Marcia Katz

Clinical Care Guidelines for Cystic Fibrosis–Related Diabetes: A position statement of the American Diabetes Association and a clinical practice guideline of the Cystic Fibrosis Foundation, endorsed by the Pediatric Endocrine Society

Cystic fibrosis–related diabetes (CFRD) is the most common comorbidity in people with cystic fibrosis (CF), occurring in ∼20% of adolescents and 40–50% of adults (1). While it shares features of type 1 and type 2 diabetes, CFRD is a distinct clinical entity. It is primarily caused by insulin insufficiency, although fluctuating levels of insulin resistance related to acute and chronic illness also play a role. The additional diagnosis of CFRD has a negative impact on pulmonary function and survival in CF, and this risk disproportionately affects women (2–4). In contrast to patients with other types of diabetes, there are no documented cases of death from atherosclerotic vascular disease in patients with CFRD, despite the fact that some now live into their sixth and seventh decades. These guidelines are the result of a joint effort between the Cystic Fibrosis Foundation (CFF), the American Diabetes Association (ADA), and the Pediatric Endocrine Society (PES). They are intended for use by CF patients, their care partners, and health care professionals and include recommendations for screening, diagnosis, and medical management of CFRD. This report focuses on aspects of care unique to CFRD. A comprehensive summary of recommendations for all people with diabetes can be found in the ADA Standards of Medical Care, published annually in the January supplement to Diabetes Care (5). In 2009, CFF in collaboration with ADA and PES convened a committee of CF and diabetes experts to update clinical care guidelines for CFRD. Investigators at Johns Hopkins University conducted evidence reviews on relevant clinical questions identified by the guidelines committee. The reviews were provided to the committee to use in developing recommendations. Where possible, the evidence for each recommendation was considered and graded by the committee using the ADA (5) and the U.S. Preventive Services Task Force (USPSTF) (6 …

Randomized Trial of Biofilm Testing to Select Antibiotics for Cystic Fibrosis Airway Infection

In cystic fibrosis (CF), conventional antibiotic susceptibility results correlate poorly with clinical outcomes. We hypothesized that biofilm testing would more accurately reflect the susceptibilities of bacteria infecting CF airways.

Computed axial tomography evidence of left atrial enlargement: a predictor of elevated pulmonary capillary wedge pressure in pulmonary hypertension

Background: One of the commonest causes of pulmonary hypertension (PH) is left heart dysfunction associated with elevated pulmonary capillary wedge pressure (PCWP). In contrast, the pathology of pulmonary arterial hypertension (PAH) originates in the pulmonary vascular bed. Accurate diagnosis of PAH requires right heart catheterization (RHC) with normal PCWP. This study examines the role of computed tomography of the chest (CT chest) in evaluating left atrial (LA) size as an indicator of elevated PCWP in patients undergoing PH evaluation. Methods: CT chest and RHC data were reviewed in 37 subjects at the Baylor PH Center. Both subjective estimates and objective measurements of left atrial size from the CT chest were recorded separately by 3 investigators. Patients were categorized as Group I (small-normal LA) and Group II (large LA) and RHC results compared.The objective and subjective measurements were compared by receiver operator characteristic (ROC). Results: The mean PCWP was 12 ± 6 mmHg in Group I and 21 ± 7 mmHg in Group II (P = 0.001). The estimated LA area was 19.4 ± 4.9 cm2 in Group I and 39.9 ± 7.6 cm2 in Group II (mean ± SD; P < 0.001). The estimated LA area, corrected for the chest wall length, was 0.78 ± 0.19 cm2 and 1.65 ± 0.26 cm2 in Groups I and II, respectively (P < 0.001). Significant correlations were found between uncorrected PCWP and LA area (R = 0.45, P = 0.005), corrected PCWP and LA area (R = 0.47, P = 0.003), and the subjective observer impression of LA enlargement and measured PCWP (R = 0.51, P = 0.001). Conclusion: In this pilot study, enlarged LA area on the CT chest was associated with an elevated PCWP on RHC. For patients undergoing PH evaluation, increased LA area on CT chest could suggest left heart dysfunction in patients as a possible cause of PH.

Characterization of a recurrent 3.8kb deletion involving exons 17a and 17b within the CFTR gene.

BACKGROUND Large deletions within CFTR have been estimated to constitute 1-2% pathogenic alleles, but the occurrence could be much higher in classical cystic fibrosis (CF) patients with one mutation detectable by the routine screening/sequencing work-up. Currently, evaluation of major CFTR rearrangements is not included in the mutation analysis for the reproductive partner of a CF patient/carrier. METHODS Exon sequencing and Multiplex Ligation-dependent Amplification (MLPA) analyses were used to make a molecular diagnosis of two unrelated CF patients. Long PCR, restriction mapping, cloning, and hot start sequencing were employed to accurately annotate the rearrangement junctions. RESULTS Both patients had a heterozygous single amino acid deletion mutation identified by sequencing, and a heterozygous deletion of CFTR exons 17a and 17b detected by MLPA. Molecular characterization of the rearrangement breakpoints indicated that the two patients had an identical complex c.2988+1616_c.3367+356del3796ins62 change, flanked by a pair of perfectly inverted repeats of 32 nucleotides. CONCLUSIONS The c.2988+1616_c.3367+356del3796ins62 complex rearrangement is a recurrent mutation from patients of different ethnic backgrounds. This mutation can be detected through a simple PCR based analysis.