Systems genetics identifies miRNA-mediated regulation of host response in COVID-19.

BACKGROUND: Individuals infected with SARS-CoV-2 vary greatly in their disease severity, ranging from asymptomatic infection to severe disease. The regulation of gene expression is an important mechanism in the host immune response and can modulate the outcome of the disease. miRNAs play important roles in post-transcriptional regulation with consequences on downstream molecular and cellular host immune response processes. The nature and magnitude of miRNA perturbations associated with blood phenotypes and intensive care unit (ICU) admission in COVID-19 are poorly understood. RESULTS: We combined multi-omics profiling-genotyping, miRNA and RNA expression, measured at the time of hospital admission soon after the onset of COVID-19 symptoms-with phenotypes from electronic health records to understand how miRNA expression contributes to variation in disease severity in a diverse cohort of 259 unvaccinated patients in Abu Dhabi, United Arab Emirates. We analyzed 62 clinical variables and expression levels of 632 miRNAs measured at admission and identified 97 miRNAs associated with 8 blood phenotypes significantly associated with later ICU admission. Integrative miRNA-mRNA cross-correlation analysis identified multiple miRNA-mRNA-blood endophenotype associations and revealed the effect of miR-143-3p on neutrophil count mediated by the expression of its target gene BCL2. We report 168 significant cis-miRNA expression quantitative trait loci, 57 of which implicate miRNAs associated with either ICU admission or a blood endophenotype. CONCLUSIONS: This systems genetics study has given rise to a genomic picture of the architecture of whole blood miRNAs in unvaccinated COVID-19 patients and pinpoints post-transcriptional regulation as a potential mechanism that impacts blood traits underlying COVID-19 severity. The results also highlight the impact of host genetic regulatory control of miRNA expression in early stages of COVID-19 disease.

Chimiotherapie des cancers du col de l'uterus au stade IV a vesical a l'Institut Curie de Dakar

Les cancers du col de l'uterus au stade IV ne relevent plus de la combinaison standard radio-chirurgicale. Aussi dans notre contexte marque par les difficultes de tous ordres pour correctement appliquer la chimiotherapie; nous avons pense opportun de retracer notre experience dans l'utilisation de moyen therapeutique dans les cancers du col uterin classes IVa vesical a Dakar. Sur 91 dossiers retenus; 80 ont concerne la mise en oeuvre de la combinaison chimiotherapie et radio-therapie selon diverses modalites. Les resultats enregistres dans la pratique de cette modalite nous poussent a proposer la procedure chimiotherapie neoadjuvante suivie de radiochimiotherapie dans notre contexte en l'absence de curietherapie pour ameliorer la survie

Use of immunoglobulins in the prevention of GvHD in a xenogeneic NOD/SCID/γc- mouse model.

The efficacy of IVIG in preventing GvHD has not been definitely demonstrated clinically. Using a xenogeneic model of GvHD in NOD/SCID/γc- (NSG) mice, we showed that weekly administration of IVIG significantly reduced the incidence and associated mortality of GvHD to a degree similar to CsA. Unlike CsA and OKT3, IVIG were not associated with inhibition of human T-cell proliferation in mice. Instead, IVIG significantly inhibited the secretion of human IL-17, IL-2, IFN-γ and IL-15 suggesting that IVIG prevented GvHD by immunomodulation. Furthermore, the pattern of modification of the human cytokine storm differed from that observed with CsA and OKT3. Finally, in a humanized mouse model of immune reconstitution, in which NSG mice were engrafted with human CD34(+) stem cells, IVIG transiently inhibited B-cell reconstitution, whereas peripheral T-cell reconstitution and thymopoiesis were unaffected. Together these in vivo data raise debate related to the appropriateness of IVIG in GvHD prophylaxis. In addition, this model provides an opportunity to further elucidate the precise mechanism(s) by which IVIG inhibit GvHD.

[Gynaecological and breast cancers at the Dakar Cancer Institute]. / Les cancers gynécologiques et mammaires à l'Institut du cancer de Dakar.

OBJECTIVE: To determine the frequency of gynaecological and breast cancers among women and to study their risk factors and diagnostic aspects at the Institut Curie of Dakar. PATIENTS AND METHOD: This retrospective study included all cancers seen at the Institute in 2001. Epidemiological and clinical variables were collected from the patients' medical records and analysed. RESULTS: This study showed that of all 786 cancers in women, 507 were gynaecological or breast cancers. Cancer of the uterine cervix accounted for 240 cases (47.3%), followed by 213 cancers of the breast (42%), 35 of the ovaries (6.9%), 10 of the corpus uteri (2%) and 7 of the vulva (1.4%). Mean age was 49.9 years old. There was a statistically significant (p<0.05) between primary tumour sites and all of the following: age at menarche, age at first sexual relations, and number of sexual partners. Mean time until consultation for all patients was 8.24 months and 96% had clinical signs before diagnosis. The histological confirmation rate was 73%. Local or regional tissue involvement was noted in 60% of cases. CONCLUSION: Gynaecological and breast cancers are frequent in Dakar and have the characteristics common to cancers in developing countries. Further efforts are needed to study their risk factors and effective screening for them.

[Squamous cell carcinoma of the uterine cervix at the Dakar Cancer Institute]. / Les carcinomes épidermoïdes du col utérin à l'Institut du cancer de Dakar.

OBJECTIVES: To determine the epidemiological characteristics of patients with squamous cell carcinoma of the cervix, to describe its forms and to assess the treatment they received. MATERIAL AND METHODS: This retrospective study examined records of 616 cervical carcinomas at Dakar Cancer Institute from 1977 to 1999. All cases of squamous cell carcinoma were included, and their epidemiological, clinical and therapeutic aspects described. Five-year survival was calculated by the actuarial method. RESULTS: Patients' mean age was 35 years, and 86% were older than 35 years. Mean parity was 8 and 44.4% of patients had reached menopause. According to the FIGO classification, 419 patients had advanced stage (IIb, III, IV) cancers, and tumours were histologically differentiated in 20.1% of cases. Radical hysterectomies were performed for 252 patients (40.9%). In all, 152 patients (24.67%) received external neoadjuvant radiation therapy and 69 (11.2%) adjuvant radiation therapy. Postoperative complications included urinary fistulas, lymphoceles, and phlebitis. Recurrence was seen in 133 cases and was significantly associated with stage and time until radiation therapy. CONCLUSION: Curietherapy might improve our treatment of these advanced cervical cancers. Their prevention requires the establishment of facilities for early diagnosis and population screening for detection of precancerous lesions of the cervix. The vaccinal approach recently introduced in developed countries appears to be too costly for developing countries today.

[Head and neck paragangliomas in Senegal. About 8 cases]. / Paragangliomes de la tête et du cou au Sénégal.

UNLABELLED: Paragangliomas are uncommon neoplasms with rare occurrence in the head and neck area. OBJECTIVE: The purpose of this study was to report the experience of management of these rare tumors by a team of Ear, Nose, and Throat (ENT) surgeons working in the context of a sub-Saharan country. MATERIAL AND METHODS: We conducted a retrospective study in the Ear, Nose and throat Department of a Dakar university hospital. The study concerned 8 patients with a highly vascular tumor located in the neck and temporal bone. The preoperative investigations were computed tomography scanning (CT scan) using contrast injection in 88% and Doppler ultrasonography for the patients with a neck mass. All the patients underwent surgery except one. In 2 cases, the management with a team of vascular surgeons was necessary. Histological examination of the tumor was realized in all cases. RESULTS: The tumor was located in the neck in 5 cases (62,5%) with a carotid body tumor in three patients (37,5%) and vagal location in two (25%). The temporal bone was involved in three patients with a tympano-jugular location (37,5%). All the neck masses were operated on via a unique cervical approach. The tympano-jugular tumors were treated by radical mastoidectomy in two patients. In the third patient with a tympano-jugular tumor, with important involvement of the temporal bone, only the neck extension was operated. The histological diagnosis of paraganglioma was confirmed in all patients. Radiation therapy was delivered in two patients (25%), to complete surgery in the event of extensive temporal bone tumor and exclusive in one case of an inoperable vagal tumor. The outcomes, marked early death in one patient (14%), were good in the short and mid term for the others patients. CONCLUSION: With the improvement of technological infrastructures, particularly with developing modern imaging, we have better knowledge of paragangliomas in the head and neck area, in our experience in a developing country. However, therapeutic approaches are still limited by modest humans and material resources.

[Primary lymphoma of the thyroid: a case report]. / Lymphome primitif de la thyroïde: a propos d'un cas.

Primary lymphoma of the thyroid is an uncommon disease. It diagnosis is difficult without immunohistochemestry. We report a case of thyroid lymphoma diagnosed at the A. Le Dantec Hospital of Dakar. A 22-year old young man presented anterior neck mass. Clinical examination showed a thyroid mass with a susclavicular palpable lymph node. The scintigraphy demonstrated that the mass was cold. Total thyroidectomy with cervical lymphadenectomy was the first treatment. Histological examination of the surgical specimen concluded that the mass was an anaplastic lymphoma (large cells type) involving the sus clavicular lymph nodes (stage IIE). Chemotherapy was administrated after one month with C-MOPP schedule. The patient presented no recurrent sign after 30 month. Fine needle aspiration and immunocytochemestry of the thyroid cold masses will contribute in an accurate diagnosis and the management of disease in our institution.

[Toward strengthening the health politics in Africa: the military health system and its contribution to health policy in Senegal]. / Pour le renforcement des politiques de santé en Afrique: le cas de la contribution de l'armée à l'effort en matière de santé au Sénégal.

Since the following days of independences, the Senegalese army mission has mainly consisted in defending the national territory integrity and in ensuring the protection of the populations and their goods. In the public health system, thanks to the quality of its human resources the army intervenes specifically at every level of the health care structure. The mission assigned to the Senegalese army health unit is therefore multidimensional. In 2001, the operational budget of the army health services is estimated at 177 millions CFA F (265500 euros), its medical consumption at 212 millions CFA F (323 000 Euros) and its health expenditure at 385 millions CFA F (585 000 euros). The army supports the government health policies in different ways: on the one hand, availability of the ministry of health staff, on the other hand, the direct involvement in health care and the implementation of the national and international health programmes.