Pathway Maps of Orphan and Complex Diseases Using an Integrative Computational Approach.

Orphan diseases (ODs) are progressive genetic disorders, which affect a small number of people. The principal fundamental aspects related to these diseases include insufficient knowledge of mechanisms involved in the physiopathology necessary to access correct diagnosis and to develop appropriate healthcare. Unlike ODs, complex diseases (CDs) have been widely studied due to their high incidence and prevalence allowing to understand the underlying mechanisms controlling their physiopathology. Few studies have focused on the relationship between ODs and CDs to identify potential shared pathways and related molecular mechanisms which would allow improving disease diagnosis, prognosis, and treatment. We have performed a computational approach to studying CDs and ODs relationships through (1) connecting diseases to genes based on genes-diseases associations from public databases, (2) connecting ODs and CDs through binary associations based on common associated genes, and (3) linking ODs and CDs to common enriched pathways. Among the most shared significant pathways between ODs and CDs, we found pathways in cancer, p53 signaling, mismatch repair, mTOR signaling, B cell receptor signaling, and apoptosis pathways. Our findings represent a reliable resource that will contribute to identify the relationships between drugs and disease-pathway networks, enabling to optimise patient diagnosis and disease treatment.

Predictors of Mortality in Mechanically Ventilated Critical Pertussis in a low Income Country.

BACKGROUND: Critical pertussis is characterized by severe respiratory failure, important leukocytosis, pulmonary hypertension, septic shock and encephalopathy. AIM: To describe the clinical course of critical pertussis, and identify predictors of death at the time of presentation for medical care. METHODOLOGY: Retrospective study conducted in children's hospital Tunisian PICU between 01 January and 31 October 2013. Patients with critical pertussis confirmed by RT-PCR and requiring mechanical ventilation were included. Predictors of death were studied. RESULTS: A total of 17 patients was studied. Median age was 50 days. Mortality was 23%. Predictors risk of mortality were : high PRISM score (Pediatric Risk of Mortality Score) (p=0,007), shock (p=0,002), tachycardia (p=0,005), seizures (p=0,006), altered mental status (p=0,006), elevated WBC count (p=0,003) and hemodynamic support (p=0022). However, the difference did not reach statistical significance in comorbidity, pneumoniae, high pulmonary hypertension or exchange transfusion. Concomitant viral or bacterial co-infection was not related to poor outcome. CONCLUSION: Young infants are at high risk to have critical pertussis. Despite advances in life support and the treatment of organ failure in childhood critical illness, critical pertussis remains difficult to treat.