RESUMEN
Gastroschisis (GS) is a congenital abdominal wall defect, in which the bowel eviscerates from the abdominal cavity. It is a non-lethal isolated anomaly and its pathogenesis is hypothesized to occur as a result of two hits: primary rupture of the 'physiological' umbilical hernia (congenital anomaly) followed by progressive damage of the eviscerated bowel (secondary injury). The second hit is thought to be caused by a combination of mesenteric ischemia from constriction in the abdominal wall defect and prolonged amniotic fluid exposure with resultant inflammatory damage, which eventually leads to bowel dysfunction and complications. GS can be classified as either simple or complex, with the latter being complicated by a combination of intestinal atresia, stenosis, perforation, volvulus and/or necrosis. Complex GS requires multiple neonatal surgeries and is associated with significantly greater postnatal morbidity and mortality than is simple GS. The intrauterine reduction of the eviscerated bowel before irreversible damage occurs and subsequent defect closure may diminish or potentially prevent the bowel damage and other fetal and neonatal complications associated with this condition. Serial prenatal amnioexchange has been studied in cases with GS as a potential intervention but never adopted because of its unproven benefit in terms of survival and bowel and lung function. We believe that recent advances in prenatal diagnosis and fetoscopic surgery justify reconsideration of the antenatal management of complex GS under the rubric of the criteria for fetal surgery established by the International Fetal Medicine and Surgery Society (IFMSS). Herein, we discuss how conditions for fetoscopic repair of complex GS might be favorable according to the IFMSS criteria, including an established natural history, an accurate prenatal diagnosis, absence of fully effective perinatal treatment due to prolonged need for neonatal intensive care, experimental evidence for fetoscopic repair and maternal and fetal safety of fetoscopy in expert fetal centers. Finally, we propose a research agenda that will help overcome barriers to progress and provide a pathway toward clinical implementation. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
Asunto(s)
Pared Abdominal/cirugía , Fetoscopía/tendencias , Feto/cirugía , Gastrosquisis/cirugía , Intestinos/cirugía , Pared Abdominal/embriología , Femenino , Fetoscopía/métodos , Feto/anomalías , Feto/embriología , Gastrosquisis/embriología , Humanos , Intestinos/embriología , Selección de Paciente , EmbarazoRESUMEN
OBJECTIVES: We reported previously on an exteriorized-uterus fetoscopic repair for open neural tube defect (ONTD) using a single-layer closure (SLC) technique. However, because SLC was associated with a high rate of cerebrospinal fluid (CSF) leakage at birth, we developed a three-layer closure (3LC) technique comprising a bovine collagen patch, a myofascial layer and a skin layer. The aims of this study were to compare SLC and 3LC in terms of intraoperative, postoperative and obstetric outcomes, as well as short-term neonatal neurologic and non-neurologic outcomes. METHODS: This was a retrospective analysis of prospectively collected data, from 32 consecutive SLC controls and 18 consecutive 3LC cases, that underwent exteriorized-uterus two-port fetoscopic repair of ONTD at our center, between April 2014 and December 2018. All patients satisfied the Management of Myelomeningocele Study (MOMS) criteria. Obstetric, maternal, fetal and early neonatal outcomes were compared between the SLC and 3LC groups. RESULTS: Maternal demographics and mean gestational age (GA) at fetal surgery (25.0 ± 0.7 vs 25.0 ± 0.5 weeks' gestation; P = 0.96), and at delivery (36.5 ± 3.5 vs 37.6 ± 3.0 weeks; P = 0.14), were similar between the SLC and 3LC groups, respectively. The rate of preterm prelabor rupture of membranes (PPROM) < 37 weeks (28% vs 29%; P = 0.9), mean GA at PPROM (32.3 ± 3.4 vs 32.7 ± 1.9 weeks; P = 0.83) and rate of vaginal delivery (50% vs 47%; P = 0.84) were similar for the SLC vs 3LC groups, respectively. In pregnancies that had SLC compared with those that had 3LC, there was a significantly higher incidence of CSF leakage at birth (8/32 (25%) vs 0/17 (0%); P = 0.02) and a significantly lower rate of reversal of hindbrain herniation at 6 weeks postoperatively (18/30 (60%) vs 14/15 (93%); P = 0.02). The rate of infants that met the MOMS criteria for shunt placement or died before 12 months of age (23/31 (74%) vs 7/12 (58%); P = 0.31) and those that required treatment for hydrocephalus by 12 months (15/32 (47%) vs 4/12 (33%); P = 0.42) were similar between the SLC and 3LC groups, respectively. CONCLUSIONS: Compared to SLC, 3LC preserves the fetal and obstetric benefits of fetoscopic repair and shows improved rates of CSF leakage and reversal of hindbrain herniation at 6 weeks postoperatively. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.
Asunto(s)
Fetoscopía/métodos , Defectos del Tubo Neural/cirugía , Procedimientos Neuroquirúrgicos/métodos , Complicaciones Posoperatorias/epidemiología , Técnicas de Cierre de Heridas , Adulto , Pérdida de Líquido Cefalorraquídeo/epidemiología , Pérdida de Líquido Cefalorraquídeo/etiología , Femenino , Fetoscopía/efectos adversos , Humanos , Hidrocefalia/epidemiología , Hidrocefalia/etiología , Lactante , Recién Nacido , Defectos del Tubo Neural/embriología , Procedimientos Neuroquirúrgicos/efectos adversos , Complicaciones Posoperatorias/etiología , Embarazo , Estudios Prospectivos , Estudios Retrospectivos , Resultado del Tratamiento , Técnicas de Cierre de Heridas/efectos adversosRESUMEN
OBJECTIVE: Fetal endoscopic tracheal occlusion (FETO) is associated with increased perinatal survival and reduced need for extracorporeal membrane oxygenation (ECMO) in fetuses with severe congenital diaphragmatic hernia (CDH). This study evaluates the impact of FETO on the resolution of pulmonary hypertension (PH) in fetuses with isolated CDH. METHODS: We reviewed retrospectively the medical records of all fetuses evaluated for CDH between January 2004 and July 2017 at a single institution. Fetuses with additional major structural or chromosomal abnormalities were excluded. CDH cases were classified retrospectively into mild, moderate and severe groups based on prenatal magnetic resonance imaging indices (observed-to-expected total fetal lung volume and percentage of intrathoracic liver herniation). Presence of PH was determined based on postnatal echocardiograms. Logistic regression analyses were performed to evaluate the relationship between FETO and resolution of PH by 1 year of age while controlling for side of the CDH, use of ECMO, gestational age at diagnosis, gestational age at delivery, fetal gender, sildenafil use at discharge and CDH severity. Resolution of PH by 1 year of age was compared between a cohort of fetuses with severe CDH that underwent FETO and a cohort that did not have the procedure (non-FETO). A subanalysis was performed restricting the analysis to isolated left CDH. Parametric and non-parametric tests were used for comparisons. RESULTS: Of 257 CDH cases evaluated, 72% (n = 184) had no major structural or chromosomal anomalies of which 58% (n = 107) met the study inclusion criteria. The FETO cohort consisted of 19 CDH cases and the non-FETO cohort (n = 88) consisted of 31 (35%) mild, 32 (36%) moderate and 25 (28%) severe CDH cases. All infants with severe CDH, regardless of whether they underwent FETO, had evidence of neonatal PH. FETO (OR, 3.57; 95% CI, 1.05-12.10; P = 0.041) and ECMO (OR, 5.01; 95% CI, 2.10-11.96; P < 0.001) were independent predictors of resolution of PH by 1 year of age. A higher proportion of infants with severe CDH that underwent FETO had resolution of PH by 1 year after birth compared with infants with severe CDH in the non-FETO cohort (69% (11/16) vs 28% (7/25); P = 0.017). Similar results were observed when the analysis was restricted to cases with left-sided CDH (PH resolution in 69% (11/16) vs 28% (5/18); P = 0.032). CONCLUSION: In infants with severe CDH, FETO and ECMO are independently associated with increased resolution of PH by 1 year of age. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.
Asunto(s)
Hernias Diafragmáticas Congénitas/complicaciones , Hernias Diafragmáticas Congénitas/cirugía , Hipertensión Pulmonar/cirugía , Tráquea/cirugía , Ecocardiografía/métodos , Endoscopía/métodos , Oxigenación por Membrana Extracorpórea/normas , Femenino , Fetoscopía/métodos , Edad Gestacional , Hernias Diafragmáticas Congénitas/clasificación , Humanos , Hipertensión Pulmonar/prevención & control , Lactante , Hígado/patología , Mediciones del Volumen Pulmonar/métodos , Imagen por Resonancia Magnética/métodos , Masculino , Atención Posnatal/normas , Embarazo , Atención Prenatal/normas , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Tráquea/diagnóstico por imagen , Tráquea/embriología , Resultado del TratamientoRESUMEN
Recently, there has been considerable interest in using 4-methylumbelliferone (4-MU) to inhibit hyaluronan (HA) synthesis in mouse models of cancer, autoimmunity and a variety of other inflammatory disorders where HA has been implicated in disease pathogenesis. In order to facilitate future studies in this area, we have examined the dosing, treatment route, treatment duration and metabolism of 4-MU in both C57BL/6 and BALB/c mice. Mice fed chow containing 5% 4-MU, a dose calculated to deliver 250 mg/mouse/day, initially lose substantial weight but typically resume normal weight gain after 1 week. It also takes up to a week to see a reduction in serum HA in these animals, indicating that at least a 1-week loading period on the drug is required for most protocols. At steady state, more than 90% of the drug is present in plasma as the glucuronidated metabolite 4-methylumbelliferyl glucuronide (4-MUG), with the sulphated metabolite, 4-methylumbelliferyl sulphate (4-MUS) comprising most of the remainder. Chow containing 5% but not 0·65% 4-MU was effective at preventing disease in the experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis, as well as in the DORmO mouse model of autoimmune diabetes. While oral 4-MU was effective at preventing EAE, daily intraperitoneal injections of 4-MU were not. Factors potentially affecting 4-MU uptake and plasma concentrations in mice include its taste, short half-life and low bioavailability. These studies provide a practical resource for implementing oral 4-MU treatment protocols in mice.
Asunto(s)
Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Ácido Hialurónico/antagonistas & inhibidores , Ácido Hialurónico/biosíntesis , Himecromona/administración & dosificación , Himecromona/farmacocinética , Administración Oral , Animales , Disponibilidad Biológica , Modelos Animales de Enfermedad , Encefalomielitis Autoinmune Experimental/inducido químicamente , Encefalomielitis Autoinmune Experimental/inmunología , Encefalomielitis Autoinmune Experimental/prevención & control , Semivida , Ácido Hialurónico/sangre , Himecromona/sangre , Himecromona/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BLRESUMEN
INTRODUCTION: In 2001, in response to an overwhelming increase in patient visits for various pediatric abscesses, burns, and other wounds, an ambulatory burn and procedural sedation program (Pediatric Acute Wound Service, or PAWS) was developed to minimize operating room utilization. The purpose of this study is to report our initial 7-year experience with the PAWS program. METHODS: The hospital records of all children managed through PAWS from 2001 to 2007 were reviewed. Outcomes measured include patient demographics, number and location of visits per patient, procedure information, cause of wounds, and reimbursement. chi(2) test and linear regression were performed using GraphPad Prism (GraphPad Software Inc, San Diego, CA). RESULTS: Overall, 7620 children (age 0-18 years) received wound care through PAWS from 2001 to 2007. There were no differences in patient age, race, and sex during this time period. Between 2001 and 2007, the percentage of patients seen as outpatients increased from 51% to 68% (P < .05), and the average number of visits per patient decreased from 3.9 to 2.4 (P = .05). In, 2007, 46% of the children required only 1 visit. In 2007, 74% of the visits were for management of wound and soft tissue infections, compared with only 9% in 2001 (P < .05). The contribution margin of a PAWS visit and total contribution margin in 2007 were $1052 and $4.0 million, respectively. CONCLUSION: The creation of PAWS has allowed for the transition in management of most pediatric skin and soft tissue wounds and infections to an independent ambulatory setting, alleviating the need for operating room resources, while functioning at a profitable cost margin for the hospital.
Asunto(s)
Drenaje/economía , Hospitales Pediátricos/economía , Hospitales Pediátricos/estadística & datos numéricos , Heridas y Lesiones/economía , Heridas y Lesiones/cirugía , Enfermedad Aguda , Adolescente , Niño , Preescolar , Procedimientos Quirúrgicos Dermatologicos , Drenaje/métodos , Encuestas de Atención de la Salud/estadística & datos numéricos , Costos de Hospital/estadística & datos numéricos , Registros de Hospitales/estadística & datos numéricos , Hospitales Pediátricos/organización & administración , Humanos , Lactante , Estudios Longitudinales , Servicio Ambulatorio en Hospital/economía , Servicio Ambulatorio en Hospital/organización & administración , Servicio Ambulatorio en Hospital/estadística & datos numéricos , Piel/lesiones , Infecciones de los Tejidos Blandos/economía , Infecciones de los Tejidos Blandos/cirugía , Traumatismos de los Tejidos Blandos/economía , Traumatismos de los Tejidos Blandos/cirugía , Resultado del TratamientoRESUMEN
A young woman with pre-eclampsia became unresponsive shortly after delivery. Examination revealed extensive brain stem dysfunction with absent pupillary light reflexes and decerebrate posturing. Computed tomography showed hypodensity throughout the brain stem, and it was initially thought that she had suffered catastrophic brain stem infarction. However, magnetic resonance diffusion imaging and apparent diffusion coefficient mapping showed that she had brain stem vasogenic oedema (posterior reversible encephalopathy syndrome, PRES), rather than cytotoxic oedema. With antihypertensive and supportive treatment, she recovered rapidly, and had no abnormalities on repeat imaging.
Asunto(s)
Edema Encefálico/complicaciones , Edema Encefálico/diagnóstico , Coma/etiología , Síndromes de Neurotoxicidad/complicaciones , Preeclampsia/complicaciones , Adulto , Barrera Hematoencefálica , Edema Encefálico/etiología , Edema Encefálico/fisiopatología , Coma/fisiopatología , Femenino , Humanos , Imagen por Resonancia Magnética , Síndromes de Neurotoxicidad/etiología , Síndromes de Neurotoxicidad/fisiopatología , Preeclampsia/fisiopatología , EmbarazoRESUMEN
A liquid chromatographic-mass spectrometric method for the determination of 14-beta-n-pentylaminomorphinone (pentamorphone) and 14-beta-n-pentylaminocodeinone (PAC) as internal standard is developed. Concentration levels in serum were calculated by the ratio of the peak areas of pentamorphone to PAC versus the concentration of pentamorphone. Peak areas were measured using selected-ion-recording of the pseudo-molecular ions of pentamorphone and PAC (m/z 369 and m/z 383, respectively). Aliquots (50 microliters) of sample were injected on a C18 mu Bondapak column following solid-phase extraction. The lowest limit of quantitation observed was 43 pg/ml. The sensitivity, accuracy and reproducibility of the method were demonstrated to be satisfactory for application in pharmacokinetic study of pentamorphone.
Asunto(s)
Analgésicos/sangre , Cromatografía Liquida/métodos , Hidromorfona/análogos & derivados , Espectrometría de Masas/métodos , Animales , Cromatografía Liquida/instrumentación , Perros , Humanos , Hidromorfona/sangre , Espectrometría de Masas/instrumentación , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: IgE antibodies reactive with the group II allergens of Dermatophagoides species (house dust mite [HDM]) are a major component of the allergic immune response in HDM-allergic atopic individuals. METHODS: Here we demonstrate, with the use of overlapping synthetic peptides of the group II allergen of Dermatophagoides pteronyssinus (Der p II), that polyclonal T cells isolated from the majority of atopic HDM-allergic individuals and healthy nonatopic control subjects respond to Der p II and that T-cell epitopes are present in all regions of the protein. RESULTS: From comparison of peptide-specific T-cell proliferation in both groups of individuals, it appears that together peptides 61-86 and 78-104 are the most frequently recognized (16 of 18 individuals). We also observed that nine of the 18 individuals responded to T-cell epitopes in the region 11-50, and with Der p II-reactive T-cell clones, three distinct T-cell epitopes were mapped within the sequence 11-35. Also, with the use of T-cell clones, two additional epitopes were identified at residues 81-96 and 91-101. CONCLUSIONS: These results suggest that T-cell epitopes located in these regions (11-50 and 61-104) are immunodominant. The value of this information in the potential application of Der p II peptides to desensitize HDM allergic responses is discussed.