Long-term protection of hematopoiesis against the cytotoxic effects of multiple doses of nitrosourea by retrovirus-mediated expression of human O6-alkylguanine-DNA-alkyltransferase

A human O6-alkylguanine-DNA-alkyltransferase (ATase) cDNA-containing retrovirus was used to infect murine long-term primary bone marrow cultures. High levels of ATase expression were obtained, and colony- forming cells of the granulocyte-macrophage lineage from the cultures transduced with the human ATase retrovirus were three times more resistant to the alkylating agent, N-methyl-N-nitrosourea (MNU), than control cultures. Furthermore, expression of the human ATase protected long-term hematopoiesis, measured as the output of progenitor cells to the nonadherent fraction of the culture, against the cytotoxic effects of repeated exposures to MNU. These results clearly show that a human ATase cDNA-containing retrovirus can be used to infect long-term primary bone marrow cultures and that this attenuates their sensitivity to nitrosoureas.     

Persistent systemic inflammatory response syndrome is predictive of nosocomial infection in trauma

BACKGROUND: Admission systemic inflammatory response syndrome (SIRS) score has been previously reported to be an accurate predictor of infection and outcome in trauma. However, these data were limited to only one SIRS score at admission. A prior study in surgical intensive care unit (ICU) patients reported that the SIRS score on ICU day 2 declined after completion of resuscitation, and was a more accurate predictor of outcome. Our objective in this follow-up study was to prospectively evaluate the utility of daily SIRS scores in prediction of nosocomial infection and outcome in high-risk trauma patients. METHODS: Prospective data were collected on 702 consecutive trauma patients admitted over a 12-month period to the ICU. SIRS scores were calculated daily. Centers for Disease Control and Prevention guidelines were used for the diagnosis of infection. Multivariate linear regression was used for statistical analysis. RESULTS: Five hundred seventy-three (82%) patients sustained blunt injuries and 129 (18%) sustained penetrating injuries. The mean age was 43 +/- 21 years, with an overall mortality of 11.4%. Two hundred ninety (41.3%) of the study patients acquired a nosocomial infection (respiratory site most common), with an associated mortality rate of 12.4%. SIRS (defined as SIRS score >/= 2) on hospital days 3 through 7 was a significant predictor of nosocomial infection and hospital length of stay. Persistent SIRS to hospital day 7 was associated with a significant risk for increased mortality (relative risk, 4.7; 95% confidence interval, 1.41-12.87; p = 0.047). CONCLUSION: Persistent SIRS is predictive of nosocomial infection in trauma. Daily monitoring of SIRS scores is easily accomplished and should be considered in all high-risk trauma patients. Persistent SIRS in trauma should initiate early diagnostic interventions for determination of source of infection, and consideration of early empiric antimicrobial therapy.     

A Simple and Safe Minimally Invasive Technique for Laparoscopic Gastrostomy

Introduction:

Percutaneous endoscopic gastrostomy (PEG) is the procedure of choice in the nutritional management of patients requiring gastrostomies. However, PEG tubes are not always feasible. The aim of the present study was to determine the feasibility, complications, and adequacy of feeding support of a novel laparoscopic gastrostomy technique in adults where PEG tubes were neither feasible nor safe.

Methods:

A retrospective chart review of patients who underwent a laparoscopic gastrostomy from August 2007 to July 2008 was performed. Demographic and outcome data were abstracted.

Results:

Fourteen patients underwent laparoscopic gastrostomy. Nine had obstructing head/neck cancer, 2 had severe head trauma, and one was morbidly obese. Nine patients had previous abdominal surgery. The mean operative time was 29.8 minutes (±7.2). There were no conversions to open gastrostomy. Two ports (5mm and 10mm) were used in the majority of patients (78.5%). No major complications were observed. The mean follow-up was 3.1 months (range, 2 to 8).

Conclusion:

This innovative 2-port laparoscopic technique for gastrostomy tube placement is safe and effective. It allows for the quick, accurate, and safe insertion of the feeding tube under direct visualization and avoids open techniques in patients where PEG tubes are not feasible.     

Hepatic Intra-Arterial Injection of Drug-Eluting Bead, Irinotecan (DEBIRI) in Unresectable Colorectal Liver Metastases Refractory to Systemic Chemotherapy: Results of Multi-Institutional Study

Introduction

Response rates and overall outcome for patients who have failed first-line and in some cases second-line chemotherapy are as low as 12% and 7 months, respectively. The aim of this study is to evaluate the efficacy of hepatic arterial sulfonate hydrogel microsphere (drug-eluting beads), irinotecan preloaded therapy (DEBIRI) in metastatic colorectal cancer refractory to systemic chemotherapy.

Methods

This was a multicenter multinational single-arm study of metastatic colorectal cancer patients who received DEBIRI after failing systemic chemotherapy from 10/2006 to 8/2008. Primary endpoints were safety, tolerance, tumor response rates, and overall survival.

Results

Fifty-five patients who had received prior systemic chemotherapy and who underwent a total of 99 DEBIRI treatments were reviewed. The median number of DEBIRI treatments was 2 (range 1–5), median treatment dose was 100 mg (range 100–200 mg), with total hepatic treatment of 200 mg (range 200–650 mg), with 86% of treatments performed as lobar infusion and 30% of patients treated with concurrent simultaneous chemotherapy. Adverse events occurred in 28% of patients with median grade of 2 (range 1–3) with no deaths at 30 days post procedure. Response rates were 66% at 6 months and 75% at 12 months. Overall survival in these patients was 19 months, with progression-free survival of 11 months.

Conclusions

Hepatic arterial drug-eluting bead, irinotecan (DEBIRI) was safe and effective in treatment of metastatic colorectal cancer (MCC) refractory to multiple lines of systemic chemotherapy. DEBIRI is an acceptable therapy for treatment of metastatic colorectal cancer to the liver.     

Outcome Analysis of Blood Product Transfusion in Trauma Patients: A Prospective,Risk-Adjusted Study

BACKGROUND: Studies have confirmed adverse outcome associated with transfusion of packed red blood cells (PRBCs) in trauma; however, little data are available regarding other blood product transfusion, such as fresh frozen plasma (FFP) and platelets. The objective of this study was to examine risk-adjusted outcome in trauma with stratification by blood product type. METHODS: Prospective data were collected daily for 1,172 consecutive trauma patients admitted to the intensive care unit (ICU) during a 2-year period, including transfusion rates of blood products (PRBCs, FFP, platelets). Outcome assessment included infection rate, ventilator days (Vdays), ICU and hospital length of stay (LOS), and mortality. RESULTS: Blood products were transfused in 786 (67%) patients. The study cohort had a mean age of 43 +/- 21 years and Injury Severity Score (ISS) of 24 +/- 13. Although the majority of patients were men, women were more likely to be transfused (p < 0.001). Mean transfusion rates of PRBCs (5.5 +/- 9.6 U), FFP (5.4 +/- 11.4), and platelets (3.7 +/- 11.1) were high. Univariate analysis identified that blood product transfusion (any type) was associated with a significantly greater infection rate (34% vs. 9.4%; p < 0.001), hospital LOS (18.6 vs. 9 days; p < 0.001), ICU LOS (13.7 vs. 7.4 days; p < 0.001), Vdays (12.9 vs. 6.3 days; p < 0.001), and mortality (19% vs. 8.3%; p < 0.001). Multivariate analysis (risk-adjusted for severity of injury by ISS, age, sex, and race, and stratified by blood product type) confirmed that risk of infection increased by 5%, and hospital LOS, ICU LOS, and Vdays increased by 0.64, 0.42, and 0.47 days, respectively, for every unit of PRBCs given. Risk of death increased by 3.5% for every unit of FFP transfused. CONCLUSION: There is a dose-dependent correlation between blood product transfusion and adverse outcome (increased mortality and infection) in trauma patients.     

Sedation and anesthesia care for ophthalmologic surgery during local/regional anesthesia

Anesthesia care for the patients undergoing ophthalmologic surgical procedures during local/regional anesthesia balances goals of patient comfort with safety and an optimal outcome in a highly cost-conscious environment. This article discusses current practices and trends in anesthesia care with respect to sedation for eye surgery during local/regional anesthesia. Although there is no evidence that one local/regional anesthesia technique or sedation analgesia regimen is superior to the others, this review highlights important differences between these varied approaches. The type of block used for the ophthalmologic surgery alters the sedation requirements. Changes in surgical techniques have increased the popularity of topical anesthesia, which reduces the need for sedation analgesia and may lessen the need for an anesthesia practitioner. The involvement of an anesthesia practitioner in eye surgery varies from facility to facility based on costs, anesthesiologist availability, and local standards. Anesthesia care choices are often made based on surgeon skill and anesthesiologist comfort, as well as the expectations and needs of the patient.