugía , Extremidad Inferior/diagnóstico por imagen , Extremidad Inferior/patología , Extremidad Inferior/cirugía , Masculino , Tomografía Computarizada Multidetector , Embarazo , Anomalías Urogenitales/cirugía , Sistema Urogenital/patología , Sistema Urogenital/cirugía , Urografía
7.
Pediatr Dermatol ; 30(4): 462-8, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23432099

RESUMEN

Dermatofibrosarcoma protuberans (DFSP) in childhood is a rare tumor with high recurrence rates. Wide local excision can result in disfiguring mutilation, whereas Mohs micrographic surgery (MMS) reduces surgical margins. MMS in children is not performed routinely, as the required infrastructures such as a histopathology lab in close proximity to the operating room is often lacking. We retrospectively reviewed children diagnosed with DFSP treated at our hospital over 2 years. We recorded surgical treatment details, including margins, duration of inpatient stay, outcome, follow-up, and molecular genetic tumor tissue analysis. Four children with a median age of 6.8 years (range 6.0-8.8 years) were identified who had a diagnostic delay of a median of 2.5 years (range 0.5-4.0 years); all underwent complete tumor excision using the slow MMS technique using vacuum-assisted closure systems between repeated excisions and before wound closure. The median maximal safety margins were 1.5 cm (range 1.0-3.0 cm). By using vacuum-assisted closure systems, no dressing changes were needed, pain was limited, and full mobility was maintained in all children. The median total time in the hospital was 11 days (range 10-14 days). No relapses occurred during a median follow-up of 25.8 months (range 11.3-32.6 months). Collagen 1A1/platelet-derived growth factor B (COL1A1/PDGFB) translocation on chromosomes 17 and 22 was detected in all three analyzable specimens. Lesions suspected of being DFSP warrant prompt histologic evaluation; interdisciplinary management is mandatory in particular for children. Micrographic surgery allows smaller surgical margins than wide excision and should be considered as the treatment of choice in children with DFSP. The interim usage of vacuum-assisted closure systems increases patient comfort. Translocations in the COL1A1/PDGFB gene imply susceptibility to targeted treatment modalities for therapy-resistant cases.


Asunto(s)
Dermatofibrosarcoma/cirugía , Cirugía de Mohs/métodos , Terapia de Presión Negativa para Heridas/métodos , Neoplasias Cutáneas/cirugía , Niño , Diagnóstico Tardío , Dermatofibrosarcoma/diagnóstico , Femenino , Estudios de Seguimiento , Humanos , Tiempo de Internación , Masculino , Recurrencia Local de Neoplasia/prevención & control , Estudios Retrospectivos , Neoplasias Cutáneas/diagnóstico , Resultado del Tratamiento
8.
Int J Colorectal Dis ; 27(6): 817-29, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22315170

RESUMEN

INTRODUCTION: The transplantation of neural crest derived stem cells (NCSC) is a potent alternative for the treatment of Hirschsprung's disease (HSCR). Cells to be transplanted should find an appropriate microenvironment to survive and differentiate. Influences of HSCR-smooth-muscle-protein extracts upon isolated myenteric plexus cells, dissociated dorsal root ganglia and NCSC were studied in vitro to investigate the quality of this microenvironment effects. METHODS: Postnatal human gut from children undergoing colonic resection due to HSCR was divided in segments. Smooth muscle was dissected and homogenized. Glial-cell-line-derived-neurotrophic-factor (GDNF) and transforming-growth-factor-ß-1 (TGFß-1) concentration were measured in the homogenates from the individual segment using ELISA. Myenteric plexus and dissociated dorsal root ganglia (DRG) cultures, as well as NCSCs were exposed to protein extracts derived from ganglionic and aganglionic HSCR segments, and their effect upon neurite outgrowth, survival, and branching was evaluated. RESULTS AND CONCLUSIONS: The amount of the factors varied considerably between the individual segments and also from patient to patient. Four major expression patterns could be detected. While all extracts tested lead to a significant increase in neurite outgrowth compared to the control, extracts from proximal segments tended to have more prominent effects. In one experiment, extracts from all individual segments of a single patient were tested. Neurite outgrowth, neuronal survival, and branching pattern varied from segment to segment, but all HSCR-muscle-protein extracts increased neuronal survival and network formation. Smooth muscle protein from aganglionic bowel supports the survival and outgrowth of myenteric neurons and NCSCs and is so an appropriate target for neural stem cell treatment.


Asunto(s)
Microambiente Celular , Tracto Gastrointestinal/patología , Enfermedad de Hirschsprung/patología , Plexo Mientérico/crecimiento & desarrollo , Plexo Mientérico/patología , Agregación Celular , Diferenciación Celular , Proliferación Celular , Supervivencia Celular , Células Cultivadas , Preescolar , Ensayo de Inmunoadsorción Enzimática , Ganglios Espinales/metabolismo , Ganglios Espinales/patología , Regulación de la Expresión Génica , Factor Neurotrófico Derivado de la Línea Celular Glial/genética , Factor Neurotrófico Derivado de la Línea Celular Glial/metabolismo , Enfermedad de Hirschsprung/genética , Enfermedad de Hirschsprung/cirugía , Humanos , Lactante , Recién Nacido , Proteínas Musculares/metabolismo , Neuritas/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Extractos de Tejidos , Factor de Crecimiento Transformador beta/metabolismo
9.
Pediatr Surg Int ; 28(2): 135-42, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22048648

RESUMEN

BACKGROUND AND AIMS: The transplantation of neural crest derived stem cells (NCSC's) is a potent alternative for the treatment of Hirschsprung's disease (HSCR). Cells to be transplanted should find an appropriate microenvironment to survive and differentiate. To investigate the quality of this microenvironment, effects of HSCR-smooth-muscle-protein extracts upon NCSC's were studied in vitro. METHODS: Postnatal human gut from children undergoing colonic resection due to HSCR was divided in segments. Smooth muscle was dissected and homogenized. Glial-cell-line-derived-neurotrophic-factor (GDNF) concentration was measured in the homogenates from the individual segment using ELISA. NCSC's were exposed to protein extracts derived from ganglionic and aganglionic HSCR segments, and their effect upon neurite outgrowth, survival and branching was evaluated. RESULTS: The amount of the factors varied considerably between the proximal and distal segments, and also from patient to patient. While extracts from proximal segments tended to have more prominent effects, all HSCR-muscle-protein extracts increased neuronal survival and network formation. CONCLUSION: Muscle protein from aganglionic bowel supports the survival and outgrowth of NCSC's and is so an appropriate target for neural stem cell treatment.


Asunto(s)
Colon/patología , Enfermedad de Hirschsprung/patología , Proteínas Musculares/metabolismo , Músculo Liso/metabolismo , Células Madre/citología , Diferenciación Celular , Preescolar , Colectomía , Colon/metabolismo , Ensayo de Inmunoadsorción Enzimática , Regulación de la Expresión Génica , Enfermedad de Hirschsprung/metabolismo , Enfermedad de Hirschsprung/cirugía , Humanos , Inmunohistoquímica , Lactante , Recién Nacido , Proteínas Musculares/genética , ARN Mensajero/genética , Trasplante de Células Madre/métodos , Células Madre/metabolismo
10.
Eur J Pediatr Surg ; 32(4): 334-345, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34327690

RESUMEN

INTRODUCTION: Surgical treatment of esophageal atresia (EA) has markedly improved, allowing the focus to shift from short-term complications and mortality to long-term complications and quality of life. Health-related quality of life (HRQoL) is variable and reported to range from reduced to unimpaired in patients with repaired EA. We assessed the HRQoL, determined the prevalence of long-term complications and their possible impact on the HRQoL in patients who had correction of EA in Switzerland. Further, we also investigated in the general well-being of their parents. MATERIALS AND METHODS: Patients with EA repair in Switzerland between 1985 and 2011 were enrolled. Long-term complications were assessed by enquiring disease-related symptoms, standardized clinical examinations, and analysis of radiographs. HRQoL was inquired using different validated questionnaires (KIDSCREEN-27, World Health Organization [WHO]-5, and Gastrointestinal Quality of Life Index [GIQLI]). Patients were grouped according to their age. In underage patients, general well-being of the parents was assessed using the WHO-5 questionnaire. RESULTS: Thirty patients were included with a mean age of 11.3 ± 5.7 years. Long-term complications were present in 63% of all patients. HRQoL in underage patients was comparable to the provided reference values and rated as good, while adult patients reported a reduced HRQoL. The presence of gastroesophageal reflux disease symptoms was associated with reduced HRQoL in underage patients. Parents of underage patients stated a good general well-being. CONCLUSION: Long-term complications among patients with repair of EA in Switzerland are common. HRQoL in underage patients is good and general well-being of their parents is unimpaired. Adult patients reported a reduced HRQoL, consistent with other reports. As long-term complications may manifest only later in life, a structured follow-up of patients with an EA repair during childhood and adolescence is needed.


Asunto(s)
Atresia Esofágica , Esofagoplastia , Adolescente , Adulto , Niño , Preescolar , Atresia Esofágica/complicaciones , Atresia Esofágica/cirugía , Humanos , Calidad de Vida , Encuestas y Cuestionarios , Suiza/epidemiología
11.
Mol Ther Methods Clin Dev ; 24: 268-279, 2022 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-35211639

RESUMEN

Hepatic gene therapy by delivering non-integrating therapeutic vectors in newborns remains challenging due to the risk of dilution and loss of efficacy in the growing liver. Previously we reported on hepatocyte transfection in piglets by intraportal injection of naked DNA vectors. Here, we established delivery of naked DNA vectors to target periportal hepatocytes in weaned pigs by hydrodynamic retrograde intrabiliary injection (HRII). The surgical procedure involved laparotomy and transient isolation of the liver. For vector delivery, a catheter was placed within the common bile duct by enterotomy. Under optimal conditions, no histological abnormalities were observed in liver tissue upon pressurized injections. The transfection of hepatocytes in all tested liver samples was observed with vectors expressing luciferase from a liver-specific promoter. However, vector copy number and luciferase expression were low compared to hydrodynamic intraportal injection. A 10-fold higher number of vector genomes and luciferase expression was observed in pigs using a non-integrating naked DNA vector with the potential for replication. In summary, the HRII application was less efficient (i.e., lower luciferase activity and vector copy numbers) than the intraportal delivery method but was significantly less distressful for the piglets and has the potential for injection (or re-injection) of vector DNA by endoscopic retrograde cholangiopancreatography.

12.
Eur J Pediatr ; 170(4): 493-501, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-20936416

RESUMEN

UNLABELLED: Beta-blockers are a highly promising treatment modality for complicated infantile hemangiomas (IH). However, data on propranolol as first-line treatment, objective outcome measures and impact on hemodynamics in young infants is limited. We retrospectively evaluated a homogenous group of infants with proliferating complicated IH treated with propranolol (2 mg/kg/day). Outcome was assessed by blinded evaluation of clinical photographs by visual analogue scale (VAS), ultrasound examination and ophthalmological review (if appropriate). Tolerance and hemodynamic variables were recorded over time, including a 2-day in-patient observation at the initiation of therapy. Twenty-five infants (median age 3.6 (1.5-9.1) months) were included in the study. The median follow-up-time was 14 (9-20) months and 14 patients completed treatment at a median age of 14.3 (11.4-22.1) months, after a duration of 10.5 (7.5-16) months. In all patients, there was significant fading of colour (with a VAS of -9 (-6 to -9) after 7 months) and significant decrease in size of the IH (with a VAS of -8 (-3 to -10) after 7 months). Median thickness of the lesions assessed by ultrasound at baseline and after 1 month was 14 (7-28) mm and 10 (5-23) mm, respectively (p < 0.01). In children with periocular involvement, astigmatism and amblyopia resolved rapidly within 8 weeks. The overall tolerance of propranolol was good, and no relevant hemodynamic changes were noted. CONCLUSION: Our report supports the excellent effect and good tolerance of this novel therapy, and we propose the use of propranolol as first-line treatment for IH.


Asunto(s)
Antagonistas Adrenérgicos beta/uso terapéutico , Hemangioma/tratamiento farmacológico , Propranolol/uso terapéutico , Neoplasias Cutáneas/tratamiento farmacológico , Antagonistas Adrenérgicos beta/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Esquema de Medicación , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Lactante , Masculino , Propranolol/administración & dosificación , Estudios Retrospectivos , Resultado del Tratamiento
13.
Front Immunol ; 12: 781147, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-35069554

RESUMEN

Infants affected by Hirschsprung disease (HSCR), a neurodevelopmental congenital disorder, lack ganglia of the intrinsic enteric nervous system (aganglionosis) in a variable length of the colon, and are prone to developing severe Hirschsprung-associated enterocolitis (HAEC). HSCR patients typically show abnormal dense innervation of extrinsic cholinergic nerve fibers throughout the aganglionic rectosigmoid. Cholinergic signaling has been reported to reduce inflammatory response. Consequently, a sparse extrinsic cholinergic innervation in the mucosa of the rectosigmoid correlates with increased inflammatory immune cell frequencies and higher incidence of HAEC in HSCR patients. However, whether cholinergic signals influence the pro-inflammatory immune response of intestinal epithelial cells (IEC) is unknown. Here, we analyzed colonic IEC isolated from 43 HSCR patients with either a low or high mucosal cholinergic innervation density (fiber-low versus fiber-high) as well as from control tissue. Compared to fiber-high samples, IEC purified from fiber-low rectosigmoid expressed significantly higher levels of IL-8 but not TNF-α, IL-10, TGF-ß1, Muc-2 or tight junction proteins. IEC from fiber-low rectosigmoid showed higher IL-8 protein concentrations in cell lysates as well as prominent IL-8 immunoreactivity compared to IEC from fiber-high tissue. Using the human colonic IEC cell line SW480 we demonstrated that cholinergic signals suppress lipopolysaccharide-induced IL-8 secretion via the alpha 7 nicotinic acetylcholine receptor (a7nAChR). In conclusion, we showed for the first time that the presence of a dense mucosal cholinergic innervation is associated with decreased secretion of IEC-derived pro-inflammatory IL-8 in the rectosigmoid of HSCR patients likely dependent on a7nAChR activation. Owing to the association between IL-8 and enterocolitis-prone, fiber-low HSCR patients, targeted therapies against IL-8 might be a promising immunotherapy candidate for HAEC treatment.


Asunto(s)
Colon , Sistema Nervioso Entérico/metabolismo , Células Epiteliales/metabolismo , Enfermedad de Hirschsprung/metabolismo , Interleucina-8/metabolismo , Línea Celular , Colon/inervación , Colon/metabolismo , Femenino , Humanos , Lactante , Masculino
14.
Cell Mol Gastroenterol Hepatol ; 12(2): 507-545, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33741501

RESUMEN

BACKGROUND & AIMS: Hirschsprung's disease (HSCR) is a congenital intestinal motility disorder defined by the absence of enteric neuronal cells (ganglia) in the distal gut. The development of HSCR-associated enterocolitis remains a life-threatening complication. Absence of enteric ganglia implicates innervation of acetylcholine-secreting (cholinergic) nerve fibers. Cholinergic signals have been reported to control excessive inflammation, but the impact on HSCR-associated enterocolitis is unknown. METHODS: We enrolled 44 HSCR patients in a prospective multicenter study and grouped them according to their degree of colonic mucosal acetylcholinesterase-positive innervation into low-fiber and high-fiber patient groups. The fiber phenotype was correlated with the tissue cytokine profile as well as immune cell frequencies using Luminex analysis and fluorescence-activated cell sorting analysis of colonic tissue and immune cells. Using confocal immunofluorescence microscopy, macrophages were identified in close proximity to nerve fibers and characterized by RNA-seq analysis. Microbial dysbiosis was analyzed in colonic tissue using 16S-rDNA gene sequencing. Finally, the fiber phenotype was correlated with postoperative enterocolitis manifestation. RESULTS: The presence of mucosal nerve fiber innervation correlated with reduced T-helper 17 cytokines and cell frequencies. In high-fiber tissue, macrophages co-localized with nerve fibers and expressed significantly less interleukin 23 than macrophages from low-fiber tissue. HSCR patients lacking mucosal nerve fibers showed microbial dysbiosis and had a higher incidence of postoperative enterocolitis. CONCLUSIONS: The mucosal fiber phenotype might serve as a prognostic marker for enterocolitis development in HSCR patients and may offer an approach to personalized patient care and new therapeutic options.


Asunto(s)
Neuronas Colinérgicas/patología , Enterocolitis/etiología , Enfermedad de Hirschsprung/complicaciones , Mucosa Intestinal/inervación , Mucosa Intestinal/patología , Acetilcolinesterasa/metabolismo , Niño , Preescolar , Estudios de Cohortes , Citocinas/metabolismo , Disbiosis/inmunología , Disbiosis/microbiología , Disbiosis/patología , Células Epiteliales/metabolismo , Células Epiteliales/patología , Femenino , Enfermedad de Hirschsprung/patología , Enfermedad de Hirschsprung/cirugía , Humanos , Lactante , Recién Nacido , Inflamación/inmunología , Receptores de Lipopolisacáridos/metabolismo , Macrófagos/metabolismo , Masculino , Fenotipo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Factores de Riesgo
15.
J Hand Surg Eur Vol ; 44(6): 640-647, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-30704329

RESUMEN

The purpose of this single-centre randomized controlled trial was to assess the non-inferiority of buddy taping versus splint immobilization of extra-articular paediatric finger fractures. Secondary fracture displacement was the primary outcome; patient comfort, cost and range of finger motion were secondary outcomes. Ninety-nine children were randomly assigned to taping or splinting. Sixty-nine fractures were undisplaced; 31 were displaced and required reduction before taping or splinting. Secondary displacement occurred in one patient in the taping and three in the splinting group. The risk difference was below the predefined non-inferiority level of 5%. All secondary displacements occurred in the 31 displaced fractures after reduction and were in little fingers. Patient comfort was significantly higher and cost lower in the taping group. We conclude from this study the non-inferiority of buddy taping versus splint immobilization of extra-articular paediatric finger fractures in general. We advise treatment may need to be individualized for patients with displaced fractures because we cannot make any absolute conclusions for these fractures. Level of evidence: I.


Asunto(s)
Cinta Atlética , Falanges de los Dedos de la Mano/lesiones , Fracturas Óseas/terapia , Férulas (Fijadores) , Adolescente , Cinta Atlética/economía , Niño , Preescolar , Femenino , Humanos , Masculino , Comodidad del Paciente , Férulas (Fijadores)/economía
16.
Eur J Trauma Emerg Surg ; 45(3): 567, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30778613

RESUMEN

The original version of this article unfortunately contained a mistake in the author name Sasha Job Tharakan. The corrected name is given above.

17.
Eur J Trauma Emerg Surg ; 45(3): 493-497, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30715553

RESUMEN

PURPOSE: Needle manometry is a tool to confirm suspected acute compartment syndrome (ACS). There is scarce evidence of normal pressure values of the lower extremities in children. The aim of this study is to assess the normal compartment pressures in non-injured lower extremities of children. METHODS: This prospective study included children up to the age of 16 years with lower extremity fractures that needed reduction. Between June 2009 and August 2015, 20 children were included. We used needle manometry to measure the pressures in the superficial (SPC), deep posterior (DPC) and in the anterior compartments (AC) on both the lower legs. RESULTS: On the healthy leg, the mean compartment pressure was 15.15 mmHg in the AC (range 7-30 mmHg), 14.32 mmHg in the SPC (range 8-24 mmHg) and 13.00 mmHg in the DPC (range 4-21 mmHg). On the injured leg, the mean compartment pressure was 24.07 mmHg in the AC (range 5-40 mmHg), 17.21 mmHg in the SPC (range 7-29 mmHg) and 17.13 mmHg in the DPC (range 6-37 mmHg). We found a perfusion gradient (diastolic blood pressure-compartment pressure) < 30 mmHg in at least one compartment of the fractured and healthy leg in 13 patients. Five patients underwent fasciotomy for suspected ACS and their data was excluded for the injured leg. CONCLUSION: We could show that children have higher normal compartment pressures than adults in the lower leg. They seem to be able to tolerate higher absolute compartment pressures and lower pressure gradients before ACS occurs. More studies are needed to make a final statement on tolerable compartment pressures in children.


Asunto(s)
Síndromes Compartimentales/diagnóstico , Fracturas Óseas/cirugía , Extremidad Inferior/lesiones , Presión , Adolescente , Estudios de Casos y Controles , Niño , Preescolar , Síndromes Compartimentales/etiología , Femenino , Fracturas Óseas/complicaciones , Humanos , Masculino , Manometría , Valores de Referencia
18.
J Pediatr Gastroenterol Nutr ; 47(1): 81-6, 2008 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-18607273

RESUMEN

OBJECTIVES: Recently, our group detected that polyvinyl chloride (PVC) perfusion lines leach large amounts of the toxic plasticizer diethylhexylphthalate (DEHP) under conditions typical of intensive care units. In the present study, we investigated the extraction of DEHP from PVC connecting tubes that are commonly used for total parenteral nutrition (TPN) solutions. The aim of the study was to estimate the amount of DEHP to which children receiving home TPN are exposed for months and years. MATERIALS AND METHODS: 1000 mL of TPN, identical in constitution and amount to the home TPN of 1 of our patients, were perfused through 5 different connecting tube systems and collected in hexane-rinsed glass bottles. The concentration of DEHP in the TPN was analyzed before and after perfusion. RESULTS: Before perfusion of the lines, the solution had a DEHP concentration of 0.05 to 0.69 microg/mL (baseline value). After perfusion of the lines, the load of DEHP in the solution varied between 1.41 and 2.07 microg/mL. This TPN was established for children weighing 20 kg. The daily dosage is between 71 and 104 microg x kg(-1) x day(-1). TPN is administered at home for many months and years. The monthly charge of DEHP is between 42.3 and 62.1 mg. Children weighing 20 kg therefore receive a dosage between 2.1 and 3.1 mg x kg(-1) x month(-1). CONCLUSIONS: Diethylhexylphthalate and its metabolite monoethylhexylphthalate have been demonstrated to be carcinogenic, embryotoxic, hepatotoxic, pneumotoxic, and cardiotoxic and are known to disrupt endocrine pathways and liver detoxifying capacity in animals. They are suspected of having multiple effects in humans as well. The doses presented above should therefore be avoided in children receiving home TPN by the use of tubing systems that are completely free of DEHP. Such systems are available.


Asunto(s)
Dietilhexil Ftalato/aislamiento & purificación , Emulsiones Grasas Intravenosas/análisis , Bombas de Infusión , Nutrición Parenteral Total en el Domicilio/instrumentación , Plastificantes/aislamiento & purificación , Niño , Dietilhexil Ftalato/efectos adversos , Dietilhexil Ftalato/química , Contaminación de Medicamentos , Humanos , Infusiones Intravenosas/efectos adversos , Plastificantes/efectos adversos , Plastificantes/química , Cloruro de Polivinilo/efectos adversos , Cloruro de Polivinilo/química , Factores de Tiempo
19.
Eur J Pediatr Surg ; 28(2): 183-193, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28183146

RESUMEN

INTRODUCTION: Evidence-based guidelines or protocols regarding the perinatal management of babies born with gastroschisis are lacking. The aim of this work is to evaluate the different current treatment modalities for newborns with gastroschisis during the perinatal period in the German-speaking countries Germany, Austria, and Switzerland. These data could serve as a starting point for the development of a multicenter randomized controlled trial. MATERIALS AND METHODS: A questionnaire was developed with 30 questions divided into five sections: (1) prenatal diagnosis, (2) fetal therapy, (3) mode and timing of delivery, (4) operative management, and (5) postoperative management. All pediatric surgery institutions that treat newborns with gastroschisis were identified and asked to participate. Data were categorized by country and analyzed using descriptive statistics (frequency and percentage). RESULTS: The return rate of the questionnaire was 95% (89 hospitals). A standard procedure was identified regarding prenatal ultrasound monitoring, interdisciplinary team approach, planned delivery through cesarean section, postnatal coverage of the intestine with a silastic bag, first intervention within the first 6 hours after birth, attempt of primary abdominal wall closure, and perioperative antibiotic treatment. For many crucial parameters, management was not standardized. CONCLUSIONS: There is no gold standard in German-speaking countries on how to manage fetuses and babies with gastroschisis. Moreover, this report unveils some questionable elements of daily practice for which there is no evidence at all and which can jeopardize outcome and even prove fatal (fetal therapy, preterm delivery, lack of abdominal pressure monitoring). Prospective randomized-controlled multicenter studies are needed to set a standard.


Asunto(s)
Gastrosquisis/cirugía , Atresia Intestinal/cirugía , Intestinos/cirugía , Austria , Criptorquidismo/complicaciones , Criptorquidismo/cirugía , Parto Obstétrico/estadística & datos numéricos , Femenino , Terapias Fetales , Gastrosquisis/complicaciones , Gastrosquisis/diagnóstico , Alemania , Edad Gestacional , Humanos , Recién Nacido , Atresia Intestinal/complicaciones , Masculino , Cuidados Posoperatorios , Guías de Práctica Clínica como Asunto , Embarazo , Diagnóstico Prenatal , Encuestas y Cuestionarios , Suiza
20.
J Pediatr Gastroenterol Nutr ; 44(1): 71-6, 2007 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-17204957

RESUMEN

OBJECTIVES: Except for polyadipate, which is used as an alternative in polyvinylchloride (PVC) feeding tubes, diethylhexylphthalate (DEHP) is the plasticizer used almost exclusively in PVC medical products. A clear response to the chronic intake of DEHP has been shown in several organ systems from different species. In the present study, we compared the extraction of DEHP and polyadipate from PVC gastric tubes. METHODS: An in vivo setting was simulated. We used 5 cm of PVC nasogastric tubes containing DEHP or polyadipate, which were incubated with gastric juice for 1 week and a feeding solution for 4 weeks. The leakage of these plasticizers was measured daily in the gastric juice group and weekly in the feeding solution group. The amount of plasticizer extracted was compared between groups and days. RESULTS: In the feeding solution group, the extraction of DEHP ranged from 200 to 542 microg after 1 week and from 660 to 1700 microg after 4 weeks. The extraction of polyadipate was 10 times lower than that of DEHP. In the gastric juice group, extracted DEHP ranged from 635 to 1043 microg, whereas the extraction of polyadipate was 100 times lower. CONCLUSIONS: Within 1 week, the extraction of DEHP from a 5-cm PVC tube reaches up to 1 mg. Extrapolated, this represents an in vivo load of up to 4 mg. The load accumulated by a newborn in an intensive care unit can therefore easily reach several milligrams of DEHP per day. Polyadipate nasogastric tubes may therefore be an alternative and help to reduce the daily load of DEHP.


Asunto(s)
Dietilhexil Ftalato/análisis , Nutrición Enteral , Jugo Gástrico/química , Intubación Gastrointestinal , Cloruro de Polivinilo , Adipatos/química , Adolescente , Niño , Preescolar , Humanos , Lactante , Recién Nacido , Plastificantes , Polímeros/química
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