Glycemia and Insulin Secretion in Cystic Fibrosis Two Years After Elexacaftor/Tezacaftor/Ivacaftor: PROMISE-ENDO.

Background: Elexacaftor/tezacaftor/ivacaftor (ETI) is a highly effective therapy that improves lung disease in people with cystic fibrosis (pwCF), but its effect on glucose tolerance and insulin secretion is unclear.

Methods: PROMISE is a multicenter prospective, observational study of ETI in pwCF ≥12 years and at least one F508del allele. The PROMISE Endocrine sub-study (PROMISE-ENDO) enrolled participants at 10 CF Centers where hemoglobin A1c (HbA1c) was collected and 3-hour oral glucose tolerance tests (OGTT) conducted to examine glucose tolerance, glucose excursions, insulin secretory rates (deconvolution of C-peptide) and sensitivity (oral minimal model) prior to ETI and 12-18 months (mos) and 24-30 mos following ETI initiation.

Elexacaftor/tezacaftor/ivacaftor and gastrointestinal outcomes in cystic fibrosis: Report of promise-GI.

Background: Elexacaftor/tezacaftor/ivacaftor (ETI) improves pulmonary disease in people with cystic fibrosis (PwCF), but its effect on gastrointestinal symptoms, which also affect quality of life, is not clear.

Methods: PROMISE is a 56-center prospective, observational study of ETI in PwCF >12 years and at least one F508del allele. Gastrointestinal symptoms, evaluated by validated questionnaires: Patient Assessment of Upper Gastrointestinal Disorders-Symptom (PAGI-SYM), Patient Assessment of Constipation-Symptom (PAC-SYM), Patient Assessment of Constipation-Quality of Life (PAC-QOL)), fecal calprotectin, steatocrit and elastase-1 were measured before and 6 months after ETI initiation.

Clinical Effectiveness of Elexacaftor/Tezacaftor/Ivacaftor in People with Cystic Fibrosis: A Clinical Trial.

The cystic fibrosis (CF) modulator drug, elexacaftor/tezacaftor/ivacaftor (ETI), proved highly effective in controlled clinical trials for individuals with at least one F508del allele, which occurs in at least 85% of people with CF. PROMISE is a postapproval study to understand the broad effects of ETI through 30 months' clinical use in a more diverse U.S.

PROMISE: Working with the CF community to understand emerging clinical and research needs for those treated with highly effective CFTR modulator therapy.

Highly effective CFTR modulator drug therapy is increasingly available to those with cystic fibrosis. Multiple observational research studies are now being conducted to better understand the impacts of this important therapeutic milestone on long-term outcomes, patient care needs, and future research priorities. PROMISE is a large, multi-disciplinary academic study focused on the broad impacts of starting elexacaftor/tezacaftor/ivacaftor in the US population age 6 years and older.

Comparative Effectiveness of Vancomycin Versus Linezolid for the Treatment of Acute Pulmonary Exacerbations of Cystic Fibrosis.

Data are limited regarding the preferred antibiotics for treatment of acute pulmonary exacerbations (APEs) of cystic fibrosis (CF), when methicillin-resistant (MRSA) is suspected. To compare the rate of return to baseline lung function among individuals with APEs of CF treated with either vancomycin or linezolid. This retrospective study included individuals hospitalized for APEs of CF from May 1, 2015, to April 30, 2017 who were infected with MRSA and treated with vancomycin or linezolid.

Vancomycin Versus Vancomycin Plus Rifampin for the Treatment of Acute Pulmonary Exacerbations of Cystic Fibrosis.

Objectives: This study aimed to compare the change in pulmonary function in children and adolescents with cystic fibrosis (CF) who were infected with methicillin-resistant Staphylococcus aureus (MRSA) treated with either vancomycin (VAN) alone or vancomycin plus rifampin (VAN-RIF).

Methods: Included patients were ages 6 to 20 years; hospitalized for an acute pulmonary exacerbation (APE) of CF from May 1, 2012, to April 30, 2014; had a respiratory tract culture positive for MRSA within 1 month of index hospital admission; received at least 48 consecutive hours of VAN or VAN-RIF; and had admission and discharge pulmonary function tests. The primary end point was change in percent predicted forced expiratory volume in 1 second (FEV).

Association of Vancomycin Trough Concentration With Response to Treatment for Acute Pulmonary Exacerbation of Cystic Fibrosis.

Background: Our goal was to determine the relationship between serum vancomycin trough concentrations (VTCs) and changes in pulmonary function among individuals with an acute pulmonary exacerbation (APE) of cystic fibrosis (CF).

Methods: We included subjects who were ≥6 years of age, were hospitalized for an APE of CF between May 1, 2012, and April 30, 2014, were administered vancomycin for ≥48 hours, and had a history of airway infection with methicillin-resistant Staphylococcus aureus. Pearson correlations were performed to characterize the relationship between VTC and pulmonary function.

Clinical and molecular characterization of S1118F-CFTR.

Background: Cystic fibrosis is a lethal autosomal recessive disorder usually associated with lung disease, pancreatic insufficiency and high sweat chloride levels.

Clinical Case: A patient admitted to Le Bonheur Children's Medical Center (LBCMC, Memphis, TN) showed symptoms of meconium ileus which required exploratory laparotomy, bowel resection and ileostomy. Genotyping showed DeltaF508/I1027T on one chromosome and S1118F on the other.