CYP2R1 polymorphisms are important modulators of circulating 25-hydroxyvitamin D levels in elderly females with vitamin insufficiency, but not of the response to vitamin D supplementation.

We studied the association between CYP2R1 genetic polymorphisms and circulating 25-hydroxyvitamin D [25(OH)D] before and after supplementation with vitamin D3 in 218 elderly. We found differences between 3 and 8 ng/ml in circulating levels at baseline in women but not in the response after 1 year of supplementation. INTRODUCTION: This study evaluated the association between polymorphisms in four single nucleotide polymorphisms (SNPs) of the CYP2R1 gene and 25(OH)D levels before and 1 year after supplementation with two different doses of vitamin D3 (600 IU daily or a dose equivalent to 3750 IU daily), in a cohort of 218 (96 men and 122 women) Lebanese elderly overweight subjects. METHODS: Genotyping was performed for rs12794714, rs10741657, rs1562902, and rs10766197 SNPs using real-time PCR. The 25(OH)D levels were measured by liquid chromatography tandem mass spectrometry. RESULTS: At baseline, the mean ± SD age was 71.0 ± 4.7 years, BMI 30.3 ± 4.6 kg/m2, and 25(OH)D level was 20.5 ± 7.6 ng/ml. There were significant differences in mean 25(OH)D levels between genotypes in women, but not in men. After adjustment for age, season, and BMI, the homozygous for the low frequency gene variant (HLV) of rs1562902 and rs10741657 SNPs had the highest mean 25(OH)D levels with difference of 7.6 ng/ml for rs1562902 SNP (p < 0.01) and of 5.9 ng/ml for rs10741657 (p = 0.05) compared to the homozygous for the major polymorphisms (HMPs). Conversely, for rs10766197 and rs12794714 SNPs, HMP had the highest mean 25(OH)D levels with difference of 6 ng/ml for rs10766197 (p = 0.003) and of 4.8 ng/ml (p = 0.02) for rs12794714, compared to the HLV. CYP2R1 genetic polymorphisms explained 4.8 to 9.8 % of variability in 25(OH)D in women. After 1 year, there was no difference in the response to vitamin D3 supplementation between genotypes in either gender. CONCLUSION: This study showed a difference in 25(OH)D levels between CYP2R1 genotypes that equates a daily supplementation of 400-800 IU vitamin D, depending on genotype. It underscores possible important genetic contributions for the high prevalence of hypovitaminosis D in the Middle East.

Elbow arthroscopy: An alternative to anteromedial portals.

BACKGROUND: Elbow arthroscopy is considered to be a difficult procedure with a high complication rate. These two disadvantages are due to the proximity of neurovascular structures. HYPOTHESIS: The aim of our study was to evaluate the efficacy and complication rate of a new elbow arthroscopy technique without anteromedial portals. This approach was taken because of the high rate of ulnar nerve damage using the medial portal, and the difficulty of performing triangulation of opposite portals in a patient in the lateral decubitus position. MATERIAL AND METHODS: Fifteen patients were operated on by the same surgeon between 2010 and 2012. Range of motion and the "MEPS" elbow score were calculated preoperatively and at the final postoperative follow-up. The average age of patients was 38.3 years. The follow-up was 11.1 months. Personal portals (high anterolateral and intermediate anterolateral portals) were used instead of the anteromedial portals. RESULTS: Elbow flexion increased from 113° preoperatively to 129° at the final follow-up (P=0.009). Extension increased from -33° to -10° (P<0.0001). The preoperative and final postoperative "MEPS" scores were 56.3 and 94 respectively (P<0.0001). Two patients (13.3%) had radial nerve palsy with complete recovery 6 and 9 months after surgery. DISCUSSION: The rate of nerve complications following elbow arthroscopy varies from 0 to 14%. The rate in our series (13.3%) is comparable to the results of the literature. This rate should be placed in perspective (since one patient had multiple open surgery elbow operations before arthroscopy). All complications were transient. Improved elbow range of motion in our study is consistent with the results in literature.

Waiting time and explant pathology in transplant recipients with hepatocellular carcinoma: a novel study using national data.

Risk factors for hepatocellular carcinoma (HCC) recurrence after liver transplantation have been well described. It has been surmised that longer time on the waitlist may select for tumors with a lower-risk of recurrence posttransplant, as patients with unfavorable tumor characteristics would be delisted due to tumor progression. Utilizing national explant pathology records from transplant recipients waitlisted with T2 HCC exception points, this study explored the correlation between waiting time and the development of pathologic HCC features associated with increased risk of tumor recurrence. Of 1976 explant pathology reports submitted nationally between April 8, 2012 and June 30, 2013, 1453 (73.5%) were from recipients with automatic T2 HCC exception points. There was no association between pretransplant waiting time and the proportion of HCC explants with either: (i) a poorly differentiated tumor; (ii) macrovascular invasion; (iii) HCC beyond Milan or University of California San Francisco criteria; (iv) HCC beyond the "up-to-seven" criteria; or (v) extra-hepatic or lymph node involvement. Though there was a statistically significant increase in microvascular invasion in recipients with pretransplant waiting 6-12 months, this association was not seen when adjusted for United Network for Organ Sharing region. These findings suggest that waiting time alone may not select for tumors with more favorable characteristics.

Waitlist priority for hepatocellular carcinoma beyond milan criteria: a potentially appropriate decision without a structured approach.

Due to the risk of waitlist dropout from tumor progression, liver transplant candidates with hepatocellular carcinoma (HCC) within Milan criteria (MC) receive standardized exception points. An expansion of this process to candidates with HCC beyond MC has been proposed, though it remains controversial. This study sought to better define the utilization of exception points in candidates with HCC beyond MC and the associated outcomes. We reviewed all nonstandardized HCC applications that underwent formal regional review board evaluation between January 1, 2005 and March 2, 2011; 2184 initial HCC exception point applications were submitted. Of these, 41.9% fulfilled MC, 26.6% fulfilled University of California-San Francisco (UCSF) criteria and 17.6% exceeded UCSF criteria. The majority of applications were accepted: 89.8% within UCSF and 71.2% beyond UCSF. There was a significantly (p < 0.001) higher risk of death on the waitlist or within 90 days of waitlist removal for candidates within UCSF (12.4%) or beyond UCSF (13.0%) criteria, compared to candidates with HCC within MC (6.0%). However, posttransplant outcomes were similar. While these results suggest increasing access to candidates with HCC beyond MC, comprehensive documentation of tumor characteristics and of successful downstaging is needed to ensure priority is restricted to those with the highest likelihood of favorable posttransplant outcome.

Osteoporotic fractures, DXA, and fracture risk assessment: meeting future challenges in the Eastern Mediterranean Region.

The purpose was to report on the burden of osteoporotic fractures in the Eastern Mediterranean Region (EMR) and the use of bone mineral density (BMD) dual-energy X-ray absorptiometry (DXA) databases for osteoporosis diagnosis. PubMed electronic database was reviewed using the following MeSH terms: "Hip fractures," "Fractures, Compression," "Radius Fractures," "Osteoporosis," "Bone density," and "Middle East" up to July 2009. Incidence of hip fractures varied across the EMR between 100 and 295 per 100,000 person-years in women and 71 and 200 per 100,000 person-years in men. No data were found on other nonvertebral osteoporotic fractures. Prevalence of radiographic vertebral fractures older than 65 yr ranged between 15% and 25% in women and 7.3% and 18% in men. By 2020, the number of hip fractures older than 50 yr would increase by 20%. DXA manufacturer's reference curves for the spine were higher than population-specific ones. At the hip, National Health and Nutrition Examination Survey (NHANES) and population-based curves were comparable. Estimates of the relative risk of vertebral fracture per SD decrease in BMD using NHANES and local data set were similar, that is, 1.61 (1.17-2.23) and 1.49 (1.14-1.95), respectively. The EMR is similar to southern Europe regarding incidence rates of hip fracture, suggesting the health burden to be significant. Using DXA at the hip, population-specific reference databases did not perform better than NHANES on which the FRAX model has been developed highlighting the need for reviewing fracture risk assessment strategies in the EMR.