Thomas, Colleen S.

The primary aim was to explore the safety and tolerability of inhaled treprostinil when used in patients with pulmonary hypertension (PH) with concomitant chronic obstructive pulmonary disease (COPD). Patients with a diagnosis of pre‐capillary PH (defined as pulmonary artery mean pressure of ≥ 25 mmHg and pulmonary artery wedge pressure or left ventricular end diastolic pressure of ≤ 15 mmHg) who were being initiated on inhaled treprostinil and had concomitant COPD (defined as FEV1/FVC ratio ≤ 70% with FEV1 ≥ 40% predicted) were considered for inclusion in this pilot study. Assessments included adverse events, physical exam, World Health Organization (WHO) functional class, 6‐minute walk test (6MWT), modified Borg dyspnea score, and concomitant medication. At baseline and week 16 St. George’s Respiratory Questionnaire (SGRQ), arterial blood gas (ABG), and pulmonary function test (PFT) were assessed. The median age was 65 years (age range, 56–80 years) and five patients (56%) were men. Among the nine patients, a majority had an increase in 6MWT from baseline to week 16 (median change, 19 m). Only three of the nine patients (33%) had an increase in A‐a gradient at week 16 (median change, –7). There was no difference in any of the following: arterial blood gases, WHO functional class, 6MWT results, or SGRQ scores from baseline to week 16. There was a statistically significant decline in several of the PFT measures, including FEV1 (median change, –0.18 L; P = 0.004; median change, –7% of predicted; P = 0.016), FVC (median change, –0.23 L; P = 0.027), and diffusion capacity for carbon monoxide (DLCO) (median change, –5% of predicted; P = 0.023). The small number of patients limits firm conclusions; however, inhaled treprostinil did not seem to adversely impact oxygenation in the majority of the study patients with pre‐capillary PH and COPD. While there may have an adverse impact on some pulmonary function parameters, the clinical significance is unclear.

AbstractBackground and AimsTo determine the prevalence of metabolic syndrome (MetS) – a potential phenotypical risk for pulmonary hypertension (PH) – in patients with PH and by PH diagnostic group including group 1 pulmonary arterial hypertension (PAH); group 1.1 idiopathic PAH, groups 1.2 heritable PAH, 1.3 drug and toxin induced, 1.4 associated PAH, group 2 PH with left heart disease, group 3 PH associated with lung disease and/or hypoxemia, group 4 PH owing to chronic thrombotic and/or embolic disease, and group 5 PH from multifactorial mechanisms.MethodsWe conducted a retrospective chart review of patients referred to Mayo Clinic in Florida from January 1990 to October 2013 (N = 1287). Only patients whom PH was confirmed by right heart catheterization were included (N = 640). MetS was defined with at least three of the following: systemic hypertension, diabetes mellitus, hyperlipidemia and body mass index > 30.ResultsMetS was prevalent in 247 of 640 (39%) with PH: 13% in group 1.1 PAH, 12% in groups 1.2–1.4 PAH, 54% in group 2, 55% in group 3, 23% in group 4 and 24% in group 5. After adjusting for age, sex and race, diagnostic subgroup analysis revealed a higher prevalence of MetS in WHO Group 2 PH patients [adjusted odd ratios (OR): 2.58, P < 0.0001] and WHO group 3 PH (adjusted OR: 2.77, P < 0.0001) when compared to group 1 PH.ConclusionThe prevalence of MetS was observed in 39% of patients with PH; however, among PH patients, the prevalence was higher in group 2 and 3 PH.

AbstractBackgroundConcomitant administration of the triazole antifungals, voriconazole or itraconazole, with tacrolimus can result in significant drug interaction in the transplant recipient. Limited published information exists regarding tacrolimus dosing when transitioning from voriconazole to itraconazole. The objective of this study was to evaluate the extent of the drug interaction with antifungal prophylaxis using voriconazole followed by a change to itraconazole in lung transplant recipients receiving tacrolimus.MethodsThis prospective study included lung transplant recipients receiving antifungal prophylaxis with voriconazole followed by a switch to itraconazole. Patients were followed from the time of transplant until two months after converting to itraconazole. All patients received standard immunosuppression with tacrolimus, mycophenolate mofetil, and a corticosteroid. Tacrolimus dose normalized concentrations using concentration/dose ratio were compared while receiving voriconazole versus itraconazole.ResultsTwenty lung transplant recipients were included in the final analysis. No difference was found with the tacrolimus dose normalized concentrations on voriconazole 254 ± 28 (ng/mL)/(mg/kg) compared with itraconazole 234 ± 34 (ng/mL)/(mg/kg), p = 0.65.ConclusionTacrolimus dosage adjustments were not necessary when converting from voriconazole to itraconazole. Validation in a larger population is needed to confirm these findings.

Object Management of idiopathic normal-pressure hydrocephalus (iNPH) is hard because the diagnosis is difficult and shunt surgery has high complication rates. An important complication is overdrainage, which often can be treated with adjustable–shunt valve manipulations but also may result in the need for subdural hematoma evacuation. The authors evaluated shunt surgery overdrainage complications in iNPH and their relationship to lumbar puncture opening pressure (LPOP). Methods The authors reviewed the charts of 164 consecutive patients with iNPH who underwent shunt surgery at their institution from 2005 to 2011. They noted age, sex, presenting symptoms, symptom duration, hypertension, body mass index (BMI), imaging findings of atrophy, white matter changes, entrapped sulci, LPOP, valve opening pressure (VOP) setting, number of valve adjustments, serious overdrainage (subdural hematoma requiring surgery), radiological overdrainage (subdural hematomas or hygroma seen on postoperative imaging), clinical overdrainage (sustained or postural headache), other complications, and improvements in gait, urine control, and memory. Results Eight patients (5%) developed subdural hematomas requiring surgery. All had an LPOP of greater than 160 mm H2O and an LPOP-VOP of greater than 40 mm H2O. Radiological overdrainage was more common in those with an LPOP of greater than 160 mm H2O than in those with an LPOP of less than 160 mm H2O (38% vs 21%, respectively; p = 0.024). The BMI was also significantly higher in those with an LPOP of greater than 160 mm H2O (median 30.2 vs 27.0, respectively; p = 0.005). Conclusions Serious overdrainage that caused subdural hematomas and also required surgery after shunting was related to LPOP and LPOP-VOP, which in turn were related to BMI. If this can be replicated, individuals with a high LPOP should have their VOP set close to the LPOP, or even higher. In doing this, perhaps overdrainage complications can be reduced.

AbstractScreening for the Muir‐Torre variant of Lynch Syndrome (LS) using Mismatch Repair (MMR) gene immunohistochemistry (IHC) on sebaceous neoplasms (SNs) is technically feasible. To date, research into the clinical utility of MMR IHC for this indication is limited. We conducted a retrospective chart review of 90 patients with MMR IHC completed on at least one SN from January 2005 to May 2010. SNs included were adenomas, epitheliomas, carcinomas and basal and squamous cell carcinomas with sebaceous differentiation. Of the 90 patients, 13 (14 %) had genetically confirmed or fulfilled clinical criteria for a diagnosis of MTS and 51 patients (57 %) presented with an abnormal MMR IHC result (loss of one or more MMR proteins) on at least one SN. Abnormal IHC had a sensitivity of 85 %, specificity of 48 %, positive predictive value (PPV) of 22 % and negative predictive value (NPV) of 95 % when evaluating for MTS. When personal or family history of colorectal cancer (≥2 family members with a history of colorectal cancer) was taken into consideration, ignoring IHC results, sensitivity was 92 %, specificity was 99 %, PPV was 92 % and NPV was 99 %. MMR IHC on SNs when used to screen for MTS has poor diagnostic utility. We recommend that MMR IHC not be performed routinely on SNs when the patient does not have either personal or family history of colorectal cancer.

Background Colorectal cancer (CRC) can be prevented by the early detection and removal of advanced adenomas (AAs) by colonoscopy. Our aim was to evaluate peripheral blood leukocyte (PBL) telomere length as a potential biomarker for the presence of AAs. Methods PBL telomere length was measured in patients with AAs (n=35), in a control group of similarly aged patients who had a normal colonoscopy (n=145) and in a separate population group with no history of cancer, again similarly aged (n=495). Telomere measurements were performed using a quantitative PCR assay and reported as ratios of telomere and single copy gene measurements. Results Telomere lengths tended to be lower in patients with AAs than in patients in the normal colonoscopy group (p<0.001) as well as those in the population group (p=0.011). A telomere/single copy gene ratio of 0.5 was found to have an estimated 94% sensitivity and a 56% specificity for AAs; a combination of sensitivity and specificity for which a value of >0.5 would reduce the odds of a patient having AAs by a factor of 0.11 (the negative likelihood ratio). Thirty three percent of individuals in the population group tested above this cutoff and could be considered at low risk for AAs. Conclusions PBL telomeres are shortened in patients with colorectal neoplasia, suggesting that PBL telomere length could be a promising non-invasive blood biomarker to pre-screen for risk of AAs prior to colonoscopy.

Objective Abnormalities are commonly identified during endoscopy in eosinophilic oesophagitis (EoE). There is no standardised classification to describe these features. This study aimed to evaluate the interobserver agreement of a grading system for the oesophageal features of EoE. Method The proposed system incorporated the grading of four major oesophageal features (rings, furrows, exudates, oedema) and the presence of additional features of narrow calibre oesophagus, feline oesophagus, stricture and crepe paper oesophagus. Endoscopic videos from 25 patients with EoE and controls were reviewed by 21 gastroenterologists. Interobserver agreement was assessed by estimating multi-rater κ and the proportion of pairwise agreement. Results Using the original grading system, agreement for rings, furrows and exudates was moderate (κ=0.38–0.46, 56–65% agreement) but poor for oedema (κ=0.23, 51% agreement). Identification of narrow calibre oesophagus had fair agreement (κ=0.30, 74% agreement) while feline oesophagus had poor agreement (κ=0.15, 68% agreement). After collapsing the severity grading for oedema and furrows and eliminating poorly performing features of feline oesophagus and narrow calibre oesophagus, a modified grading system demonstrated good agreement for the four major features of EoE (κ=0.40–0.54, 71–81% agreement) and additional features of stricture and crepe paper oesophagus (κ=0.52 and 0.58, 79% and 92% agreement). Conclusions The proposed system for endoscopically-identified oesophageal features of EoE defines common nomenclature and severity scores for the assessment of EoE disease activity. The system has good interobserver agreement among practising and academic gastroenterologists.