Ivacaftor in Omani children with cystic fibrosis caused by p.Ser549Arg CFTR mutation.

Background: Cystic fibrosis (CF) is a multisystemic chronic disease caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein. These mutations are classified in to six classes. Ivacaftor is a CFTR potentiator which partially restores the CFTR function for class III mutations. In Oman, p.Ser549Arg (class III) is the most common mutation (65% of cases). Our study prospectively evaluated the tolerance and clinical efficacy of ivacaftor. Methods: A prospective observational study was conducted at the Royal Hospital, Oman. All children aged 6-18 years who are followed and carry at least one copy of the p.Ser549Arg mutation were started on Ivacaftor and included in the study. Data collected included weight, height, forced expiratory volume in first second (FEV1), sweat chloride concentration, stool elastase level and liver enzymes at baseline and at 12, 24, 36, and 48 weeks after initiation of treatment. The number of CF pulmonary exacerbations one year before and during treatment were compared. Results: Twenty one children were started on Ivacaftor (90% homozygous for p.Ser549Arg). The mean age was 10.8 (SD ±3.5) years. When compared to baseline, FEV1 significantly improved by a mean of 10.8 (SD ±13.5) percentage points (pp) and 14.3 (SD ±7.5) pp at 12 and 48 weeks respectively. The sweat chloride level significantly dropped from a mean of 107 (SD ±8.5) mmol/l to 38.5 (SD ±22.3) mmol/l at 12 weeks and remained low. The Body Mass Index (BMI) improved by a mean of 1.37 (SD ±1.3) kg/m 2 and 1.9 (SD ±1.35) kg/m 2 at 24 and 48 weeks of treatment respectively. The number of admissions the year before and during treatment reduced significantly from a mean of 2.2 (SD± 1.9) to 0.7 (SD ±1) admission per year. Two children developed transaminitis. Conclusion: Ivacaftor is well tolerated and resulted in a significant improvement in FEV1, BMI and sweat chloride level in children with p.Ser549Arg CFTR mutation.

A Novel Cystic Fibrosis Gene Mutation C.4242+1G>C in an Omani Patient: A Case Report.

Cystic fibrosis (CF) is a genetic disease caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that affects multisystems in the body, particularly the lungs and digestive system. We report a case of an Omani newborn who presented with meconium ileus and high suspicion of CF. Thus, full CFTR gene sequencing was performed, which revealed a homozygous unreported C.4242+1G>C novel gene mutation. Both parents were found to be heterozygous for this mutation. This case sheds light on the importance of the extensive genetic testing of typical CF cases in the absence of family history or during neonatal presentations, especially when the sweat test cannot be performed and the diagnosis can be challenging.

Factors Affecting the Outcome of Extracorporeal Shockwave Lithotripsy in Urinary Stone Treatment.

OBJECTIVES: We sought to evaluate the factors affecting the outcome of extracorporeal shockwave lithotripsy (ESWL) in urinary stone treatment. METHODS: We conducted a retrospective review of 235 adult patients treated with ESWL, for radiopaque renal or ureteric stones between January 2015 and December 2016. Patient's age, sex, stone size, laterality, location, density, skin-to-stone distance (SSD), and presence of double J stent were studied as potential predictors. At the end of three months, the patients were divided into success and failure groups and the significance was determined. RESULTS: Of the 235 patients (188 males and 47 females) analyzed, ESWL was successful in 79.1%. Univariate analysis of both groups revealed no significant difference in patient's age and stone laterality. Statistically significant differences in gender, stone size, stone site, stone density, SSD, and patients with stents were observed. Statistically significant factors in multivariate logistic regression analysis were sex and stent. Females had three-times higher risk for ESWL failure than males (odds ratio (OR) = 3.213; 95% confidence interval (CI): 1.194-8.645; p = 0.021) and a higher failure rate when a stent was used (OR = 6.358; 95% CI: 2.228-18.143; p = 0.001). CONCLUSIONS: This study revealed that ESWL can treat renal and ureteric stones successfully with an inverse association between outcome and predictors such as stone size and density, SSD, and stent presence. These factors can help us in improving patient selection and ensure better results at lower cost.