Wnt receptors, bone mass, and fractures: gene-wide association analysis of LRP5 and LRP6 polymorphisms with replication.

OBJECTIVE: Genes explaining the susceptibility to osteoporosis have not been fully elucidated. Our objective was to explore the association of polymorphisms capturing common variations of the lipoprotein receptor-related protein (LRP) 5 and 6 genes, encoding two Wnt receptors, with femoral neck bone mineral density (BMD) and osteoporotic fractures of the spine and the hip. DESIGN: Cross-sectional, case-control, and replication genetic association study. METHODS: Thirty-nine tagging and functional single nucleotide polymorphisms (SNPs) were analyzed in a group of 1043 postmenopausal women and 394 women with hip fractures. The results were replicated in a different group of 342 women. RESULTS: Three SNPs of the LRP6 gene were associated with BMD (nominal uncorrected P values <0.05) in the discovery cohort. One showed a significant association after multiple test correction; two of them were also associated in the replication cohort, with a combined standardized mean difference of 0.51 (P=0.009) and 0.47 (P<0.003) across rs11054704 and rs2302685 genotypes. In the discovery cohort, several LRP5 SNPs were associated with vertebral fractures (odds ratio (OR) 0.67; P=0.01), with hip fractures (unadjusted ORs between 0.59 and 1.21; P=0.005-0.033, but not significant after multiple test adjustment or age adjustment), and with height and the projected femoral neck area, but not with BMD. Transcripts of LRP5 and LRP6 were similarly abundant in bone samples. CONCLUSIONS: In this study, we found common polymorphisms of LRP5 associated with osteoporotic fractures, and polymorphisms of the LRP6 gene associated with BMD, thus suggesting them as likely candidates to contribute to the explaination of the hereditary influence on osteoporosis.

Polymorphisms of the WNT10B gene, bone mineral density, and fractures in postmenopausal women.

Wnt ligands are important regulators of skeletal homeostasis. Wnt10B tends to stimulate the differentiation of common mesenchymal precursors toward the osteoblastic lineage, while inhibiting adipocytic differentiation. Hence, we decided to explore the association of WNT10B allelic variants with bone mineral density and osteoporotic fractures. A set of tag SNPs capturing most common variations of the WNT10B gene was genotyped in 1438 Caucasian postmenopausal women, including 146 with vertebral fractures and 432 with hip fractures. We found no association between single SNPs and spine or hip bone mineral density (BMD). In the multilocus analysis, some haplotypes showed a slight association with spine BMD (P = 0.03), but it was not significant after multiple-test correction. There was no association between genotype and vertebral or hip fractures. Transcripts of WNT10B and other Wnt ligands were detected in human bone samples by real-time PCR. However, there was no relationship between genotype and RNA abundance. Thus, WNT10B is expressed in the bone microenvironment and may be an important regulator of osteoblastogenesis, but we have not found evidence for a robust association of common WNT10B gene allelic variants with either BMD or fractures in postmenopausal women.

Surgical site infection during hospitalization and after discharge in patients who have undergone cardiac surgery.

During a 13-month period, 513 patients who were scheduled to undergo cardiac surgery were prospectively observed for surgical site infection during hospitalization after surgery and for 1 month after hospital discharge. Fifty-three patients showed evidence of surgical site infection (during hospitalization for 31 patients and after discharge for 22). Multivariate analysis identified that risk factors for surgical site infection differed between infections that occurred during hospitalization and those that occurred after discharge.

Nosocomial infection after lung surgery: incidence and risk factors.

STUDY OBJECTIVES: To assess the incidence and risk factors for nosocomial infection after lung surgery. DESIGN: Prospective cohort study. SETTING: Service of thoracic surgery of an acute-care teaching hospital in Santander, Spain. PATIENTS: Between June 1, 1999, and January 31, 2001, all consecutive patients undergoing lung surgery were prospectively followed up for 1 month after discharge from the hospital to assess the development of nosocomial infection, the primary outcome of the study. INTERVENTIONS: During the hospitalization period, patients were visited on a daily basis. Postdischarge surveillance was based on visits to the surgeon. MEASUREMENTS AND RESULTS: We studied 295 patients (84% men; mean age, 60.9 years), 89% of whom underwent resection operations. Ninety episodes of nosocomial infection were diagnosed in 76 patients, including pneumonia (n = 10), lower respiratory tract infection (n = 47), wound infection (n = 16; one third were detected after hospital discharge), urinary tract infection (n = 9), and bacteremia (n = 8; three fourths were catheter-related bacteremia). Twenty patients had severe infections (pneumonia or empyema), with a mortality rate of 60%. COPD (adjusted odds ratio [OR], 2.70; 95% confidence interval [CI], 1.52 to 4.84), duration of surgery with an increased risk for each additional minute (Mantel-Haenzel chi(2) test for trend, p = 0.037), and ICU admission (OR, 3.69; 95% CI, 1.94 to 7.06) were independent risk factors for nosocomial infection. The use of an epidural catheter was a protective factor (OR, 0.45; 95% CI, 0.22 to 0.95). There were no differences according to the use of amoxicillin/clavulanate or cefotaxime for surgical prophylaxis. CONCLUSIONS: Nosocomial infections are common after lung surgery. One third of wound infections were detected after hospital discharge. The profile of a high-risk patient includes COPD as underlying disease, prolonged operative time, and postoperative ICU admission.

Henoch-Schönlein purpura after intravesical administration of bacillus Calmette-Guérin.

The administration of intravesical bacille Calmette-Guérin (BCG) in early stages of bladder cancer is usually a safe therapy. Side-effects of BCG immunotherapy can be of both local and systemic nature. We report the first case of Henoch-Schönlein purpura following intravesical administration of BCG.

Diabetes mellitus following cisplatin treatment.

The association between cisplatin treatment and diabetes mellitus was analyzed retrospectively in 219 patients with locally advanced squamous cell head and neck cancer treated in two consecutive trials with cisplatin-based induction chemotherapy. It was found that 11 patients (5%) developed diabetes mellitus during the treatment period, two cases presenting as hyperosmolar coma. The literature contains only sporadic descriptions of cases of hyperosmolar coma related to cisplatin chemotherapy. The present study was initiated owing to a case of hyperosmolar coma observed by us. We suggest that glycemia levels in patients receiving chemotherapy with a cisplatin-based regimen should be monitored regularly.