Garrahan Hospital

About: Garrahan Hospital is a healthcare organization based out in Buenos Aires, Argentina. It is known for research contribution in the topics: Medicine & Population. The organization has 115 authors who have published 53 publications receiving 1010 citations. The organization is also known as: Hospital de pediatria Garrahan.

Human TYK2 deficiency: Mycobacterial and viral infections without hyper-IgE syndrome

Abstract: Autosomal recessive, complete TYK2 deficiency was previously described in a patient (P1) with intracellular bacterial and viral infections and features of hyper-IgE syndrome (HIES), including atopic dermatitis, high serum IgE levels, and staphylococcal abscesses. We identified seven other TYK2-deficient patients from five families and four different ethnic groups. These patients were homozygous for one of five null mutations, different from that seen in P1. They displayed mycobacterial and/or viral infections, but no HIES. All eight TYK2-deficient patients displayed impaired but not abolished cellular responses to (a) IL-12 and IFN-α/β, accounting for mycobacterial and viral infections, respectively; (b) IL-23, with normal proportions of circulating IL-17+ T cells, accounting for their apparent lack of mucocutaneous candidiasis; and (c) IL-10, with no overt clinical consequences, including a lack of inflammatory bowel disease. Cellular responses to IL-21, IL-27, IFN-γ, IL-28/29 (IFN-λ), and leukemia inhibitory factor (LIF) were normal. The leukocytes and fibroblasts of all seven newly identified TYK2-deficient patients, unlike those of P1, responded normally to IL-6, possibly accounting for the lack of HIES in these patients. The expression of exogenous wild-type TYK2 or the silencing of endogenous TYK2 did not rescue IL-6 hyporesponsiveness, suggesting that this phenotype was not a consequence of the TYK2 genotype. The core clinical phenotype of TYK2 deficiency is mycobacterial and/or viral infections, caused by impaired responses to IL-12 and IFN-α/β. Moreover, impaired IL-6 responses and HIES do not appear to be intrinsic features of TYK2 deficiency in humans.

Risk factors for diabetes insipidus in langerhans cell histiocytosis.

Abstract: Background Diabetes insipidus (DI) is the most frequent central nervous system (CNS)-related permanent consequence in Langerhans cell histiocytosis (LCH), which mostly requires life-long hormone replacement therapy. In an attempt to define the population at risk for DI, 1,741 patients with LCH registered on the trials DALHX 83 and DALHX 90, LCH I and LCH II were studied. Results Overall 212 of 1,741 patients (12%) was reported to have DI. In 102 of 1,741 patients (6%) DI was present at diagnosis of LCH. One thousand one hundred eighty three of 1,539 patients without DI at diagnosis had follow up information. One hundred ten of these (9%) later developed DI. The risk of developing DI was 20% at 15 years after diagnosis. Multisystem disease patients at diagnosis carried a 4.6-fold risk for DI compared to single system patients. Craniofacial lesions, in particular in the “ear,” “eye,” and oral region were associated with a significantly increased risk for DI (relative hazard rate, RHR 1.7), independent of the extent of disease. No influence of the duration of therapy could be determined, but the duration of initial disease activity (RHR 1.5) and the occurrence of reactivations (RHR 3.5) significantly increased the risk for DI. Conclusions Patients with multisystem disease and craniofacial involvement at diagnosis, in particular of the “ear,” “eye,” and the oral region carry a significantly increased risk to develop DI during their course. This risk is augmented when the disease remains active for a longer period or reactivates. © 2005 Wiley-Liss, Inc.

Closure of the patent ductus arteriosus with the Amplatzer PDA device: Immediate results of the international clinical trial

Abstract: The purpose of this article is to present the immediate and short-term results of the international registry of transcatheter closure of patent ductus arteriosus (PDA) using the Amplatzer duct occluder (ADO). Three hundred sixteen patients (221 females) in various centers with clinical and/or echocardiographic evidence of PDA underwent an attempt of catheter closure at a median age of 2.1 years and median weight of 10.7 kg. The median Qp/Qs ratio was 2.3, the median length of the PDA was 6.7 mm and the median diameter of the PDA at its narrowest point (usually the pulmonic end) was 3.8 mm. Immediately after closure and by angiography, the PDA was completely closed in 177/311 patients (56%) and within 24 hr the complete closure rate increased to 76% (235/308). Complications were encountered in 15 patients, including 1 major complication due to device embolization and subsequent death, 6 moderate complications, and 8 minor complications. The median fluoroscopy time was 12 min and the median total procedure time was 70 min. One hundred fourteen patients reached the 6-month follow-up. Color Doppler echocardiography demonstrated complete closure in 109 patients (94.6%). Thirty-eight patients reached the 1-year follow-up mark. There was complete closure in 100% of the patients as documented by color Doppler echocardiography. So far there has been no episodes of delayed device migration, endocarditis, thromboembolism, and wire fracture or device disruption. We conclude that the ADO is safe and effective in most patients with PDA up to a diameter of 10.6 mm. Further clinical trials are underway to assess its long-term safety and efficacy.

Dravet syndrome: Treatment options and management of prolonged seizures.

Abstract: Over time, with careful delineation of Dravet syndrome, we have gained experience in treatments most likely to lead to improvement in seizures, as well as those that should be avoided. Sodium valproate, clobazam, stiripentol, and topiramate are all medications that may lead to benefit, as well as the ketogenic diet. Bromides may be utilized in resistant cases. However, equally important are outlining prompt rescue treatment for prolonged seizures and avoidance of precipitants. Newer agents including cannabidiol and fenfluramine have been demonstrated to be of benefit in clinical trials. We propose an algorithm for management, but appreciate that the positioning of newer agents is yet to be established.

Problems associated with the apnea test in the diagnosis of brain death.

Abstract: evaluate complications or difficulties related to this procedure. Objective: To analyze medical problems associated with the apnea test. Methods and Patients: We analyzed clinical features, potential risk conditions, and problems in 129 brain dead patients during the apnea test. The diagnosis of brain death was made according to the American Academy of Neurology recommendations. Results: Clinical problems during the apnea test were detected in more than two thirds of patients, including: arterial hypotension (12%), acidosis (68%), and hypoxemia (23%). Four patients developed major complications, including: pneumothorax, cardiac arrest, bradycardia, atrial fibrillation and myocardial infarction. Conclusion: The apnea test is not an innocuous procedure. Complications during the AT are more common than reported and limit organ procurement for transplantation. Guidelines for performing the AT should be followed in order to avoid clinical complications.