Comparison of the structure of human intervertebral discs in the cervical,thoracic and lumbar regions of the spine

Posterior and anterior heights, cross-sectional area and shape were measured for all the intervertebral discs in four spines from elderly human cadavers. Disc height was a minimum at the T4-5 level; thoracic discs were less wedge-shaped than those in the cervical and lumbar regions. Cross-sectional area increased from the cranial to caudal extremity; at the L5-S1 level the nucleus pulposus occupied a high proportion of this area. Cervical discs tended to have an elliptical cross-sectional shape, thoracic discs were more circular and lumbar discs tended to have an elliptical cross-section which was flattened or re-entrant posteriorly. This shape distribution was quantified by defining a shape index which had a maximum value of 1 for a circular cross-section. Orientations of the reinforcing fibres in the outer lamellae of the anterior annulus fibrosus were measured from 27 discs by X-ray diffraction. For these measurements, C3-4, T7-8 and L2-3 were chosen as representative of cervical, thoracic and lumbar discs. The fibre tilt, with respect to the axis of the spine, was significantly less in the cervical discs (at 65 degrees) than in the thoracic and lumbar discs (about 70 degrees). These findings are interpreted in relation to differing functional requirements and possible mechanisms of failure in the cervical, thoracic and lumbar regions of the spine in the light of current knowledge on the biomechanics of the intervertebral disc.     

Jump-landing mechanics in patellar tendinopathy in elite youth basketballers

Patellar tendinopathy (PT) is a leading cause of morbidity in jump-landing athletes. Landing mechanics are identified as a factor associated with PT and/or patellar tendon abnormality. This study aimed to identify key jump-landing variables associated with PT. Thirty-six junior elite basketball players (men n = 18, women n = 18) were recruited from a Basketball Australia development camp. Three-dimensional (3D) kinematic and ground reaction force (GRF) data during a stop-jump task were collected as well as ultrasound scans of the patellar tendons and recall history of training load data. Mixed-model factorial analyses of variance were used to determine any significant between-group differences. Of the 23 participants included for statistical analyses, 11 had normal bilateral patellar tendons (controls) and eight reported PT (currently symptomatic); however, the four participants categorized as asymptomatic with patellar tendon abnormality on diagnostic imaging were excluded from statistical analyses due to their small sample size. Athletes with PT displayed a similar knee flexion angle at initial foot-ground contact (IC) and hip extension strategy during a stop-jump horizontal landing. Despite a similar kinematic technique, athletes with PT utilized a strategy of a longer stance duration phase from IC to peak force. This strategy did not lead to those athletes with PT decreasing their peak vertical GRF nor patellar tendon force during landing but enabled these athletes to land with a lower rate of loading (control 59.2 ± 39.3 vs. PT 29.4 ± 33.7 BW.s-1). Athletes with PT still reported significantly reduced training volume (control 4.9 ± 1.8 vs PT 1.8 ± 1.1 sessions/wk; total training time/wk control 2.4 ± 1.0 vs PT 1.4 ± 1.1 h/wk).     

Podocyte EGFR Inhibits Autophagy Through Upregulation of Rubicon in Type 2 Diabetic Nephropathy

Renal epidermal growth factor receptor (EGFR) signaling is activated in models of diabetic nephropathy (DN), and inhibition of the EGFR signaling pathway protects against the development of DN. We have now determined that in cultured podocytes, high glucose led to increases in activation of EGFR signaling but decreases in autophagy activity as indicated by decreased beclin-1 and inhibition of LC3B autophagosome formation as well as increased rubicon (an autophagy inhibitor) and SQSTM1 (autophagy substrate). Either genetic (small interfering [si]EGFR) or pharmacologic (AG1478) inhibition of EGFR signaling attenuated the decreased autophagy activity. In addition, rubicon siRNA knockdown prevented high glucose–induced inhibition of autophagy in podocytes. We further examined whether selective EGFR deletion in podocytes affected the progression of DN in type 2 diabetes. Selective podocyte EGFR deletion had no effect on body weight or fasting blood sugars in either db/db mice or nos3^−/−; db/db mice, a model of accelerated type 2 DN. However selective podocyte EGFR deletion led to relative podocyte preservation and marked reduction in albuminuria and glomerulosclerosis, renal proinflammatory cytokine/chemokine expression, and decreased profibrotic and fibrotic components in nos3^−/−; db/db mice. Podocyte EGFR deletion led to decreased podocyte expression of rubicon, in association with increased podocyte autophagy activity. Therefore, activation of EGFR signaling in podocytes contributes to progression of DN at least in part by increasing rubicon expression, leading to subsequent autophagy inhibition and podocyte injury.     

Accelerometer-Based,Portable Navigation (KneeAlign) vs Conventional Instrumentation for Total Knee Arthroplasty: A Prospective Randomized Comparative Trial

Background

Accelerometer-based, portable navigation devices have been introduced as a less invasive and simpler technique to perform navigated surgical implantation of knee prostheses. They have been postulated to have better accuracy than conventional instruments in restoration of alignment in total knee arthroplasty.

Reconstruction of Disrupted Extensor Mechanism After Total Knee Arthroplasty

Background

Disruption of the extensor mechanism after total knee arthroplasty (TKA) is a debilitating complication that results in extension lag, limited range of motion, difficulty in walking, frequent falls, and chronic pain. This study presents the clinical and radiographic results of reconstruction after extensor mechanism disruption in TKA patients.

Male breast cancer: management and follow-up recommendations

National Comprehensive Cancer Network (NCCN) guidelines for female breast cancer treatment and surveillance are well established, but similar guidelines on male breast cancers are less recognized. As an NCCN institution, our objective was to examine practice patterns and follow-up for male breast cancer compared to established guidelines for female patients. After Institutional Review Board approval, a prospective breast database from 1990 to 2009 was queried for male patients. Medical records were examined for clinico-pathological factors and follow-up. The 5-year survival rates with 95% confidence intervals were estimated using Kaplan-Meier method and Greenwood formula. Of the 19,084 patients in the database, 73 (0.4%) were male patients; 62 had complete data. One patient had bilateral synchronous breast cancer. The median age was 68.8 years (range 29-85 years). The mean/median invasive tumor size was 2.2/1.6 cm (range 0.0-10.0 cm). All cases had mastectomy (29 with axillary node dissection, 23 with sentinel lymph node biopsy only, 11 with sentinel node biopsy followed by completion axillary dissection). Lymph node involvement occurred in 25/63 (39.7%). Based on NCCN guidelines, chemotherapy, hormonal therapy, and radiation are indicated in 34 cases, 62 cases, and 14 cases, respectively. Only 20/34 (59%) received chemotherapy, 51/62 (82%) received hormonal therapy, and 10/14 (71%) received post-mastectomy radiation. Median follow-up was 26.2 months (range: 1.6-230.9 months). The 5-year survival estimates for node positive and negative diseases were 68.5% and 87.5%, respectively (p = 0.3). Despite the rarity of male breast cancer, treatment options based on current female breast tumors produce comparable results to female breast cancer. Increased awareness and a national registry for patients could help improve outcomes and tailor treatment recommendations to the male variant.     

Assessment of incident spine and hip fractures in women and men using finite element analysis of CT scans

Finite element analysis of computed tomography (CT) scans provides noninvasive estimates of bone strength at the spine and hip. To further validate such estimates clinically, we performed a 5‐year case‐control study of 1110 women and men over age 65 years from the AGES‐Reykjavik cohort (case = incident spine or hip fracture; control = no incident spine or hip fracture). From the baseline CT scans, we measured femoral and vertebral strength, as well as bone mineral density (BMD) at the hip (areal BMD only) and lumbar spine (trabecular volumetric BMD only). We found that for incident radiographically confirmed spine fractures (n = 167), the age‐adjusted odds ratio for vertebral strength was significant for women (2.8, 95% confidence interval [CI] 1.8 to 4.3) and men (2.2, 95% CI 1.5 to 3.2) and for men remained significant (p = 0.01) independent of vertebral trabecular volumetric BMD. For incident hip fractures (n = 171), the age‐adjusted odds ratio for femoral strength was significant for women (4.2, 95% CI 2.6 to 6.9) and men (3.5, 95% CI 2.3 to 5.3) and remained significant after adjusting for femoral neck areal BMD in women and for total hip areal BMD in both sexes; fracture classification improved for women by combining femoral strength with femoral neck areal BMD (p = 0.002). For both sexes, the probabilities of spine and hip fractures were similarly high at the BMD‐based interventional thresholds for osteoporosis and at corresponding preestablished thresholds for “fragile bone strength” (spine: women ≤ 4500 N, men ≤ 6500 N; hip: women ≤ 3000 N, men ≤ 3500 N). Because it is well established that individuals over age 65 years who have osteoporosis at the hip or spine by BMD criteria should be considered at high risk of fracture, these results indicate that individuals who have fragile bone strength at the hip or spine should also be considered at high risk of fracture. © 2014 American Society for Bone and Mineral Research.     

Tacrolimus dose requirements in African‐American and Caucasian kidney transplant recipients on mycophenolate and prednisone

Racial differences among kidney transplant recipients may impact the total daily tacrolimus dose required to achieve therapeutic tacrolimus concentrations. Previous studies suggest that African Americans require higher doses to achieve similar therapeutic drug concentrations compared with Caucasians. Data were collected on a total of 147 de novo kidney transplant recipients. Tacrolimus total daily dose (TDD) requirements (mg/kg/d) and tacrolimus concentrations were retrospectively reviewed at discharge and at days 30, 60, and 90 after transplant. TDD requirements in African‐American and Caucasian patients were 0.14 mg/kg/d and 0.11 mg/kg/d, respectively (p = 0.005), at day 30. TDD requirements at day of hospital discharge and days 60 and 90 following transplant were significantly higher in African‐American patients vs. Caucasian patients, with similar tacrolimus concentrations at all time points. This study suggests that when compared to Caucasians, African Americans require significantly higher TDD of tacrolimus to achieve similar tacrolimus concentrations. These findings provide transplant clinicians with a sense of certainty to more rapidly titrate daily tacrolimus doses in African‐American patients to achieve therapeutic concentrations.     

Characterization of a Factor H Mutation That Perturbs the Alternative Pathway of Complement in a Family with Membranoproliferative GN

Complement C3 activation is a characteristic finding in membranoproliferative GN (MPGN). This activation can be caused by immune complex deposition or an acquired or inherited defect in complement regulation. Deficiency of complement factor H has long been associated with MPGN. More recently, heterozygous genetic variants have been reported in sporadic cases of MPGN, although their functional significance has not been assessed. We describe a family with MPGN and acquired partial lipodystrophy. Although C3 nephritic factor was shown in family members with acquired partial lipodystrophy, it did not segregate with the renal phenotype. Genetic analysis revealed a novel heterozygous mutation in complement factor H (R83S) in addition to known risk polymorphisms carried by individuals with MPGN. Patients with MPGN had normal levels of factor H, and structural analysis of the mutant revealed only subtle alterations. However, functional analysis revealed profoundly reduced C3b binding, cofactor activity, and decay accelerating activity leading to loss of regulation of the alternative pathway. In summary, this family showed a confluence of common and rare functionally significant genetic risk factors causing disease. Data from our analysis of these factors highlight the role of the alternative pathway of complement in MPGN.