Factors Associated With Implantable Pulse Generator Site Pain: A Multicenter Cross-Sectional Study.

OBJECTIVES: Implantable pulse generator (IPG) site pain following neuromodulation procedures is a recognized complication. The site of the IPG placement varies depending on the neuromodulation type and physician preference. The incidence of IPG site pain as a function of the site of IPG implantation has not been studied systematically. MATERIALS AND METHODS: We performed a multicenter cross-sectional survey of the incidence, severity, and quality of IPG site pain, location of the IPG, the pain management needs, functional impairment, and cosmetic appearance related to the IPG placement. Contingency table analysis was conducted for categorical variables, and logistic regression analysis and linear regression model was used. RESULTS: The survey response rate was 60.5% (n = 510). Overall, 31.0% of patients reported pain at the IPG site in the last 72 hours with 31.4% reporting moderate to severe pain and 7.6% reporting severe pain. Older age was inversely associated with IPG-related pain (OR = 0.97, 95% CI = 0.96-0.99, p = 0.001). IPG implantation site did not have a statistically significant interaction with IPG site pain (p > 0.05). The most important factor for IPG site-associated pain was having a spinal cord stimulator implanted as compared to a deep brain stimulator, or sacral nerve stimulator. Most subjects reported no functional impairment related to IPG site pain (91%), found the IPG site pain as expected (80%), and found IPG site cosmetic appearance as expected (96%). CONCLUSIONS: The incidence of IPG site pain is an important complication of invasive neuromodulation. The anatomic location of the IPG placement does not appear to affect the incidence or severity of IPG site pain. However, the presence of a pre-implant chronic pain disorder does appear to affect the frequency and severity of IPG site pain.

6-Methoxyethylamino-numonafide inhibits hepatocellular carcinoma xenograft growth as a single agent and in combination with sorafenib.

Hepatocellular carcinoma (HCC) is the third leading form of cancer worldwide, and its incidence is increasing rapidly in the United States, tripling over the past 3 decades. The current chemotherapeutic strategies against localized and metastatic HCC are ineffective. Here we report that 6-methoxyethylamino-numonafide (MEAN) is a potent growth inhibitor of murine xenografts of 2 human HCC cell lines. At the same dose and with the same treatment strategies, MEAN was more efficacious in inhibiting tumor growth in mice than sorafenib, the only approved drug for HCC. Treatment by MEAN at an effective dose for 6 wk was well tolerated by animals. Combined therapy using both sorafenib and MEAN enhanced tumor growth inhibition over monotherapy with either agent. Additional experiments revealed that MEAN inhibited tumor growth through mechanisms distinct from those of either its parent compound, amonafide, or sorafenib. MEAN suppressed C-MYC expression and increased expression of several tumor suppressor genes, including Src homology region 2 domain-containing phosphatase-1 (SHP-1) and TXNIP (thioredoxin-interacting protein). As an encouraging feature for envisioned clinical application, the IC50 of MEAN was not significantly changed in several drug-resistant cell lines with activated P-glycoprotein drug efflux pumps compared to drug-sensitive parent cells, demonstrating the ability of MEAN to be effective in cells resistant to existing chemotherapy regimens. MEAN is a promising candidate for clinical development as a single-agent therapy or in combination with sorafenib for the management of HCC.-Liu, Y., Lou, G., Norton, J. T., Wang, C., Kandela, I., Tang, S., Shank, N. I., Gupta, P., Huang, M., Avram, M. J., Green, R., Mazar, A., Appella, D., Chen, Z., Huang, S. 6-Methoxyethylamino-numonafide inhibits hepatocellular carcinoma xenograft growth as a single agent and in combination with sorafenib.

Retrograde autologous priming of the cardiopulmonary bypass circuit: safety and impact on postoperative outcomes.

OBJECTIVES: Retrograde autologous priming (RAP) is a blood conservation technique used to limit the severity of hemodilution during cardiopulmonary bypass and reduce perioperative transfusions. The aim of this investigation was to examine the safety of RAP and to determine the effect of RAP on adverse outcomes after cardiac surgery. DESIGN: Retrospective cohort study. SETTING: University hospital. PARTICIPANTS: Five hundred fifty-nine undergoing cardiopulmonary bypass. INTERVENTIONS: Data were retrospectively collected on 2 cohorts of adult cardiac surgical patients operated on by a single surgeon. In the RAP group (n = 256), outcome data were analyzed on all subjects over a 2-year period during which RAP was used routinely. This group was compared with a similar cohort of patients undergoing cardiopulmonary bypass over a 2-year period immediately before the introduction of RAP into the clinical practice (no-RAP group, n = 287). MEASUREMENTS AND MAIN RESULTS: In-hospital mortality was not significantly different between the RAP group (2.7%) and the no-RAP group (3.8%, p = 0.636). The incidence of postoperative cardiac arrest was significantly less in the RAP group (1 patient) compared to the no-RAP group (9 patients, p = 0.040). There were no differences between the 2 groups in the incidence of several other postoperative complications, including postoperative delirium (1.6% RAP v 3.1% no RAP), heart block (1.6% RAP v 4.2% no RAP), atrial fibrillation (19.1% RAP v 22.7% no RAP), and requiring postoperative ventilation >24 hours (2.7% RAP v 5.2% no RAP). CONCLUSIONS: The authors observed no evidence of any increase in adverse events in the RAP group of this retrospective cohort study, but they did observe a decrease in the incidence of postoperative cardiac arrest in the RAP group. These findings suggest that RAP is a safe technique and may have a beneficial effect on postoperative outcomes.