Genome-wide scan identified QTLs underlying femoral neck cross-sectional geometry that are novel studied risk factors of osteoporosis.

A genome-wide screen was conducted using a large white sample to identify QTLs for FNCS geometry. We found significant linkage of FNCS parameters to 20q12 and Xq25, plus significant epistatic interactions and sex-specific QTLs influencing FNCS geometry variation. INTRODUCTION: Bone geometry, a highly heritable trait, is a critical component of bone strength that significantly determines osteoporotic fracture risk. Specifically, femoral neck cross-sectional (FNCS) geometry is significantly associated with hip fracture risk as well as genetic factors. However, genetic research in this respect is still in its infancy. MATERIALS AND METHODS: To identify the underlying genomic regions influencing FNCS variables, we performed a remarkably large-scale whole genome linkage scan involving 3998 individuals from 434 pedigrees for four FNCS geometry parameters, namely buckling ratio (BR), cross-sectional area (CSA), cortical thickness (CT), and section modulus (Z). The major statistical approach adopted is the variance component method implemented in SOLAR. RESULTS: Significant linkage evidence (threshold LOD = 3.72 after correction for tests of multiple phenotypes) was found in the regions of 20q12 and Xq25 for CT (LOD = 4.28 and 3.90, respectively). We also identified eight suggestive linkage signals (threshold LOD = 2.31 after correction for multiple tests) for the respective geometry traits. The above findings were supported by principal component linkage analysis. Of them, 20q12 was of particular interest because it was linked to multiple FNCS geometry traits and significantly interacted with five other genomic loci to influence CSA variation. The effects of 20q12 on FNCS geometry were present in both male and female subgroups. Subgroup analysis also revealed the presence of sex-specific quantitative trait loci (QTLs) for FNCS traits in the regions such as 2p14, 3q26, 7q21 and 15q21. CONCLUSIONS: Our findings laid a foundation for further replication and fine-mapping studies as well as for positional and functional candidate gene studies, aiming at eventually finding the causal genetic variants and hidden mechanisms concerning FNCS geometry variation and the associated hip fractures.     

Complex segregation analyses of bone mineral density in Chinese

China has the largest population in the world; approximately 7% of the total population suffers from primary osteoporosis. Osteoporosis is mainly characterized by low bone mineral density (BMD). In the present study, familial correlation and segregation analyses for spine and hip BMDs have been undertaken for the first time in a Chinese sample composed of 401 nuclear families with a total of 1,260 individuals. The results indicate a major gene of additive inheritance for hip BMD, whereas there is no evidence of a major gene influencing spine BMD. Significant familial residual effects are found for both traits, and heritability estimates (±SE) for spine and hip BMDs are 0.807(0.099) and 0.897(0.101), respectively. Sex and age differences in genotype‐specific average BMD are also observed. This study provides the first evidence quantifying the high degree of genetic determination of BMD variation in the Chinese.     

Accuracy of magnetic resonance imaging compared to computerized tomography and renal selective angiography in preoperatively staging renal cell carcinoma.

During 1986 and 1987, 47 patients with renal cell carcinoma were evaluated preoperatively with CT, angiography and MRI. The preoperative tumor stage (T), lymph node metastases and venous involvement determined with the three methods were compared to the operative and histopathological findings. For T stage, angiography proved less accurate (54%) than CT (64%) or MRI (63%). MRI was found to be superior to CT in assessing lymph nodes, with an overall accuracy of 89% and sensitivity of 100% compared to 77 and 60%, respectively, of CT. For venous involvement CT was overall more accurate (74%) than angiography (65%) or MRI (63%). All three methods expressed a low sensitivity (between 31 and 41%) and a high specificity (between 95 and 100%) for detecting venous involvement. The minimal advantages of MRI compared to its high cost do not justify its routine use. CT remains the method of choice in staging preoperatively renal cell carcinoma.     

Evidence for a major gene underlying bone size variation in the Chinese

Osteoporosis is a major public health problem defined as a loss of bone strength, of which bone size is an important determinant. In the present study, familial correlation and segregation analyses for the spine and hip bone sizes were performed for the first time in a Chinese sample composed of 393 nuclear families with a total of 1,193 individuals. The results indicate a major gene of codominant inheritance for spine bone size; however, there is no evidence of a major gene influencing hip bone size. Significant familial residual effects are found for both traits, suggesting their polygenic inheritance. Heritability estimates (±SE) for spine and hip bone size were 0.62 (0.13) and 0.59 (0.12), respectively. Sex and age differences in genotype‐specific average bone size were observed. Compared with our previous study on bone mineral density (BMD) in the same population, this study suggests that genetic determination of bone size may be different from that of BMD, and thus studying bone size as one surrogate phenotype for osteoporotic fractures may be necessary. Am. J. Hum. Biol. 16:68–77, 2004. © 2003 Wiley‐Liss, Inc.     

Life expectancy in British Marfan syndrome populations

A total of 206 patients with Marfan syndrome were ascertained throughout genetic clinics in Wales and Scotland during the period 1970–1990. There were 45 deaths representing 22% of the cohort. Mean age at death was 45.3 ± 16.5 years. 50% median cumulative survival in the total cohort (n = 206) was 53 years for males and 72 years for females. Multivariate analysis confirmed severity as the best independent indicator of survival. These findings and survival curves will assist in the counselling of British families and individuals with Marfan syndrome.     

A specific enhanced recovery protocol decreases opioid use after thyroid and parathyroid surgery

BackgroundEnhanced recovery protocols have not been investigated previously for cervical endocrine surgery. The study aim was to determine whether systematic implementation of an enhanced recovery protocol specific for thyroid/parathyroid surgery can improve postoperative outcomes.MethodsA customized enhanced recovery protocol for thyroid/parathyroid surgery was designed and utilized systematically for all patients who underwent parathyroidectomy, thyroid lobectomy, or total thyroidectomy. Outcomes were assessed 12 months before enhanced recovery protocol implementation (n = 464 patients) and after enhanced recovery protocol implementation (n = 654 patients).ResultsEnhanced recovery protocol implementation was associated with a 72% decrease in mean oral morphine equivalents utilized in-house (before 82 ± 64 versus after 23 ± 28; P < .0001) and many enhanced recovery protocol patients were entirely opioid-free (0.2% vs 21%, P < .0001). When used, the enhanced recovery protocol was associated with a lesser mean amount of ondansetron to treat postoperative nausea and vomiting (5.5 mg ± 3 vs 4.5 ± 2: P < .0001). Duration of stay was short before implementation of the enhanced recovery protocol and did not change substantially after implementation (1.1 days ± 0.7 vs 1.1 ± 0.7; P = .26).ConclusionThe systematic use of a simple, cervical, endocrine surgery-specific enhanced recovery protocol decreased perioperative opioid use by ~70%, with significantly less postoperative nausea and vomiting. Implementation of a multidisciplinary enhanced recovery protocol may be an important initial step toward limiting opioid overuse during common operative procedures.