Influence of UGT1A1 promoter polymorphism, α-thalassemia and ßs haplotype in bilirubin levels and cholelithiasis in a large sickle cell anemia cohort.

Hyperbilirubinemia in patients with sickle cell anemia (SCA) as a result of enhanced erythrocyte destruction, lead to cholelithiasis development in a subset of patients. Evidence suggests that hyperbilirubinemia may be related to genetic variations, such as the UGT1A1 gene promoter polymorphism, which causes Gilbert syndrome (GS). Here, we aimed to determine the frequencies of UGT1A1 promoter alleles, alpha thalassemia, and ßS haplotypes and analyze their association with cholelithiasis and bilirubin levels. The UGT1A1 alleles, -3.7 kb alpha thalassemia deletion and ßS haplotypes were determined using DNA sequencing and PCR-based assays in 913 patients with SCA. The mean of total and unconjugated bilirubin and the frequency of cholelithiasis in GS patients were higher when compared to those without this condition, regardless of age (P < 0.05). Cumulative analysis demonstrated an early age-at-onset for cholelithiasis in GS genotypes (P < 0.05). Low fetal hemoglobin (HbF) levels and normal alpha thalassemia genotype were related to cholelithiasis development (P > 0.05). However, not cholelithiasis but total and unconjugated bilirubin levels were associated with ßS haplotype. These findings confirm in a large cohort that the UGT1A1 polymorphism influences cholelithiasis and hyperbilirubinemia in SCA. HbF and alpha thalassemia also appear as modulators for cholelithiasis risk.

Preoperative pulmonary rehabilitation versus chest physical therapy in patients undergoing lung cancer resection: a pilot randomized controlled trial.

OBJECTIVE: To evaluate the effect of 4 weeks of pulmonary rehabilitation (PR) versus chest physical therapy (CPT) on the preoperative functional capacity and postoperative respiratory morbidity of patients undergoing lung cancer resection. DESIGN: Randomized single-blinded study. SETTING: A teaching hospital. PARTICIPANTS: Patients undergoing lung cancer resection (N=24). INTERVENTIONS: Patients were randomly assigned to receive PR (strength and endurance training) versus CPT (breathing exercises for lung expansion). Both groups received educational classes. MAIN OUTCOME MEASURES: Functional parameters assessed before and after 4 weeks of PR or CPT (phase 1), and pulmonary complications assessed after lung cancer resection (phase 2). RESULTS: Twelve patients were randomly assigned to the PR arm and 12 to the CPT arm. Three patients in the CPT arm were not submitted to lung resection because of inoperable cancer. During phase 1 evaluation, most functional parameters in the PR group improved from baseline to 1 month: forced vital capacity (FVC) (1.47L [1.27-2.33L] vs 1.71L [1.65-2.80L], respectively; P=.02); percentage of predicted FVC (FVC%; 62.5% [49%-71%] vs 76% [65%-79.7%], respectively; P<.05); 6-minute walk test (425.5±85.3m vs 475±86.5m, respectively; P<.05); maximal inspiratory pressure (90±45.9cmH(2)O vs 117.5±36.5cmH(2)O, respectively; P<.05); and maximal expiratory pressure (79.7±17.1cmH(2)O vs 92.9±21.4cmH(2)O, respectively; P<.05). During phase 2 evaluation, the PR group had a lower incidence of postoperative respiratory morbidity (P=.01), a shorter length of postoperative stay (12.2±3.6d vs 7.8±4.8d, respectively; P=.04), and required a chest tube for fewer days (7.4±2.6d vs 4.5±2.9d, respectively; P=.03) compared with the CPT arm. CONCLUSIONS: These findings suggest that 4 weeks of PR before lung cancer resection improves preoperative functional capacity and decreases the postoperative respiratory morbidity.