Safety and efficacy of etomidate and propofol anesthesia in elderly patients undergoing gastroscopy: A double-blind randomized clinical study.

The aim of the present study is to compare the safety, efficacy and cost effectiveness of anesthetic regimens by compound, using etomidate and propofol in elderly patients undergoing gastroscopy. A total of 200 volunteers (65-79 years of age) scheduled for gastroscopy under anesthesia were randomly divided into the following groups: P, propofol (1.5-2.0 mg/kg); E, etomidate (0.15-0.2 mg/kg); P+E, propofol (0.75-1 mg/kg) followed by etomidate (0.075-0.1 mg/kg); and E+P, etomidate (0.075-0.01 mg/kg) followed by propofol (0.75-1 mg/kg). Vital signs and bispectral index were monitored at different time points. Complications, induction and examination time, anesthesia duration, and recovery and discharge time were recorded. At the end of the procedure, the satisfaction of patients, endoscopists and the anesthetist were evaluated. The recovery (6.1±1.2 h) and discharge times (24.8±2.8 h) in group E were significantly longer compared with groups P, P+E and E+P (P<0.05). The occurrence of injection pain in group P+E was significantly higher compared with the other three groups (P<0.05). In addition, the incidence of myoclonus and post-operative nausea and vomiting were significantly higher in group P+E compared with the other three groups (P<0.05). There was no statistical difference among the four groups with regards to the patients' immediate, post-procedure satisfaction (P>0.05). Furthermore, there was no difference in the satisfaction of anesthesia, as evaluated by the anesthetist and endoscopist, among the four groups (P>0.05). The present study demonstrates that anesthesia for gastroscopy in elderly patients can be safely and effectively accomplished using a drug regimen that combines propofol with etomidate. The combined use of propofol and etomidate has unique characteristics which improve hemodynamic stability, cause minimal respiratory depression and less side effects, provide rapid return to full activity and result in high levels of satisfaction.

Ischemic post-conditioning attenuates acute lung injury induced by intestinal ischemia-reperfusion in mice: role of Nrf2.

Intestinal ischemic post-conditioning (IPo) protects against lung injury induced by intestinal ischemia-reperfusion (IIR) partly through promotion of expression and function of heme oxygenase-1 (HO-1). NF-E2-related factor-2 (Nrf2) is a key transcription factor that interacts with HO-1 and regulates antioxidant defense. However, the role of Nrf2 in IPo protection of IIR-induced pulmonary injury is not completely understood. Here we show that IPo significantly attenuated IIR-induced lung injury and suppressed oxidative stress and systemic inflammatory responses. IPo also increased the expression of both Nrf2 and HO-1. Consistently, the beneficial effects of IPo were abolished by ATRA and Brusatol, potent inhibitors of Nrf2. Moreover, the Nrf2 agonist t-BHQ showed similar activity as IPo. Taken together, our data suggest that Nrf2 activity, along with HO-1, plays an important role in the protective effects of IPo against IIR-induced acute lung injury.

Chemical shift artifact on steady-state free precession cardiac magnetic resonance sequences as a result of lipomatous metaplasia: a novel finding in chronic myocardial infarctions.

BACKGROUND: Because balanced steady-state free precession (SSFP) sequences are opposed-phase gradient echo techniques, linear low signal due to chemical shift artefact is observed at fat-water interfaces. We observed that some patients with chronic myocardial infarctions had linear low signal along the inner myocardial wall in areas of infarction, which we postulated was due to chemical shift artefact, as a result of lipomatous metaplasia. The purpose of this retrospective review was to evaluate whether subendocardial low signal on SSFP, likely related to chemical shift artifact, could be used to identify chronic myocardial infarctions. METHODS: Of 128 patients who underwent cardiac magnetic resonance, 79 with myocardial infarctions were included in this retrospective study. RESULTS: Of the 79 patients, 35 (44%) demonstrated areas of linear subendocardial decreased signal. In 16 of those 35 (46%), the infarcts were confirmed as fatty by correlation with CT. In 29 of 35 (83%) of these patients, the infarcts were likely chronic based on fixed wall thinning to less than 4 mm. In 3 patients, chemical shift artifact due to lipomatous metaplasia was also confirmed with conventional in-phase and opposed-phase T1-weighted sequences. Subendocardial chemical shift artefacts were not seen in any of the 19 patients with known, acute infarcts included in this series. Aneurysms were more common when subendocardial chemical shift artefact was present (22 of 35), in comparison to patients who did not have this finding (10 of 44, P = 0.02). CONCLUSIONS: Identification of linear subendocardial chemical shift artefacts on SSFP sequences is a sign of lipomatous metaplasia in chronic myocardial infarcts and is associated with an increased incidence of ventricular aneurysms.

Improved survival for stage IV melanoma from an unknown primary site.

PURPOSE We previously demonstrated a survival advantage for nodal metastasis of melanoma from an unknown primary (MUP) versus melanoma from a known primary (MKP). We hypothesized that this survival benefit would extend to MUP patients with distant (stage IV) metastasis. PATIENTS AND METHODS We reviewed prospectively acquired data for 2,247 patients diagnosed with American Joint Committee on Cancer stage IV melanoma at our cancer center between 1971 and 2005. Cox regression analysis in a multivariate model identified prognostic factors significant for survival. MUP and MKP patients were then matched by significant covariates. Overall survival (OS) was estimated by Kaplan-Meier method and compared by log-rank analysis. Results There were 1,849 MKP and 398 MUP patients. Multivariate analysis of patients with complete data sets identified known/unknown primary (hazard ratio [HR], 1.141; P = .032) and five other significant covariates: age (HR, 1.148; P = .007), sex (HR, 1.17; P = .001), site of metastasis (HR, 1.336; P < .001), number of different metastatic sites (HR, 1.303; P < .001), and decade of diagnosis (HR, 0.713; P < .001). Prognostic matching yielded 392 MUP-MKP pairs. Median OS and 5-year OS rate were significantly greater (P < .001) for MUP patients than for all matched MKP patients or for MKP patients matched by M1 category (for M1b and M1c) or number of metastatic sites. CONCLUSION The survival advantage previously reported for patients with stage III MUP also applies to patients with stage IV MUP. The mechanism responsible for this improved survival may provide clues for more effective treatment of stage IV melanoma and therefore warrants further investigation. The improved results for MUP suggest that these patients deserve aggressive therapy.

Solitary dermal melanoma: beginning or end of the metastatic process?

BACKGROUND: Solitary dermal melanoma (SDM) is confined to the dermal and/or subcutaneous tissue without an epidermal component. It is unclear whether this lesion is a subtype of primary melanoma or distant cutaneous metastasis from an unknown primary. We evaluated our large experience to determine the prognosis and optimal management of SDM. METHODS: Our melanoma referral center's database of prospectively acquired records was used for identification and clinicopathologic analysis of patients presenting with SDM between 1971 and 2005. RESULTS: Of 12,817 database patients seen during a 34-year period, 101 (0.8%) had SDM. Of 92 patients free of distant metastasis on initial presentation, 55 (60%) were observed and 37 (40%) underwent surgical nodal staging: regional metastases were identified in 7 (19%). Nodal recurrence occurred in 1 of 30 patients (3.3%) with histopathology-negative nodes compared with 13 of 55 patients (24%) who underwent nodal observation instead of nodal staging. Thus, 21 of 92 patients (23%) had nodal metastasis identified during surgical nodal staging or postoperative nodal observation. At a median follow-up of 68 months, estimated 5-year overall survival rate was 73% for 71 patients with localized disease versus 67% for 21 patients with regional disease (P=0.25) versus 22% for 9 patients with distant disease (P=0.009, regional versus distant disease). CONCLUSIONS: SDM resembles intermediate-thickness primary cutaneous melanoma with respect to prognostic characteristics and clinical evolution, but its rate of distant metastasis justifies radiographic staging and its high rate of regional node metastasis justifies wide excision and sentinel node biopsy.

Training tissue bank operators: the International Atomic Energy Agency (IAEA)/National University of Singapore (NUS) 10 years of experience.

National University of Singapore (NUS) was appointed by IAEA to become IAEA/NUS Regional Training Centre (RTC) for Asia and the Pacific region in September 1996. The Government of Singapore (represented by the Ministry of Environment) with the National Science and Technology Board as the funding agency awarded a grant of S$225,500 to build a new purpose-built tissue bank to be the Regional Training Centre. National University Hospital provided a space of 2,000 square feet for this purpose. The first Diploma Course was launched on 3 November 1997 with 17 candidates with the first NUS Diploma Examination being held in October 1998. Between November 1997 and April 2007, a total of nine courses were conducted by RTC with a total of 180 tissue bank operators, 133 from Asia and the Pacific region (13 countries including 2 from Iran), 14 from Africa (Algeria, Egypt, Libya, Egypt, South Africa and Zambia), 6 from Latin America (Brazil, Chile, Cuba, Peru and Uruguay), 9 from Europe (Greece, Slovakia, Poland, Ukraine) and 2 from Australia. The last batch (ninth batch) involved twenty students registered in April 2007 and will be due to sit for the terminal examination only in April 2008.

Improved survival after lymphadenectomy for nodal metastasis from an unknown primary melanoma.

PURPOSE: No primary lesion is identified in 10% to 20% of patients presenting with palpable evidence of regional metastatic melanoma. Because the prognostic significance of unknown primary melanoma (MUP) is unclear, we compared clinical outcomes of patients with MUP and known primary melanoma (MKP) with regional nodal metastases. PATIENTS AND METHODS: We reviewed our 13,000-patient prospective melanoma database (1971 through 2005) to identify patients managed with regional lymphadenectomy for palpable nodal metastases from MUP or MKP. Multivariate analysis identified prognostic factors significant for survival. MUP and MKP were then matched by significant covariates. Overall survival (OS) was estimated by Kaplan-Meier method and compared by log-rank analysis. RESULTS: Multivariate analysis of data from 1,571 study patients identified four significant covariates associated with worse prognosis: age >or= 60 years (hazard ratio [HR] = 1.294; P = .0017), male sex (HR = 1.335; P = .0004), nodal tumor burden >or= one (HR = 1.256; P < .0001), and known primary (HR = 1.507; 95% CI, 1.220 to 1.862; P = .0001). Five-year OS was significantly higher for 262 patients with MUP than for 1,309 patients with MKP (55% +/- 6% v 44% +/- 3%; P = .0021). Computerized matching of MUP and MKP by four significant covariates (age, sex, nodal tumor burden, and decade of diagnosis) yielded 221 matched pairs. Median and 5-year OS rates were 165 months and 58% +/- 7%, respectively, for MUP as compared with 34 months and 40% +/- 7%, respectively, for MKP (P = .0006). CONCLUSION: Lymphadenectomy is effective for nodal metastasis from MUP. The significantly better postoperative survival for MUP versus MKP suggests a strong endogenous immune response against the primary melanoma. Immunologic studies to identify cell-mediated and antibody components of this response may lead to new approaches for determining melanoma prognosis and treatment.

Management of T2 gallbladder cancer: are practice patterns consistent with national recommendations?

BACKGROUND: The national recommendation for the management of localized T2 gallbladder cancer (GBCA) is radical cholecystectomy. Although reported survival for localized T2 disease has been poor, groups have documented improvement with radical resection. We hypothesized that a discrepancy exists between national recommendations and current practice patterns. METHODS: Patients diagnosed with localized T2 GBCA between 1988 and 2002 were identified from the Surveillance, Epidemiology, and End Results registry. Age, sex, race, ethnicity, extent of surgery, and overall survival were assessed. Surgical procedure was categorized as cholecystectomy alone (CS), cholecystectomy plus lymph node dissection (CS+LN), radical cholecystectomy (RCS), or other. Survival calculations were made using the Kaplan-Meier method and compared with the log-rank test. RESULTS: Of 382 patients with pathologically confirmed T2 GBCA, 280 were women. The median patient age was 75 years. A total of 238 patients underwent CS, 76 underwent CS+LN, and 14 underwent RCS. The remaining 54 patients underwent a lesser or no procedure and were excluded from comparative analysis. The median survival was 14 months for all patients and 14, 14, and 8 months for subgroups treated with CS, CS+LN, and RCS, respectively. Rates of 5-year survival were 23%, 24%, and 36% for CS, CS+LN, and RCS subgroups, respectively. There was no significant difference in survival rates between RCS and CS+LN, or between RCS and CS. CONCLUSIONS: The majority of patients with T2 GBCA in the United States are not managed according to current national recommendations.

Aprotinin may decrease blood loss in complex adult spinal deformity surgery, but it may also increase the risk of acute renal failure.

STUDY DESIGN: Matched cohort comparison. OBJECTIVE: This study examines the potential for aprotinin to conserve blood in adults undergoing long thoracolumbar deformity procedures and characterizes patients at risk for acute renal failure. SUMMARY OF BACKGROUND DATA: Aprotinin has been shown to reduce intraoperative blood loss and reduce transfusion requirement in pediatric spine and cardiac surgery populations. Previous literature (before 2006) has not reported acute renal failure as a potential complication. This study was designed to examine the efficacy of aprotinin in reducing operative blood loss following long spinal arthrodesis in adult spinal deformity patients and to analyze complications. METHODS: Adult spinal deformity patients undergoing long spinal arthrodesis at 1 institution between 2001 and 2005 were analyzed. Patients were matched according to age and type of procedure performed. Forty patients received high-dose aprotinin (Group A) intraoperatively, and 41 patients matched as controls (Group NA) received no aprotinin. Outcome variables included intraoperative blood loss, intraoperative transfusion requirement, early postoperative blood loss and transfusion requirement, and postoperative complications. RESULTS: Average blood loss for Group A was 906 mL and 1.3 L for Group NA. The difference was statistically significant with a P < 0.05. Complications seen in Group A included 4 cases of acute renal failure requiring dialysis and 1 deep venous thrombosis. In Group NA, there was only 1 case of acute renal failure (presumed to be secondary to inadvertent gentamycin overdose) and 1 case of pulmonary embolus. The 4 Group A patients with acute renal failure were female, 61 to 73 years of age, with various comorbidities. All required inpatient hemodialysis. Three averaged 2 months of continued outpatient dialysis before resolution of renal compromise while 1 patient is on chronic dialysis. CONCLUSION: In long spinal arthrodesis for complex adult spinal deformity surgery, aprotinin does reduce intraoperative blood loss, but may increase the risk of acute renal failure, especially in women over the age of 60.

Hepatic cytoreductive surgery for neuroendocrine cancer.

Patients with gut-based metastatic neuroendocrine tumors (NET) often present late in the course of their slowly progressive disease, when cancer has extended beyond the point of reasonable expectation for surgical cure. At this stage of disease, the tumor's overwhelming hormonal production often significantly impairs the patient's quality of life. Unlike patients with other malignancies that might involve a heavy burden of hepatic metastatic disease, many patients with metastatic NET continue to live for a long time despite escalating hormone-related symptoms. This establishes the justification and rationale for cytoreduction, a noncurative surgical intervention that reduces tumor burden and hormonal burden and thereby can significantly increase symptom-free survival in the setting of an often slow but inevitable disease progression.

Candida parapsilosis keratitis following treatment of epithelial ingrowth after laser in situ keratomileusis.

PURPOSE: To present a case of Candida parapsilosis following laser in situ keratomileusis (LASIK). METHODS: Retrospective chart review. RESULTS: A case report of a 51-year-old woman who underwent bilateral LASIK is presented. Two weeks after the procedure, the patient presented with epithelial ingrowth OD. The ingrowth was treated with flap lifting and scraping, followed by postoperative antibiotics. Four weeks later, the patient presented with numerous interface infiltrates. Smears were positive for yeast forms and cultures grew Candida parapsilosis. Administration of topical and systemic antifungal therapy resulted in clearing of the infection with partial visual recovery. CONCLUSIONS: To our knowledge, this represents the first reported case of a post-LASIK Candida parapsilosis keratitis. A high degree of suspicion coupled with rapid and appropriate treatment can result in visual recovery.

The role of fluorine-18 deoxyglucose positron emission tomography in the management of patients with metastatic melanoma: impact on surgical decision making.

Malignant melanoma can metastasize to almost any organ site. Optimal management requires sensitive radiographic evaluation of the entire body. The optimal management of patients with metastatic melanoma requires accurate assessment of extent of disease (EOD). The objective of this study was to evaluate the accuracy of fluorine-18 deoxyglucose (FDG) whole-body positron emission tomography (PET) in determination of EOD in patients with metastatic melanoma and its impact on surgical and medical management decisions. Forty-nine patients (30 men, 19 women; aged 25-83 years) with known or suspected metastatic melanoma underwent EOD evaluation using computerized tomography (CT) of the chest, abdomen, and pelvis, and magnetic resonance imaging (MRI) of the brain. After formulation of an initial treatment plan, the patients underwent FDG-PET imaging. The EOD determined by PET was compared with physical examination and conventional radiography findings. Fifty-one lesions were pathologically evaluated. The impact of PET on patient management was assessed based on the alterations made in the initial treatment plan after reevaluation of the patients using the information obtained by PET. The PET scan identified more metastatic sites in 27 of 49 (55%) of the patients who had undergone a complete set of imaging studies, including CT scans of the chest, abdomen, and pelvis, and MRI of the brain. In 6 of those 27 patients, PET detected disease outside the fields of CT and MRI. Fifty-one lesions were resected surgically. Of these, 44 were pathologically confirmed to be melanoma. All lesions larger than 1 cm (29 of 29) were positive on PET, whereas only 2 of 15 (13%) lesions smaller than 1 cm were detected by PET. The results of PET led treatment changes in 24 patients (49%). Eighteen of these changes (75%) were surgical. In 12 cases (67%), the planned operative procedure was cancelled, and in 6 cases (33%), an additional operation(s) was performed. In 6 of 24 (25%) patients, biochemotherapy, radiation therapy, or an experimental immunotherapy protocol was prompted by identification of new foci of disease. Compared with conventional imaging, FDG-PET provides more accurate assessment of EOD in patients with metastatic melanoma. Significant surgical and medical treatment alterations were made based on PET results.

Structure analysis of peptide deformylases from Streptococcus pneumoniae, Staphylococcus aureus, Thermotoga maritima and Pseudomonas aeruginosa: snapshots of the oxygen sensitivity of peptide deformylase.

Peptide deformylase (PDF) has received considerable attention during the last few years as a potential target for a new type of antibiotics. It is an essential enzyme in eubacteria for the removal of the formyl group from the N terminus of the nascent polypeptide chain. We have solved the X-ray structures of four members of this enzyme family, two from the Gram-positive pathogens Streptococcus pneumoniae and Staphylococcus aureus, and two from the Gram-negative bacteria Thermotoga maritima and Pseudomonas aeruginosa. Combined with the known structures from the Escherichia coli enzyme and the recently solved structure of the eukaryotic deformylase from Plasmodium falciparum, a complete picture of the peptide deformylase structure and function relationship is emerging. This understanding could help guide a more rational design of inhibitors. A structure-based comparison between PDFs reveals some conserved differences between type I and type II enzymes. Moreover, our structures provide insights into the known instability of PDF caused by oxidation of the metal-ligating cysteine residue.