Doubling of 30-Day Mortality by 90 Days After Esophagectomy: A Critical Measure of Outcomes for Quality Improvement.

OBJECTIVES: Our objectives were to (1) compare 30- and 90-day mortality rates after esophagectomy, (2) compare drivers of 30- and 90-day mortality, and (3) examine whether 90-day mortality affects hospital rankings. BACKGROUND: Operative mortality has traditionally been assessed at 30 days. Ninety-day mortality has been suggested as a more appropriate indicator of quality, particularly after complex cancer surgery. METHODS: Esophagectomies for nonmetastatic esophageal cancer patients diagnosed between 2007 and 2011 were identified in the National Cancer Data Base. Mortality rates were examined by patient demographics, tumor characteristics, and hospital procedural volume. Risk-adjusted hierarchical logistic regression models examined hospital performance for mortality. RESULTS: A total of 15,796 esophagectomy patients at 977 hospitals were available for analysis. Ninety-day overall mortality was more than double the 30-day mortality (8.9% vs 4.2%; P < 0.0001). In multivariate analysis, while both 30- and 90-day mortality were associated with patient factors such as age, comorbidity, and hospital volume, only 90-day mortality was influenced by tumor- and management-related variables such as stage, tumor location, and receipt of neoadjuvant therapy. Hospital performance was examined as top 10%, middle 10% to 90%, and lowest 10% as ranked using risk-adjusted odds of mortality. There was moderate correlation between ranking based on 30- and 90-day mortality [weighted κ = 0.45 (95% confidence interval, 0.39-0.52)]. Compared with 30-day mortality rankings, nearly 20% of hospitals changed their ranking category when 90-day mortality rankings were used. CONCLUSIONS: Examination of 90-day mortality after esophagectomy reflects cancer patient management decisions and may provide actionable targets for quality improvement.

Pathological outcome and biochemical recurrence-free survival after radical prostatectomy in African-American, Afro-Caribbean (Jamaican) and Caucasian-American men: an international comparison.

OBJECTIVE: To compare pathological and biochemical outcomes of radical prostatectomy (RP) among African-American (AA), Afro-Caribbean (AC; Jamaican) and Caucasian-American (CA) men using an international cohort of patients who underwent RP in the USA and Jamaica. MATERIALS AND METHODS: A retrospective review was performed of men who underwent RP for clinically organ-confined (OC) prostate cancer between 2000 and 2011 at Columbia University Medical Center (New York, USA) and the University Hospital of the West Indies (Kingston, Jamaica) between 2000 and 2007. Men who had received neoadjuvant or adjuvant (within 3 months) therapy were excluded. Clinicopathological variables were compared among the three groups, focusing on age, stage, PSA level, Gleason sum (GS) and margin status. Multivariate analysis was performed to determine the predictors of biochemical recurrence (BCR; PSA >0.2 ng/mL), and Kaplan-Meier analysis was performed to determine BCR-free survival rates in AA, AC and CA men. RESULTS: A total of 483 men underwent RP for clinically OC disease (CM, n = 309, AA, n = 93 and AC, n = 81). The mean patient age was 59 years, with AA men being younger than CA men (58 vs 60 years, P< 0.05). The mean (range) follow-up was 49 (13-133) months with no significant difference among the groups. The men in the AC cohort had a higher mean PSA level than AA and CA men (8.8 vs 6.2 and 5.0 ng/mL, respectively, P< 0.05) and more clinical GS ≥7 (44%) tumours than AA (8%) and CA men (0%; P< 0.01). On multivariate analysis, controlling for stage, grade, PSA level and margins, AA and AC race were independent predictors of BCR. AA and AC men had significantly lower 5-year BCR-free survival (76 and 74%, respectively) than CA men (98% [P < 0.001]). CONCLUSIONS: This international comparison of clinicopathological outcomes in AA, AC and CA men undergoing RP shows that AA and AC men present similarly with more aggressive disease features than CA men and have lower 5-year BCR-free survival. Both AA and AC race are significant predictors of BCR, independently of stage, grade, PSA level and margin status. Further research is needed to elucidate and correct the mechanisms behind the observed difference in outcome among these populations.

Transgenic biosynthesis of trypanothione protects Escherichia coli from radiation-induced toxicity.

Trypanothione is a unique diglutathionyl-spermidine conjugate found in abundance in trypanosomes but not in other eukaryotes. Because trypanothione is a naturally occurring polyamine thiol reminiscent of the synthetic drug amifostine, it may be a useful protector against radiation and oxidative stress. For these reasons we hypothesized that trypanothione might serve as a radioprotective agent when produced in bacteria. To accomplish this objective, the trypanothione synthetase and reductase genes from T. cruzi were introduced into E. coli and their expression was verified by qPCR and immunoblotting. Trypanothione synthesis in bacteria, detected by HPLC, resulted in decreased intracellular levels of reactive oxygen species as determined by H(2)DCFDA oxidation. Moreover, E. coli genomic DNA was protected from radiation-induced DNA damage by 4.6-fold in the presence of trypanothione compared to control bacteria. Concordantly, the transgenic E. coli expressing trypanothione were 4.3-fold more resistant to killing by (137)Cs gamma radiation compared to E. coli devoid of trypanothione expression. Thus we have shown for the first time that E. coli can be genetically engineered to express the trypanothione biosynthetic pathway and produce trypanothione, which results in their radioresistance. These results warrant further research to explore the possibility of developing trypanothione as a novel radioprotective agent.

Bombesin Immunoreactivity in the stomach and small intestine of alloxan-diabetics Sprague Dawley rats.

Bombesin is a neuroendocrine peptide found in the submucosal nerve endings in the esophagus, stomach and small intestine. It is reported to stimulate the release of gastrointestinal hormones, control satiety, stimulate gastrointestinal motility, and also stimulate cellular proliferation which results in wound healing. Transient increases in bombesin concentration in the brain and serum (later followed by decrease in serum concentrations) have been reported in hyperglycemic states. The aim of this investigation is to determine the effect of hyperglycemia on bombesin secreting neurons in the submucosa of the GIT and the possible contribution of such changes to some diabetic complications. Result showed decreased immunoreactivity to bombesin in the sub mucosal neurons of the stomach and small intestine of alloxan-diabetic Sprague-Dawley rats. We conclude that the reduced immunoreactivity of bombesin in these submucosal neurons, may contribute to the reduced paracrine-induced peristalsis, observed in diabetics. It may also contribute to poor wounds healing in diabetics.

Glucagon-like Peptide-1 (GLP-1) immunoreactivity in the intestine of Alloxan-diabetic Sprague Dawley rat.

Intestinal L-cells synthesize a proglucagon molecule which is processed to form glucagons-like peptide 1(GLP-1) and glucagons-like peptide-2 (GLP-2) together with other peptides. The L-cells contain the enzyme proglucagon convertase1 (PC1) and proglucagon convertase3 (PC3). Plasma levels of GLP-1 have been reported to vary in types 1 and 2 diabetes and in experimental type 1 diabetic rats. The â-cell of the pancreatic islets contain predominantly PC2, and the predominant peptide secreted are glucagon and GLP-1; the latter is reported to stimulate the release of insulin from pancreatic â-cells, and also to stimulate the proliferation of â-cells. The antidiabetogenic potential of GLP-1 has been reported, and the analogue has been used to control blood glucose levels in type 2 diabetics. In this experiment the immunoreactivity of GLP-1 in the L-cells of the small intestine and colon of alloxan diabetic Sprague Dawley rats was investigated. Results showed that the immunoreactivity of GLP-1 was significantly reduced in the L-cells of the small intestine and the colon of alloxan diabetic rats.

Bombesin Immunoreactivity in the stomach and small intestine of alloxan-diabetics Sprague Dawley rats.

Bombesin is a neuroendocrine peptide found in the submucosal nerve endings in the esophagus, stomach and small intestine. It is reported to stimulate the release of gastrointestinal hormones, control satiety, stimulate gastrointestinal motility, and also stimulate cellular proliferation which results in wound healing. Transient increases in bombesin concentration in the brain and serum (later followed by decrease in serum concentrations) have been reported in hyperglycemic states. The aim of this investigation is to determine the effect of hyperglycemia on bombesin secreting neurons in the submucosa of the GIT and the possible contribution of such changes to some diabetic complications. Result showed decreased immunoreactivity to bombesin in the sub mucosal neurons of the stomach and small intestine of alloxan-diabetic Sprague-Dawley rats. We conclude that the reduced immunoreactivity of bombesin in these submucosal neurons, may contribute to the reduced paracrine-induced peristalsis, observed in diabetics. It may also contribute to poor wounds healing in diabetics.

Glucagon-like Peptide-1 (GLP-1) immunoreactivity in the intestine of Alloxan-diabetic Sprague Dawley rat.

Intestinal L-cells synthesize a proglucagon molecule which is processed to form glucagons-like peptide 1(GLP-1) and glucagons-like peptide-2 (GLP-2) together with other peptides. The L-cells contain the enzyme proglucagon convertase1 (PC1) and proglucagon convertase3 (PC3). Plasma levels of GLP-1 have been reported to vary in types 1 and 2 diabetes and in experimental type 1 diabetic rats. The â-cell of the pancreatic islets contain predominantly PC2, and the predominant peptide secreted are glucagon and GLP-1; the latter is reported to stimulate the release of insulin from pancreatic â-cells, and also to stimulate the proliferation of â-cells. The antidiabetogenic potential of GLP-1 has been reported, and the analogue has been used to control blood glucose levels in type 2 diabetics. In this experiment the immunoreactivity of GLP-1 in the L-cells of the small intestine and colon of alloxan diabetic Sprague Dawley rats was investigated. Results showed that the immunoreactivity of GLP-1 was significantly reduced in the L-cells of the small intestine and the colon of alloxan diabetic rats.

Effect of alloxan diabetes, on glicentin-secreting L-cells in the small intestine of Sprague Dawley rats,

The L-cells of the small intestine synthesize a proglucagon molecule which is processed to form glicentin, oxyntomodulin, glucagon-like peptide 1 (GLP-1) and glucagons-like peptide 2 (GLP-2). Glicentin and oxyntomodulin inhibit gastric secretion, and delay tansit time through the stomach. Serum concentrations of GLP-1 and GLP-2 have been reported to vary in types 1 and 2 diabetes and in streptozocin induced diabetic rats. It was initially thought that these variations were due to the activity of intestinal L- cells, but it was later found that this was from pancreatic alpha cells. Very little work had been done on the effect of diabetes on glicentin producing cells of the gut. In this experiment the effects of alloxan diabetes on glicentin producing L-cells of the intestines was investigated using immunohistochemical techniques. Results showed that the immunoreactivity of glicentin was noticeablly reduced in the L-cells of the small intestine of alloxan-diabetic rats.

Effect of alloxan diabetes, on glicentin-secreting L-cells in the small intestine of Sprague Dawley rats,

The L-cells of the small intestine synthesize a proglucagon molecule which is processed to form glicentin, oxyntomodulin, glucagon-like peptide 1 (GLP-1) and glucagons-like peptide 2 (GLP-2). Glicentin and oxyntomodulin inhibit gastric secretion, and delay tansit time through the stomach. Serum concentrations of GLP-1 and GLP-2 have been reported to vary in types 1 and 2 diabetes and in streptozocin induced diabetic rats. It was initially thought that these variations were due to the activity of intestinal L- cells, but it was later found that this was from pancreatic alpha cells. Very little work had been done on the effect of diabetes on glicentin producing cells of the gut. In this experiment the effects of alloxan diabetes on glicentin producing L-cells of the intestines was investigated using immunohistochemical techniques. Results showed that the immunoreactivity of glicentin was noticeablly reduced in the L-cells of the small intestine of alloxan-diabetic rats.

Effect of water extract of Coraili (Momordica charantia) on blood glucose levels in Sprague Dawley Rays [abstract]

Water extracts from the fruit of the coraili plant, Mormordica charantia, have been reported to have hypoglycaemic effect. The fruit of this plant is eaten as a vegetable by man. Significant lowering of blood glucose levels has been observed following the oral administration of coraili fruit extracts. However, some authors have shown that there are no beneficial hypoglycaemic effect from fruit extracts. In this experiment, water extract of the entire coraili fruit was administered orally to alloxan-diabetic Sprague Dawley Rats ad libitum for 7 hours. The rats were placed on normal diet during the experiment. Results showed that 7 hours after the administration of this extract, blood glucose levels dropped significantly. It was also observed that, 7 hours after the discontinuation of the administration of the extract in alloxan-diabetic rats, blood glucose levels rose close to the pre-administration levels. The implications of these findings will be discussed. (AU)

Identification of Anopheles aquasalis as a possible vector of malaria in Guyana, South America

Adult female mosquitoes were collected in Mahdia, Guyana, to determine the incidence of malaria in Anopheles species found during the month of June 2000. Centers for Disease Control miniature white (incandescent) light traps, model 512, and miniature black (ultraviolet) light traps, model 912, were used to capture female mosquitoes. Numbers of mosquitoes collected were compared between white and black light traps and between traps set outside and inside of buildings. Adult female Anopheles mosquitoes were identified and an ELISA dipstick test for Plasmodium vivax and Plasmodium falciparum was performed on each mosquito. An aquasalis, An oswaldoi, and An braziliensis were attracted to white light traps. An triannulatus and An darlingi were collected from black light traps. Approximately the same numbers of all female Anopheles mosquitoes 28/45 (62) were caught inside buildings as outside. Numbers of female non-anopheles mosquitoes captured in light traps varied between the traps set outside of buildings and inside of buildings with bright light traps collecting 91/122 (75). A total of 45 Anopheles mosquitoes were captured and 122 non-anopheles species. Of the two known vectors of malaria in Guyana, An darlingi mosquitoes were not infected with P vivax but An aquasalis was found to be a carrier. The findings of this study suggest a need for further surveying and identification of current malaria vectors in Guyana.

A randomized, double-blind study of triple nucleoside therapy of abacavir, lamivudine, and zidovudine versus lamivudine and zidovudine in previously treated human immunodeficiency virus type 1-infected children. The CNAA3006 Study Team.

OBJECTIVES: Abacavir (ABC) is a potent inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase. We compared the efficacy, safety, and tolerability of combination therapy with ABC, lamivudine (3TC), and zidovudine (ZDV) versus 3TC and ZDV in antiretroviral experienced HIV-1-infected children over 48 weeks. METHODS: Two hundred five HIV-1-infected children who had received previous antiretroviral therapy and had CD4(+) cell counts >/=100 cells/mm(3) were stratified by age and by previous treatment. Participants were randomly assigned to receive ABC (8 mg/kg twice daily [BID]) plus 3TC (4 mg/kg BID) and ZDV (180 mg/m(2) BID; ABC/3TC/ZDV group) or ABC placebo plus 3TC (4 mg/kg BID) and ZDV (180 mg/m(2); 3TC/ZDV group). Participants who met a protocol-defined switch criteria (plasma HIV-1 RNA >0.5 log(10) copies/mL above baseline at week 8 or >10 000 copies/mL after week 16) had the option to switch to open-label ABC plus any antiretroviral combination or continue randomized therapy or withdraw from the study. RESULTS: The Kaplan-Meier estimates (95% confidence interval) of the proportion of participants who maintained HIV-1 RNA levels 10 000 copies/mL, a significantly higher proportion of participants in the ABC/3TC/ZDV group had HIV-1 RNA

Identification of Anopheles aquasalis as a possible vector of malaria in Guyana, South America.

Adult female mosquitoes were collected in Mahdia, Guyana, to determine the incidence of malaria in Anopheles species found during the month of June 2000. Centers for Disease Control miniature white (incandescent) light traps, model 512, and miniature black (ultraviolet) light traps, model 912, were used to capture female mosquitoes. Numbers of mosquitoes collected were compared between white and black light traps and between traps set outside and inside of buildings. Adult female Anopheles mosquitoes were identified and an ELISA dipstick test for Plasmodium vivax and Plasmodium falciparum was performed on each mosquito. An aquasalis, An oswaldoi, and An braziliensis were attracted to white light traps. An triannulatus and An darlingi were collected from black light traps. Approximately the same numbers of all female Anopheles mosquitoes 28/45 (62%) were caught inside buildings as outside. Numbers of female non-anopheles mosquitoes captured in light traps varied between the traps set outside of buildings and inside of buildings with bright light traps collecting 91/122 (75%). A total of 45 Anopheles mosquitoes were captured and 122 non-anopheles species. Of the two known vectors of malaria in Guyana, An darlingi mosquitoes were not infected with P vivax but An aquasalis was found to be a carrier. The findings of this study suggest a need for further surveying and identification of current malaria vectors in Guyana.

Effect of prenatal zidovudine on disease progression in perinatally HIV-1-infected infants.

OBJECTIVE: To determine the influence of prenatal zidovudine (ZDV) prophylaxis on the course of HIV- 1 infection in children by comparing the clinical outcome of infants born to HIV- 1-seropositive mothers who did versus those who did not receive ZDV during pregnancy. METHODS: Medical records of HIV-1-seropositive mothers and their infants were reviewed retrospectively. Participants were divided according to maternal ZDV use: no ZDV (n = 152); ZDV (n = 139). The main outcome measure was rapid disease progression (RPD) in the infant, defined as occurrence of a category C disease or AIDS-related death before 18 months of age. RESULTS: HIV vertical transmission rates were significantly different (no ZDV versus ZDV: 22.3% versus 12.2%; p = .034). Among infected infants, the RPD rate was 29.4% in the no ZDV group compared with 70.6% in the ZDV group (p = .012), and prematurity was significantly associated with a higher risk of RPD (p = .027). CONCLUSIONS: The rate of RPD was significantly higher among perinatally infected infants born to HIV-infected mothers treated with ZDV than among infected infants born to untreated mothers. The decreased proportion of infected infants with nonrapid disease progression in the former group might be related to the ability of ZDV to block intrapartum transmission preferentially and also to nonrapid disease progression resulting from intrapartum transmission.

Expression of heat shock protein 70 in leukocytes of patients with sepsis.

The heat shock proteins are known to protect cells against diverse injuries such as cytotoxicity by TNFalpha acting mainly as chaperones for denatured proteins. Lipopolysaccharide stimulates the production and the release of numerous endogenous mediators of sepsis: tumor necrosis factor alpha, interleukin-1, and interleukin-6 that induce fever production. Moreover, temperature at 40 degrees C is sufficient to induce heat shock and attenuate both TNFalpha and IL-1 expression. We demonstrate a distinct profile in gene expression of HSP 70 family in leukocytes obtained from different phases of septic patients. Our findings strongly suggest that HSP 70 may play a role in the outcome of septic shock patients.

Identification of mayaro virus nucleocapsid protein in nucleus of Aedes albopictus cells.

The modifications in the pattern of nuclear proteins of Aedes albopictus cells in response to Mayaro virus infection were analysed early and late after infection. The viral capsid (C) protein of 34 kDa (p34) could be detected in the nuclear compartment 4 h after infection, soon after its synthesis in the cytoplasm. In addition to p34, a group of high molecular weight proteins was also present in this compartment late after infection. The exposition of infected cells to supra optimal temperature of growth modifies significantly the pattern of nuclear proteins. However, the stress condition does not inhibit the transport of p34 to the nucleus. The transport of proteins into nuclei was also followed under "in vitro' conditions by incubating radiolabeled post-mitochondrial extract of infected cells with unlabeled nuclei. Under these conditions, as observed "in vivo', a specific transport of viral C protein and of a group of proteins of high molecular weight to the nuclei was also detected. These results indicate that Mayaro virus infection modifies the nuclear protein pattern in invertebrate cells.

Transmission of western equine encephalomyelitis virus by Argentine Aedes albifasciatus (Diptera: Culicidae).

Aedes albifasciatus (Macquart) has been considered a potential vector of western equine encephalitis (WEE) virus in Argentina because it has been found naturally infected, it is susceptible to infection per os, and its distribution and feeding habits are compatible with those of an epizootic and epidemic vector. Ae. albifasciatus females collected in the vicinity of Cordoba, Argentina, were highly susceptible to WEE virus perorally (ID50 less than 0.5 Vero cell plaque-forming units) when fed on viremic chicks. Virus transmission trials were done 9 to 16 d after infection by feeding potentially infected mosquitoes individually on chicks. Among 31 mosquitoes that survived the incubation period, six refed on susceptible chicks. Virus transmission by bite was demonstrated by five of six (83%) mosquitoes. Therefore, the final piece of evidence incriminating Ae. albifasciatus as a natural vector of WEE virus has been obtained. This is the first mosquito species to be incriminated as a vector of WEE virus in South America.

Vector competence of North and South American strains of Aedes albopictus for certain arboviruses: a review.

Since the introduction of Aedes albopictus into North and South America, 18 viruses in 3 families have been used in vector competence studies involving 10 North American and 4 South American geographic strains of Ae. albopictus. This review summarizes the results of these studies and discusses the potential of Ae. albopictus to become a vector of arboviruses of public health importance in areas of the Western Hemisphere where it has recently become established.