WHO absolute fracture risk models (FRAX): Do clinical risk factors improve fracture prediction in older women without osteoporosis?

Bone mineral density (BMD) is a strong predictor of fracture, yet most fractures occur in women without osteoporosis by BMD criteria. To improve fracture risk prediction, the World Health Organization recently developed a country‐specific fracture risk index of clinical risk factors (FRAX) that estimates 10‐year probabilities of hip and major osteoporotic fracture. Within differing baseline BMD categories, we evaluated 6252 women aged 65 or older in the Study of Osteoporotic Fractures using FRAX 10‐year probabilities of hip and major osteoporotic fracture (ie, hip, clinical spine, wrist, and humerus) compared with incidence of fractures over 10 years of follow‐up. Overall ability of FRAX to predict fracture risk based on initial BMD T‐score categories (normal, low bone mass, and osteoporosis) was evaluated with receiver‐operating‐characteristic (ROC) analyses using area under the curve (AUC). Over 10 years of follow‐up, 368 women incurred a hip fracture, and 1011 a major osteoporotic fracture. Women with low bone mass represented the majority (n = 3791, 61%); they developed many hip (n = 176, 48%) and major osteoporotic fractures (n = 569, 56%). Among women with normal and low bone mass, FRAX (including BMD) was an overall better predictor of hip fracture risk (AUC = 0.78 and 0.70, respectively) than major osteoporotic fractures (AUC = 0.64 and 0.62). Simpler models (eg, age + prior fracture) had similar AUCs to FRAX, including among women for whom primary prevention is sought (no prior fracture or osteoporosis by BMD). The FRAX and simpler models predict 10‐year risk of incident hip and major osteoporotic fractures in older US women with normal or low bone mass. © 2011 American Society for Bone and Mineral Research     

Medical epidemiology of patients surviving ten years after liver transplantation

Simo KA, Sereika S, Bitner N, Newton KN, Gerber DA. Medical epidemiology of patients surviving ten years after liver transplantation.
Clin Transplant 2011: 25: 360–367. © 2010 John Wiley & Sons A/S. Abstract: The transition into extended long‐term follow‐up after liver transplantation raises a new series of issues with respect to continuing care of this population. A retrospective study was performed, analyzing patients who underwent orthotopic liver transplant (OLT) and survived ≥10 yr at a single institution. Long‐term comorbidities such as diabetes mellitus (DM), hypertension (HTN), chronic kidney disease (CKD), coronary artery disease (CAD), and obesity were identified and standardized prevalence ratios ([SPR]) utilized to compare with the general US population. There was an increased prevalence of HTN ([SPR] = 2.25 ± 0.61), DM ([SPR] = 2.67 ± 0.72), and CKD ([SPR] = 15.3 ± 4.04) but not CAD or obesity. In multivariate analysis, non‐viral etiology of end‐stage liver disease was associated with CKD (OR 3.42 CI 1.11–10.53), and an initial glomerular filtration rate (GFR) <60 mL/min per 1.73 m² (CKD stages III–V) was associated with HTN (OR 4.62 CI 1.14–18.73) after OLT. Creatinine ≥1.5 mg/dL at 10 yr was associated with an initial GFR <60 mL/min per 1.73 m² (p = 0.000) and CAD after OLT (p = 0.012). Patients, 10 yr after OLT, have a significantly higher prevalence of HTN, DM, and CKD than the general population, which is not confounded by obesity. Increased vigilance and proactive management are required to further improve long‐term outcomes.     

Chemoradiation followed by chemotherapy before resection for borderline pancreatic adenocarcinoma

BACKGROUND: For patients with borderline resectable pancreatic cancer, preoperative chemoradiation and standalone chemotherapy may allow for R0 resection and improved survival. METHODS: A retrospective review of patients with borderline resectable pancreatic cancer treated with preoperative chemoradiation and standalone chemotherapy was undertaken. Clinical variables, including disease-free and overall survival, were collected. Univariate analysis was used to identify factors impacting survival. RESULTS: Thirteen patients with borderline resectable pancreatic cancer were treated with preoperative chemoradiation and chemotherapy. Morbidity and mortality were 38% and 0. There were 2 R1 and 11 R0 resections. Nine patients are alive with a median follow-up of 20 months. Five patients recurred at a median of 4 months. Tumor fibrosis < or = 60% was associated with recurrence and poor survival. CONCLUSIONS: Preoperative chemoradiation and chemotherapy allow a select group of patients with borderline resectable pancreatic cancer to undergo an R0 or R1 resection with acceptable morbidity and mortality. Tumor response may be associated with survival.     

Hypermethylation of MCAM gene is associated with advanced tumor stage in prostate cancer

BACKGROUND: DNA methylation has emerged as a promising biomarker for prostate cancer detection. In this report, we screened 36 candidate genes generated by a bioinformatic analysis of the human genome, and found that the melanoma cell adhesion molecule (MCAM) was an excellent candidate for cancer-specific methylation in prostate cancer. METHODS: Direct sequencing of bisulfite-treated genomic DNA, conventional methylation-specific PCR (MSP), real-time quantitative methylation-specific PCR, immunohistochemistry, colony formation assay, and statistical analysis. RESULTS: We found that the melanoma cell adhesion molecule (MCAM) gene promoter was specifically methylated in prostate cancer cell lines and primary prostate cancer (PCa) but not in non-neoplastic prostate (BPH) tissues by direct sequencing of bisulfite-treated genomic DNA and conventional methylation-specific PCR (MSP). Further analysis with quantitative MSP showed greater hypermethylation of the MCAM promoter (80%, 70/88) in primary prostate cancer compared to 12.5% (3/24) in BPH. Prostatic intraepithelial neoplasias (PIN), potential precursors of prostate carcinoma, showed an intermediate methylation rate of 23% (7/30). We further observed that MCAM promoter methylation was directly correlated with tumor stage (pT3+pT4) (P = 0.001) and Gleason score (P = 0.018) in primary prostate carcinoma. CONCLUSIONS: Our results suggest that MCAM promoter hypermethylation deserves further attention as a potential diagnostic prostatic DNA marker in human prostate cancer.     

Critical roles for JNK, c-Jun, and Fas/FasL-Signaling in vitamin E analog-induced apoptosis in human prostate cancer cells

BACKGROUND: Alpha-tocopherol ether-linked acetic acid (alpha-TEA), an analog of vitamin E (RRR-alpha-tocopherol), is a potent pro-apoptotic agent for human cancer cells in vivo and in vitro. METHODS: alpha-TEA-induced apoptosis was investigated in LNCaP and PC-3 human prostate cancer cells. Apoptosis was measured by DAPI-staining and FACS analyses of the sub-G1 fraction. Signaling molecules involved in apoptosis were measured by Western immunoblot analyses with or without prior immunoprecipitation, FACS analyses of cell surface membrane expression, RT-PCR analyses of mRNA levels, and chromatin immunoprecipitation. Functional significance was determined using siRNAs, dominant negative mutant, chemical inhibitor, or neutralizing antibody. RESULTS: Alpha-TEA treatment increased Fas and Fas ligand mRNA and protein levels; as well as, levels of cell surface membrane Fas in both cell lines. Blockage of Fas signaling attenuated alpha-TEA-induced apoptosis. alpha-TEA treatment also produced prolonged, elevated levels of activated (phosphorylated) c-Jun N-terminal kinase (JNK) and its substrate c-Jun, both of which were demonstrated to be necessary for alpha-TEA-induced apoptosis. Chromatin immunoprecipitation results showed binding of c-Jun to the promoters of both Fas and FasL in alpha-TEA treated cells. Investigations of alpha-TEA-triggered apoptosis showed dual signaling from Fas with essential roles for both FADD and Daxx with FADD initiating the classical pathway mediated by caspase-8 activation and Daxx initiating an alternate pathway involving activation of JNK, c-Jun, and increased levels of Fas and FasL. CONCLUSIONS: Collectively, data support critical roles for JNK, c-Jun, and dual signaling from Fas/FasL via FADD and Daxx in alpha-TEA-induced apoptosis of human prostate cancer cells.     

Intraspinal meningioma in a 101-year old: should age determine the aggressiveness of intervention?

BACKGROUND: Intraspinal meningiomas are less frequent in occurrence as compared with their intracranial counterparts. Typical presentation is onset of new spinal pain followed by other deficits in the sixth decade of life. Although total surgical removal is the optimum treatment, various tumor- and patient-related factors can determine the aggressiveness of the surgical endeavor. We present our experience of diagnosis and management of cervical intraspinal meningioma in the oldest reported patient (101 years) with an atypical clinical presentation and remarkable dissociation between clinical and radiologic findings. METHOD: The patient, a 101-year-old woman, experienced progressive weakness in her legs. Motor examination revealed no definite weakness. There was stocking type sensory loss to just below the knees bilaterally. The MRI of the cervical spine showed an enhancing mass anterolateral to the cord at the region C7 through T1. It markedly compressed the cord. RESULT: The tumor was removed in total, and the dural attachment was thoroughly coagulated. CONCLUSION: The presented experience supports the belief that, in spinal meningiomas, a good clinical outcome can be expected even in patients who may be less than perfect candidates for an aggressive surgical approach.     

Avascular necrosis of the talus after McKay clubfoot release for idiopathic congenital clubfoot

Avascular necrosis of the talus is a serious potential complication of clubfoot surgery. In the few cases described in the literature, the necrosis has involved the entire talus and resulted in progressive fragmentation and collapse. Serial postoperative radiographs of 96 idiopathic clubfeet in 70 patients are reviewed here to determine the incidence of avascular necrosis after McKay soft tissue release. Based on criteria in the literature for making the diagnosis, no cases of avascular necrosis were seen. Growth lines were observed in the cuboids and calcanei of all the feet during the follow-up period. Eight feet failed to develop growth lines in the talus during follow-up. Five of these feet showed flattening of the dome of the talus and three hypoplasia of the talar head and neck at the most recent follow-up. Absence of normal growth lines in the talus after operation seems to predict talar abnormalities.     

Urethral and bladder current perception thresholds: normative data in women

PURPOSE: Given increased evidence of sensory dysfunction in lower urinary tract pathology, we determined normative current perception threshold values in the lower urinary tract of asymptomatic women. MATERIALS AND METHODS: After receiving institutional review board approval women without lower urinary tract symptoms underwent current perception threshold testing of the urethra and bladder using a Neurometer constant current stimulator. Current perception threshold values were determined at 3 frequencies, including 2,000 Hz (corresponding to A-beta fibers), 250 Hz (corresponding to A-delta fibers) and 5 Hz (corresponding to C fibers). RESULTS: A total of 48 women with a mean age of 38 years (range 23 to 67) underwent current perception threshold testing. Normative values were established for the urethra and bladder at 2,000, 250 and 5 Hz. Median urethral current perception thresholds at 2,000, 250 and 5 Hz were 1.2 (IQR 0.76-1.5), 0.45 (IQR 0.33-0.56) and 0.11 mA (IQR 0.07-0.24), respectively. Median bladder current perception thresholds at 2,000, 250 and 5 Hz were 4.1 (IQR 2.0-6.3), 2.3 (IQR 0.87-5.5) and 1.4 mA (IQR 0.22-2.9), respectively. Urethral and bladder current perception thresholds increased significantly with subject age at all 3 frequencies (p<0.0005). Prior pelvic surgery was associated with an increased bladder current perception threshold at all 3 frequencies (p<0.005) but not with the urethral current perception threshold. CONCLUSIONS: We report urethral and bladder current perception thresholds for a large sample of asymptomatic women. These reference values may help elucidate changes in afferent nerve function in women with lower urinary tract dysfunction.     

Low recurrence rate after Gore-Tex/Marlex composite patch repair for posterolateral congenital diaphragmatic hernia

Purpose

Many different prosthetic materials have been used for repair of large posterolateral congenital diaphragmatic hernias (CDH), with high recurrence rates for hernias that cannot be primarily repaired. Since 1993, we have used a composite patch of Gore-Tex/Marlex to repair large CDHs and hypothesized that this repair leads to fewer recurrences.

Methods

This is a retrospective review of 137 consecutive patients with CDH cared for at a single institution from 1993 to 2004. Data collected include timing and method of repair and use of extracorporeal membrane oxygenation. Outcomes include hernia recurrence, complications, and death.

Results

One hundred thirty-seven patients with CDH were analyzed. Repair was not attempted in 12 because of disease severity. Primary repair was accomplished in 79 and 46 required patch repair. Of the 46 patients with patch repairs, 32 required extracorporeal membrane oxygenation, and 18 died before discharge. Of the 28 patch repair survivors, 1 (3.57%) developed a recurrence over a median follow-up of 47 months (range, 2-115 months). Overall survival was 77%.

Conclusions

Gore-Tex/Marlex composite patch repair of large CDHs in this complex patient population results in a lower recurrence rate than has been reported for other types of prosthetic diaphragm repair.     

Women and minorities in orthopaedic residency programs

Women and underrepresented minorities make up smaller proportions of orthopaedic residency programs than their numbers in medical school would predict, according to our evaluation of self-reported orthopaedic residency data from 1998 and 2001, as well as information on medical students published in 2002. Based on race, ethnicity, and sex, comparisons were made between students entering and graduating from medical school and those in orthopaedic residency programs. With few exceptions, the percentages of women and underrepresented minorities were statistically significantly lower among those training in orthopaedic residency programs compared with those same groups entering and graduating from medical school. The percentage of women and minorities in orthopaedic residency programs remained constant between 1998 and 2001. Further study is necessary to determine whether fewer students of color and women apply to orthopaedic residency programs because of lack of interest, lack of appropriate mentoring and role models, or other factors.