Which comorbidity classification is best suited to identify patients at risk for 90-day and long-term non-bladder cancer mortality after radical cystectomy?

PURPOSE: There is no consensus on the best comorbidity measure in candidates for radical cystectomy. The aim of this study was to identify tool best suited to identify patients at risk for 90-day or premature long-term non-bladder cancer mortality. METHODS: We studied 1268 patients who underwent radical cystectomy to identify patients at risk for 90-day and later-than-90-day mortality, respectively. Six classifications were investigated as possible predictors of both types of mortality. Multivariable models including age as continuous variable and each classification separately were calculated. A heuristic ranking was based on the evaluation of the hazard ratios, p values, Akaike's information criteria, and concerning the logit models also the areas under the curve. RESULTS: The median follow-up was 5.7 years. Within 90 days after surgery, the mortality rate was 4.2%. The greatest independent contribution concerning the prediction of 90-day mortality was seen with the American Society of Anesthesiologists (ASA) physical status classification (classes 3-4 versus 1-2: hazard ratio 7.98, 95% confidence interval 3.54-18.01, p < 0.0001). In the longer term, countable diseases (Canadian Cardiovascular Society classification of angina pectoris, conditions contributing the Charlson score) were of greater importance. The results of heuristic ranking were confirmed by multivariate analyses including age and all classifications together. CONCLUSIONS: Besides to chronological age, clinicians should pay particular attention to the ASA classification to identify patients at risk for 90-day mortality after radical cystectomy, whereas long-term mortality is more determined by countable comorbid diseases.

Socioeconomic Status-Related Parameters as Predictors of Competing (Non-Bladder Cancer) Mortality after Radical Cystectomy.

OBJECTIVE: To investigate the impact of socioeconomic status-related parameters on competing (non-bladder cancer) mortality after radical cystectomy. PATIENTS AND METHODS: A total of 1,268 consecutive patients who underwent radical cystectomy for urothelial or undifferentiated bladder cancer at our institution between 1993 and 2016 with a mean age of 69 years (median 70 years) were studied. The mean -follow-up of the censored patients was 7.2 years (median 5.7 years). Proportional hazard models for competing risk were used to identify predictors of non-bladder cancer (competing) mortality. The following parameters were included into multivariate analyses: age, American Society of Anesthesiologists physical status classification, Charlson score, gender, level of education, smoking status, marital status, local tumour stage, lymph node status, adjuvant and neoadjuvant chemotherapy. RESULTS: Besides age and both comorbidity classifications, the socioeconomic status-related parameters gender (female versus male, hazard ratio [HR] 0.58, 95% CI 0.40-0.84, p = 0.0042), level of education (university degree or master craftsman versus others, HR 0.76, 95% CI 0.56-0.1.03, p = 0.0801), smoking status (current smoking versus others, HR 1.47, 95% CI 1.10-1.96, p = 0.0085) and marital status (married versus others, HR 0.68, 95% CI 0.50-0.92, p = 0.0133) were independent predictors of competing mortality after radical cystectomy. If considered in combination (multiplication of HRs), the prognostic impact of socioeconomic parameters superseded that of the investigated comorbidity classifications. CONCLUSION: Socioeconomic status-related parameters may provide important information on the long-term competing mortality risk after radical cystectomy supplementary to chronological age and comorbidity.

Validation of a Questionnaire-Suitable Comorbidity Index in Patients Undergoing Radical Cystectomy.

OBJECTIVE: To investigate the capability of a modified self-administrable comorbidity index recommended in the standard sets for neoplastic diseases published by the International Consortium for Health Outcomes Measurement (ICHOM) to predict 90-day and long-term mortality after radical cystectomy. METHODS: A single-center series of 1,337 consecutive patients who underwent radical cystectomy for muscle-invasive or high-risk non-muscle-invasive urothelial or undifferentiated bladder cancer were stratified by the modified self-administrable comorbidity index and Charlson score, respectively. Multivariate logit models (for 90-day mortality) and proportional-hazards models (for overall and non-bladder cancer mortality) were used for statistical workup. RESULTS: Considering 90-day mortality, both comorbidity indexes contributed independent information when analyzed together with age (p < 0.0001). The Charlson score performed slightly better (area under the curve [AUC] 0.74 vs. 0.72 for the ICHOM-recommended comorbidity index). Considering 5-year overall mortality in 727 patients with complete observation, the performance of both measures was similar (AUC 0.63 vs. 0.62, including age AUC 0.66 for both indexes). With 6-sided stratifications, the modified self-administrable comorbidity index separated the risk groups slightly better (p values for directly neighboring curves: 0.0068-0.1043 vs. 0.0001-0.8100). CONCLUSION: The ICHOM-recommended modified self-administrable comorbidity index is capable of predicting 90-day mortality and long-term non-bladder cancer mortality after radical cystectomy similarly to the commonly used Charlson score.

Rational application of antibiotics-The influence of anaesthetists' gender on self-confidence and knowledge.

BACKGROUND: High rates of multiresistant pathogens require detailed knowledge about rational utilization of antibiotics. Many physicians consider themselves uncertain about the interpretation of microbiological diagnostics. We examined whether self-confidence, self-rated knowledge, and objective knowledge regarding the use of antibiotics are associated with gender. METHODS: For this survey study, in 2017, anaesthesiologists and residents of 16 anaesthetic departments in Germany were asked to complete the Multiinstitutional Reconnaissance of practice with Multiresistant bacteria (MR2) survey. It consists of 55 items evaluating self-confidence regarding the practical use of antibiotics (n = 6), self-rated theoretical knowledge (n = 16), and objective knowledge (n = 5). Their answers to these items in relation to their gender were analysed using Chi-square, Kruskal-Wallis-H-Tests, and unadjusted as well as adjusted logistic regression models. RESULTS: Six hundred eighty-four (response rate: 53.9 %) questionnaires were returned and were available for analysis. Female doctors (35.5 %) felt less self-confident (P < 0.001). Self-rated knowledge differed in overall mean (P = 0.014) and the unadjusted (odds ratio [OR]: 0.55; P = 0.013) but not in the adjusted logistic regression (OR: 0.84; P = 0.525). Objective knowledge differed after pooling questions (61.2% correct answers vs 65.4%, P = 0.01) but not with respect to single items and the adjusted logistic regression (OR: 0.83, P = 0.356). CONCLUSION: Less self-confidence and a lower self-rated knowledge were found in female anaesthetists; this is consistent to the gender phenomena observed by other researchers. Nevertheless, between the 2 groups objective knowledge did not differ significantly in any item.

Predicting 90-day and long-term mortality in octogenarians undergoing radical cystectomy.

BACKGROUND: Radical cystectomy bears a considerable perioperative mortality risk particularly in elderly patients. In this study, we searched for predictors of perioperative and long-term competing (non-bladder cancer) mortality in elderly patients selected for radical cystectomy. METHODS: We stratified 1184 consecutive patients who underwent radical cystectomy for high risk superficial or muscle-invasive urothelial or undifferentiated carcinoma of bladder into two groups (age < 80 years versus 80 years or older). Multivariable and cox proportional hazards models were used for data analysis. RESULTS: Whereas Charlson score and the American Society of Anesthesiologists (ASA) physical status classification (but not age) were independent predictors of 90-day mortality in younger patients, only age predicted 90-day mortality in patients aged 80 years or older (odds ratio per year 1.24, p = 0.0422). Unlike in their younger counterparts, neither age nor Charlson score or ASA classification were predictors of long-term competing mortality in patients aged 80 years or older (hazard ratios 1.07-1.10, p values 0.21-0.77). CONCLUSIONS: This data suggest that extrapolations of perioperative mortality or long-term mortality risks of younger patients to octogenarians selected for radical cystectomy should be used with caution. Concerning 90-day mortality, chronological age provided prognostic information whereas comorbidity did not.

Gender and Mortality after Radical Cystectomy: Competing Risk Analysis.

BACKGROUND: Data on the impact of gender on mortality after radical cystectomy is conflicting. We investigated a large single center sample with long-term follow-up in order to determine the relationship between gender and outcome. PATIENTS AND METHODS: A total of 1,184 consecutive patients who underwent radical cystectomy for high risk superficial or muscle-invasive urothelial or undifferentiated bladder cancer between 1993 and 2015 were stratified by gender. Demographic data was compared using Mann-Whitney U test, chi-square test, or Fisher exact test. Cox proportional hazard models were used for the analysis of competing risks and logit models were used for the prediction of the receipt of adjuvant cisplatin-based chemotherapy. RESULTS: Female patients were older, healthier, less frequently current smokers and had more extravesical tumors. In the multivariate analyses, female gender was an independent predictor of (lower) non-bladder cancer (competing) mortality (hazards ratio [HR] 0.68, 95% CI 0.49-0.95, p = 0.0248) but no predictor of bladder cancer-specific mortality (HR in the full model 1.20, 95% CI 0.94-1.54, p = 0.15). Gender was no predictor of the receipt of adjuvant cisplatin-based chemotherapy. CONCLUSIONS: Female gender was associated with an increased risk of extravesical disease but was no independent predictor of bladder cancer-specific mortality. Anatomical differences might be a plausible explanation for these observations.

Age, American Society of Anesthesiologists physical status classification and Charlson score are independent predictors of 90-day mortality after radical cystectomy.

PURPOSE: Radical cystectomy (RC) is a major surgical procedure accompanied with meaningful complications and countable perioperative mortality. To identify the risk factors predicting the perioperative morbidity and mortality is essential. The study aimed to identify relevant, patient-specific factors associated with 90-day mortality following RC, which may serve as a foundation for improving healthcare delivery to patients with bladder cancer. METHODS: We investigated a sample of 1015 consecutive patients in order to identify predictors of 90-day mortality after RC. Beside tumor-related parameters, ASA classification, NYHA, Canadian Cardiovascular Society classification of angina pectoris, Charlson score, age, gender and the single conditions contributing to the Charlson score were included in the multivariable analyses. The patient data were collected retrospectively, except the ASA score that was obtained prospectively. RESULTS: We identified a model containing the parameters age (OR 1.05, p = 0.023), ASA classification of 3-4 (OR 6.19, p < 0.001) and Charlson score (OR 1.22, p = 0.003) to predict 90-day mortality. Among the single conditions to the Charlson score, moderate or severe renal disease (OR 3.94, p < 0.001) and liver disease (OR 3.24, p = 0.037) were most closely related to 90-day mortality. CONCLUSIONS: Age, ASA classification and Charlson score as well as moderate or severe renal disease and liver disease appear to be independent predictors of 90-day mortality after RC. Given the highly significant association of ASA score with 90-day mortality and the relative ease and width disposability of this measure, this classification should be, after external validation, incorporated into daily clinical practice in treatment of patients planned to RC.

Effect of perfluorohexane on the expression of cellular adhesion molecules and surfactant protein A in human mesothelial cells in vitro.

The intraperitoneal instillation of perfluorocarbons augmented systemic oxygenation and was protective in mesenteric ischemia-reperfusion and experimental lung injury. To study biocompatibility and potential anti-inflammatory effects of intraperitoneal perfluorocarbons, we evaluated the influence of perfluorohexane and/or inflammatory stimuli on human mesothelial cells in vitro. Perfluorohexane exposure neither impaired cell viability nor induced cellular activation. TNFα enhanced ICAM-1 expression, which was not attenuated by simultaneous perfluorohexane treatment. Concentration of intracellular surfactant protein A tended to be higher in perfluorohexane treated cells compared to controls. Our in vitro data add further evidence that intraperitoneal perfluorocarbon application is feasible without adverse local effects.

Decreasing Non-bladder-cancer Mortality After Radical Cystectomy.

Life expectancy is increasing in many parts of the world. Using proportional hazard models for competing risks, we investigated whether this increase has changed outcomes after radical cystectomy in a sample of 1419 consecutive patients treated between 1993 and 2018. During the observation period, the mean age and the proportion of patients with American Society of Anesthesiologists physical status class 3 or 4 increased, whereas the proportion of patients with heart disease decreased. Competing mortality (causes other than bladder cancer) decreased in all subgroups (hazard ratios [HRs] per year ranged from 0.931 to 0.963) and after controlling for increasing age (HRs ranged from 1.018 to 1.081). In an optimal model resulting from an analysis including age (HR per year 1.048, 95% confidence interval [CI] 1.027-1.070; p < 0.0001), comorbidity, tumor-related variables, body mass index, (neoadjuvant and adjuvant) chemotherapy and smoking status, the HR per increment for year of surgery was 0.928 (95% CI 0.886-0.973; p = 0.0019). The effect of year of surgery was greater than the decrease in competing mortality that may be expected with increasing life expectancy (4 yr for females, 6 yr for males). PATIENT SUMMARY: In a review of data for 1993-2018, we found that death from other causes after removal of the bladder (radical cystectomy) for bladder cancer decreased over time. This decreasing trend might increase the age limit at which bladder cancer patients can benefit from radical cystectomy in the future.

Effects of perfluorohexane vapor in the treatment of experimental lung injury.

RATIONALE: We investigated the effects of vaporized perfluorohexane (PFH) on pulmonary vascular tone, pulmonary vascular resistance and peak inspiratory pressure as well as lipid mediator formation in the treatment of calcium ionophore induced lung injury in a model of the isolated perfused and ventilated rabbit lungs. METHODS: Lung injury was induced in isolated perfused and ventilated rabbit lungs by calcium ionophore A23187. Lungs were treated with either 4.5 vol.% (4.5 vol.% PFH; n = 6) or 18 vol.% (18 vol.% PFH; n = 6) PFH. Six lungs remained untreated (Control). In addition 5 lungs (PFH-sham) remained uninjured receiving 18 vol.% PFH only. Mean pulmonary artery pressure (mPAP), peak inspiratory pressure (P(max)), and lung weight (weight) were monitored for 120 min. Experiments were terminated before when the increase in lung weight exceeded 40 g. Perfusate samples were taken at regular intervals for analysis of TXB(2), 6-keto-PGF(1) and LTB(4). RESULTS: Controls reached the study end point significantly earlier than both PFH groups. Significant differences were found for a weight gain of 10 g and 20 g between the control and the 4.5 vol.% PFH and the 18 vol.% PFH. Differences in mPAP were more pronounced in the 4.5 vol.% PFH. However increases in P(max) were more marked in 4.5 vol.% PFH. TXA(2)-, PGI(2)-, and LTB(4)-levels were significantly lower in PFH groups. Uninjured lungs remained unaffected by the presence of 18 vol.% PFH. CONCLUSION: Inflammatory lung injury was attenuated by the treatment with 4.5 vol.% PFH and 18 vol.% PFH vapor in the isolated perfused rabbit lung. Therapeutic effects were more pronounced with a concentration of 4.5 vol.% PFH.

Pretreatment with perfluorohexane vapor attenuates fMLP-induced lung injury in isolated perfused rabbit lungs.

The authors investigated the protective effects and dose dependency of perfluorohexane (PFH) vapor on leukocyte-mediated lung injury in isolated, perfused, and ventilated rabbit lungs. Lungs received either 18 vol.% (n = 7), 9 vol.% (n = 7), or 4.5 vol.% (n = 7) PFH. Fifteen minutes after beginning of PFH application, lung injury was induced with formyl-Met-Leu-Phe (fMLP). Control lungs (n = 7) received fMLP only. In addition 5 lungs (PFH-sham) remained uninjured receiving 18 vol.% PFH only. Pulmonary artery pressure (mPAP), peak inspiratory pressure (P(max)), and lung weight were monitored for 90 minutes. Perfusate samples were taken at regular intervals for analysis and representative lungs were fixed for histological analysis. In the control, fMLP application led to a significant increase of mPAP, P(max), lung weight, and lipid mediators. Pretreatment with PFH attenuated the rise in these parameters. This was accompanied by preservation of the structural integrity of the alveolar architecture and air-blood barrier. In uninjured lungs, mPAP, P(max), lung weight, and lipid mediator formation remained uneffected in the presence of PFH. The authors concluded that pretreatment with PFH vapor leads to an attenuation of leukocyte-mediated lung injury. Vaporization of perfluorocarbons (PFCs) offers new therapeutic options, making use of their protective and anti-inflammatory properties in prophylaxis or in early treatment of acute lung injury.

Variable tidal volumes improve lung protective ventilation strategies in experimental lung injury.

RATIONALE: Noisy ventilation with variable Vt may improve respiratory function in acute lung injury. OBJECTIVES: To determine the impact of noisy ventilation on respiratory function and its biological effects on lung parenchyma compared with conventional protective mechanical ventilation strategies. METHODS: In a porcine surfactant depletion model of lung injury, we randomly combined noisy ventilation with the ARDS Network protocol or the open lung approach (n = 9 per group). MEASUREMENTS AND MAIN RESULTS: Respiratory mechanics, gas exchange, and distribution of pulmonary blood flow were measured at intervals over a 6-hour period. Postmortem, lung tissue was analyzed to determine histological damage, mechanical stress, and inflammation. We found that, at comparable minute ventilation, noisy ventilation (1) improved arterial oxygenation and reduced mean inspiratory peak airway pressure and elastance of the respiratory system compared with the ARDS Network protocol and the open lung approach, (2) redistributed pulmonary blood flow to caudal zones compared with the ARDS Network protocol and to peripheral ones compared with the open lung approach, (3) reduced histological damage in comparison to both protective ventilation strategies, and (4) did not increase lung inflammation or mechanical stress. CONCLUSIONS: Noisy ventilation with variable Vt and fixed respiratory frequency improves respiratory function and reduces histological damage compared with standard protective ventilation strategies.

Quantifying the Relationship Between Increasing Life Expectancy and Nonprostate Cancer Mortality After Radical Prostatectomy.

OBJECTIVE: To investigate the relationship between increasing life expectancy and nonprostate cancer (competing) mortality after radical prostatectomy. PATIENTS AND METHODS: We studied a single-center sample of 6809 consecutive patients who underwent radical prostatectomy between 1992 and 2016 with a median age of 65 years and a median follow-up of 7.9 years. Multivariate competing risk analyses were performed with competing mortality as endpoint. Linear trends over the years of surgery for 5-year competing mortality rates and for mean ages were calculated using linear regression analyses. We estimated the number of live years gained over time using a heuristic model-based calculation: (hazard ratio year of surgery) 24 calendar years × (hazard ratio age at surgery) gained life years = 1. RESULTS: After controlling for age, nonprostate cancer mortality decreased significantly during the observation period. Accumulated over the 24 years, this decrease of mortality corresponded to the effect of 6.3 years of calendric age. Most of the decrease in nonprostate cancer mortality (predominantly attributable to noncancer causes of death) was seen in patients aged 65 years or older (8.1 years gained), whereas there was only a marginal decrease in patients younger than 65 years (only 1 year gained). The decrease in nonprostate cancer mortality was accompanied by a slight increase of mean age at surgery (2.7 years) that did not nearly compensate the decreasing risk. CONCLUSION: Clinicians should be aware of the decreasing competing mortality risk in elderly candidates for radical prostatectomy in order to avoid undertreatment.

Validation of the Preoperative Score to Predict Postoperative Mortality in Patients Undergoing Radical Cystectomy.

Standardized prediction of perioperative mortality risk is of major clinical concern in the radical cystectomy setting. We validated the recently developed Preoperative Score to Predict Postoperative Mortality (POSPOM) in a sample of 1083 consecutive cystectomy patients treated between 1993 and 2014. POSPOM was calculated as originally described based on age and 13 further parameters; three parameters which were not available in our database were ignored. Thirty-day and 90-d mortality were 1.0% and 4.1%, respectively. The areas under the receiver operator characteristic curves were 0.86 for 30-d mortality and 0.78 for 90-d mortality. Below the median of 27 POSPOM risk points, 30-d mortality was 0% and 90-d mortality was 0.5%. Above this level, the corresponding figures were 1.7% and 6.5%, respectively. The 30-d (p<0.0001) and even the 90-d mortality rates (p=0.004) were lower than the POSPOM-predicted in-hospital mortality rate for this sample (5.8%). Nevertheless, with its good discriminative accuracy, POSPOM might standardize the prediction of postoperative mortality after radical cystectomy. The absolute mortality figures in a high volume academic center were, however, lower than predicted based on nationwide collected data. PATIENT SUMMARY: With a good discriminative accuracy, Preoperative Score to Predict Postoperative Mortality might standardize the prediction of postoperative mortality after radical cystectomy. The absolute mortality figures in a high volume academic center were, however, lower than predicted based on nationwide collected data.

Only <10% of Patients Selected for Radical Prostatectomy Reach the Competing Mortality Rate of the Prostate Cancer Intervention Versus Observation Trial (PIVOT).

In the Prostate Cancer Intervention Versus Observation Trial (PIVOT), surgery was not associated with lower mortality compared with observation. However, the high competing mortality rate of approximately 33% after 10 yr among the PIVOT study population has raised concerns on the generalizability of these results. We investigated 4282 patients who underwent radical prostatectomy at our institution between 1992 and 2010 to determine which subgroups harbored a competing (non-prostate cancer) mortality risk comparable to that of PIVOT and tested several combinations of higher age and comorbidities ("worst case scenarios") to identify subgroups reaching or even superseding the competing mortality rate of the PIVOT population. The competing mortality rate of PIVOT was not reached till an age-adjusted Charlson score of 5 or higher (corresponding to an age of 70-79 yr with diabetes with end-organ damage). Only 8.9% of patients belonged to this high-risk subgroup, and only small subgroups comprising 1-5% patients superseded the competing mortality rate among the PIVOT study population. This data underline that the results of PIVOT should be used with great caution to exclude candidates for radical prostatectomy with comorbidities from curative treatment. PATIENT SUMMARY: Only <10% of patients selected for radical prostatectomy reached the competing mortality rate of approximately 33% observed in the Prostate Cancer Intervention Versus Observation Trial (PIVOT). The results of PIVOT should be used with great caution to exclude patients with concomitant diseases who seem otherwise fit for radical prostatectomy from curative treatment.

Noisy pressure support ventilation: a pilot study on a new assisted ventilation mode in experimental lung injury.

OBJECTIVE: To describe and evaluate the effects of the new noisy pressure support ventilation (noisy PSV) on lung physiologic variables. DESIGN: Crossover design with four modes of mechanical ventilation. SETTING: Experimental research facility of a university hospital. SUBJECTS: A total of 12 pigs weighing 25.0-36.5 kg. INTERVENTIONS: Animals were anesthetized, the trachea was intubated, and lungs were ventilated with a mechanical ventilator (volume-controlled mode). Acute lung injury was then induced by surfactant depletion. Biphasic intermittent airway pressure/airway pressure release ventilation (BIPAP/APRV) was initiated, and anesthesia depth was decreased to allow spontaneous breathing. After that, each animal was ventilated with four different modes of assisted mechanical ventilation (1 hr each, Latin squares sequence): 1) PSV, 2) PSV combined with intermittent sighs (PSV + Sighs), 3) BIPAP/APRV + spontaneous breathing, and 4) noisy PSV with random variation of pressure support (normal distribution). The mean level of pressure support was set identical in all PSV forms. MEASUREMENTS AND MAIN RESULTS: We found that noisy PSV increased tidal volume variability compared with PSV and PSV + Sighs (19% vs. 5% and 7%, respectively, p < .05) independently from the inspiratory effort; improved oxygenation and reduced venous admixture but did not affect the amount of nonaerated lung tissue as compared with other assisted ventilation modes; reduced mean airway pressure at comparable minute ventilation; redistributed pulmonary blood flow toward nondependent lung regions similar to other PSV forms, whereas BIPAP/APRV + spontaneous breathing did not; and reduced the inspiratory effort and cardiac output in comparison with BIPAP/APRV + spontaneous breathing. CONCLUSIONS: In the surfactant depletion model of acute lung injury, the new noisy PSV increased the variability of the respiratory pattern and improved oxygenation by a redistribution of perfusion toward the ventilated nondependent lung regions with simultaneous lower mean airway pressure, comparable minute ventilation, and no increase in the inspiratory effort or cardiac output.

Selection Effects May Explain Smoking-related Outcome Differences After Radical Cystectomy.

The impact of smoking on mortality among patients with bladder cancer is subject to controversy. We investigated 1000 patients who consecutively underwent radical cystectomy between 1993 and 2013. Proportional hazards models for competing risks were used to study the combined effects of variables on mortality. Compared to nonsmokers, current smokers were more frequently male (35.7% vs 12.0%, p<0.0001), younger (63.5 vs 70.5 yr, p<0.0001), had a lower body mass index (26.2 vs 27.1kg/m2, p<0.0001), and suffered less frequently from cardiac insufficiency (12.7% vs 19.3%, p=0.0129). Among current smokers there was a trend towards lower bladder cancer mortality and higher competing mortality in comparison to nonsmokers. On multivariable analysis, current smoking was not a predictor of bladder cancer mortality (hazard ratio [HR] in the full model 0.76; p=0.0687) but was a predictor of competing mortality (HR in the optimal model 1.62; p=0.0044). In conclusion, this study did not confirm adverse bladder cancer-related outcome among current smokers after radical cystectomy. With a younger mean age and a male predominance, there was a trend towards lower bladder cancer mortality current smokers that was eventually neutralized by higher competing mortality, illustrating that selection effects may explain some smoking-related outcome differences after radical cystectomy. The single-center design is a study limitation. PATIENT SUMMARY: Current smokers are not at higher risk of bladder cancer after radical cystectomy but have a higher risk of competing mortality.

Effects of vaporized perfluorohexane and partial liquid ventilation on regional distribution of alveolar damage in experimental lung injury.

OBJECTIVE: To determine whether the patterns of distribution of histological effects of vaporized perfluorohexane (PFH) and partial liquid ventilation (PLV) differ significantly in acute lung injury. DESIGN AND SETTING: Experimental study in an animal research laboratory. SUBJECTS: Eighteen pigs. INTERVENTIONS: After induction of acute lung injury by means of infusion of oleic acid animals were randomly assigned to PFH, PLV, or gas ventilation (GV) groups. Six hours thereafter animals were killed, and lung tissue samples were taken for analysis. MEASUREMENTS AND RESULTS: Histopathological analysis revealed less damage with PFH than with GV or PLV in the nondependent and central regions. PFH and PLV showed less injury in the dependent regions than GV. GV and PFH were associated with less histological damage in the nondependent than the dependent regions, whereas PLV presented the opposite pattern. Morphometric analysis showed increased aeration in nondependent than dependent regions with PFH and GV. PLV led to more aeration in the periphery than in central areas. CONCLUSIONS: PFH was associated with a more homogeneous attenuation of alveolar damage across the lungs, although this therapy had more pronounced effects in nondependent zones. PLV showed the opposite pattern, with more important reduction in alveolar damage in dependent lung regions. Interestingly, reduction in alveolar damage with PFH was as effective as with PLV in dependent zones. Our findings suggest that vaporized perfluorocarbon could be advantageous as adjunctive therapy in the treatment of acute lung injury.

The effects of lipid infusion on myocardial function and bioenergetics in l-bupivacaine toxicity in the isolated rat heart.

BACKGROUND: It is unclear whether improved metabolism or a "lipid sink" effect of lipid infusion is responsible for the positive effects in local anesthetic-induced myocardial depression. METHODS: We used an isolated rat heart, constant-pressure perfused, nonrecirculating Langendorff preparation and exposed hearts to 5 mug/mL l-bupivacaine and 9 microL/mL lipid emulsion. Hearts were freeze-clamped and energy was charge measured by HPLC. In a second experiment the effects of pacing hearts was evaluated. The effects of lipid addition on local anesthetic concentrations in Krebs-Henseleit buffer and human plasma were examined by using a mass spectrometer. RESULTS: With spontaneously beating hearts l-bupivacaine led to a significant decrease in heart rate (to 74% +/- 7% of baseline), +dP/dt (69% +/- 7%), systolic pressure (78% +/- 6%), coronary flow (61% +/- 8%), and to an increase in PR (177% +/- 52%) and QRS intervals (166% +/- 36%). Lipid infusion exerted a positive inotropic effect, significantly augmenting +dP/dt and systolic pressure back to 94% +/- 11% and 102% +/- 16% of baseline in l-bupivacaine-treated hearts. Heart rate, coronary flow, PR, and QRS intervals remained unchanged after lipid intervention. Lipid infusion in paced hearts had a significant effect on +dP/dt, systolic pressure, and Mvo2. Neither l-bupivacaine nor lipids had an effect on energy charge. A lipid concentration of 500 muL/mL plasma was necessary to effect changes in the plasma concentration of local anesthetics. CONCLUSION: Lipid application in l-bupivacaine-induced cardiac depression had a significant positive inotropic effect, which we would attribute to a direct inotropic effect. However, in an isolated heart model, indirect, local anesthetic plasma-binding effect of lipids cannot be excluded.

The effects of levosimendan on myocardial function in ropivacaine toxicity in isolated guinea pig heart preparations.

BACKGROUND: Levosimendan is a novel drug used for inotropic support in heart failure, but its efficacy in local anesthetic-induced myocardial depression is not known. Therefore, we investigated the effects of levosimendan on the negative inotropic response to ropivacaine in isolated heart preparations of guinea pigs. METHODS: Action potentials and force of contraction were studied with conventional techniques in guinea-pig papillary muscles. Heart rate, systolic pressure, the first derivative of left ventricular pressure (+dP/dt(max)), coronary flow, and PR and QRS intervals were measured in isolated constant-pressure perfused, nonrecirculating Langendorff heart preparations. Single or cumulatively increasing concentrations of levosimendan and ropivacaine were used either alone or in combination. RESULTS: In isolated papillary muscle, ropivacaine reduced force of contraction in a concentration-dependent manner. Exposure to 10 microM levosimendan in the presence of 10 muM ropivacaine almost completely reversed the negative inotropic response. Sensitivity to the positive inotropic effect of levosimendan was not altered by 10 muM ropivacaine (-logEC50 [M] = 7.03 without versus 6.9 with ropivacaine, respectively). Action potential parameters were influenced only at the highest concentration. In the Langendorff heart, levosimendan significantly reversed the ropivacaine-induced reduction in heart rate, systolic pressure, coronary flow, and +dP/dt(max) to baseline values. CONCLUSION: Levosimendan is an effective inotropic drug in ropivacaine-induced myocardial depression and levosimendan myocardial sensitivity, and efficacy was not affected by the local anesthetic. Our results suggest that the calcium-sensitizing action of levosimendan is effective in local anesthetic-induced cardiac depression.