Ciliopathy due to POC1A deficiency: clinical and metabolic features, and cellular modeling.

OBJECTIVE: SOFT syndrome (MIM#614813), denoting Short stature, Onychodysplasia, Facial dysmorphism, and hypoTrichosis, is a rare primordial dwarfism syndrome caused by biallelic variants in POC1A, encoding a centriolar protein. SOFT syndrome, characterized by severe growth failure of prenatal onset and dysmorphic features, was recently associated with insulin resistance. This study aims to further explore its endocrinological features and pathophysiological mechanisms. DESIGN/METHODS: We present clinical, biochemical, and genetic features of 2 unrelated patients carrying biallelic pathogenic POC1A variants. Cellular models of the disease were generated using patients' fibroblasts and POC1A-deleted human adipose stem cells. RESULTS: Both patients present with clinical features of SOFT syndrome, along with hyperinsulinemia, diabetes or glucose intolerance, hypertriglyceridemia, liver steatosis, and central fat distribution. They also display resistance to the effects of IGF-1. Cellular studies show that the lack of POC1A protein expression impairs ciliogenesis and adipocyte differentiation, induces cellular senescence, and leads to resistance to insulin and IGF-1. An altered subcellular localization of insulin receptors and, to a lesser extent, IGF1 receptors could also contribute to resistance to insulin and IGF1. CONCLUSIONS: Severe growth retardation, IGF-1 resistance, and centripetal fat repartition associated with insulin resistance-related metabolic abnormalities should be considered as typical features of SOFT syndrome caused by biallelic POC1A null variants. Adipocyte dysfunction and cellular senescence likely contribute to the metabolic consequences of POC1A deficiency. SOFT syndrome should be included within the group of monogenic ciliopathies with metabolic and adipose tissue involvement, which already encompasses Bardet-Biedl and Alström syndromes.

Fighting COVID-19 in the West Africa after experiencing the Ebola epidemic.

Coronavirus disease 2019 (COVID-19) dissemination occurred from December 2019 and quickly spread to all countries. Infected patients with COVID-19 have had a wide range of symptoms, ranging from mild to severe illness. The most mortality was observed in patients with underlying disease and over 45 years. World statistics have shown that the COVID-19 outbreak is most expanded in Middle Eastern, West Asian, European, North, and South American countries, and is least expanded in African countries. Therefore, the aim of the paper was the evaluation of six African countries including Mali, Mauritania, Niger, Guinea, Togo, and Djibouti to find why this disease is least expanded in African countries. Study was conducted by Questioner for countries health organizers to define their different aspect exposure and fight with COVID-19 including epidemiology, clinical aspects of the disease, case definitions, diagnosis laboratory confirmation, and referral of cases by the portal of entry, case management, and disease prevention in these countries. According to this opinion review, due to the low international flights and low domestic travel, the spread, and prevalence of COVID-19 was low and the return of the immigrants of these countries has caused the spread of COVID-19 among these countries. Experience, preparation, and impact of previous infections epidemic such as the Ebola virus epidemic would have beneficial, which have promoted certain reflexes among people that cause low dissemination in these countries.

Stem Cell Transplantation for Diamond-Blackfan Anemia. A Retrospective Study on Behalf of the Severe Aplastic Anemia Working Party of the European Blood and Marrow Transplantation Group (EBMT).

Data on stem cell transplantation (SCT) for Diamond-Blackfan Anemia (DBA) is limited. We studied patients transplanted for DBA and registered in the EBMT database. Between 1985 and 2016, 106 DBA patients (median age, 6.8 years) underwent hematopoietic stem cell transplantation from matched-sibling donors (57%), unrelated donors (36%), or other related donors (7%), using marrow (68%), peripheral blood stem cells (20%), both marrow and peripheral blood stem cells (1%), or cord blood (11%). The cumulative incidence of engraftment was 86% (80% to 93%), and neutrophil recovery and platelet recovery were achieved on day +18 (range, 16 to 20) and +36 (range, 32 to 43), respectively. Three-year overall survival and event-free survival were 84% (77% to 91%) and 81% (74% to 89%), respectively. Older patients were significantly more likely to die (hazard ratio, 1.4; 95% confidence interval, 1.06 to 1.23; P < .001). Outcomes were similar between sibling compared to unrelated-donor transplants. The incidence of acute grades II to IV of graft-versus-host disease (GVHD) was 30% (21% to 39%), and the incidence of extensive chronic GVHD was 15% (7% to 22%). This study shows that SCT may represent an alternative therapeutic option for transfusion-dependent younger patients.

Automated RBC exchange compared to manual exchange transfusion for children with sickle cell disease is cost-effective and reduces iron overload.

BACKGROUND: Chronic transfusion in sickle cell disease (SCD) remains the gold standard therapy for stroke prevention and for patients with severe disease despite adequate hydroxyurea treatment. The aim of our study was to assess the safety and efficacy of automated red blood cell exchange (aRBX) in patients with SCD previously treated with manual exchange transfusion (MET). Costs related to transfusion and chelation overtime were evaluated. STUDY DESIGN AND METHODS: Beginning in January 2012, children with SCD who weighed 30 kg or more on MET could switch to aRBX. Clinical, biological, and procedures' data, including costs, were recorded for the last 6 months on MET and compared to those after the first and the second year on aRBX. RESULTS: Ten patients switched from MET to aRBX at a median age of 11.8 years. After the switch, median hemoglobin S (HbS) increased significantly (33.5% on MET compared to 45% on aRBX; p < 0.001) but remained in the target values for all patients. Median ferritin decreased significantly (663.3 µg/L on MET compared to 126.8 µg/L on aRBX; p < 0.001) and intervals between procedures were significantly longer. The requirements of red blood cells (RBCs)/kg/year were not different on MET (0.88 unit/kg/year) than during the second year on aRBX (1.07 unit/kg/year; p = NS). MET costs were similar compared to aRBX since chelation was stopped in previously treated patients. CONCLUSION: Erythrocytapheresis reduces iron overload and allows a longer interval between procedures without a higher RBC requirement from the second year on aRBX. The cost did not increase as estimated in our Belgian Health Care System.

How women are treated during facility-based childbirth: development and validation of measurement tools in four countries - phase 1 formative research study protocol.

BACKGROUND: Every woman has the right to dignified, respectful care during childbirth. Recent evidence has demonstrated that globally many women experience mistreatment during labour and childbirth in health facilities, which can pose a significant barrier to women attending facilities for delivery and can contribute to poor birth experiences and adverse outcomes for women and newborns. However there is no clear consensus on how mistreatment of women during childbirth in facilities is defined and measured. We propose using a two-phased, mixed-methods study design in four countries to address these research gaps. This protocol describes the Phase 1 qualitative research activities. METHODS/DESIGN: We will employ qualitative research methodologies among women, healthcare providers and administrators in the facility catchment areas of two health facilities in each country: Ghana, Guinea, Myanmar and Nigeria. In-depth interviews (IDIs) and focus group discussions (FGDs) will be conducted among women of reproductive age (15-49 years) to explore their perceptions and experiences of facility-based childbirth care, focused on how they were treated by healthcare workers and perceived factors affecting how they were treated. IDIs will also be conducted with healthcare providers of different cadres (e.g.: nurses, midwives, medical officers, specialist obstetricians) and facility administrators working in the selected facilities to explore healthcare providers' perceptions and experiences of facility-based childbirth care and how staff are treated, colleagues and supervisors. Audio recordings will be transcribed and translated to English. Textual data will be analysed using a thematic framework approach and will consist of two levels of analysis: (1) conduct of local analysis workshops with the research assistants in each country; and (2) line-by-line coding to develop a thematic framework and coding scheme. DISCUSSION: This study serves several roles. It will provide an in-depth understanding of how women are treated during childbirth in four countries and perceived factors associated with this mistreatment. It will also provide data on where and how an intervention could be developed to reduce mistreatment and promote respectful care. The findings from this study will contribute to the development of tools to measure the prevalence of mistreatment of women during facility-based childbirth.