Risk of prostate cancer-specific death in men with baseline metabolic aberrations treated with androgen deprivation therapy for biochemical recurrence.

OBJECTIVES: To investigate the associations of host metabolic factors and metabolic syndrome on prostate cancer-specific death (PCSD) and overall survival (OS) in patients treated with androgen deprivation therapy (ADT) for biochemically recurrent disease. PATIENTS AND METHODS: The analysis included 273 patients with prostate cancer treated with ADT for rising prostate-specific antigen level after surgery or radiotherapy. Patients were assessed for the presence of diabetes, hypertension, dyslipidaemia and obesity before commencing ADT, and Adult Treatment Panel III criteria were used to assess the presence of the composite diagnosis of metabolic syndrome. A competing risks regression model was used to assess associations of time to PCSD with the metabolic conditions, while a multivariable Cox regression model was used to assess associations of OS with metabolic syndrome and metabolic conditions. RESULTS: During a median follow-up of 11.6 years, 157 patients (58%) died, of whom 58 (21%) died from prostate cancer. At the start of ADT the median (range) patient age was 74 (46-92) years and the median PSA level was 3.0 ng/mL. Metabolic syndrome was observed in 31% of patients; hypertension (68%) and dyslipidaemia (47%) were the most common metabolic conditions. No association of PCSD and metabolic syndrome status was observed. Patients with hypertension tended to have a higher cumulative incidence of PCSD than those without hypertension (sub-distribution hazard ratio [HR] 1.59, 95% confidence interval [CI] 0.89, 2.84; P = 0.11) although the difference was not statistically significant. Patients with metabolic syndrome had an increased risk of death from all causes (HR 1.56, 95% CI 1.07, 2.29; P = 0.02) when compared with patients without metabolic syndrome, as did patients with hypertension (HR 1.72, 95% CI 1.18, 2.49; P = 0.004). CONCLUSIONS: No association of PCSD and metabolic syndrome was observed in this cohort of men receiving ADT for biochemically recurrent prostate cancer. Metabolic syndrome was associated with an increased risk of death from all causes and a similar effect was also observed for patients with prostate cancer with hypertension alone.

Parturition pit: the bony imprint of vaginal birth.

PURPOSE: To retrospectively evaluate for pits along the dorsum of the pubic body in females and compare the presence/absence of these pits to vaginal birth data. MATERIALS AND METHODS: We retrospectively reviewed females with vaginal birth data who underwent pelvic CT. The presence of pits along the dorsum of the pubic body, pit grade (0 = not present; 1 = faintly imperceptible; 2 = present; 3 = prominent), and the presence of osteitis condensans ilii, preauricular sulcus, and sacroiliac joint vacuum phenomenon were assessed on imaging. Musculoskeletal radiologists who were blinded to the birth data evaluated the CTs. 48 males were also evaluated for the presence of pits. RESULTS: 482 female patients underwent CT pelvis and 171 were excluded due to lack of vaginal birth data. Of the 311 study patients, 262 had prior vaginal birth(s) and 194 had pits on CT. Only 7 of the 49 patients without prior vaginal birth had pits. There was a statistically significant association between vaginal birth and presence of pits (p < 0.0001). Patients with more prominent pits (grades 2/3) had a greater number of vaginal births. As vaginal deliveries increased, the odds of having parturition pits greatly increased, adjusting for age and race at CT (p < 0.0001). No males had pits. CONCLUSION: Our study indicates that parturition pits are associated with prior vaginal birth and should be considered a characteristic of the female pelvis. The lytic appearance of prominent pits on imaging can simulate disease and create a diagnostic dilemma for interpreting radiologists.

Genetic variation in the toll-like receptor 4 and prostate cancer incidence and mortality.

BACKGROUND: Common genetic variants in the Toll-like receptor 4 (TLR4), which is involved in inflammation and immune response pathways, may be important for prostate cancer. METHODS: In a large nested case-control study of prostate cancer in the Physicians' Health Study (1982-2004), 10 single nucleotide polymorphisms (SNPs) were selected and genotyped to capture common variation within the TLR4 gene as well as 5 kb up and downstream. Unconditional logistic regression was used to assess associations of these SNPs with total prostate cancer incidence, and with prostate cancers defined as advanced stage/lethal (T3/T4, M1/N1(T1-T4), lethal) or high Gleason grade (7 (4 + 3) or greater). Cox-proportional hazards regression was used to assess progression to metastases and death among prostate cancer cases. RESULTS: The study included 1,267 controls and 1,286 incident prostate cancer cases, including 248 advanced stage/lethal and 306 high grade cases. During a median follow-up of 10.6 years, 183 men died of prostate cancer or developed distant metastases. No statistically significant associations between the TLR4 SNPs were found for total prostate cancer incidence, including SNPs for which an association was reported in other published studies. Additionally, there were no significant associations with TLR4 SNPS and the incidence of advanced stage/lethal, or high grade cancers; nor was there evidence among prostate cancer cases for associations of TLR4 SNPs with progression to prostate cancer specific mortality or bony metastases. CONCLUSIONS: Results from this prospective nested case-control study suggest that genetic variation across TLR4 alone is not strongly associated with prostate cancer risk or mortality.

Validation of diagnostic codes for subtrochanteric, diaphyseal, and atypical femoral fractures using administrative claims data.

Administrative claims databases have large samples and high generalizability. They have been used to evaluate associations of atypical femoral fractures with bisphosphonates. We developed and assessed accuracy of claims-based algorithms with hospital and physician diagnosis codes for these fractures. Medical records and radiology reports of all adults admitted at University of Alabama at Birmingham Health System from 2004 to 2008 with International Classification of Diseases, Ninth Revision hospital discharges and surgeons' fracture repair codes for subtrochanteric femoral fractures and random sample of other femoral fractures were reviewed. We identified 137 persons with suspected subtrochanteric femoral fractures and randomly selected 50 persons with either suspected diaphyseal femoral fractures or hip fractures other than subtrochanteric and diaphyseal femoral fractures (typical hip fractures). Eleven patients had radiographic features indicative of atypical femoral fractures. The positive predictive value (PPV) of claims-based algorithms varied with primary or secondary positions on discharge diagnoses and the sources of diagnosis codes. The PPV for fractures ranged 69-89% for subtrochanteric femoral, 89-98% for diaphyseal femoral, and 85-98% for typical hip fractures. The PPV of administrative codes for defining a femoral fracture as atypical was low and imprecise. Claims-based algorithms combining hospital discharges with surgeon's diagnosis codes had high PPV to identify the site of subtrochanteric or diaphyseal femoral fractures vs typical hip fractures. However, claims-based data were not accurate in identifying atypical femoral fractures. These claims algorithms will be useful in future population-based observational studies to evaluate associations between osteoporosis medications and subtrochanteric and diaphyseal femoral fractures.

Association of the presence of bone bars on radiographs and low bone mineral density.

OBJECTIVE: Bone bars (BB) are struts of normal trabecular bone that cross the medullary portions of the metaphysis and diaphysis at right angles to the long axis of the shaft. The purpose of this investigation was to determine whether the presence of bone bars (BB) identified on radiographs of the proximal femurs and tibia, predict lower bone mineral density (BMD) as evaluated with dual-energy x-ray absorptiometry (DXA) in the lumbar spine, total hip, or femoral neck. MATERIALS AND METHODS: A total of 134 sequential DXA patients underwent radiography of the pelvis, hips, and both knees. The radiographs were evaluated for the presence of BB by two musculoskeletal radiologists who were blinded to DXA results. A t test was used to evaluate the relationship of BB to BMD and a Chi-square test was used to determine if BB were equally distributed among the categories of normal BMD, low bone mass (osteopenia), and osteoporosis. RESULTS: BB were associated with lower BMD at all measured sites. BB at the intertrochanteric and proximal tibial sites were the most predictive of low BMD while supraacetabular and distal femur BB were less predictive. Osteoporosis or osteopenia is seen in 60-91% of those with BB depending on the side and reader. It is only seen in about 40% of those without BB. CONCLUSIONS: We conclude that the presence of BB suggest decreased BMD and when correlated with other clinical information, might support further evaluation of BMD.

A novel beta-oxa polyunsaturated fatty acid downregulates the activation of the IkappaB kinase/nuclear factor kappaB pathway, inhibits expression of endothelial cell adhesion molecules, and depresses inflammation.

Several novel polyunsaturated fatty acids (PUFAs) that contain either an oxygen or sulfur atom in the beta-position were found to exhibit more selective antiinflammatory properties than their natural PUFA counterparts. One of these, beta-oxa-23:4n-6, unlike natural PUFAs, lacked ability to stimulate oxygen radical production in neutrophils but caused marked inhibition of agonist-induced upregulation of leukocyte adhesion to cultured human umbilical vein endothelial cells (HUVEC) and E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 expression. In addition, beta-oxa-23:4n-6 inhibited acute and chronic inflammatory responses in mice as well as the upregulation of adhesion molecule expression in arterial endothelium. This action of beta-oxa-23:4n-6 required a functional 12- but not 5-lipoxygenase or cyclooxygenases, consistent with its metabolism via the 12-lipoxygenase pathway. Whereas beta-oxa-23:4n-6 did not affect the activation of mitogen-activated protein kinases by tumor necrosis factor, activation of the IkappaB kinase/nuclear factor kappaB pathway was selectively inhibited. These novel PUFAs could form the basis for a potential new class of pharmaceuticals for treating inflammatory diseases, including atherosclerosis.

Massive prepatellar bursitis in cerebral palsy.

This case report describes a 36-year-old African American male with cerebral palsy and bilateral slowly enlarging knee masses. He has 90 degrees fixed flexion knee contractures bilaterally. Although he has poor communication skills, he does not have discomfort while ambulating. He has developed massive bilateral prepatellar bursitis from chronic and repetitive injury to the region bearing his body weight while ambulating. As the result of a protective response, the bursa provides a cushion for the underlying bone prominences of the tibial tubercle and patella. This compensatory mechanism has allowed the patient to have functional, painless household ambulation.

Pellegrini-Stieda ossification can also involve the posterior attachment of the MPFL.

PURPOSE: To evaluate for development of Pellegrini-Stieda (PS)-type ossification following injury to the posterior attachment of the medial patellofemoral ligament (MPFL). MATERIALS AND METHODS: This retrospective study evaluated 27 patients with acute knee injury with initial radiographs, magnetic resonance imaging within 1 week of injury, and follow-up radiographs assessing for development of PS. RESULTS: Of the 27 patients who developed PS ossification, 7 patients (25.9%) had isolated MPFL injury with the ossification slightly more proximal than the traditional PS. CONCLUSION: Isolated injury to the posterior MPFL also leads to PS ossification, which is slightly superior in location to the traditional PS.

The TMPRSS2:ERG rearrangement, ERG expression, and prostate cancer outcomes: a cohort study and meta-analysis.

BACKGROUND: Whether the genomic rearrangement transmembrane protease, serine 2 (TMPRSS2):v-ets erythroblastosis virus E26 oncogene homolog (ERG) has prognostic value in prostate cancer is unclear. METHODS: Among men with prostate cancer in the prospective Physicians' Health and Health Professionals Follow-Up Studies, we identified rearrangement status by immunohistochemical assessment of ERG protein expression. We used Cox models to examine associations of ERG overexpression with biochemical recurrence and lethal disease (distant metastases or cancer-specific mortality). In a meta-analysis including 47 additional studies, we used random-effects models to estimate associations between rearrangement status and outcomes. RESULTS: The cohort consisted of 1,180 men treated with radical prostatectomy between 1983 and 2005. During a median follow-up of 12.6 years, 266 men experienced recurrence and 85 men developed lethal disease. We found no significant association between ERG overexpression and biochemical recurrence [hazard ratio (HR), 0.99; 95% confidence interval (CI), 0.78-1.26] or lethal disease (HR, 0.93; 95% CI, 0.61-1.43). The meta-analysis of prostatectomy series included 5,074 men followed for biochemical recurrence (1,623 events), and 2,049 men followed for lethal disease (131 events). TMPRSS2:ERG was associated with stage at diagnosis [risk ratio (RR)(≥T3 vs. T2), 1.23; 95% CI, 1.16-1.30) but not with biochemical recurrence (RR, 1.00; 95% CI, 0.86-1.17) or lethal disease (RR, 0.99; 95% CI, 0.47-2.09). CONCLUSIONS: These results suggest that TMPRSS2:ERG, or ERG overexpression, is associated with tumor stage but does not strongly predict recurrence or mortality among men treated with radical prostatectomy. IMPACT: This is the largest prospective cohort study to examine associations of ERG overexpression and lethal prostate cancer among men treated with radical prostatectomy.

Aggressive osteoblastoma: a case report involving a unique chromosomal aberration.

Osteoblastomas are rare bone-producing neoplasms that generally occur in the young and can be misdiagnosed as an osteosarcoma if correlation with clinical history, radiology, and histology is not carefully considered or if the several variants of osteoblastoma are not recognized. These variants lie on a morphologic spectrum between conventional osteoblastoma and osteosarcoma. Aggressive osteoblastoma is one such subtype. As the name implies, the histologic features of aggressive osteoblastoma may appear malignant, and its biologic behavior may separate it from conventional osteoblastoma. We report a case of aggressive osteoblastoma occurring in the femoral diaphysis of a 12-year-old girl; this osetoblastoma was dyssynchronous from the radiologic appearance and a diagnostic challenge. Cytogenetic evaluation of the neoplasm revealed a pseudodiploid clone with a balanced translocation involving chromosomes 4, 7, and 14. Using the premise that cytogenetics might be useful as a diagnostic tool for a more specific classification, we reviewed the literature in order to compare our findings with known chromosomal aberrations.

Index Metacarpal Fractures in Karate.

Improperly executed karate thrusts result in an unusually high incidence of this uncommon injury.