Correlation between cervical spine sagittal alignment and clinical outcome after anterior cervical discectomy and fusion

Studies have shown that maintenance of lordosis improves outcomes after anterior cervical discectomy and fusion (ACDF). The relationship between maintenance or restoration of lordosis after ACDF and health-related quality of life (HRQOL) measures has not been evaluated. Preoperative and 2-year postoperative cervical lordosis (C2-C7) and segmental lordosis were measured from upright lateral cervical spine radiographs in patients who had ACDF. Data on the Neck Disability Index (NDI), Short- Form-36 Physical Composite Summary Score, arm, and neck pain scores were also collected. Paired t-tests were used to compare preoperative and 2-year postoperative radiographic measures and HRQOL measures. Receiver operating characteristic curves were constructed to identify sagittal parameters that predict achievement of a Minimum Clinically Important Difference (MCID) in outcome measures. One hundred one patients (75 female; mean age, 52 years) were included. There was improvement in all HRQOL measures from preoperative to 2 years postoperative. There was no significant difference in preoperative and 2-year postoperative sagittal alignment. Receiver operating characteristic curve analysis showed that a postoperative cervical lordosis of at least 6° predicted achievement of MCID for NDI (8 point change in NDI). This suggests that maintenance or restoration of overall cervical lordosis is important in achieving a successful result after ACDF.     

Multiple quantitative trait loci for cortical and trabecular bone regulation map to mid‐distal mouse chromosome 4 that shares linkage homology to human chromosome 1p36

The mid‐distal region of mouse chromosome 4 (Chr 4) is homologous with human Chr 1p36. Previously, we reported that mouse Chr 4 carries a quantitative trait locus (QTL) with strong regulatory effect on volumetric bone mineral density (vBMD). The intent of this study is to utilize nested congenic strains to decompose the genetic complexity of this gene‐rich region. Adult females and males from 18 nested congenic strains carrying discrete C3H sequences were phenotyped for femoral mineral and volume by pQCT and for trabecular bone volume (BV), tissue volume (TV), trabecular number (Trab.no), and trabecular thickness (Trab.thk) by MicroCT 40. Our data show that the mouse Chr 4 region consists of at least 10 regulatory QTL regions that affected either or both pQCT and MicroCT 40 phenotypes. The pQCT phenotypes were typically similar between sexes, whereas the MicroCT 40 phenotypes were divergent. Individual congenic strains contained one to seven QTL regions. These regions conferred large positive or negative effects in some congenic strains, depending on the particular bone phenotype. The QTL regions II to X are syntenic with human 1p36, containing from 1 to 102 known genes. We identified 13 candidate genes that can be linked to bone within these regions. Six of these genes were linked to osteoblasts, three linked to osteoclasts, and two linked to skeletal development. Three of these genes have been identified in Genome Wide Association Studies (GWAS) linked to 1p36. In region III, there is only one gene, Lck, which conferred negative pQCT and MicroCT 40 phenotypes in both sexes. This gene is important to development and functioning of T cells, has been associated with osteoclast activity, and represents a novel bone regulatory gene that merits further experimental evaluation. In summary, congenic strains are powerful tools for identifying regulatory regions that influence bone biology and offer models for testing hypotheses about gene‐gene and gene‐environment interactions that are not available to experimental work in humans. © 2012 American Society for Bone and Mineral Research     

Serum Testosterone and Dihydrotestosterone and Prostate Cancer Risk in the Placebo Arm of the Reduction by Dutasteride of Prostate Cancer Events Trial

Background

Findings of studies on the association between androgens and prostate cancer (PCa) are mixed. Androgens may affect prostate-specific antigen (PSA) levels, thereby influencing biopsy recommendations. Also, androgens may stimulate prostate growth at very low levels with no additional effects at higher levels (saturation model).

Objective

To test whether androgens were associated with PCa risk in the placebo arm of a prospective study in which biopsies were performed regardless of PSA level.

Design, setting, and participants

Of 8122 men in the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial, 4073 men (50.1%) received placebo. Key entry criteria were PSA 2.5–10 ng/ml and one prior negative biopsy.

Intervention

Per-protocol biopsies at 2 and 4 yr; for-cause biopsies at physician discretion.

Outcome measurements and statistical analysis

Multivariable logistic regression was used to test the association between baseline log-transformed testosterone and dihydrotestosterone (DHT) levels and the risk of detecting either PCa or low-grade PCa (Gleason score <6) compared with high-grade PCa (Gleason score >7). In secondary analysis, we stratified the analysis by low baseline androgen levels (testosterone <10 nmol/l; DHT <0.76 nmol/l) compared with normal baseline androgen levels.

Results and limitations

Of 4073 men, 3255 (79.9%) had at least one biopsy after randomization and were analyzed. Androgen levels tested continuously or by quintiles were generally unrelated to PCa detection or grade. PCa detection was similar among men with low compared with normal baseline testosterone levels (25.5% and 25.1%; p = 0.831). In secondary analysis, higher testosterone levels at baseline were associated with higher PCa detection (odds ratio: 1.23; 95% confidence interval, 1.06–1.43; p = 0.006) only if men had low baseline testosterone (<10 nmol/l). For men with normal baseline testosterone (≥10 nmol/l), higher testosterone levels at baseline were unrelated to PCa risk (p = 0.33). No association was found for DHT and PCa (all p > 0.85).

Conclusions

Baseline serum testosterone and DHT levels were unrelated to PCa detection or grade. Our findings of the lowest testosterone levels being associated with the lowest PCa risk with no further changes with higher testosterone support a saturation model but must be confirmed in future studies using an a priori defined hypothesis.

ClinicalTrials.gov identifier

NCT00056407.     

Enhanced recombinant adeno-associated virus-mediated vascular endothelial growth factor expression in the adult mouse retina: a potential model for diabetic retinopathy

Diabetic retinopathy, one of the most serious complications of long-term diabetes, could clinically be divided into two stages: 1) background retinopathy that does not cause visual impairment and 2) proliferative retinopathy, which is a potentially blinding condition. This study aims to investigate the correlation between enhancement of vascular endothelial growth factor (VEGF) expression and neovascular changes. A binary recombinant adeno-associated virus construct producing green fluorescent protein (GFP) and VEGF under the control of the human cytomegalovirus promoter, recombinant adeno-associated virus (rAAV).VEGF.GFP, was produced and injected into the subretinal space of C57BL mice. GFP expression was tracked by fluorescence fundus photography, and VEGF expression was confirmed by immunohistochemistry and enzyme-linked immunoassay. Neovascular changes were monitored by fluorescein angiography and histology and by quantifying the number of inner retinal vessels. GFP expression was found in 100% of injected eyes, and vascular changes were detected in 9 of 10 rAAV.VEGF.GFP-injected eyes. Of these, four demonstrated microaneurysms and five showed moderate to severe leakage. There was a statistically significant increase in blood vessel number in the inner nuclear layer (P < 0.03) and dilatation of retinal veins (P < or = 0.05). This work has demonstrated that the development of different stages of diabetic retinopathy is closely correlated with an increased VEGF level in the retina.     

Improvement in perioperative outcome after hepatic resection: analysis of 1,803 consecutive cases over the past decade

OBJECTIVE: To assess the nature of changes in the field of hepatic resectional surgery and their impact on perioperative outcome. METHODS: Demographics, extent of resection, concomitant major procedures, operative and transfusion data, complications, and hospital stay were analyzed for 1,803 consecutive patients undergoing hepatic resection from December 1991 to September 2001 at Memorial Sloan-Kettering Cancer Center. Factors associated with morbidity and mortality and trends in operative and perioperative variables over the period of study were analyzed. RESULTS: Malignant disease was the most common diagnosis (1,642 patients, 91%); of these cases, metastatic colorectal cancer accounted for 62% (n = 1,021). Three hundred seventy-five resections (21%) were performed for primary hepatic or biliary cancers and 161 (9%) for benign disease. Anatomical resections were performed in 1,568 patients (87%) and included 544 extended hepatectomies, 483 hepatectomies, and 526 segmental resections. Sixty-two percent of patients had three or more segments resected, 42% had bilobar resections, and 37% had concomitant additional major procedures. The median blood loss was 600 mL and 49% of patients were transfused at any time during the index admission. Median hospital stay was 8 days, morbidity was 45%, and operative mortality was 3.1%. Over the study period, there was a significant increase in the use of parenchymal-sparing segmental resections and a decrease in the number of hepatic segments resected. In parallel with this, there was a significant decline in blood loss, the use of blood products, and hospital stay. Despite an increase in concomitant major procedures, operative mortality decreased from approximately 4% in the first 5 years of the study to 1.3% in the last 2 years, with 0 operative deaths in the last 184 consecutive cases. On multivariate analysis, the number of hepatic segments resected and operative blood loss were the only independent predictors of both perioperative morbidity and mortality. CONCLUSIONS: Over the past decade, the use of parenchymal-sparing segmental resections has increased significantly. The number of hepatic segments resected and operative blood loss were the only predictors of both perioperative morbidity and mortality, and reductions in both are largely responsible for the decrease in perioperative mortality, which has occurred despite an increase in concomitant major procedures.     

Increased risk of PTLD in lung transplant recipients with cystic fibrosis

Background

Post-transplant lymphoproliferative disease (PTLD) is an important cause of morbidity and mortality following lung transplantation. Recipients with cystic fibrosis (CF) may have an increased risk of PTLD although the literature is limited to single center cohorts. Our primary aim is to examine PTLD in an adult lung transplant population by utilizing the International Society for Heart and Lung Transplantation Registry.

A survey of the use of propranolol in burn centers: Who,what, when,why

Introduction

Many burn centers utilize propranolol in both adult and pediatric burn patients to attenuate the hypermetabolic response related to thermal injury despite the relative paucity of data in adults compared to children. The purpose of this study was to identify practice patterns related to propranolol, for which groups it is being used, length of use, and the intended benefit.

Video-assisted thoracoscopic diaphragm plication using a running suture technique is durable and effective

Objective

Surgeons have hesitated to adopt minimally invasive diaphragm plication techniques because of technical limitations rendering the procedure cumbersome or leading to early failure or reduced efficacy. We sought to demonstrate efficacy and durability of our thoracoscopic plication technique using a single running suture.