Outcomes after transplantation for “failed” Fontan: A single-institution experience

ObjectiveDespite the excellent outcomes in the current era after the Fontan procedure, it continues to have an inherent risk of failure. Cardiac transplantation provides 1 option for treating these patients; however, the indications for, timing of, and outcomes after, transplantation remain undefined. We examined our own institutional experience with transplantation for failed Fontan.MethodsThe records of 155 patients transplanted for congenital heart disease at a single institution from June 1984 to September 2007 were reviewed. Of these patients, 43 had undergone a previous Fontan procedure (25 male, 15 female; median age, 14.5 years; range, 1–47; 23 classic Fontan, 13 lateral tunnel, 4 extracardiac conduit, and 3 revised to shunt). The predictors of short- and long-term survival were evaluated, and the Fontan patients were compared with all other patients with congenital heart disease (n = 129, 78 male, 51 female).ResultsThe most common indications for transplantation included protein-losing enteropathy (PLE) (39.5%), chronic heart failure (41.8%), and acute post-Fontan failure (9.3%). The transplants performed in Fontan patients were more likely to require pulmonary artery reconstruction (85.4% vs 42.9%; P < .0001) and had longer cardiopulmonary bypass times (278 vs 179 minutes; P < .0001). The 90-day mortality rate was greater in the Fontan group (35.0% vs 20.0%; P = .055). No correlation was observed between the interval from Fontan to transplantation and morality; however, renal failure was a strong predictor of early mortality (odds ratio, 10.8; 95% confidence interval, 1.5–75.7).ConclusionsTransplantation is an acceptable treatment for patients with a failed Fontan. Clinical factors (instead of the indication for transplantation) appear to have the greatest correlation with early mortality

Cerebrospinal fluid cannot be used to distinguish inflammatory myelitis from congestive myelopathy due to spinal dural arteriovenous fistula: case series.

Patients with congestive myelopathy due to spinal dural arteriovenous fistula (SDAVF) typically present with progressive sensory and motor disturbance in association with sphincter dysfunction. Spinal MRI usually shows longitudinally extensive T2 signal change. Here, we report four patients with progressive myelopathy due to SDAVF who also presented with findings on cerebrospinal fluid (CSF) examination suggestive of an inflammatory aetiology. Such CSF findings in SDAVF are important to recognise, to avoid the erroneous diagnosis of an inflammatory myelitis and inappropriate treatment with immunosuppression. SDAVF can be difficult to detect and may require repeated investigation, with formal angiography as the gold standard

Damage imaging post processing for delamination size assessment of CFRP aeronautic structures

Thanks to their high strength to mass ratio, composite materials are now widespread in the aerospace industry. Nevertheless, this type of material is sub- ject to internal damages like delamination. In order to detect and localize these damages, robust and precise Structural Health Monitoring algorithms exist for this purpose and have been validated experimentally. However, in order to avoid struc- tures catastrophic failures and to estimate their residual life, there is still a huge need of reliable damage size assessment methods. In this paper, a damage quanti cation method is proposed. This strategy is based on the extraction of a damage size sen- sitive feature computed from damage imaging results. Here damage imaging stands for methods that use ultrasonic Lamb waves-based map of damage localization like- lihood index. This feature is extracted from each labelled example of a training set in order to infer a mathematical model used to predict the area of a delamination of unknown damages. The proposed method is successfully validated on experimental data carried out on CFRP plate samples equipped with a piezoelectric transducers network.This work has received funding from the European Union's Horizon 2020 research and innovation program under the REMAP project (grant agreement number 769288). https://h2020-remap.eu

Matrix metalloproteinase-9 activity and a downregulated Hedgehog pathway impair blood-brain barrier function in an <i>in vitro</i> model of CNS tuberculosis

Central nervous system tuberculosis (CNS TB) has a high mortality and morbidity associated with severe inflammation. The blood-brain barrier (BBB) protects the brain from inflammation but the mechanisms causing BBB damage in CNS TB are uncharacterized. We demonstrate that Mycobacterium tuberculosis (Mtb) causes breakdown of type IV collagen and decreases tight junction protein (TJP) expression in a co-culture model of the BBB. This increases permeability, surface expression of endothelial adhesion molecules and leukocyte transmigration. TJP breakdown was driven by Mtb-dependent secretion of matrix metalloproteinase (MMP)-9. TJP expression is regulated by Sonic hedgehog (Shh) through transcription factor Gli-1. In our model, the hedgehog pathway was downregulated by Mtb-stimulation, but Shh levels in astrocytes were unchanged. However, Scube2, a glycoprotein regulating astrocyte Shh release was decreased, inhibiting Shh delivery to brain endothelial cells. Activation of the hedgehog pathway by addition of a Smoothened agonist or by addition of exogenous Shh, or neutralizing MMP-9 activity, decreased permeability and increased TJP expression in the Mtb-stimulated BBB co-cultures. In summary, the BBB is disrupted by downregulation of the Shh pathway and breakdown of TJPs, secondary to increased MMP-9 activity which suggests that these pathways are potential novel targets for host directed therapy in CNS TB

Evidence of amyloid-β cerebral amyloid angiopathy transmission through neurosurgery

Amyloid-β (Aβ) is a peptide deposited in the brain parenchyma in Alzheimer’s disease and in cerebral blood vessels, causing cerebral amyloid angiopathy (CAA). Aβ pathology is transmissible experimentally in animals and through medical procedures in humans, such as contaminated growth hormone or dura mater transplantation in the context of iatrogenic prion disease. Here, we present four patients who underwent neurosurgical procedures during childhood or teenage years and presented with intracerebral haemorrhage approximately three decades later, caused by severe CAA. None of these patients carried pathogenic mutations associated with early Aβ pathology development. In addition, we identified in the literature four patients with a history of neurosurgical intervention and subsequent development of CAA. These findings raise the possibility that Aβ pathology may be transmissible, as prion disease is, through neurosurgical procedures

Heart transplantation in children with congenital heart disease

ObjectivesThe aim of this study was to describe heart transplantation in children with congenital heart disease and to compare the results with those in children undergoing transplantation for other cardiac diseases.BackgroundReports describe decreased survival after heart transplantation in children with congenital heart disease compared with those with cardiomyopathy. However, transplantation is increasingly being considered in the surgical management of children with complex congenital heart disease. Present-day results from this group require reassessment.MethodsThe diagnoses, previous operations and indications for transplantation were characterized in children with congenital heart disease. Pretransplant course, graft ischemia time, posttransplant survival and outcome (rejection frequency, infection rate, length of hospital stay) were compared with those in children undergoing transplantation for other reasons (n = 47).ResultsThirty-seven children (mean [±SD] age 9 ± 6 years) with congenital heart disease underwent transplantation; 86% had undergone one or more previous operations. Repair of extracardiac defects at transplantation was necessary in 23 patients. Causes of death after transplantation were donor failure in two patients, surgical bleeding in two, pulmonary hemorrhage in one, infection in four, rejection in three and graft atherosclerosis in one. No difference in 1- and 5-year survival rates (70% vs. 77% and 64% vs. 65%, respectively), rejection frequency or length of hospital stay was seen between children with and without congenital heart disease. Cardiopulmonary bypass and donor ischemia time were significantly longer in patients with congenital heart disease. Serious infections were more common in children with than without congenital heart disease (13 of 37 vs. 6 of 47, respectively, p = 0.01).ConclusionsDespite the more complex cardiac surgery required at implantation and longer donor ischemic time, heart transplantation can be performed in children with complex congenital heart disease with success similar to that in patients with other cardiac diseases

Coding of coronary arterial origin and branching in congenital heart disease: The modified Leiden Convention

Objectives: Variations in coronary anatomy are common and may relate to the position of the coronary ostium relative to the aortic sinus, the angle of coronary take-off, or the course of the coronary arterial branches. Several classification systems have been proposed. However, they all lack a simple rationale that is applicable irrespective of the relative position of the great arteries, as well as in bicuspid aortic valves. We present a modification of a relatively simple system introduced in the early 1980s, designated the “Leiden Convention.” Methods: The first step of the Leiden Convention is that the clinician takes position in the nonfacing sinus of the aorta looking toward the pulmonary orifice. The right-hand facing sinus is sinus 1, and the left-hand facing sinus is sinus 2. The coronary branches arising from sinus 1 are annotated proceeding in a counterclockwise fashion toward sinus 2. “Usual” (normal) coronary anatomy would be 1R-2LCx. Given their clinical relevance, single sinus coronary arteries are discussed separately. Results: This system was originally designed and highly applicable in hearts with an altered great artery relationship, such as in the var

Tissue-engineered dermo-epidermal skin analogs exhibit de novo formation of a near natural neurovascular link 10 weeks after transplantation

PURPOSE: Human autologous tissue-engineered skin grafts are a promising way to cover skin defects. Clearly, it is mandatory to study essential biological dynamics after transplantation, including reinnervation. Previously, we have already shown that human tissue-engineered skin analogs are reinnervated by host nerve fibers as early as 8 weeks after transplantation. In this study, we tested the hypothesis that there is a de novo formation of a "classical" neurovascular link in tissue-engineered and then transplanted skin substitutes. METHODS: Keratinocytes, melanocytes, and fibroblasts were isolated from human skin biopsies. After expansion in culture, keratinocytes and melanocytes were seeded on dermal fibroblast-containing collagen type I hydrogels. These human tissue-engineered dermo-epidermal skin analogs were transplanted onto full-thickness skin wounds on the back of immuno-incompetent rats. Grafts were analyzed after 3 and 10 weeks. Histological sections were examined with regard to the ingrowth pattern of myelinated and unmyelinated nerve fibers into the skin analogs using markers such as PGP9.5, NF-200, and NF-160. Blood vessels were identified with CD31, lymphatic vessels with Lyve1. In particular, we focused on alignment patterns between nerve fibers and either blood and/or lymphatic vessels with regard to neurovascular link formation. RESULTS: 3 weeks after transplantation, blood vessels, but no nerve fibers or lymphatic vessels could be observed. 10 weeks after transplantation, we could detect an ingrowth of myelinated and unmyelinated nerve fibers into the skin analogs. Nerve fibers were found in close proximity to CD31-positive blood vessels, but not alongside Lyve1-positive lymphatic vessels. CONCLUSION: These data suggest that host-derived innervation of tissue-engineered dermo-epidermal skin analogs is initiated by and guided alongside blood vessels present early post-transplantation. This observation is consistent with the concept of a cross talk between neurovascular structures, known as the neurovascular link