A Trial of Intranasal Corticosteroids to Treat Childhood OSA Syndrome.

BACKGROUND: Intranasal corticosteroids (INCS) are frequently used to treat OSA syndrome (OSAS) in children. However, their efficacy has not been rigorously tested. RESEARCH QUESTION: Do INCS result in improved OSAS symptoms, polysomnography findings, behavior, and quality of life compared with placebo? STUDY DESIGN AND METHODS: In this randomized, double-blind, placebo-controlled trial, children with OSAS aged 5 to 12 years (N = 134) were randomized 2:1 to receive 3 months of INCS or placebo. Children in the INCS arm were then re-randomized to receive 9 months of INCS or placebo. Polysomnography, symptoms, and neurobehavioral findings were measured at baseline, 3 months, and 12 months. The primary outcome was change in obstructive apnea hypopnea index (OAHI) at 3 months, available for 122 children. The secondary outcome was OAHI change at 12 months, available for 70 children. RESULTS: Median (interquartile range) age and OAHI at baseline for the entire group were 7.9 (6.3 to 9.9) years and 5.8 (3.6 to 9.7) events per hour. OAHI changes at 3 months (-1.72 [-3.91 to 1.92] events per hour) and 12 months (-1.2 [-4.22 to 1.71] events per hour) were not different between the two groups (P = not significant). OSAS symptoms and neurobehavioral results did not differ between the INCS and placebo groups at 3 and 12 months. The 38 children who received INCS for 12 months reported a significant OAHI decrease from 7.2 (3.62 to 9.88) events per hour to 3.7 (1.56 to 6.4) events per hour (P = .039). INTERPRETATION: In children with OSAS, treatment with INCS did not result in significant polysomnography, neurobehavioral, or symptom changes at 3 and 12 months of treatment. Twelve months of INCS treatment resulted in a statistically significant but not clinically relevant OAHI reduction. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT02180672; URL: www. CLINICALTRIALS: gov.

Sacral protuberance with cleft lip and palate: Prenatal presentation of 3MC syndrome.

3MC syndromes are rare heterogeneous autosomal recessive conditions previously designated as Mingarelli, Malpuech, Michels, and Carnevale syndromes, characterized by dysmorphic facial features, facial clefts, growth restriction, and intellectual disability. 3MC is secondary to mutations in the MASP1, MASP3, COLEC11, and COLEC10 genes. The number of patients with 3MC syndrome with known mutations in the COLEC11 or MASP1 is, to date, less than 50. At the time this case presented (2015), the only gene identified in Online Mendelian Inheritance in Man to be associated with 3MC syndrome was MASP1. We present, to the best of our knowledge, the first prenatal report of 3MC syndrome, secondary to a homozygous variant in MASP1. Fetal findings included bilateral cleft lip and palate, abnormality of the sacral spine, a right echogenic pelvic kidney, and brachycephaly. 3MC syndrome should be considered as part of the differential diagnosis when fetal ultrasound detects facial clefts and spinal defects, as the risk of recurrence is significant and a molecularly confirmed diagnosis allows for alternate reproductive options.

Laparoscopic IPOM repair of an acquired abdominal intercostal hernia.

Acquired abdominal intercostal hernia (AAIH) is an infrequent occurrence whereby intra-abdominal contents herniate into intercostal space directly from the peritoneal cavity through an acquired defect in the abdominal wall musculature and fascia. These hernias are difficult to diagnose and should always be suspected when a chest wall swelling occur after major or minor trauma. Surgical repair is warranted in symptomatic patients. The majority of AAIHs are repaired through an open approach using tension-free mesh, with significant recurrence risk. Recently, laparoscopic and robot-assisted repairs have been proposed. We discuss a 49-year-old man presented through outpatient setting with a 5-year history of ongoing left subcostal discomfort and a reducible lump. His history included a workplace accident 5 years ago. Contrast-enhanced abdominal CT confirmed AAIH with omentum herniation into the sac. A successful laparoscopic repair with intraperitoneal onlay mesh technique using composite mesh was performed.

Familial Recurrence of 3MC Syndrome in Consanguineous Families: A Clinical and Molecular Diagnostic Approach With Review of the Literature.

We report four individuals from two unrelated consanguineous families with 3MC syndrome. In the first family, chromosome microarray data revealed that the two affected sisters, born to first-cousin parents, shared a unique homozygous C-terminal deletion in the COLEC11 gene. Two affected brothers from a second family, also born to first-cousin parents, shared a region of homozygosity that included the second gene known to cause the 3MC syndrome, MASP1. We discuss the diagnostic approach of craniofacial disorders born to consanguineous parents and highlight a literature search and reference a helpful dysmorphology solution powered by FDNA (Facial Dysmorphology Novel Analysis) technology.

Routine measurement of amniotic fluid alpha-fetoprotein and acetylcholinesterase: the need for a reevaluation.

OBJECTIVE: The objective of the study was to evaluate whether the current screening regimen of measuring amniotic fluid alpha-fetoprotein (AF-AFP) at the time of amniocentesis and reflex acetylcholinesterase testing vs ultrasound alone to detect neural tube and ventral wall defects offers improved diagnostic accuracy and cost benefit. STUDY DESIGN: A retrospective chart review on all patients who had amniocentesis performed at 1 center over the past 11 years was performed. Those with an elevated AF-AFP were compared with those whose AF-AFP was within normal limits. Ultrasound findings and outcomes were reviewed in all cases to assess whether neural tube defects (NTDs) or ventral wall defects (VWDs) were missed by AF-AFP or ultrasound screening. A cost-benefit analysis was then performed. RESULTS: Of 6232 women who underwent amniocentesis between January 2002 and December 2012, 81 had an elevated AF-AFP with or without a positive acetylcholinesterase (AChE). Of these 81 women, 13 had NTDs and 5 had VWDs. The sensitivity of the detailed ultrasound was 100% in detecting NTDs and VWDs, whereas that of the AF-AFP ranged from 22% to 77%, with the inclusion of AChE. The total expenditure for AF-AFP in our sample set (n = 6232 amniocentesis at $76.00 per AF-AFP) was $473,632, and all NTDs and VWDs were detected by ultrasound. Translated to a national laboratory (>42,447 samples/year), the cost savings in 2011 alone would be $3,225,972. CONCLUSION: Given the accuracy of high-resolution ultrasound in the detection of both NTDs and VWDs, measuring AF-AFP and AChE as a reflex-screening test is not a cost-effective approach.

The x-ray crystal structure of mannose-binding lectin-associated serine proteinase-3 reveals the structural basis for enzyme inactivity associated with the Carnevale, Mingarelli, Malpuech, and Michels (3MC) syndrome.

The mannose-binding lectin associated-protease-3 (MASP-3) is a member of the lectin pathway of the complement system, a key component of human innate and active immunity. Mutations in MASP-3 have recently been found to be associated with Carnevale, Mingarelli, Malpuech, and Michels (3MC) syndrome, a severe developmental disorder manifested by cleft palate, intellectual disability, and skeletal abnormalities. However, the molecular basis for MASP-3 function remains to be understood. Here we characterize the substrate specificity of MASP-3 by screening against a combinatorial peptide substrate library. Through this approach, we successfully identified a peptide substrate that was 20-fold more efficiently cleaved than any other identified to date. Furthermore, we demonstrated that mutant forms of the enzyme associated with 3MC syndrome were completely inactive against this substrate. To address the structural basis for this defect, we determined the 2.6-Å structure of the zymogen form of the G666E mutant of MASP-3. These data reveal that the mutation disrupts the active site and perturbs the position of the catalytic serine residue. Together, these insights into the function of MASP-3 reveal how a mutation in this enzyme causes it to be inactive and thus contribute to the 3MC syndrome.

Effect of copaiba oil on correction of abdominal wall defect treated with the use of polypropylene/polyglecaprone mesh.

PURPOSE: To evaluate the effects of copaiba oil on the correction of abdominal defect treated with the use of polypropylene/polyglecaprone mesh in rats. METHODS: A defect in the abdominal wall was created and corrected with polypropylene/polyglecaprone mesh in 36 rats. They were randomly distributed into three groups: control, copaiba by oral administration (gavage) and copaiba oil dip in the mesh. Euthanasia was performed after seven, 14 and 21 post-operative days. The healing process was analyzed regarding the meshes and macroscopic and microscopic aspects. RESULTS: All animals had abdominal adhesions, which were smaller in the copaiba (gavage) group (p<0.05). In microscopy, all animals had an acute inflammation stage and the inflammatory response was best characterized by foreign body-type granulomas around the mesh fragments, which was not found in the mesh fragments within the copaiba dip group. There was a greater area of necrosis and fibrosis in the copaiba dip group compared to the control group (p<0.05). The copaiba (gavage) group had a greater quantity of collagen fibers compared to the control group. CONCLUSION: Copaiba oil administered by gavage decreased the amount of abdominal adhesions, besides accelerating the process of collagen fibers formation, without damages within the early stages of healing. However, when used by dip directly on the mesh, it had corrosive effects compromising the healing process of the abdominal wall.

Effect of copaiba oil on correction of abdominal wall defect treated with the use of polypropylene/polyglecaprone mesh

PURPOSE: To evaluate the effects of copaiba oil on the correction of abdominal defect treated with the use of polypropylene/polyglecaprone mesh in rats. METHODS: A defect in the abdominal wall was created and corrected with polypropylene/polyglecaprone mesh in 36 rats. They were randomly distributed into three groups: control, copaiba by oral administration (gavage) and copaiba oil dip in the mesh. Euthanasia was performed after seven, 14 and 21 post-operative days. The healing process was analyzed regarding the meshes and macroscopic and microscopic aspects. RESULTS: All animals had abdominal adhesions, which were smaller in the copaiba (gavage) group (p<0.05). In microscopy, all animals had an acute inflammation stage and the inflammatory response was best characterized by foreign body-type granulomas around the mesh fragments, which was not found in the mesh fragments within the copaiba dip group. There was a greater area of necrosis and fibrosis in the copaiba dip group compared to the control group (p<0.05). The copaiba (gavage) group had a greater quantity of collagen fibers compared to the control group. CONCLUSION: Copaiba oil administered by gavage decreased the amount of abdominal adhesions, besides accelerating the process of collagen fibers formation, without damages within the early stages of healing. However, when used by dip directly on the mesh, it had corrosive effects compromising the healing process of the abdominal wall.

Mannan-binding lectin-associated serine protease (MASP)-1 is crucial for lectin pathway activation in human serum, whereas neither MASP-1 nor MASP-3 is required for alternative pathway function.

The lectin pathway of complement is an important component of innate immunity. Its activation has been thought to occur via recognition of pathogens by mannan-binding lectin (MBL) or ficolins in complex with MBL-associated serine protease (MASP)-2, followed by MASP-2 autoactivation and cleavage of C4 and C2 generating the C3 convertase. MASP-1 and MASP-3 are related proteases found in similar complexes. MASP-1 has been shown to aid MASP-2 convertase generation by auxiliary C2 cleavage. In mice, MASP-1 and MASP-3 have been reported to be central also to alternative pathway function through activation of profactor D and factor B. In this study, we present functional studies based on a patient harboring a nonsense mutation in the common part of the MASP1 gene and hence deficient in both MASP-1 and MASP-3. Surprisingly, we find that the alternative pathway in this patient functions normally, and is unaffected by reconstitution with MASP-1 and MASP-3. Conversely, we find that the patient has a nonfunctional lectin pathway, which can be restored by MASP-1, implying that this component is crucial for complement activation. We show that, although MASP-2 is able to autoactivate under artificial conditions, MASP-1 dramatically increases lectin pathway activity at physiological conditions through direct activation of MASP-2. We further demonstrate that MASP-1 and MASP-2 can associate in the same MBL complex, and that such cocomplexes are found in serum, providing a scenario for transactivation of MASP-2. Hence, in functional terms, it appears that MASP-1 and MASP-2 act in a manner analogous to that of C1r and C1s of the classical pathway.

Morphological aspects in a urogenital malformation, complex and rare, in a child.

The aim of this study follows the detailed evolution of a child diagnosed with prune-belly syndrome. This syndrome is a complex dysplasia, a rare pathology in children, characterized by the triad--the classic--hypo- or aplasia of righteous abdominal, cryptorchidism, abnormality of the urinary tract; also, it can be associated with pulmonary, cardiac, digestive, osteoarticular, and other malformations. Diagnostic criteria and etiopathogeny aspects are presented showing embryopathy and X-linked hereditary transmission theories as the most plausible, as proofed by recent genetic studies. Analyzing therapeutic aspects, it is stressed that medical treatment precedes or follows surgery, which cannot resolve urinary infection unless dysplastic urinary reconstruction is performed. Serious forms of prune-belly syndrome have a development and poor prognosis. Intrauterine and neonatal mortality is 20% and 50% in the first two years of life. The risk of urinary infection and/or lungs burdens the patient's clinical condition, allowing further appreciation on evolution of the disease. For cases solvable by plastic surgical reconstruction, as those who respond to medical therapy, differentiation will be monitored in territory and check-ups by the specialized consulting room from Polyclinic Health Center. Urinary infection relapse danger is permanent, requiring differentiated supervision. These case interest practitioners, by at least two aspects: the rarity of the disease, and complexity of dysplasia constituent, which has serious implications on the body economy.

Factors affecting the outcome in patients with gastroschisis: how important is immediate repair?

BACKGROUND: Since 30 years, we have attempted to repair gastroschisis as early as possible, often even in the delivery room. We examined 12 recent years of patient records to evaluate the effect of immediate repair and other factors on the outcome of gastroschisis. METHODS: We reviewed the medical records of patients presenting with gastroschisis (87) at the Children's Hospital of Michigan between 1998 and 2009. Data were evaluated specifically to determine the effect of the place of repair [obstetric hospital ("DR") vs. children's hospital ("OR")], the time of repair [less than an hour after delivery ("IR") or more than one hour ("ER")], and the type of repair [primary fascial repair and skin closure ("PR") vs. staged repair ("SR")]. RESULTS: Patients in the PR group were more likely to spend one week or less on MV (66% in PR vs. 11% in SR, p<0.01). Patients in the DR group were more likely to spend 2 weeks or less on TPN, as were patients in the PR group (51% in PR vs. 17% in SR, p<0.01). Patients in the PR group were more likely to stay in hospital for less than 3 weeks, but the IR and ER groups had almost same hospital stay. Major associated anomalies were present in 19 patients (29%). These patients and those with little or no peel tended to outperform those with peel in each of our outcome measures. CONCLUSION: Repair immediately after delivery is beneficial in terms of achieving primary closure of the defect, leading to shorter times on assisted ventilation and parenteral nutrition, and shorter hospital stays.

MASP1 mutations in patients with facial, umbilical, coccygeal, and auditory findings of Carnevale, Malpuech, OSA, and Michels syndromes.

Distinctive facial features consisting of hypertelorism, telecanthus, blepharophimosis, blepharoptosis, epicanthus inversus, periumbilical defects, and skeletal anomalies are seen in autosomal-recessive Carnevale, Malpuech, Michels, and oculo-skeletal-abdominal (OSA) syndromes. The gene or genes responsible for these syndromes were heretofore unknown. We report on three individuals from two consanguineous Turkish families with findings characteristic of these syndromes, including facial dysmorphism, periumbilical depression, mixed hearing loss, radioulnar synostosis, and coccygeal appendage. Homozygosity mapping yielded an autozygous region on chromosome 3q27 in both families. In one family, whole exome sequencing revealed a missense mutation, MASP1 c.2059G>A (p.G687R), that cosegregated with the phenotype. In the second family, Sanger sequencing of MASP1 revealed a nonsense mutation, MASP1 c.870G>A (p.W290X), that also cosegregated with the phenotype. Neither mutation was found in 192 Turkish controls or 1200 controls of various other ancestries. MASP1 encodes mannan-binding lectin serine protease 1. The two mutations occur in a MASP1 isoform that has been reported to process IGFBP-5, thereby playing a critical role in insulin growth factor availability during craniofacial and muscle development. These results implicate mutations of MASP1 as the cause of a human malformation syndrome and demonstrate the involvement of MASP1 in facial, umbilical, and ear development during the embryonic period.

Prevalencia de defectos de la pared abdominal al nacer: estudio ECLAMC / Prevalence of abdominal wall defects in newborns: ECLAMC Study, 1982-2005

Introducción: Onfalocele y gastrosquisis son los defectos de la pared abdominal (DPA) más frecuentes. Ambos necesitan un diagnóstico precoz y tratamiento quirúrgico oportuno para sobrevivir. Objetivos: Determinar la prevalencia al nacimiento de los DPA en la maternidad del Hospital Clínico de la Universidad de Chile (HCUCH) y compararla con la del total de maternidades chilenas (MCh) y los resultados del Estudio Colaborativo Latino Americano de Malformaciones Congénitas (ECLAMC). Resultados: La prevalencia global de onfalocele fue de 3,4/ 10 000 nacimientos y 3,8/10 000 para gastrosquisis. La prevalencia de onfalocele fue 9/10.000 en HCUCH y 2,77/10 000 en MCh (p = 0,006) y la de gastrosquisis fue 1,9/10 000 en HCUCH y 1,1/10 000 en MCh (p = 0,036). El promedio de edad materna fue 24,2 años para gastrosquisis y 33,6 para onfalocele (p < 0,004). La sobrevida de gastrosquisis fue 100 por ciento versus 31,7 por ciento en onfalocele (p < 0,0425). Todos los RN con onfalocele, salvo uno, presentaban asociación con otras MC graves. El peso de nacimiento y edad gestacional fueron significativamente menores en onfalocele. Conclusión: La prevalencia de DPA fue significativamente mayor en el HCUCH que en el resto de las maternidades chilenas. Gastrosquisis se presentó en hijos de mujeres más jóvenes y onfalocele en las de mayor edad.

The acute abdomen in the newborn.

The acute abdomen in the newborn provides challenging problems from many aspects, not only with regard to diagnosis, resuscitation and treatment, but also now with prenatal management. Most conditions are uncommon and treatment in specialist centres enables concentration of appropriate resources and expertise. Co-morbidity is common, particularly in the preterm or low birth weight infant. A multi-disciplinary team of surgeons, anaesthetists, neonatologists, radiologists, cardiologists, obstetricians, nurses, physiotherapists and other health professionals experienced in dealing with extremely small infants will provide the best outcome. The infant should be resuscitated and, as soon as conditions permit, transferred to a specialist surgical centre with intravenous fluids, gastric tube drainage and circulatory, respiratory and general support as needed. This involves close liaison within healthcare networks and readily available patient transfer facilities. Surgery itself should be carried out in a theatre fully equipped for neonatal surgery. A gentle touch is essential because of the fragility of the tissues, and painstaking care should be taken with blood loss.

An unusual abdominal wall hernia.

An unusual hernia is described involving a defect in the right rectus sheath at the junction of its middle and lower third. This was associated with an extension of the sac anteriorly between the right rectus muscle and its overlying sheath.

[Advances in the treatment of newborns with congenital malformations]. / Postepy w leczeniu noworodków z wadami wrodzonymi wymagajacymi operacji bezposrednio po urodzeniu.

Authors analyzed the type and the number of treated congenital malformations in 544 newborns operated between 1992-2001 in the Department of Paediatric Surgery in the Institute of Mother and Child. The patients were divided in the following groups: digestive tract defects, abdominal wall and diaphragm defects, neural tube defects, urinary track defects, craniofacial and brain defects and others anomalies occurring rarely. Most of the operations were preformed in the first 48 hours of life. Since 1995 special newborn transport, early cardiac surgery and neonatal intensive care have been introduced. Total mortality of operated newborns and death in particular groups were analyzed. The implemented elements caused a decrease in mortality from 36 to 13 percent. In the authors' opinion improvement in treatment results is due to earlier diagnosis and better understanding of pathophysiology of the defects, introduction of noninvasive pre- and postnatal diagnostics and establishment of centres specialized in neonatal surgery and intensive care.

Abdominal wall defects.

The frequent use of prenatal diagnostic techniques including ultrasound and maternal serum alpha-fetoprotein has increasingly led to detection of abdominal wall defects before birth. This prenatal detection creates the opportunity to influence neonatal outcome by alteration in management of pregnancy or delivery. The optimal management of an individual fetus depends on careful prenatal assessment of the abdominal wall defect, combined with experience and knowledge of the natural history for that particular lesion. A multidisciplinary approach to the fetus can improve neonatal outcome. Careful assessment for other structural anomalies and karyotype analysis should be performed. Delivery at a high-risk perinatal center should be encouraged. Currently, there is no convincing evidence to support routine cesarean section for most abdominal wall defects.