Novel ITGB2 Mutation Is Responsible for a Severe Form of Leucocyte Adhesion Deficiency Type 1.

Leukocyte adhesion deficiency type 1 (LAD1) is a rare autosomal recessive hereditary disorder characterized by recurrent infections, impaired pus formation, delayed wound healing, omphalitis, and delayed separation of the umbilical cord as hallmark features of the disease. It results from mutations in the integrin ß2 subunit gene ITGB2, which encodes the integrin beta chain-2 protein CD18. In this study, we aimed to investigate the case of a five-month-old boy who presented with a clinical phenotype and flow cytometry results suggesting LAD1 disease. Sanger sequencing of all exons and intron boundaries of ITGB2 identified a novel in-frame deletion in exon 7 (ITGB2 c.844_846delAAC, p.Asn282del) in the patient. The p.Asn282del mutation was heterozygous in the child's parents, whereas it was absent in the 96 control individuals from North Africa. This variant was evaluated by two in silico mutation analysis tools, PROVEAN and MutationTaster, which predicted that the mutation was likely to be pathogenic. In addition, molecular modeling with the YASARA View software suggested that this novel mutation may affect the structure of integrin beta-2 and, subsequently, its interaction with integrin alpha-X. In summary, we report a novel pathogenic mutation p.Asn282del associated with LAD1 that expands the mutation diversity of ITGB2 and suggest the combination of flow cytometry and ITGB2 sequencing as a first-line diagnostic approach for LAD disease.

Identification of the novel SDR42E1 gene that affects steroid biosynthesis associated with the oculocutaneous genital syndrome.

Hereditary connective tissue diseases form a heterogeneous group of disorders that affect collagen and extracellular matrix components. The cornea and the skin are among the major forms of connective tissues, and syndromes affecting both organs are often due to mutations in single genes. Brittle cornea syndrome is one of the pathologies that illustrates this association well. Furthermore, sex hormones are known to play a role in the maintenance of the structure and the integrity of the connective tissue including the skin and cornea, and may be involved in pathogenesis of oculocutaneous diseases. Herein, a double consanguineous family of Moroccan origin with two affected siblings, with suspected brittle cornea syndrome, was recruited. Ophthalmic examinations and genetic testing were performed in all the nuclear family individuals. Clinical examinations showed that the two affected boys presented with thinning of the cornea, blue sclera, keratoconus, hyperelasticity of the skin, joint hypermobility, muscle weakness, hearing loss and dental abnormalities that are compatible with the diagnosis of BCS disease. They showed however additional clinical signs including micropenis, hypospadias and cryptorchidism, suggesting abnormalities in endocrine pathways. Using a duo exome sequencing analysis performed in the mother and the propositus, we identified the novel homozygous missense mutation c.461G > A (p.Arg154Gln) in the short-chain dehydrogenase/reductase family 42E member 1 (SDR42E1) gene. This novel mutation, which co-segregated with the disease in the family, was predicted to be pathogenic by bioinformatics tools. SDR42E1 stability analysis using DynaMut web-server showed that the p.Arg154Gln mutations has a destabilizing effect with a ΔΔG value of -1.039 kcal/mol. As this novel gene belongs to the large family of short-chain dehydrogenases/reductases (SDR) thought to be involved in steroid biosynthesis, endocrinological investigations subsequently revealed that the two patients also had low levels of cholesterol. Karyotyping revealed a normal 46,XY karyotype for the two boys, excluding other causes of disorders of sex development due to chromosomal rearrangements. In conclusion, our study reveals that mutation in the novel SDR42E1 gene alters the steroid hormone synthesis and associated with a new syndrome we named oculocutaneous genital syndrome. In addition, this study highlights the role of SDR42E1 in the regulation of cholesterol metabolism in the maintenance of connective tissue and sexual maturation in humans.

High levels of eicosanoids and docosanoids in the lungs of intubated COVID-19 patients.

Severe acute respiratory syndrome coronavirus 2 is responsible for coronavirus disease 2019 (COVID-19). While COVID-19 is often benign, a subset of patients develops severe multilobar pneumonia that can progress to an acute respiratory distress syndrome. There is no cure for severe COVID-19 and few treatments significantly improved clinical outcome. Dexamethasone and possibly aspirin, which directly/indirectly target the biosynthesis/effects of numerous lipid mediators are among those options. Our objective was to define if severe COVID-19 patients were characterized by increased bioactive lipids modulating lung inflammation. A targeted lipidomic analysis of bronchoalveolar lavages (BALs) by tandem mass spectrometry was done on 25 healthy controls and 33 COVID-19 patients requiring mechanical ventilation. BALs from severe COVID-19 patients were characterized by increased fatty acids and inflammatory lipid mediators. There was a predominance of thromboxane and prostaglandins. Leukotrienes were also increased, notably LTB4 , LTE4 , and eoxin E4 . Monohydroxylated 15-lipoxygenase metabolites derived from linoleate, arachidonate, eicosapentaenoate, and docosahexaenoate were also increased. Finally yet importantly, specialized pro-resolving mediators, notably lipoxin A4 and the D-series resolvins, were also increased, underscoring that the lipid mediator storm occurring in severe COVID-19 involves pro- and anti-inflammatory lipids. Our data unmask the lipid mediator storm occurring in the lungs of patients afflicted with severe COVID-19. We discuss which clinically available drugs could be helpful at modulating the lipidome we observed in the hope of minimizing the deleterious effects of pro-inflammatory lipids and enhancing the effects of anti-inflammatory and/or pro-resolving lipid mediators.

Impact of Disparities in Reimbursement Rules Between Public and Private Sectors on Accessibility to Care in Moroccan Mandatory Health Insurance: A Cross-Sectional Study.

BACKGROUND: Disparities in the reimbursement rules between the 2 funds that manage mandatory health insurance in Morocco could negatively affect the accessibility of insured persons to healthcare services and products. OBJECTIVE: The objective is to analyze the impact of these disparities on access to care and to assess the insured's copayment difference between the 2 funds. METHODS: Healthcare utilization rates of the insured population in the 2 funds were analyzed by sector, sex, and age groups for 2014. We also looked at the percentage of copayment paid by the insured depending on the fund, methods of reimbursement, type of care, and nature of diseases. The analysis was based on data retrieved and aggregated at the National Agency for Health Insurance. RESULTS: The healthcare utilization rate differs significantly between the 2 funds. It is higher for the insured in the public sector (45%) compared with those in the private sector (18.5%) (P < .001). The healthcare utilization rate differs significantly according to the age groups in the 2 sectors (P < .001, respectively), and according to the sex of the insured in the 2 sectors (the healthcare utilization rate is higher for women than for men [P < .001, respectively]). The copayment percentage incurred by insured persons was 32.1% for employees in the public sector and 36.4% for employees in the private sector. CONCLUSION: Differences in reimbursement rules between the 2 funds may be the cause of inequity in access to care between insured persons. This situation can jeopardize the objectives of a universal and equitable health insurance scheme.

Contribution of fibrin glue in the surgery of cyanogenic and non-cyanogenic congenital cardiopathies: retrospective cohort study.

BACKGROUND: Postoperative bleeding in cardiovascular surgery is a frequent and complicated situation for the surgical team, and may also be responsible for significant hospital expenditures. Fibrin glue are indicated in surgery to improve hemostasis when conventional techniques such as compression, sutures or electrocoagulation are insufficient. Through this study, we tried to study the contribution of fibrin glue to the improvement of the clinical parameters (volume of postoperative bleeding, length of stay in intensive care, volume of blood transfusion ...) in two populations having undergone cardiac surgery, one in which we used the fibrin glue and one without fibrin glue. METHODS: This was a retrospective cohort study conducted in the cardiovascular surgery department of our Hospital in Rabat between June 2012 and June 2015. Fibrin glue (Tissucol® of BAXTER) was used in one group with an haemostatic aim. The pre and post-operative clinical data of the patients were analyzed and compared with data from patients who were operated without the use of fibrin glue because it was not yet available in the hospital. The clinical parameters were collected analyzed using the SPSS 13.0 software. RESULTS: One hundred ten patients were included in this study. The fibrin glue was used intraoperatively in 55 patients and not used in 55 patients. 43 (39.1%) had cyanogenic diseases and 67 (60.9%) had non-cyanogenic pathologies. The volume of transfused red blood cells was lower in patients in whom we used biological glue (p = 0.005), as well as the number of days spent in intensive care (p = 0.02). However, the difference was not significant between the two groups for other parameters such as bleeding volume per kg, the number of units of fresh frozen plasma and the platelet units count transfused. CONCLUSIONS: The results we found show that fibrin glue reduces the duration of hospitalization in resuscitation and reduces the number of units of transfused red blood cells to patients after surgery. However, it does not reduce significantly the total postoperative bleeding volume per weight, the number of fresh frozen plasma units or platelets units transfused. The fibrin glue could therefore be of moderate benefit in pediatric cardiac surgery.

Prevalence and management of coronary artery anomalies in tetralogy of Fallot at Cheikh Zaid Hospital's Pediatric Cardiac Surgery Department in Morocco: retrospective study.

INTRODUCTION: Tetralogy of Fallot (TOF) is one of the most common cyanogenic congenital heart defects. It represents 10% of congenital heart diseases in children. Coronary artery anomalies (CAA) have been reported in 2% to 14% of cases in patients with TOF, according to angiographic, surgical and autopsy series. Many of these anomalies are difficult to detect during surgery. The objective of this article is to study the prevalence of the coronary artery anomalies in patients with TOF as well as their surgical management in our hospital between 2007 and 2015. METHODS: A retrospective study was conducted on 90 patients with TOF aged 1 month to 10 years who were operated on in the Department of Paediatric Cardiac Surgery of Cheikh Zaid Hospital between 2007 and 2015. None of the patients had preoperative coronary angiography and all the anomalies were diagnosed during surgery. Patient clinical data were collected from patient records and from the hospital information system. The qualitative variables are expressed as mean and standard deviation and the quantitative variables are expressed as a percentage. Statistical analyses were performed using SPSS 13.0 software. RESULTS: Of the 90 patients with TOF followed in the study period, 9 (10%) patients had coronary artery anomalies. We found in 3 (33%) patients an anomalous origin of the left anterior descending coronary artery (LAD) from the right coronary artery (RCA), an anomalous origin of the RCA from the left coronary trunk (LCT) in 1 (11%) patient and a large infundibular branch blocking the pulmonary infundibulum in 5 (56%) patients. All the patients underwent a complete surgical treatment (closure of the ventricular septal defect (VSD) by patch plus stenosis resection plus infundibular enlargement by patch). Eight (89%) patients progressed well in postoperative care and 1 (11%) died immediately after surgery in intensive care. CONCLUSION: The coronary anomalies detected in patients with TOF are rare but represent a challenge for the surgical team because of the difficulty of diagnosing them pre-operatively. The management of these anomalies is mainly surgical and the technique used by our team is proved to be safe and effective.

Enterobacteriaceae producing extended-spectrum ß-lactamases (ESBLs) colonization as a risk factor for developing ESBL infections in pediatric cardiac surgery patients: "retrospective cohort study".

BACKGROUND: Children with cardiac defects need many hospitalizations and repetitive antibiotic therapies, with an increasing risk of colonization with multidrug-resistant bacteria (MDRB) such as extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E) Post-operative infections with these bacteria in paediatric cardiac surgery are life threatening. This article aims to study the prevalence of ESBL colonization among paediatric cardiac surgery patients, and to compare occurrence of post-operative infections with and without ESBL colonization. We also aim to study the correlation between the onset of postoperative infection and other parameters such as age, length of stay and preoperative antibiotic therapy. METHODS: A retrospective cohort study included paediatric cardiac surgery patients in Cheikh Zaid hospital in Rabat, Morocco, between the 1st of January 2011 and 31 December 2014. A screening for ESBL colonization was requested for children who had a risk factor (previous hospitalization and/or taking antibiotics) at admission. Swabs were collected from three sites (throat, nose and anus). Two groups were compared - patients colonized and not colonized with ESBLs. Statistical analysis was performed using R software. RESULTS: ESBL colonization screening was performed in 111 patients. Positive colonization was detected in 17 cases (15%). Klebsiella pneumoniae (KP): 9 (53%) was the most frequently isolated species. Among the 17 patients, 23.5% (4/17) developed a postoperative infection due to ESBLs versus only one patient without colonization (1%). There was a statically significant difference in terms of occurrence of postoperative infection between the two groups (p = 0.001). Relative risk of developing a postoperative infection with positive colonization was 22 (95% CI, 8.37-58.5). CONCLUSIONS: The analysis of colonization with multidrug-resistant bacteria and the prevention of nosocomial infections appear to be important challenges for paediatric cardiac surgery. Systematic screening of ESBL colonization for cardiac surgery could have a significant contribution, on one hand to guide prophylactic antibiotic therapy of patients, and on the other, to prevent spread of those infections.

Fetal outcome in emergency versus elective cesarean sections at Souissi Maternity Hospital, Rabat, Morocco.

INTRODUCTION: Perinatal mortality rates have come down in cesarean sections, but fetal morbidity is still high in comparison to vaginal delivery and the complications are more commonly seen in emergency than in elective cesarean sections. The objective of the study was to compare the fetal outcome and the indications in elective versus emergency cesarean section performed in a tertiary maternity hospital. METHODS: This comparative cross-sectional prospective study of all the cases undergoing elective and emergency cesarean section for any indication at Souissi maternity hospital of Rabat, Morocco, was carried from January 1, to February 28, 2014. Data were analyzed with emphasis on fetal outcome and cesarean sections indications. Mothers who had definite antenatal complications that would adversely affect fetal outcome were excluded from the study. RESULTS: There was 588 (17.83%) cesarean sections among 3297 births of which emergency cesarean section accounted for 446 (75.85%) and elective cesarean section for 142 cases (24.15%). Of the various factors analyzed in relation to the two types of cesarean sections, statistically significant associations were found between emergency cesarean section and younger mothers (P < 0.001), maternal illiteracy (P = 0.049), primiparity (P = 0.005), insufficient prenatal care (P < 0.001), referral from other institution for pregnancy complications or delivery (P < 0.001), cesarean section performed under general anesthesia (P < 0.001), lower birth weight (P < 0.016), neonatal morbidity and early mortality (P < 0.001), and admission in neonatal intensive care unit (P = 0.024). The commonest indication of emergency cesarean section was fetal distress (30.49%), while the most frequent indication in elective cesarean section was previous cesarean delivery (47.18%). CONCLUSION: The overall fetal complications rate was higher in emergency cesarean section than in elective cesarean section. Early recognition and referral of mothers who are likely to undergo cesarean section may reduce the incidence of emergency cesarean sections and thus decrease fetal complications.

Evaluation of the cost of cervical cancer at the National Institute of Oncology, Rabat.

INTRODUCTION: The Cervical Cancer (CC) is one of the heavy and costly diseases for the population and the health system. We want to know through this study, the first in Morocco, the annual cost of the treatment of this disease at the National Institute of Oncology (NIO) in Rabat, we also want to explore the possibility of flat-rate management of this disease in order to standardize medical practices and improve reimbursement by health insurance funds. METHODS: 550 patients were treated for their cervical cancer in the Rabat's NIO. Data of all of medical and surgical services offered to patients were collected from the NIO registry. The cost of care was assessed using the method of micro-costing. We will focus to the total direct cost of all the services lavished to patients in NIO. RESULTS: The global cost was about US$ 1,429,673 with an average estimated at US$ 2,599 ± US$ 839. Radiotherapy accounts for 55% of total costs, followed by brachytherapy (27%) and surgery (7%). This three services plus chemotherapy influence the overall cost of care (p <0.001). Other services (radiology, laboratory tests and consultations) represent only 10%. The overall cost is influenced by the stage of the disease, this cost decreased significantly evolving in the stage of CC (p <0.001). CONCLUSION: The standardization of medical practices is essential to the equity and efficiency in access to care. The flat-rate or lump sum by stage of disease is possible and interesting for standardizing medical practices and improving the services of the health insurance plan.

Measles in Morocco: epidemiological profile and impact of vaccination strategy.

INTRODUCTION: Measles continues to persist as one of the leading causes of infant mortality due to preventable diseases through vaccination. This study aims to highlight measles in Morocco, and to present the vaccination strategy implemented to control and eliminate the disease in this country. METHODS: Throughout this study, and based on data from the Directorate of Epidemiology and Control of Diseases and those of the Directorate of Population, we present an overview on the epidemiological trends of measles from 1997 to 2012, while evoking the plans established by the Ministry of Health (MoH) for the control and elimination of this disease. RESULTS: The number of measles cases has decreased in Morocco between 1997 and 2012 (2574-720 reported cases per year) as a result of four important steps: first, increasing the routine vaccination coverage (73-94%); second, the introduction of the second dose of the combined vaccine against measles and rubella in schools (children aged 6 years) since 2003; third, the first catch-up campaign of vaccination in Morocco in 2008, for which coverage was highly satisfactory (96% and 100% for age groups 5-59 months and 5-14 years, respectively); and fourth, the organization of a mass vaccination campaign in 2013 that targeted children from aged 9 months to 19 years. CONCLUSION: The vaccination plan and the surveillance system executed in Morocco within the framework of the regional project implemented by the World Health Organization (WHO) to eliminate measles has given remarkable results regarding the reduction of measles cases and mortality due to this disease. According to the data from MoH and WHO, the number of reported and confirmed measles cases decreased drastically during 2014. However, these efforts are still unsatisfactory compared to the prospective of eliminating the disease by 2015.

[Hospital organizational analysis based on the Mintzberg model: the case of Sheikh Zayed Hospital, Rabat]. / Analyse organisationnelle de l'hôpital à travers le modèle de Mintzberg : cas de l'Hôpital Universitaire Cheikh Zaid.

The new system of hospital governance requires health institutions to develop new managerial, financial and social skills beyond their public service duties. As part of this new approach, the organizational modernization of hospitals involves introducing good management practices. However, managing the transition requires taking into account the specificities of existing organizational systems. Organizational systems are generally difficult to model and involve diverse and sometimes competing interests, concerns, habits, languages, cultures, tools and representations. This explains the high failure rate observed in hospital development projects at an organizational level. A number of organizational theories from a range of disciplines (sociology, biology, history, etc.) have examined the question of organization in hospitals. The many theories developed in this area are not incompatible. Rather, they form a set of useful tools for the analysis of organizational management. The purpose of this study was to conduct an organizational analysis of Sheikh Zayed Hospital (Rabat) based on the Mintzberg model as a prerequisite for the development and implementation of a restructuring plan.