Clinical Profile of Pediatric Extrapulmonary Tuberculosis in a Tertiary Hospital: A 10-year Retrospective Study

Background: Young children are at increased risk of developing severe forms of tuberculosis (TB) disease. Extrapulmonary tuberculosis (EPTB) contributes significantly to TB-related morbidities. This study aimed to determine patients’ epidemiologic and clinical profile with EPTB among children aged 0-18 years old admitted and diagnosed from January 2010 to December 2019 at Southern Philippines Medical Center (SPMC).Methodology: This is a retrospective cross-sectional study. The child’s medical records for EPTB admission in SPMC were retrieved. Data including demographic, clinical presentation, treatment outcomes and survival rate were recorded and subsequently analyzed.Results: There were 136 EPTB cases from January 2010 to December 2019. Prevalence of EPTB is 17% among all pediatric TB admissions. A total of 75 EPTB patients were evaluated. The average age of patients is 9 years old. Majority of patients belong to the 11-18yo. No significant difference among male and female patients. Most of the patients were malnourished, received BCG vaccine and had TB exposure to an infected family member. The most common symptoms were fever, seizure, vomiting, and headache. Majority of cases involved the central nervous system (CNS), followed by gastrointestinal involvement and the pleura. Half of the cases completed treatment and only two cases were cured. The average survival time based on Kaplan Meier Curve survival analysis is 34 days. Survival is below 80% on the 25th hospital day and onwards.Conclusion: Extrapulmonary tuberculosis in children results in higher morbidity, mortality, and healthcare cost due to prolonged hospitalization and longer duration of treatment. Early diagnosis, intervention and treatment are the cornerstone in decreasing the burden of disease. Keywords: Extrapulmonary, tuberculosis, extrapulmonary tuberculosis, central nervous system DOI: 10.7176/JHMN/106-03 Publication date:March 31st 202

Evidence-based medicine et étudiants en médecine français : état des lieux

IntroductionL’Evidence-Based Medicine (EBM) est indispensable à l’exercice de la médecine. Notre objectif était de connaître quel en était son niveau de connaissance par les étudiants français. Matériel et Méthodes Entre avril et mai 2008, un questionnaire a été envoyé par courriel à 900 étudiants en dernière année du deuxième cycle des études médicales participant à des conférences publiques ou privées d’internat. Résultats Sur les 327 réponses, 297 (91 %), 94 (29 %) et 85 (26 %) étudiants déclaraient savoir lire, écrire et parler l’anglais médical. Quatre-vingt-dix étudiants (28 %) lisaient un article d’une revue médicale française, une fois par mois et 43 (13 %) lisaient un article d’une revue médicale internationale une fois par mois. Trois cent onze (95 %) connaissaient les bases de recherche médicale sur Internet et 219 (67 %) les utilisaient. Vingt-quatre (7 %) avaient déjà participé à la rédaction d’un article médical, sept (2 %) avait été co-auteurs. Deux cent soixante-douze (83 %) avait réalisé une présentation orale lors d’un staff médical et trois (1 %) lors d’un congrès. Enfin, 237 (73 %) comprenaient l’intérêt de l’épreuve d’analyse critique d’article à l’examen national classant (ECN) et 70 (21 %) pensaient y être préparés. Conclusion L’insuffisance de l’apprentissage de l’EBM est une des limites du système de formation français. L’introduction de la lecture critique d’article (LCA) à l’ECN est un début de réponse concret à ce problème

Cytoprotective Efficacy and Mechanisms of the Liposoluble Iron Chelator 2,2Ј-Dipyridyl in the Rat Photothrombotic Ischemic Stroke Model

ABSTRACT We examined the efficacy of the liposoluble iron chelator 2,2Ј-dipyridyl (DP) in reducing histological damage in rats submitted to cerebral ischemia and the mechanisms involved in the potential cytoprotection. For this purpose, DP (20 mg/kg, i.p.) was administered 15 min before and 1 h after induction of cortical photothrombotic vascular occlusion in rat. Histological studies were performed to assess infarct volume (at days 1 and 3 postischemia) and astromicroglial activation (at day 3 postischemia). Damage to endothelial and neuronal cells was evaluated at day 1 postischemia by quantitative measurements of Evans Blue extravasation and N-acetylaspartate levels, respectively. Cerebral blood flow was recorded in the ischemic core by laser-Doppler flowmetry within the 15 min to 2 h period after photothrombosis. At 4-h postischemia, radical oxygen species (ROS) production was evaluated by measuring brain glutathione concentrations. The cortical expression of the proteins heme oxygenase-1 (HO-1) and hypoxia-inducible factor-1␣ (HIF-1␣) was analyzed by Western blotting at day 1 postischemia. Infarct volume and ischemic damage to endothelial and neuronal cells were significantly reduced by DP treatment. This cytoprotection was associated with a reduction in ROS production, perfusion deficits, and astrocytic activation. DP treatment also resulted in significant changes in HO-1 (ϩ100%) and HIF-1␣ (Ϫ50%) protein expression at the level of the ischemic core. These results report the efficacy of the liposoluble iron chelator DP in reducing histological damage induced by permanent focal ischemia

NHC-Based Iron Sensitizers for DSSCs

Nanostructured dye-sensitized solar cells (DSSCs) are promising photovoltaic devices because of their low cost and transparency. Ruthenium polypyridine complexes have long been considered as lead sensitizers for DSSCs, allowing them to reach up to 11% conversion efficiency. However, ruthenium suffers from serious drawbacks potentially limiting its widespread applicability, mainly related to its potential toxicity and scarcity. This has motivated continuous research efforts to develop valuable alternatives from cheap earth-abundant metals, and among them, iron is particularly attractive. Making iron complexes applicable in DSSCs is highly challenging due to an ultrafast deactivation of the metal-ligand charge-transfer (MLCT) states into metal-centered (MC) states, leading to inefficient injection into TiO2. In this review, we present our latest developments in the field using Fe(II)-based photosensitizers bearing N-heterocyclic carbene (NHC) ligands, and their use in DSSCs. Special attention is paid to synthesis, photophysical, electrochemical, and computational characterization

Congenital dislocation of the hip: Optimal screening strategies in 2014

AbstractA prospective multi-centre nationwide study of patients with congenital dislocation of the hip (CDH) diagnosed after 3 months of age was conducted with support from the French Society for Paediatric Orthopaedics (Société Française d’Orthopédie Pédiatrique [SoFOP]), French Organisation for Outpatient Paediatrics (Association Française de Pédiatrie Ambulatoire [AFPA]), and French-Speaking Society for Paediatric and Pre-Natal Imaging (Société Francophone d’Imagerie Pédiatrique et Prénatale [SFIPP]). The results showed inadequacies in clinical screening for CDH that were patent when assessed quantitatively and probably also present qualitatively. These findings indicate a need for a communication and educational campaign aimed at highlighting good clinical practice guidelines in the field of CDH screening. The usefulness of routine ultrasound screening has not been established. The findings from this study have been used by the authors and French National Health Authority (Haute Autorité de Santé [HAS]) to develop recommendations about CDH screening. There is an urgent need for a prospective randomised multi-centre nationwide study, which should involve primary-care physicians

Human Galectin 3 Binding Protein Interacts with Recombinant Adeno-Associated Virus Type 6

Recombinant adeno-associated viruses (rAAVs) hold enormous potential for human gene therapy. Despite the well-established safety and efficacy of rAAVs for in vivo gene transfer, there is still little information concerning the fate of vectors in blood following systemic delivery. We screened for serum proteins interacting with different AAV serotypes in humans, macaques, dogs, and mice. We report that serotypes rAAV-1, -5, and -6 but not serotypes rAAV-2, -7, -8, -9, and -10 interact in human sera with galectin 3 binding protein (hu-G3BP), a soluble scavenger receptor. Among the three serotypes, rAAV-6 has the most important capacities for binding to G3BP. rAAV-6 also bound G3BP in dog sera but not in macaque and mouse sera. In mice, rAAV-6 interacted with another protein of the innate immune system, C-reactive protein (CRP). Furthermore, interaction of hu-G3BP with rAAV-6 led to the formation of aggregates and hampered transduction when the two were codelivered into the mouse. Based on these data, we propose that species-specific interactions of AAVs with blood proteins may differentially impact vector distribution and efficacy in different animal models

Long-term Restoration of Cardiac Dystrophin Expression in Golden Retriever Muscular Dystrophy Following rAAV6-mediated Exon Skipping

Although restoration of dystrophin expression via exon skipping in both cardiac and skeletal muscle has been successfully demonstrated in the mdx mouse, restoration of cardiac dystrophin expression in large animal models of Duchenne muscular dystrophy (DMD) has proven to be a challenge. In large animals, investigators have focused on using intravenous injection of antisense oligonucleotides (AO) to mediate exon skipping. In this study, we sought to optimize restoration of cardiac dystrophin expression in the golden retriever muscular dystrophy (GRMD) model using percutaneous transendocardial delivery of recombinant AAV6 (rAAV6) to deliver a modified U7 small nuclear RNA (snRNA) carrying antisense sequence to target the exon splicing enhancers of exons 6 and 8 and correct the disrupted reading frame. We demonstrate restoration of cardiac dystrophin expression at 13 months confirmed by reverse transcription-PCR (RT-PCR) and immunoblot as well as membrane localization by immunohistochemistry. This was accompanied by improved cardiac function as assessed by cardiac magnetic resonance imaging (MRI). Percutaneous transendocardial delivery of rAAV6 expressing a modified U7 exon skipping construct is a safe, effective method for restoration of dystrophin expression and improvement of cardiac function in the GRMD canine and may be easily translatable to human DMD patients