La Prévalence des Pathologies Thyroïdiennes chez le Sujet Âgé au Service de Médecine Interne de l’Hôpital National Donka

Introduction : Le vieillissement est associé à des modifications complexes de la fonction thyroïdienne qui interviennent à plusieurs niveaux de régulation. La sécrétion des hormones thyroïdiennes est en général dans les limites inférieures des valeurs usuelles. Méthodes : Il s’agissait d’une étude rétrospective à visée descriptive et analytique menée du 1er janvier 2013 au 31 décembre 2022 (soit 10 ans). L’étude était réalisée au service de médecine interne de l’hôpital national Donka (Guinée). Elle a porté sur les sujets âgés de 60 ans et plus suivis pour une pathologie thyroïdienne. Résultats : Durand la période d’étude nous avons colligé 88 cas de dysthyroïdies soit une prévalence de 17,95 %. Il y avait une prédominance féminine (56 cas) avec un sex ratio H/F de 0,57. L’âge moyen était de 64,5 ans (extrêmes de 60 et 85 ans). Les circonstances de diagnostic de la maladie thyroïdienne étaient principalement un goitre (59,1%), une exophtalmie (9,1%), une compression cervicale (25%), une cardiothyréose (5,7 %). Les principales manifestations de la thyrotoxicose étaient l’amaigrissement (17%), les palpitations (29,5%) et la fatigabilité (34,1%). Les signes d’hypothyroïdie prédominants étaient la constipation (17%) et le syndrome myxœdémateux (3,4%). L’hyperthyroïdie a été rencontrée chez 13,64% des patients, contre 29,54% de cas d’hypothyroïdie. L’échographie cervicale thyroïdienne avait retrouvé 36 cas de goitre diffus (40,9%), 18 cas de goitre multinodulaire (20,45%), 17 cas de nodule unique (19,31%). Les principales étiologies étaient la maladie de Basedow (11,4%), le goitre multinodulaire (46,6%), la thyroïdite de Hashimoto (17%), un goitre simple (5,7%). La thyroïdectomie avait concerné 33 patients (37,5%). Deux cas de décès étaient enregistrés en rapport avec une cardiothyréose. Conclusion : Les dysthyroïdies sont fréquentes chez le sujet âgé au CHU de Conakry et un dosage hormonal au moindre doute afin d’instaurer le traitement adéquat à temps serait requis afin de prévenir les complications.   Introduction: The aging is associated with complex changes in thyroid function that occur at several levels of regulation. Thyroid hormone secretion is generally within the lower limits of usual values. Methods: This was a retrospective study with descriptive and analytical aims carried out from January 1, 2013 to December 31, 2022 (i.e. 10 years). The study was carried out in the internal medicine department of the Donka national hospital (Guinea). It focused on subjects aged 60 and over followed for thyroid pathology. Results: During the study period we collected 88 cases of dysthyroidism, representing a prevalence of 17.95%. There was a female predominance (56 cases) with a M/F sex ratio of 0.57. The average age was 64.5 years (range 60 and 85 years). The circumstances of diagnosis of thyroid disease were mainly goiter (59.1%), exophthalmos (9.1%), cervical compression (25%), cardiothyreosis (5.7%). The main manifestations of thyrotoxicosis were weight loss (17%), palpitations (29.5%), and fatigability (34.1%). The predominant signs of hypothyroidism were constipation (17%) and myxedematous syndrome (3.4%). Hyperthyroidism was encountered in 13.64% of patients, compared to 29.54% cases of hypothyroidism. Cervical thyroid ultrasound found 36 cases of diffuse goiter (40.9%), 18 cases of multinodular goiter (20.45%), 17 cases of single nodule (19.31%). The main etiologies were Graves' disease (11.4%), multinodular goiter (46.6%), Hashimoto's thyroiditis (17%), simple goiter (5.7%). Thyroidectomy involved 33 patients (37.5%). Two cases of death were recorded in connection with cardiothyreosis. Conclusion: Dysthyroidism is common in the elderly at the Conakry University Hospital and a hormonal dosage if there is the slightest doubt in order to initiate the appropriate treatment in time would be required in order to prevent complications

Première observation malienne d’histoplasmose africaine disséminée à prédominance osseuse chez un enfant VIH négatif. Revue de la littérature

Endemic deep fungal infections are still under recognised diseases in daily medical practice because of their rarity in sub-Saharan area. The African histoplasmosis Histoplasma capsulatum var. duboisii (H. capsulatum duboisii) is the most frequent variety described in Mali through limited studies in adult patients, since the first case described by Catanei and Kervran (1945). Our case report is a disseminated histoplasmosis in a young 6-year-old african child. He was male and rural. The infectious localisations were mucosae, skin, lymphnodes, urinary tract and bones. Evolution has been marred by an episode of worsening of symptoms despite initial clinical improvement with ketoconazole. After healing of mucocutaneous lesions, we noticed a limitation of ampliation of both wrists. The radiographic bone lesions were lysis of the right lower end of the right radius and cubitus and fragmentation of cubital epiphysis of the same arm. Lacunes were present on the fifth right finger in metatarsus and phalanx; lacune and blowing aspect of the second phalanx of the left third finger was noted. The disseminated form of African histoplasmosis may occur in HIV-negative subject. The prognosis depends on early diagnosis and administration of appropriate and well-conducted therapy

Cryptococcose extra-neuroméningée au cours du sida à Bamako, Mali (à propos de 2 observations)

Non-neuromeningeal cryptococcosis forms resulting from disseminated infection are rarely reported in African literature and are non-documented in Malian medical ward. We report two clinical observations. Case 1: a 26-year-old patient, carrying the HIV-1 infection, in which the clinical examination revealed skin lesions simulating molluscum contagiosum and functional impairment of the lower limbs. Radiography of the lumbar spine showed vertebral osteolysis on L4–L5. Cryptococcal research remained negative in the CSF but positive at histological examination of the skin lesions and in pathological products of lumbosacral drainage. The treatment with fluconazole and ARV led to a favorable outcome. Case 2: a 42-year-old patient, admitted for fever cough, known for his non-compliance to ARVs and in which the examination found a syndrome of pleural condensation and a painful swelling of the outer third of the right clavicle (around the acromio-clavicular joint). Paraclinical investigations concluded in osteolysis of the acromial end of the right clavicle and an image of the right lung with abundant effusion. Cryptococcal research was positive in the pleural effusion and in the product of aspiration of acromio-clavicular tumefaction, negative in CSF. It seems important to think of a cryptococcal etiology even in the absence of clinical meningeal signs in front of any cutaneous sign and any fluctuating swelling in HIV+ patient

La cryptococcose neuro-méningée au Mali

Cryptococcal meningitis is the most common fatal central nervous system infection in AIDS patients in Sub-Saharan Africa. The purpose of this prospective study conducted from March 2003 to February 2004 in the internal medicine and infectious diseases departments of the Point G University Hospital Center was to investigate the clinical, prognostic and epidemiological profile of Cryptococcus neoformans infection in patients hospitalized for brain and meningeale infection (BMI). Diagnosis of neuromeningeal cryptococcosis (NMC) was based on positive identification of Cryptococcus by direct exam of the cebrospinal fluid (CSF) after India ink staining and/or culture on Sabouraud medium without actidione. During the study period, a total of 569 patients were hospitalized including 235 (41.3%) with HIV infection. Overall C. neoformans was identified in 14 patients. Median patient age was 39 ± 8 years. There was a male preponderance with a sex ratio of 1.8 (9 men/5 women). Patients with BMI were HIV positive in 85.7% of cases (n=12) and HIV-negative in 14.3% (n=2). The overall and HIV-specific prevalence of BMI was 2.5% and 5.1% respectively. The CD4 lymphocyte count was between 1 and 49 cells/mm3 in 64.3% of cases. The main clinical symptoms were cephalea in 85.7% of cases, altered consciousness in 50% and nausea/vomiting in 35.7%. Neurological manifestations (hemiparesis and cranial nerve deficit) were noted in 14.3%. HIV infection is the main purveyor of NMC in Mali. The actual incidence of cryptococcosis is unclear due to the poor sensitivity of diagnostic techniques. This study highlights diagnostic difficulties related to clinical polymorphism and poor technical facilities. Agglutination testing of blood and CSF is recommended, but mortality remains

Aqueous Methanol Extracts of Cochlospermum tinctorium (A. Rich) Possess Analgesic and Anti-inflammatory Activities

Cochlopermum tinctorium A. Rich. (Cochlospermaceae) is a commonly used medicinal plant in the West Africa sub-region for the management of various conditions including pain and inflammatory conditions. In the present study, we report the analgesic and anti-inflammatory activities of the aqueous methanol leaf (20–80 mg/kg), root (7.5–30 mg/kg), and root bark (20–80 mg/kg) extracts of the plant. The analgesic potentials of the extracts were studied using acetic acid induced writhing and hot plate tests in mice while the anti-inflammatory activity was investigated using carrageenan-induced paw edema in rats.The extracts significantly and dose dependently inhibited the acetic acid-induced writhing in mice. However, the highest protection against writhing was produced by aqueous methanol leaf extract at the dose of 80 mg/kg (96.65%) which even was greater than that of the standard agent, ketoprofen (82.30%). The extracts did not significantly increase mean latency of response in the hot plate test. However, aqueous methanol root bark extract at the dose of 20 mg/kg significantly (P < 0.05) increased the mean latency of pain response. While the extracts of the root and root bark extracts of the plant afforded non dose-dependent protection against carrageenan-induced edema, the aqueous methanol leaf extract significantly and dose-dependently inhibited carrageenan-induced hind paw edema at the end of the third hour.The present study suggests that the aqueous methanol leaf, root, and root bark extracts of Cochlopermum tinctorium possess analgesic and anti-inflammatory activities which lend some credence to the ethnomedical claim of the use of the plant in the management of pain and inflammatory conditions

Octyl itaconate enhances VSVΔ51 oncolytic virotherapy by multitarget inhibition of antiviral and inflammatory pathways

The presence of heterogeneity in responses to oncolytic virotherapy poses a barrier to clinical effectiveness, as resistance to this treatment can occur through the inhibition of viral spread within the tumor, potentially leading to treatment failures. Here we show that 4-octyl itaconate (4-OI), a chemical derivative of the Krebs cycle-derived metabolite itaconate, enhances oncolytic virotherapy with VSVΔ51 in various models including human and murine resistant cancer cell lines, three-dimensional (3D) patient-derived colon tumoroids and organotypic brain tumor slices. Furthermore, 4-OI in combination with VSVΔ51 improves therapeutic outcomes in a resistant murine colon tumor model. Mechanistically, we find that 4-OI suppresses antiviral immunity in cancer cells through the modification of cysteine residues in MAVS and IKKβ independently of the NRF2/KEAP1 axis. We propose that the combination of a metabolite-derived drug with an oncolytic virus agent can greatly improve anticancer therapeutic outcomes by direct interference with the type I IFN and NF-κB-mediated antiviral responses.</p

Octyl itaconate enhances VSVΔ51 oncolytic virotherapy by multitarget inhibition of antiviral and inflammatory pathways

The presence of heterogeneity in responses to oncolytic virotherapy poses a barrier to clinical effectiveness, as resistance to this treatment can occur through the inhibition of viral spread within the tumor, potentially leading to treatment failures. Here we show that 4-octyl itaconate (4-OI), a chemical derivative of the Krebs cycle-derived metabolite itaconate, enhances oncolytic virotherapy with VSVΔ51 in various models including human and murine resistant cancer cell lines, three-dimensional (3D) patient-derived colon tumoroids and organotypic brain tumor slices. Furthermore, 4-OI in combination with VSVΔ51 improves therapeutic outcomes in a resistant murine colon tumor model. Mechanistically, we find that 4-OI suppresses antiviral immunity in cancer cells through the modification of cysteine residues in MAVS and IKKβ independently of the NRF2/KEAP1 axis. We propose that the combination of a metabolite-derived drug with an oncolytic virus agent can greatly improve anticancer therapeutic outcomes by direct interference with the type I IFN and NF-κB-mediated antiviral responses.</p

First-in-class small molecule potentiators of cancer virotherapy

The use of engineered viral strains such as gene therapy vectors and oncolytic viruses (OV) to selectively destroy cancer cells is poised to make a major impact in the clinic and revolutionize cancer therapy. In particular, several studies have shown that OV therapy is safe and well tolerated in humans and can infect a broad range of cancers. Yet in clinical studies OV therapy has highly variable response rates. The heterogeneous nature of tumors is widely accepted to be a major obstacle for OV therapeutics and highlights a need for strategies to improve viral replication efficacy. Here, we describe the development of a new class of small molecules for selectively enhancing OV replication in cancer tissue. Medicinal chemistry studies led to the identification of compounds that enhance multiple OVs and gene therapy vectors. Lead compounds increase OV growth up to 2000-fold in vitro and demonstrate remarkable selectivity for cancer cells over normal tissue ex vivo and in vivo. These small molecules also demonstrate enhanced stability with reduced electrophilicity and are highly tolerated in animals. This pharmacoviral approach expands the scope of OVs to include resistant tumors, further potentiating this transformative therapy. It is easily foreseeable that this approach can be applied to therapeutically enhance other attenuated viral vectors

Acromegaly at diagnosis in 3173 patients from the Liège Acromegaly Survey (LAS) Database

Acromegaly is a rare disorder caused by chronic growth hormone (GH) hypersecretion. While diagnostic and therapeutic methods have advanced, little information exists on trends in acromegaly characteristics over time. The Liège Acromegaly Survey (LAS) Database, a relational database, is designed to assess the profile of acromegaly patients at diagnosis and during long-term follow-up at multiple treatment centers. The following results were obtained at diagnosis. The study population consisted of 3173 acromegaly patients from ten countries; 54.5% were female. Males were significantly younger at diagnosis than females (43.5 vs 46.4 years; P 3100 patients is the largest international acromegaly database and shows clinically relevant trends in the characteristics of acromegaly at diagnosis

Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men