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     

NRAMP1 and hGPX1 gene polymorphism and response to bacillus Calmette-Guérin therapy for bladder cancer

Background

The natural resistance-associated macrophage protein 1 (NRAMP1) gene is associated with susceptibility to Mycobacterium tuberculosis in humans and to bacillus Calmette-Guérin (BCG) in mice. The detoxification enzyme, human glutathione peroxidase 1 (hGPX1), is associated with recurrence of bladder cancer (BCa).

Objective

To determine whether NRAMP1 and hGPX1 gene polymorphisms correlate with response to BCG immunotherapy for non–muscle-invasive BCa (NMIBC).

Design, setting, and participants

DNA was obtained from the peripheral blood of 99 NMIBC patients who were prospectively randomized to receive postresection intravesical BCG (81 mg [n = 50] or 27 mg [n = 19]) or BCG (27 mg) with interferon alpha (IFN-α; n = 30). The median follow-up time was 60 mo.

Intervention

Intravesical BCG or BCG–IFN-α.

Measurements

Restriction fragment length polymorphism (RFLP) analysis was performed to identify polymorphisms in the NRAMP1 promoter region (GT repeat number) and at position 543 (aspartate [D] and/or asparagine [N] expression) within the NRAMP1 protein (D543N) and position 198 (proline and/or leucine expression) within the hGPX1 protein (Pro198Leu). Data were analyzed using χ² analysis, multivariate analysis, and Kaplan-Meier curves.

Results and limitations

On univariate analysis, the NRAMP1 D543N G:G genotype had decreased cancer-specific survival (CSS; p = 0.036). The hGPX1 CT genotype (Pro-Leu) had decreased recurrence time (p = 0.03) after BCG therapy. On multivariate analysis, patients with the NRAMP1 D543N G:G genotype and allele 3 (GT)n polymorphism had decreased recurrence time (p = 0.014 and p = 0.03) after BCG therapy. The limitation of this study was its small sample size.

Conclusions

Polymorphisms of the NRAMP1 and hGPX1 genes may be associated with recurrence of BCa after BCG immunotherapy.     

High-volume FES-cycling partially reverses bone loss in people with chronic spinal cord injury

Spinal cord injury (SCI) leads to severe bone loss in the paralysed limbs and to a resulting increased fracture risk thereof. Since long bone fractures can lead to comorbidities and a reduction in quality of life, it is important to improve bone strength in people with chronic SCI. In this prospective longitudinal cohort study, we investigated whether functional electrical stimulation (FES) induced high-volume cycle training can partially reverse the loss of bone substance in the legs after chronic complete SCI. Eleven participants with motor-sensory complete SCI (mean age 41.9+/-7.5 years; 11.0+/-7.1 years post injury) were recruited. After an initial phase of 14+/-7 weeks of FES muscle conditioning, participants performed on average 3.7+/-0.6 FES-cycling sessions per week, of 58+/-5 min each, over 12 months at each individual's highest power output. Bone and muscle parameters were investigated in the legs by means of peripheral quantitative computed tomography before the muscle conditioning (t1), and after six (t2) and 12 months (t3) of high-volume FES-cycle training. After 12 months of FES-cycling, trabecular and total bone mineral density (BMD) as well as total cross-sectional area in the distal femoral epiphysis increased significantly by 14.4+/-21.1%, 7.0+/-10.8% and 1.2+/-1.5%, respectively. Bone parameters in the femoral shaft showed small but significant decreases, with a reduction of 0.4+/-0.4% in cortical BMD, 1.8+/-3.0% in bone mineral content, and 1.5+/-2.1% in cortical thickness. These decreases mainly occurred between t1 and t2. No significant changes were found in any of the measured bone parameters in the tibia. Muscle CSA at the thigh increased significantly by 35.5+/-18.3%, while fat CSA at the shank decreased by 16.7+/-12.3%. Our results indicate that high-volume FES-cycle training leads to site-specific skeletal changes in the paralysed limbs, with an increase in bone parameters at the actively loaded distal femur but not the passively loaded tibia. Thus, we conclude that high-volume FES-induced cycle training has clinical relevance as it can partially reverse bone loss and thus may reduce fracture risk at this fracture prone site.     

Pharmacodynamic and efficacy profile of TGN 255, a novel direct thrombin inhibitor, in canine cardiopulmonary bypass and simulated mitral valve repair

Heparin-induced thrombocytopenia can be a life-threatening sequel to conventional use of unfractionated heparin in cardiopulmonary bypass (CPB). This study evaluated the pharmacokinetic/pharmacodynamic (PK/PD) and efficacy profile of a novel direct thrombin inhibitor, TGN 255, during cardiac surgery in dogs. Point-of-care coagulation monitoring was also compared against the plasma concentrations of TRI 50c, the active metabolite of TGN 255. The study was conducted in three phases using 10 animals: phase 1 was a dose-ranging study in conscious animals (n = 6), phase 2 was a similar but terminal dose-ranging study in dogs undergoing CPB (n = 6), and phase 3 was with animals undergoing simulated mitral valve repair (terminal) using optimal TGN 255 dose regimens derived from phases I and II (n = 4). During the study, PD markers and drug plasma levels were determined. In addition, determinations of hematologic markers and blood loss were undertaken. Phase 1 studies showed that a high-dose regimen of a 5-mg/kg bolus and infusion of 20 mg/kg/h elevated PD markers in conscious animals, at which time there were no measured effects on platelet or red blood cell counts, and the mean plasma concentration of TRI 50C was 20.6 microg/mL. In the phase 2 CPB dose-ranging study, this dosing regimen significantly elevated all the PD markers and produced hemorrhagic and paradoxical thrombogenic effects. In the phase 3 surgical study, a lower TGN 255 dose regimen of a 2.5-mg/kg bolus plus 10 mg/kg/h produced anticoagulation, elevated PD markers, and produced minimal post-operative blood loss in the animals. Plasma levels of TRI 50C trended well with the conventional point-of-care coagulation monitoring. TGN 255 provided effective anticoagulation in a canine CPB procedure, enabling successful completion with minimal blood loss. These findings support further evaluation of TGN 255 as an anticoagulant for CPB.     

The effect of thoracoscopic sympathectomy on quality of life and symptom management of hyperhidrosis

BACKGROUND: Success with thoracoscopic sympathectomy (TS) for hyperhidrosis is 93% to 100%. We wished to determine if hyperhidrosis patients who do not undergo TS have decreased quality of life (QOL). STUDY DESIGN: Data collection was retrospective, with telephone calls to hyperhidrosis patients who qualified for sympathectomy. Data collection included assessing sweating severity; overall QOL; social, professional, and cosmetic satisfaction; and comfort with daily activities. RESULTS: Between 1998 and 2005, 60 patients met the criteria for sympathectomy. Twenty-two patients who qualified but did not undergo operations (no TS) and 26 TS patients were contacted. Change in symptoms on a 10-point scale for hands was: no TS, -0.30 and TS, -6.25, p < 0.0001, and QOL, on a 1-to-5 scale, increased (no TS, 0.27 and TS, 1.65, p=0.0003). Satisfaction was very good/excellent socially for 9 of 22 no TS patients and 23 of 26 TS patients (p=0.002); professionally for 12 of 22 no TS patients and 23 of 26 TS patients (p=0.021); and cosmetically for 10 of 22 no TS patients and 23 of 26 TS patients (p=0.004). Patients were very satisfied with shaking hands (9 of 22 no TS patients and 24 of 26 TS patients, p=0.0003); writing (9 of 11 no TS patients and 25 of 26 TS patients, p=0.0001); eating (11 of 22 no TS patients and 25 of 25 TS patients, p=0.0008). TS patients had more sweating on the abdomen (no TS patients, 0.0 and TS patients, 1.75, p=0.0001), on the groin (no TS patients, 0.00 and TS patients, 2.9, p=0.0009), and on the back (no TS patients, 0.48 and TS patients, 4.96, p=0.0001). QOL was very good/excellent at followup for 13 of 22 no TS patients and 23 of 26 TS patients (p=0.04). CONCLUSIONS: TS controls palmar hyperhidrosis, and, despite compensatory sweating, patients having the procedure are very satisfied. Patients who did not have surgery have decreased satisfaction, comfort, and QOL, and increased symptoms.     

Bilateral cavernous nerve interposition grafting during radical retropubic prostatectomy: Memorial Sloan-Kettering Cancer Center experience

PURPOSE: Cavernous nerve graft is an option for men requiring bilateral cavernous nerve resection for cancer control during radical prostatectomy. We determined the success rate and identified determinants of success of bilateral cavernous nerve grafting following resection of the 2 nerves during radical prostatectomy in patients who were potent preoperatively. MATERIALS AND METHODS: We retrospectively reviewed the records of 44 consecutive patients who underwent bilateral nerve grafting from 1999 to 2004. Postoperative erectile function was defined as the achievement of erections satisfactory for intercourse with or without oral medication. We calculated cumulative erectile function recovery rates using Kaplan-Meier curves. The log rank test was used to compare variables affecting erectile function recovery with p <0.0083 considered significant after adjusting for the number of variables evaluated using the Bonferroni correction. RESULTS: The overall 5-year cumulative recovery of erectile function permitting penetration was 34% and the rate of consistent penetration was 11%. None of the analyzed variables were significantly associated with recovery of postoperative erectile function, including patient age (p = 0.3), incomplete bilateral cavernous nerve resection (p = 0.045), sural nerve grafts compared to genitofemoral or ilioinguinal nerves as donor sites (p = 0.067), post-radiation salvage radical prostatectomy (p = 0.15), neoadjuvant hormone therapy (p = 0.7) and comorbidities (p = 0.15) or medications (p = 0.4) affecting EF. CONCLUSIONS: Bilateral cavernous nerve grafts might be beneficial in select patients. A definitive answer awaits the performance of a multi-institutional, randomized, controlled trial.     

Burkholderia gladioli: five year experience in a cystic fibrosis and lung transplantation center.

BACKGROUND: The impact of infection with Burkholderia gladioli in cystic fibrosis, other chronic airway diseases and immunosuppressed patients is unknown. METHODS: A six-year retrospective review of all patients with B. gladioli infection was performed in a tertiary referral center with cystic fibrosis and lung transplantation programs. In addition, a targeted survey of all 251 lung transplant recipients was performed. Available B. gladioli isolates were analyzed via pulsed field gel electrophoresis. RESULTS: Thirty-five patients were culture positive for B. gladioli, including 33 CF patients. No bacteremia was identified. Isolates were available in 18 patients and all were genetically distinct. Two-thirds of these isolates were susceptible to usual anti-pseudomonal antibiotics. After acquisition, only 40% of CF patients were chronically infected (> or =2 positive cultures separated by at least 6 months). Chronic infection was associated with resistance to > or =2 antibiotic groups on initial culture and failure of eradication after antibiotic therapy. The impact of acquisition of B. gladioli infection in chronic infection was variable. Three CF patients with chronic infection underwent lung transplantation. One post-transplant patient developed a B. gladioli mediastinal abscess, which was treated successfully. CONCLUSIONS: The majority of patients' culture positive for B. gladioli at our center have CF. B. gladioli infection is often transient and is compatible with satisfactory post-lung transplantation outcomes.     

Intraoperative somatosensory evoked potential monitoring during anterior cervical discectomy and fusion in nonmyelopathic patients--a review of 1,039 cases.

BACKGROUND CONTEXT: Intraoperative somatosensory evoked potential (SSEP) monitoring has been shown to reduce the incidence of new postoperative neurological deficits in scoliosis surgery. However, its usefulness during cervical spine surgery remains a subject of debate. PURPOSE: To determine the utility of intraoperative SSEP monitoring in a specific patient population (those with cervical radiculopathy in the absence of myelopathy) who underwent anterior cervical discectomy and fusion (ACDF) surgery. STUDY DESIGN: Retrospective review. PATIENT SAMPLE: A total of 1,039 nonmyelopathic patients who underwent single or multilevel ACDF surgery. The control group (462 patients) did not have intraoperative SSEP monitoring, whereas the monitored group (577 patients) had continuous intraoperative SSEP monitoring performed. OUTCOME MEASURE: A new postoperative neurological deficit. METHODS: SSEP tracings were reviewed for all 577 patients in the monitored group and all significant signal changes were noted. Medical records were reviewed for all 1,039 patients to determine if any new neurological deficits developed in the immediate postoperative period. RESULTS: None of the patients in the control group had any new postoperative neurological deficits. In the monitored group there were six instances of transient SSEP changes (1 due to suspected carotid artery compression; 5 thought to be due to transient hypotension) which resolved with the appropriate intraoperative intervention (repositioning of retractors; raising the arterial blood pressure). Upon waking up from anesthesia, one patient in the monitored group had a new neurological deficit (partial central cord syndrome) despite normal intraoperative SSEP signals. CONCLUSIONS: ACDF appears to be a safe surgical procedure with a low incidence of iatrogenic neurological injury. Transient SSEP signal changes, which improved with intraoperative interventions, were not associated with new postoperative neurological deficits. An intraoperative neurological deficit is possible despite normal SSEP signals.     

Use of small suture anchors in cervical laminoplasty to maintain canal expansion: a technical note

OBJECTIVE: Open door laminoplasty is a commonly performed procedure for the treatment of cervical spine pathology. One complication of this procedure is closure of the hinge and subsequent restenosis. A simple and effective method of using suture anchors to stabilize posterior elements has been previously described. The aim of this paper is to describe our experience using 2.0-mm suture anchors to maintain canal expansion. METHODS: Results of 42-consecutive patients who were treated with a modified cervical open-door laminoplasty were reviewed. The modification involves the use of original Hirabayashi technique, but augmenting the canal expansion with 2.0-mm suture anchors at C3, C5, and C7 levels. Additionally, nonabsorbable sutures are placed at C4 and C6 levels as described by Hirabayashi. The technical issues and short-term radiographic outcomes were evaluated. RESULTS: None of the 42 patients who had the door secured with 2.0-mm suture anchors had closure of the hinge. Additionally, the suture anchors maintained their position without loosening or "pull-outs" on postoperative follow-up radiographs. There were 3 short-term complications: 1 was a small dural-tear which was repaired intraoperatively without further sequelae, and the other 2 were both epidural hematomas that required emergent return to the operating room for evacuation. All 3 patients had an uneventful recovery without a new neurologic deficit. CONCLUSIONS: This paper reviews a simple and effective method for maintaining canal expansion in open-door laminoplasty. Because of its technical simplicity, 2.0-mm suture anchors may be a safer alternative than other devices currently popular for this purpose.     

Randomized trial of laparoscopic v open nephrectomy

BACKGROUND AND PURPOSE: Clayman and associates first described laparoscopic nephrectomy in 1990. This paper describes the first randomized controlled trial to compare laparoscopic with open surgery for simple and radical nephrectomy. PATIENTS AND METHODS: Between 2001 and 2004, 45 patients requiring simple or radical nephrectomy (tumors as large as 8 cm) were randomized to either open surgery through a loin incision or laparoscopic nephrectomy (transperitoneal). Outcome measures included operative time, complications, hospital stay, pain scores, time to return to normal activities, and quality of life scores (EuroQol). RESULTS: The mean operative time was 105 minutes in the laparoscopic group and 93 minutes in the open-surgery group (P = 0.4). Blood loss, complications, and the mortality rate were similar in the two groups, as was the hospital stay at a median of 4 days in the laparoscopic group and 5 days in the open group (P = 0.9). Postoperative visual analog pain scores averaged 3.6 in the laparoscopic group compared with 5.4 in the open group (P = 0.02). There was no difference in pain scores at 3 months. Return to normal activities was faster in the laparoscopic group at 42 days v 62 days in the open group (P = 0.04). CONCLUSIONS: Laparoscopic nephrectomy is associated with less postoperative pain and a faster return to normal activities than open nephrectomy.