Phenotypic Expressions of CCR5-Δ32/Δ32 Homozygosity

Objective: As blockade of CC-chemokine receptor 5 (CCR5) has been proposed as therapy for HIV-1, we examined whether the CCR5-Δ32/Δ32 homozygous genotype has phenotypic expressions other than those related to HIV-1. Design: Study subjects were white homosexual men or men with hemophilia who were not infected with HIV-1. In this study, 15 CCR5-Δ32/Δ32 homozygotes were compared with 201 CCR5 wild-type (+/+) subjects for a wide range of clinical conditions and laboratory assay results ascertained during prospective cohort studies and routine clinical care. CCR5-Δ32 genotype was determined by polymerase chain reaction, followed by single-stranded conformational polymorphism analysis. Results: Hypertension and conditions attributable to hemophilia were the only diagnoses frequently found in clinical records of CCR5-Δ32/Δ32 study subjects. Based on blood pressure measurement and treatment history, CCR5-Δ32/Δ32 homozygotes had a 2.8-fold higher prevalence of hypertension than age-matched CCR5-+/+ study subjects (95% confidence interval [CI], 1.2-6.4; p = .01); none of the homozygotes had severe hypertension. Hematologic measures were generally similar across the genotypes, but total lymphocyte counts were ~20% higher in CCR5-Δ32/Δ32 study subjects than in CCR5-+/+ study subjects (p \u3c .05). Among patients with hemophilia who were infected with hepatitis C virus (HCV), mean alanine aminotransferase levels were 117% higher among CCR5-Δ32/Δ32 homozygotes (p \u3c .05), but serum HCV levels did not differ by CCR5-Δ32 genotype. CCR5-Δ32/Δ32 homozygous study subjects had a lower prevalence of antibodies to measles virus than those with other genotypes, but this association was not confirmed in a group of blood donors. The prevalence of antibodies to nine other common viruses, HBV, and HCV was not related to CCR5 genotype. Conclusions: CCR5-Δ32/Δ32 homozygotes are generally similar to wild-type persons. Confirmatory investigations are required to determine whether hypertension, increased lymphocyte counts, and higher hepatic enzyme levels in the presence of HCV infection represent true phenotypic expressions of this genotype. CCR5-Δ32/Δ32 homozygosity does not provide broad protection against viral infections

Anemia and the Need for Intravenous Iron Infusion after Roux-en-Y Gastric Bypass

The frequency of anemia, iron deficiency, and the long-term need for IV iron following Roux-en-y gastric bypass (RYGB) surgery has not been well characterized. Three-hundred and nineteen out of 904 consecutive subjects who underwent RYGB at Penn State Hershey Medical Center from 1999 to 2006 met the inclusion criteria for a preoperative complete blood count (CBC) and at least one CBC >6 months following surgery. Cumulative incidence of anemia 7 years post procedure was 58%. Menstruation status and presence of preoperative anemia were predictive of anemia by univariate analysis and multivariable Cox regression ( P = 0.0014 and 0.044, respectively). Twenty-seven subjects, primarily premenopausal women, representing 8.5% of the cohort and 22% of the 122 anemic subjects, needed intravenous (IV) iron a mean of 51 months postoperatively for anemia unresponsive or refractory to oral iron. The risk for development of anemia necessitating IV iron therapy following RYGB is highest in menstruating women and continues to increase for many years, even in post-menopausal women. Well-designed prospective studies are needed to identify the incidence of iron deficiency anemia and the patient populations at increased risk for requiring IV iron replacement after RYGB surgery

Anemia and the Need for Intravenous Iron Infusion after Roux-en-Y Gastric Bypass.

The frequency of anemia, iron deficiency, and the long-term need for IV iron following Roux-en-y gastric bypass (RYGB) surgery has not been well characterized. Three-hundred and nineteen out of 904 consecutive subjects who underwent RYGB at Penn State Hershey Medical Center from 1999 to 2006 met the inclusion criteria for a preoperative complete blood count (CBC) and at least one CBC \u3e6 months following surgery. Cumulative incidence of anemia 7 years post procedure was 58%. Menstruation status and presence of preoperative anemia were predictive of anemia by univariate analysis and multivariable Cox regression (P = 0.0014 and 0.044, respectively). Twenty-seven subjects, primarily premenopausal women, representing 8.5% of the cohort and 22% of the 122 anemic subjects, needed intravenous (IV) iron a mean of 51 months postoperatively for anemia unresponsive or refractory to oral iron. The risk for development of anemia necessitating IV iron therapy following RYGB is highest in menstruating women and continues to increase for many years, even in post-menopausal women. Well-designed prospective studies are needed to identify the incidence of iron deficiency anemia and the patient populations at increased risk for requiring IV iron replacement after RYGB surgery

Evaluation of the efficacy and safety of etoricoxib in the treatment of hemophilic arthropathy

This 2-part, double-blind, placebo-controlled study was conducted to determine the safety and efficacy of etoricoxib, a COX-2 selective inhibitor, for the treatment of hemophilic arthropathy. In part 1 (6 weeks), 102 patients (≥ 12 years old) with hemophilic arthropathy were randomized to receive 90 mg etoricoxib once daily or placebo (1:1 ratio). In part 2 (6 months), 51 patients taking placebo in part 1 were randomized to receive 90 mg etoricoxib or 25 mg rofecoxib once daily; patients taking etoricoxib in part 1 continued the same treatment. Efficacy end points included Patient Assessment of Arthropathy Pain, Patient Global Assessment of Arthropathy Disease Status, and Investigator Global Assessment of Arthropathy Disease Status. Safety was evaluated at each study visit. Etoricoxib provided significant improvement in all end points versus placebo (P < .001). Fewer patients taking etoricoxib discontinued due to a lack of efficacy versus placebo (P = .048). During part 2, efficacy was maintained; etoricoxib and rofecoxib demonstrated similar results. The most common adverse experiences were upper respiratory infection and headache. The incidence of joint bleeding during part 1 was similar between etoricoxib (66.7%) and placebo (72.6%) and during part 2 between etoricoxib (77.0%) and rofecoxib (78.9%). We conclude that etoricoxib provided superior efficacy versus placebo for the treatment of hemophilic arthropathy and was generally safe and well tolerated

Correlates of spontaneous clearance of hepatitis C virus among people with hemophilia

People with hemophilia were formerly at very high risk of infection with hepatitis C virus (HCV). Approximately 20% of HCV-infected patients spontaneously clear the virus. To identify correlates of spontaneous clearance of HCV, we studied a cohort of HCV-infected hemophilic subjects without human immunodeficiency virus infection who had never been treated with interferon. Plasma HCV RNA was persistently undetectable in 192 (27.0%) of 712 HCV-seropositive subjects. In multivariate analyses, HCV clearance was more likely in subjects infected with HCV at younger age, especially with infection before age 2 years (40.1%) compared with after age 15 years (14.9%, Ptrend < .0001), and with relatively recent infection, especially after 1983 (42.8%) compared with before 1969 (18.2%, Ptrend < .0001). HCV clearance was marginally reduced with African ancestry (19%) and greatly increased with chronic hepatitis B virus (HBV) infection (59.1%, P = .001). Resolved HBV infection, coagulopathy types and severity, types of clotting factor treatment, and sex were not associated with HCV clearance. In conclusion, hemophilic subjects coinfected with chronic HBV and those infected with HCV before age 2 years or after 1983 were significantly more likely to spontaneously clear HCV viremia. These data highlight and clarify the importance of nongenetic determinants in spontaneous recovery from HCV infection