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Dihydroartemisinin-piperaquine is efficacious for the treatment of uncomplicated malaria and its use is increasing globally. Despite the positive results in fighting malaria, inhibition of the Kv11.1 channel (hERG; encoded by the KCNH2 gene) by piperaquine has raised concerns about cardiac safety. Whether genetic factors could modulate the risk of piperaquine-mediated QT prolongations remained unclear. Here, we first profiled the genetic landscape of KCNH2 variability using data from 141,614 individuals. Overall, we found 1,007 exonic variants distributed over the entire gene body, 555 of which were missense. By optimizing the gene-specific parametrization of 16 partly orthogonal computational algorithms, we developed a KCNH2 -specific ensemble classifier that identified a total of 116 putatively deleterious missense variations. To evaluate the clinical relevance of KCNH2 variability, we then sequenced 293 Malian patients with uncomplicated malaria and identified 13 variations within the voltage sensing and pore domains of Kv11.1 that directly interact with channel blockers. Cross-referencing of genetic and electrocardiographic data before and after piperaquine exposure revealed that carriers of two common variants, rs1805121 and rs41314375, experienced significantly higher QT prolongations (ΔQTc of 41.8 ms and 61 ms, respectively, vs 14.4 ms in controls) with more than 50% of carriers having increases in QTc >30 ms. Furthermore, we identified three carriers of rare population-specific variations who experienced clinically relevant delayed ventricular repolarization. Combined, our results map population-scale genetic variability of KCNH2 and identify genetic biomarkers for piperaquine-induced QT prolongation that could help to flag at-risk patients and optimize efficacy and adherence to antimalarial therapy., Competing Interests: V.M.L. is co-founder, CEO, and shareholder of HepaPredict AB, as well as co-founder and shareholder of PersoMedix AB.

Introduction: High blood pressure is a major cardiovascular risk factor. Patients with cardiovascular risk factors are at risk of developing COVID-19. The objective of this study was to determine epidemiology of Covid-19 infected in patients with high blood pressure., Patients and Method: Descriptive cross-sectional study from April 2020 to June 2020 about patients hospitalized for Covid 19 by PCR diagnosis at the Hopital du Mali Bamako and having high blood pressure. Admission registry and patient charts were used to collect data., Results: We collected 78 out of 484 in patients which mean hospital frequency of 16.11%. The mean age was 55.21 +/- 14.61 years. Sex ratio M / F was 1.36. Patients were followed for high blood pressure in 59% of cases. Medical history was ischemic heart disease in 2.6% and dilated cardiomyopathy in 2.6%. Main functional signs were cough in 41.02% and lost of taste in 11.53%. High blood pressure on admission was grade 2 in 37.2% and grade 3 in 3.8%. Treatments received were calcium channel blockers 41.02%, inhibitors of the reninangiotensinaldosterone system 16.66% and combinations 15.38%. Hospital mortality was 10.3%. There was no statistically significant difference in mortality between known hypertensive patients and de novo hypertensive patients. There was also no statistically significant difference in mortality by grade of hypertension., Conclusion: High blood pressure can be associated to Covid 19. Treatment is based on calcium channel blockers and reninangiotensinaldosterone system inhibitors. It has an impact on the prognosis of the disease with significant mortality., (Le comité de rédaction se réserve le droit de renvoyer aux auteurs avant toute soumission à l'avis des lecteurs les manuscrits qui ne seraient pas conformes à ces modalités de présentation. En outre il leur conseille de conserver un exemplaire du manuscrit, des figures et des tableaux.)

Introduction: Dysthyroidism (hyperthyroidism or hypothyroidism) in children and adolescents is much rarer than in adults. The purpose of our study was to study the epidemiological, clinical, paraclinical, etiological and etiological aspects and to specify the therapeutic and evolutionary modalities of this condition., Method: This was a five-year descriptive, retrospective and prospective study of children and adolescents under 18 years of age with dysthyroidism., Results: We collected 90 children and adolescents with dysthyroidism (hyperthyroidism 77.8% (n=70) and hypothyroidism 22.2% (n=20). For hyperthyroidism (n=70): the average age was 13.07 years and the sex ratio was 0.16. The family history of dysthyroidism was found in 24.3% (n=17). Clinical manifestations were dominated by tachycardia 88.57% (n=62), weight loss 87.14% (n=61), vibrating pulse 87.14% (n=61) and palpitation 81.42% (n=57). Bilateral exophthalmos was present in 70% of patients (n=49) with palpebral retraction in 51.42% (n=56). Goitre was present in 54 patients (77.1%). It was diffuse in 62.9% (n=44) and nodular in 12.9% (n=9). Basedow's disease represented the first etiology with 84.3% (n=59), followed by toxic multinodular goitre12, 9% (n=9). Sixty-eight patients (97.1%) received medical treatment with synthetic antithyroid drugs. Clinical remission was achieved in 64.3% (n=45) and 54.3% of patients were in biological euthyroidism at 6 months follow-up. For hypothyroidism (n=20): the average age was 10.70 years and the sex ratio was 0.53. Six family cases of hypothyroidism and three cases of family goitre were found. The clinical picture was dominated by signs of hypo metabolism at hypersomnia type 95% (n=19) and anorexia 75% (n=15). The skin was dry in 60% (n=12). A staturo-weight delay in 65% (n=13), behavioural disorders in 55% (n=11), weight gain in 40% (n=8) and puberty delay in 10% (n=2). Goitre was nodular in 25% (n=5) with cervical adenopathy present in 15% (n=3). Hashimoto's thyroiditis accounted for 45% (n=9) of etiologies followed by iodine deficiency disorders in 15% (n=3) and iatrogenic causes (2 cases of thyroidectomy). All patients were started on hormone replacement therapy for life. Five patients with large multinodular goiter received total thyroidectomy in addition to medical treatment. Euthyroidism was observed in 55% (n=11) of patients at 6 months follow-up., Conclusion: Dysthyroidism in children and adolescents exists in our health facilities. Its management is deficient because of the technical and financial platform. Our public health decision-makers must help implement a screening strategy to facilitate faster diagnosis and treatment., (Le comité de rédaction se réserve le droit de renvoyer aux auteurs avant toute soumission à l'avis des lecteurs les manuscrits qui ne seraient pas conformes à ces modalités de présentation. En outre il leur conseille de conserver un exemplaire du manuscrit, des figures et des tableaux.)

Several antimalarial drugs are known to prolong ventricular repolarization as evidenced by QT/QTc interval prolongation. This can lead to Torsades de Pointes, a potentially lethal ventricular arrhythmia. Whether this is the case with artemisinin-based combination therapies (ACTs) remains uncertain. Assessment of the extent of QTc prolongation with antimalarials is hampered by important variations of heart rate during malaria crises and previous studies have reported highly variable values of QTc prolongations with ACTs. We assessed QTc prolongation with four ACTs, using high quality ECG recording and measurement techniques, during the first episode of malaria in 2,091 African patients enrolled in the WANECAM study which also monitored clinical safety. Using an original and robust method of QTc assessment, independent from heart rate changes and from the method of QT correction, we were able to accurately assess the extent of mean maximum QTc prolongation with the four ACTs tested. There was no evidence of proarrhythmia with any treatment during the study although dihydroartemisinin-piperaquine, artesunate-amodiaquine and artemether-lumefantrine significantly prolonged QTc. The extent of prolongation of ventricular repolarization can be accurately assessed in studies where heart rate changes impede QTc assessment.

Introduction: The diabetic foot wound is a real public health problem, 10% of the reasons for hospitalization. The risk of amputation is 10 to 30 times higher in diabetics than the general population., Objective: To study the problem of amputations of the diabetic foot., Method: This was a descriptive and cross-sectional study that took place in the Department of Medicine and Endocrinology of the Mali Hospital from July 1st, 2016 to June 30th, 2017., Results: Twenty-five (25) diabetic patients were enrolled in our study. The sex ratio was 0.66. At admission, 100% of our patients had arterial disease, 96% neuropathy, and mixed foot in 80%. Poor glycemic control in 64% of patients; osteitis in 52% of cases; 92% of the patients had a 100% amputation risk according to the University of Texas classification. Nearly half or 46% of patients had amputations in the leg. We recorded 1 death case that is 4%., Conclusion: The problem of amputation of diabetic feet is a function of the poor equilibrium and progressive neurological and vascular complications of diabetes., (Le comitée de rédaction se réserve le droit de revoyer aux auteurs avant toute soumission à l'avis des lecteurs les manuscrits qui ne seraient pas conformes à ces modalités de présentation. En outre il leur conseille de sonserver un examplaire du manuscrit, des figures et des tableaux.)

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, clinically aggressive hematologic malignancy, that most commonly manifests as cutaneous lesions. A 19-year-old Malian female was admitted to the Unit of Medicine of Hopital du Mali with anemia, fever, weakness, and weight loss. On physical examination she was wasted, pale, febrile (37.4°C), and had inguinal and axillary lymphadenopathies. The complete blood count found pancytopenia with Hemoglobin level of 4.8 g/dL, Leucocytes count of 1900/μL (neutrophil: 300/μL), and platelets count of 56 000/μL. The ultrasonographic examination found hepatomegaly and splenomegaly. The bone marrow biopsy and flow cytometer analysis were in keeping with a diagnosis of BPDCN. The patient, unfortunately, was lost four months later after her hospital admission due to late diagnosis by septicemia. The early diagnosis and availability of specific drugs for acute leukemia could improve the clinical outcome of patients with BPDCN in Mali.