Catheter-direct thrombolysis versus pharmacomechanical thrombectomy for treatment of symptomatic lower extremity deep venous thrombosis

BACKGROUND: Rheolytic mechanical thrombectomy using the AngioJet catheter (Possis Medical, Minneapolis, MN) has been shown to be effective in the treatment of deep venous thrombosis (DVT). Additional infusion of thrombolytic agents via the device creates a novel treatment strategy of pharmacomechanical thrombectomy (PMT), which further enhances thrombectomy efficacy. The purpose of the current study was to compare the treatment outcome in patients with symptomatic DVT who underwent either catheter-directed thrombolysis (CDT) or PMT intervention. METHODS: During a recent 8-year period, clinical records of all patients with symptomatic lower leg DVT undergoing catheter-directed interventions were evaluated. Patients were divided into 2 treatment groups: CDT or PMT. Comparisons were made with regards to the treatment outcome between the 2 groups. RESULTS: A total of 93 patients who underwent 98 catheter-directed interventions for DVT were included in the study. Among them, CDT or PMT was performed in 46 (47%) and 52 (53%) procedures, respectively. In the CDT group, complete or partial thrombus removal was accomplished in 32 (70%) and 14 (30%) cases, respectively. In the PMT cohort, complete or partial thrombus removal was accomplished in 39 (75%) and 13 (25%) cases, respectively. Venous balloon angioplasty and/or stenting in the CDT or PMT groups was necessary in 36 (78%) and 43 (82%), respectively (difference not significant [NS]). Patients in the CDT groups underwent a mean of 2.5 venograms during the hospital course, in contrast to 0.4 venograms per patient in PMT cohorts (P < .001). Immediate (<24 hours) improvement in clinical symptoms in CDT and PMT groups was achieved in 33 (72%) and 42 (81%) cases, respectively (NS). Significant reductions in the intensive care unit (ICU) and hospital lengths of stay was noted in the PMT group (0.6 and 4.6 days) when compared to the CDT group (2.4 and 8.4 days). During follow-up visits, the primary patency rates at 1 year of CDT and PMT groups were 64% and 68%, respectively (NS). Hospital cost analysis showed significant cost reduction in the PMT group compared to the CDT group (P < .01). CONCLUSIONS: PMT with adjunctive thrombolytic therapy is an effective treatment modality in patients with significant DVT. When compared to CDT, this treatment provides similar treatment success with reduced ICU, total hospital length of stay, and hospital costs.     

Experimental testing of a DEXA-derived curved beam model of the proximal femur

This study was designed to test whether, using curved beam theory, a structural model of the proximal femur derived from two-dimensional dual energy x-ray absorptiometry could be used to predict femoral strength in an experimental simulation of a fall on the greater trochanter. A set of 22 fresh cadaveric femoral specimens were scanned with use of two-dimensional dual energy x-ray absorptiometry and then were tested to failure in a materials testing system, under three-point loading, with the ground impact vector, aligned within the plane and along the bisector of the femoral neck-shaft angle. Failure locations generally corresponded to stress peak locations predicted by the curved beam model. Predicted failure loads correlated well with measured failure loads for femoral neck fractures (r = 0.89; percent SE of estimate = 23%) and somewhat less well for intertrochanteric fractures (r = 0.83; percent SE of estimate = 29%). Overall predictions for failure load calculated from the maximum stress peak value over both locations corresponded to measured failure loads with an r value of 0.91 (percent SE of estimate = 21%). This kind of structural approach to the analysis of data for hip bone mass has the potential to provide mechanistic interpretations of the statistical associations frequently shown between conventional bone mineral measures and either hip fracture risk in vivo or bone strength in vitro.     

Adenosine A(2A) receptor ligation inhibits osteoclast formation

Adenosine is generated in increased concentrations at sites of injury/hypoxia and mediates a variety of physiological and pharmacological effects via G protein-coupled receptors (A(1), A(2A), A(2B), and A(3)). Because all adenosine receptors are expressed on osteoclasts, we determined the role of A(2A) receptor in the regulation of osteoclast differentiation. Differentiation and bone resorption were studied as the macrophage colony-stimulating factor-1-receptor activator of NF-κB ligand formation of multinucleated tartrate-resistant acid phosphatase (TRAP)-positive cells from primary murine bone marrow-derived precursors. A(2A) receptor and osteoclast marker expression levels were studied by RT-PCR. Cytokine secretion was assayed by enzyme-linked immunosorbent assay. In vivo examination of A(2A) knockout (KO)/control bones was determined by TRAP staining, micro-computed tomography, and electron microscopy. The A(2A) receptor agonist, CGS21680, inhibited osteoclast differentiation and function (half maximal inhibitory concentration, 50 nmol/L), increased the percentage of immature osteoclast precursors, and decreased IL-1β and tumor necrosis factor-α secretion, an effect that was reversed by the A(2A) antagonist, ZM241385. Cathepsin K and osteopontin mRNA expression increased in control and ZM241385-pretreated osteoclasts, and this was blocked by CGS21680. Micro-computed tomography of A(2A)KO mouse femurs showed a significantly decreased bone volume/trabecular bone volume ratio, decreased trabecular number, and increased trabecular space. A(2A)KO femurs showed an increased TRAP-positive osteoclast. Electron microscopy in A(2A)KO femurs showed marked osteoclast membrane folding and increased bone resorption. Thus, adenosine, acting via the A(2A) receptor, inhibits macrophage colony-stimulating factor-1-receptor activator of NF-κB ligand-stimulated osteoclast differentiation and may regulate bone turnover under conditions in which adenosine levels are elevated.     

Similar muscles contribute to horizontal and vertical acceleration of center of mass in forward and backward walking: implications for neural control

Leg kinematics during backward walking (BW) are very similar to the time-reversed kinematics during forward walking (FW). This suggests that the underlying muscle activation pattern could originate from a simple time reversal, as well. Experimental electromyography studies have confirmed that this is the case for some muscles. Furthermore, it has been hypothesized that muscles showing a time reversal should also exhibit a reversal in function [from accelerating the body center of mass (COM) to decelerating]. However, this has not yet been verified in simulation studies. In the present study, forward simulations were used to study the effects of muscles on the acceleration of COM in FW and BW. We found that a reversal in function was indeed present in the muscle control of the horizontal movement of COM (e.g., tibialis anterior and gastrocnemius). In contrast, muscles' antigravity contributions maintained their function for both directions of movement. An important outcome of the present study is therefore that similar muscles can be used to achieve opposite functional demands at the level of control of the COM when walking direction is reversed. However, some muscles showed direction-specific contributions (i.e., dorsiflexors). We concluded that the changes in muscle contributions imply that a simple time reversal would be insufficient to produce BW from FW. We therefore propose that BW utilizes extra elements, presumably supraspinal, in addition to a common spinal drive. These additions are needed for propulsion and require a partial reconfiguration of lower level common networks.     

Trends of Retroperitoneal Lymphadenectomy Use in Patients with Nonseminomatous Germ Cell Tumor of the Testis: A Population-Based Study

Background

Retroperitoneal lymphadenectomy (RPLND), chemotherapy, and active surveillance represent treatment options for patients with nonseminomatous germ-cell tumors of the testis (NSGCTT). Our objective was to assess the utilization rate of RPLND in patients with NSGCTT.

Methods

Within the Surveillance, Epidemiology and End Results (SEER) cohort, 4,620 and 1,671 patients with stage I and II NSGCTT were diagnosed between the years 1988 and 2006. Univariable and multivariable logistic regression analyses were performed to test the predictors of RPLND use in respectively patients with stage I and II NSGCTT.

Results

The rate of RPLND according to stage I and II was 27 and 58%, respectively. In patients with stage I disease, the rate of RPLND decreased from 39% in 1988–1995 to 18% in 2004–2006 (P < 0.001), and remained stable for stage II patients (62–56%, P = 0.2). Regional variability existed regarding the rate of RPLND use only in stage I (Utah: 51% vs. Louisiana: 16%). Multivariable analyses performed in stage I NSGCTT revealed that year of diagnosis, SEER registry, and age were significant predictors of RPLND use. However, none of these variables achieved statistical significance within stage II NSGCTT patients.

Conclusions

In patients with stage I NSGCCT, the RPLND utilization rate decreased during the study span. This observation may be ascribed to wider use of surveillance or chemotherapy. No temporal difference was recorded in patients with stage II NSGCCT.     

A Contemporary Population-Based Assessment of the Rate of Lymph Node Dissection for Penile Carcinoma

Background

The adherence rate to National Cancer Institute (NCI) recommendations regarding inguinal lymph nodes dissection (ILND) in high grade T1 (G3T1) and T2-4 squamous cell carcinoma of the penis (SCCP) is not known. We assessed ILND rates in a North American cohort.

Materials and Methods

The 17 registries of the Surveillance, Epidemiology, and End Results (SEER) database included 868 patients with SCCP, diagnosed between 1988 and 2006. Analyses consisted of univariable and multivariable logistic regression models.

Results

Overall, 27.6% of patients underwent an ILND. ILND rates were directly proportional with T stage: 19.0%, 30.5%, 30.6%, and 32.6% for, respectively, G3T1, T2, T3, and T4 SCCP (chi-square trend, P = 0.01). ILND rates also increased over time and were 19.3, 27.3, 30.7, and 30.8% for respectively, 1988–1995, 1996–2000, 2001–2003, and 2004–2006 periods (chi-square trend, P = 0.03). Finally, ILND rates decreased with patient age and were 42.6, 33.2, 24.7, and 7.3% for, respectively, patients aged ≤57, 58–68, 69–78 and ≥79 years of age (chi-square trend, P < 0.001). All 3 variables (T-stage, year of primary tumor excision and patient age) achieved independent predictor status in multivariable analyses.

Conclusions

The overall rate of ILND is low. Nonetheless, there is an upward trend over time. Our data indicate that the adherence to the NCI ILND guidelines is suboptimal. In consequence, ILNDs should be more strongly encouraged.