Vienna General Hospital

BACKGROUND: The comparative efficacy and safety of infliximab and azathioprine therapy alone or in combination for Crohn's disease are unknown. METHODS: In this randomized, double-blind trial, we evaluated the efficacy of infliximab monotherapy, azathioprine monotherapy, and the two drugs combined in 508 adults with moderate-to-severe Crohn's disease who had not undergone previous immunosuppressive or biologic therapy. Patients were randomly assigned to receive an intravenous infusion of 5 mg of infliximab per kilogram of body weight at weeks 0, 2, and 6 and then every 8 weeks plus daily oral placebo capsules; 2.5 mg of oral azathioprine per kilogram daily plus a placebo infusion on the standard schedule; or combination therapy with the two drugs. Patients received study medication through week 30 and could continue in a blinded study extension through week 50. RESULTS: Of the 169 patients receiving combination therapy, 96 (56.8%) were in corticosteroid-free clinical remission at week 26 (the primary end point), as compared with 75 of 169 patients (44.4%) receiving infliximab alone (P=0.02) and 51 of 170 patients (30.0%) receiving azathioprine alone (P<0.001 for the comparison with combination therapy and P=0.006 for the comparison with infliximab). Similar numerical trends were found at week 50. At week 26, mucosal healing had occurred in 47 of 107 patients (43.9%) receiving combination therapy, as compared with 28 of 93 patients (30.1%) receiving infliximab (P=0.06) and 18 of 109 patients (16.5%) receiving azathioprine (P<0.001 for the comparison with combination therapy and P=0.02 for the comparison with infliximab). Serious infections developed in 3.9% of patients in the combination-therapy group, 4.9% of those in the infliximab group, and 5.6% of those in the azathioprine group. CONCLUSIONS: Patients with moderate-to-severe Crohn's disease who were treated with infliximab plus azathioprine or infliximab monotherapy were more likely to have a corticosteroid-free clinical remission than those receiving azathioprine monotherapy. (ClinicalTrials.gov number, NCT00094458.)

They selected references within their field of expertise and experience and graded the references according to the GRADE system. 1 The selection of references for the guideline was based on a validation of the appropriateness of the study design for the stated purpose, a relevant number of patients under study, and confidence in the participating centers and authors.References on original data were preferred and those that were found unsatisfactory in any of these respects were excluded from further evaluation.There may be limitations in this approach when recommendations are needed on rare problems or problems on which scant original data are available.In such cases, it may be necessary to rely on less-qualified references with a low grading.As a result of the important changes in the treatment of complications of cirrhosis (renal failure, infections, and variceal bleeding [VB]), studies performed more than 30 years ago have generally not been considered for these guidelines. Recommendation StrongFactors influencing the strength of recommendation included the quality of evidence, presumed patient-important outcomes, and costs. 1 Weak Variability in preferences and values, or more uncertainty.Recommendation is made with less certainty, higher costs, or resource consumption.

Research on hepatic encephalopathy is hampered by the imprecise definition of this disabling complication of liver disease. Under this light, the Organisation Mondiale de Gastroentérologie commissioned a Working Party to reach a consensus in this area and to present it at the 11th World Congress of Gastroenterology in Vienna (1998). The Working Party continued its work thereafter and now present their final report. In summary, the Working Party has suggested a modification of current nomenclature for clinical diagnosis of hepatic encephalopathy; proposed guidelines for the performance of future clinical trials in hepatic encephalopathy; and felt the need for a large study to redefine neuropsychiatric abnormalities in liver disease, which would allow the diagnosis of minimal (subclinical) encephalopathy to be made on firm statistical grounds. In the interim, it proposes the use of a psychometric hepatic encephalopathy score, based on the result of 5 neuropsychologic tests. Finally, the need for a careful evaluation of the newer neuroimaging modalities for the diagnosis of hepatic encephalopathy was stressed.

BACKGROUND: The role of fibrinolytic therapy in patients with intermediate-risk pulmonary embolism is controversial. METHODS: In a randomized, double-blind trial, we compared tenecteplase plus heparin with placebo plus heparin in normotensive patients with intermediate-risk pulmonary embolism. Eligible patients had right ventricular dysfunction on echocardiography or computed tomography, as well as myocardial injury as indicated by a positive test for cardiac troponin I or troponin T. The primary outcome was death or hemodynamic decompensation (or collapse) within 7 days after randomization. The main safety outcomes were major extracranial bleeding and ischemic or hemorrhagic stroke within 7 days after randomization. RESULTS: Of 1006 patients who underwent randomization, 1005 were included in the intention-to-treat analysis. Death or hemodynamic decompensation occurred in 13 of 506 patients (2.6%) in the tenecteplase group as compared with 28 of 499 (5.6%) in the placebo group (odds ratio, 0.44; 95% confidence interval, 0.23 to 0.87; P=0.02). Between randomization and day 7, a total of 6 patients (1.2%) in the tenecteplase group and 9 (1.8%) in the placebo group died (P=0.42). Extracranial bleeding occurred in 32 patients (6.3%) in the tenecteplase group and 6 patients (1.2%) in the placebo group (P<0.001). Stroke occurred in 12 patients (2.4%) in the tenecteplase group and was hemorrhagic in 10 patients; 1 patient (0.2%) in the placebo group had a stroke, which was hemorrhagic (P=0.003). By day 30, a total of 12 patients (2.4%) in the tenecteplase group and 16 patients (3.2%) in the placebo group had died (P=0.42). CONCLUSIONS: In patients with intermediate-risk pulmonary embolism, fibrinolytic therapy prevented hemodynamic decompensation but increased the risk of major hemorrhage and stroke. (Funded by the Programme Hospitalier de Recherche Clinique in France and others; PEITHO EudraCT number, 2006-005328-18; ClinicalTrials.gov number, NCT00639743.).

BACKGROUND: Thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome are severe microvascular disorders of platelet clumping with similar signs and symptoms. Unusually large multimers of von Willebrand factor, capable of agglutinating circulating platelets under high shear stress, occur in the two conditions. We investigated the prevalence of von Willebrand factor-cleaving protease deficiency in patients with familial and nonfamilial forms of these disorders. METHODS: Plasma samples were obtained from 53 patients with thrombotic thrombocytopenic purpura or hemolytic-uremic syndrome. Von Willebrand factor-cleaving protease was assayed in diluted plasma samples with purified normal von Willebrand factor as the substrate. The extent of the degradation of von Willebrand factor was assessed by electrophoresis in sodium dodecyl sulfate-agarose gels and immunoblotting. To determine whether an inhibitor of von Willebrand factor-cleaving protease was present, we measured the protease activity in normal plasma after incubation with plasma from the patients. RESULTS: We examined 30 patients with thrombotic thrombocytopenic purpura and 23 patients with the hemolytic-uremic syndrome. Of 24 patients with nonfamilial thrombotic thrombocytopenic purpura, 20 had severe and 4 had moderate protease deficiency during an acute event. An inhibitor found in 20 of these patients was shown to be IgG in five of five tested plasma samples. Of 13 patients with nonfamilial hemolytic-uremic syndrome, 11 had normal levels of activity of von Willebrand factor-cleaving protease during the acute episode, whereas in 2 patients, the activity was slightly decreased. All 6 patients with familial thrombotic thrombocytopenic purpura lacked von Willebrand factor-cleaving protease activity but had no inhibitor, whereas all 10 patients with familial hemolytic-uremic syndrome had normal protease activity. In vitro proteolytic degradation of von Willebrand factor by the protease was studied in 5 patients with familial and 7 patients with nonfamilial hemolytic-uremic syndrome and was normal in all 12 patients. CONCLUSIONS: Nonfamilial thrombotic thrombocytopenic purpura is due to an inhibitor of von Willebrand factor-cleaving protease, whereas the familial form seems to be caused by a constitutional deficiency of the protease. Patients with the hemolyticuremic syndrome do not have a deficiency of von Willebrand factor-cleaving protease or a defect in von Willebrand factor that leads to its resistance to protease.

Soft tissue sarcomas (STSs) gather over 80 histological entities, with even more molecular subsets, characterised by a low to very low incidence in all populations. The majority of sarcomas arise from the soft tissue (close to 75%), with ∼15% gastrointestinal stromal tumours (GISTs) and 10% bone sarcomas. These ESMO–EURACAN (European Society for Medical Oncology–European Reference Network for rare adult solid cancers) Clinical Practice Guidelines cover STSs, while GISTs are covered by dedicated ESMO–EURACAN Clinical Practice Guidelines [1].

OBJECTIVE: To develop a model to assess severity of illness and predict vital status at hospital discharge based on ICU admission data. DESIGN: Prospective multicentre, multinational cohort study. PATIENTS AND SETTING: A total of 16,784 patients consecutively admitted to 303 intensive care units from 14 October to 15 December 2002. MEASUREMENTS AND RESULTS: ICU admission data (recorded within +/-1 h) were used, describing: prior chronic conditions and diseases; circumstances related to and physiologic derangement at ICU admission. Selection of variables for inclusion into the model used different complementary strategies. For cross-validation, the model-building procedure was run five times, using randomly selected four fifths of the sample as a development- and the remaining fifth as validation-set. Logistic regression methods were then used to reduce complexity of the model. Final estimates of regression coefficients were determined by use of multilevel logistic regression. Variables selection and weighting were further checked by bootstraping (at patient level and at ICU level). Twenty variables were selected for the final model, which exhibited good discrimination (aROC curve 0.848), without major differences across patient typologies. Calibration was also satisfactory (Hosmer-Lemeshow goodness-of-fit test H=10.56, p=0.39, C=14.29, p=0.16). Customized equations for major areas of the world were computed and demonstrate a good overall goodness-of-fit. CONCLUSIONS: The SAPS 3 admission score is able to predict vital status at hospital discharge with use of data recorded at ICU admission. Furthermore, SAPS 3 conceptually dissociates evaluation of the individual patient from evaluation of the ICU and thus allows them to be assessed at their respective reference levels.

Acute renal failure increases risk of death after cardiac surgery. However, it is not known whether more subtle changes in renal function might have an impact on outcome. Thus, the association between small serum creatinine changes after surgery and mortality, independent of other established perioperative risk indicators, was analyzed. In a prospective cohort study in 4118 patients who underwent cardiac and thoracic aortic surgery, the effect of changes in serum creatinine within 48 h postoperatively on 30-d mortality was analyzed. Cox regression was used to correct for various established demographic preoperative risk indicators, intraoperative parameters, and postoperative complications. In the 2441 patients in whom serum creatinine decreased, early mortality was 2.6% in contrast to 8.9% in patients with increased postoperative serum creatinine values. Patients with large decreases (DeltaCrea <-0.3 mg/dl) showed a progressively increasing 30-d mortality (16 of 199 [8%]). Mortality was lowest (47 of 2195 [2.1%]) in patients in whom serum creatinine decreased to a maximum of -0.3 mg/dl; mortality increased to 6% in patients in whom serum creatinine remained unchanged or increased up to 0.5 mg/dl. Mortality (65 of 200 [32.5%]) was highest in patients in whom creatinine increased > or =0.5 mg/dl. For all groups, increases in mortality remained significant in multivariate analyses, including postoperative renal replacement therapy. After cardiac and thoracic aortic surgery, 30-d mortality was lowest in patients with a slight postoperative decrease in serum creatinine. Any even minimal increase or profound decrease of serum creatinine was associated with a substantial decrease in survival.

To survey the burden of liver disease in Europe and its causes 260 epidemiological studies published in the last five years were reviewed. The incidence and prevalence of cirrhosis and primary liver cancer are key to understand the burden of liver disease. They represent the end-stage of liver pathology and thus are indicative of the associated mortality. About 0.1% of Hungarian males will die of cirrhosis every year compared with 0.001% of Greek females. WHO estimate that liver cancer is responsible for around 47,000 deaths per year in the EU. Harmful alcohol consumption, viral hepatitis B and C and metabolic syndromes related to overweight and obesity are the leading causes of cirrhosis and primary liver cancer in Europe. Chronic hepatitis B affects 0.5-0.7% of the European population. In the last decade the prevalence of chronic hepatitis C was 0.13-3.26%. It is of great concern that about 90% of people in Europe infected by viral hepatitis are unaware of their status. Available data suggest the prevalence rate of NAFLD is 2-44% in the general European population (including obese children) and 42.6-69.5% in people with type 2 diabetes. Each of these four major causes of liver disease is amenable to prevention and treatment, reducing the burden of liver disease in Europe and saving lives. Further surveys are urgently needed to implement cost-effective prevention programmes and novel treatments to tackle this problem.

BACKGROUND: Whether to perform valve replacement in patients with asymptomatic but severe aortic stenosis is controversial. Therefore, we studied the natural history of this condition to identify predictors of outcome. METHODS: During 1994, we identified 128 consecutive patients with asymptomatic, severe aortic stenosis (59 women and 69 men; mean [+/-SD] age, 60+/-18 years; aortic-jet velocity, 5.0+/-0.6 m per second). The patients were prospectively followed until 1998. RESULTS: Follow-up information was available for 126 patients (98 percent) for a mean of 22+/-18 months. Event-free survival, with the end point defined as death (8 patients) or valve replacement necessitated by the development of symptoms (59 patients), was 67+/-5 percent at one year, 56+/-5 percent at two years, and 33+/-5 percent at four years. Five of the six deaths from cardiac disease were preceded by symptoms. According to multivariate analysis, only the extent of aortic-valve calcification was an independent predictor of outcome, whereas age, sex, and the presence or absence of coronary artery disease, hypertension, diabetes, and hypercholesterolemia were not. Event-free survival for patients with no or mild valvular calcification was 92+/-5 percent at one year, 84+/-8 percent at two years, and 75+/-9 percent at four years, as compared with 60+/-6 percent, 47+/-6 percent, and 20+/-5 percent, respectively, for those with moderate or severe calcification. The rate of progression of stenosis, as reflected by the aortic-jet velocity, was significantly higher in patients who had cardiac events (0.45+/-0.38 m per second per year) than those who did not have cardiac events (0.14+/-0.18 m per second per year, P<0.001), and the rate of progression of stenosis provided useful prognostic information. Of the patients with moderately or severely calcified aortic valves whose aortic-jet velocity increased by 0.3 m per second or more within one year, 79 percent underwent surgery or died within two years of the observed increase. CONCLUSIONS: In asymptomatic patients with aortic stenosis, it appears to be relatively safe to delay surgery until symptoms develop. However, outcomes vary widely. The presence of moderate or severe valvular calcification, together with a rapid increase in aortic-jet velocity, identifies patients with a very poor prognosis. These patients should be considered for early valve replacement rather than have surgery delayed until symptoms develop.

BACKGROUND: Destruction by oxidation, or oxidative killing, is the most important defense against surgical pathogens and depends on the partial pressure of oxygen in contaminated tissue. An easy method of improving oxygen tension in adequately perfused tissue is to increase the concentration of inspired oxygen. We therefore tested the hypothesis that the supplemental administration of oxygen during the perioperative period decreases the incidence of wound infection. METHODS: We randomly assigned 500 patients undergoing colorectal resection to receive 30 percent or 80 percent inspired oxygen during the operation and for two hours afterward. Anesthetic treatment was standardized, and all patients received prophylactic antibiotic therapy. With use of a double-blind protocol, wounds were evaluated daily until the patient was discharged and then at a clinic visit two weeks after surgery. We considered wounds with culture-positive pus to be infected. The timing of suture removal and the date of discharge were determined by the surgeon, who did not know the patient's treatment-group assignment. RESULTS: Arterial oxygen saturation was normal in both groups; however, the arterial and subcutaneous partial pressure of oxygen was significantly higher in the patients given 80 percent oxygen than in those given 30 percent oxygen. Among the 250 patients who received 80 percent oxygen, 13 (5.2 percent; 95 percent confidence interval, 2.4 to 8.0 percent) had surgical-wound infections, as compared with 28 of the 250 patients given 30 percent oxygen (11.2 percent; 95 percent confidence interval, 7.3 to 15.1 percent; P=0.01). The absolute difference between groups was 6.0 percent (95 percent confidence interval, 1.2 to 10.8 percent). The duration of hospitalization was similar in the two groups. CONCLUSIONS: The perioperative administration of supplemental oxygen is a practical method of reducing the incidence of surgical-wound infections.

BACKGROUND: Because stent implantation for disease of the superficial femoral artery has been associated with high rates of late clinical failure, percutaneous transluminal angioplasty is preferred for endovascular treatment, and stenting is recommended only in the event of suboptimal technical results. We evaluated whether primary implantation of a self-expanding nitinol (nickel-titanium) stent yielded anatomical and clinical benefits superior to those afforded by percutaneous transluminal angioplasty with optional secondary stenting. METHODS: We randomly assigned 104 patients who had severe claudication or chronic limb ischemia due to stenosis or occlusion of the superficial femoral artery to undergo primary stent implantation (51 patients) or angioplasty (53 patients). Restenosis and clinical outcomes were assessed at 6 and 12 months. RESULTS: The mean (+/-SD) length of the treated segment was 132+/-71 mm in the stent group and 127+/-55 mm in the angioplasty group. Secondary stenting was performed in 17 of 53 patients (32 percent) in the angioplasty group, in most cases because of a suboptimal result after angioplasty. At 6 months, the rate of restenosis on angiography was 24 percent in the stent group and 43 percent in the angioplasty group (P=0.05); at 12 months the rates on duplex ultrasonography were 37 percent and 63 percent, respectively (P=0.01). Patients in the stent group were able to walk significantly farther on a treadmill at 6 and 12 months than those in the angioplasty group. CONCLUSIONS: In the intermediate term, treatment of superficial-femoral-artery disease by primary implantation of a self-expanding nitinol stent yielded results that were superior to those with the currently recommended approach of balloon angioplasty with optional secondary stenting. (ClinicalTrials.gov number, NCT00281060.).

Crohn's disease is a heterogeneous entity. Previous attempts of classification have been based primarily on anatomic location and behavior of disease. However, no uniform definition of patient subgroups has yet achieved broad acceptance. The aim of this international Working Party was to develop a simple classification of Crohn's disease based on objective variables. Eight outcome-related variables relevant to Crohn's disease were identified and stepwise evaluated in 413 consecutive cases, a database survey, and by clinical considerations. Allocation of variables was conducted with well-defined Crohn's disease populations from Europe and North America. Cross-table analyses were performed by chi-square testing. Three variables were finally elected: Age at Diagnosis [below 40 years (A1), equal to or above 40 years (A2)], Location [terminal ileum (L1), colon (L2), ileocolon (L3), upper gastrointestinal (L4)], and Behavior [nonstricturing nonpenetrating (B1), stricturing (B2), penetrating (B3)]. The allocation of patients to these 24 subgroups proved feasible and resulted in specific disease clusters. Cross-table analyses revealed associations between Age at Diagnosis and Location, and between Behavior and Location (all p < 0.001). The Vienna classification of Crohn's disease provides distinct definitions to categorize Crohn's patients into 24 subgroups. Operational guidelines should be used for the characterization of patients in clinical trials as well as for correlation of particular phenotypes with putative biologic markers or environmental factors.

BACKGROUND: The role of adjuvant treatment in high-risk muscle-invasive urothelial carcinoma after radical surgery is not clear. METHODS: In a phase 3, multicenter, double-blind, randomized, controlled trial, we assigned patients with muscle-invasive urothelial carcinoma who had undergone radical surgery to receive, in a 1:1 ratio, either nivolumab (240 mg intravenously) or placebo every 2 weeks for up to 1 year. Neoadjuvant cisplatin-based chemotherapy before trial entry was allowed. The primary end points were disease-free survival among all the patients (intention-to-treat population) and among patients with a tumor programmed death ligand 1 (PD-L1) expression level of 1% or more. Survival free from recurrence outside the urothelial tract was a secondary end point. RESULTS: A total of 353 patients were assigned to receive nivolumab and 356 to receive placebo. The median disease-free survival in the intention-to-treat population was 20.8 months (95% confidence interval [CI], 16.5 to 27.6) with nivolumab and 10.8 months (95% CI, 8.3 to 13.9) with placebo. The percentage of patients who were alive and disease-free at 6 months was 74.9% with nivolumab and 60.3% with placebo (hazard ratio for disease recurrence or death, 0.70; 98.22% CI, 0.55 to 0.90; P<0.001). Among patients with a PD-L1 expression level of 1% or more, the percentage of patients was 74.5% and 55.7%, respectively (hazard ratio, 0.55; 98.72% CI, 0.35 to 0.85; P<0.001). The median survival free from recurrence outside the urothelial tract in the intention-to-treat population was 22.9 months (95% CI, 19.2 to 33.4) with nivolumab and 13.7 months (95% CI, 8.4 to 20.3) with placebo. The percentage of patients who were alive and free from recurrence outside the urothelial tract at 6 months was 77.0% with nivolumab and 62.7% with placebo (hazard ratio for recurrence outside the urothelial tract or death, 0.72; 95% CI, 0.59 to 0.89). Among patients with a PD-L1 expression level of 1% or more, the percentage of patients was 75.3% and 56.7%, respectively (hazard ratio, 0.55; 95% CI, 0.39 to 0.79). Treatment-related adverse events of grade 3 or higher occurred in 17.9% of the nivolumab group and 7.2% of the placebo group. Two treatment-related deaths due to pneumonitis were noted in the nivolumab group. CONCLUSIONS: In this trial involving patients with high-risk muscle-invasive urothelial carcinoma who had undergone radical surgery, disease-free survival was longer with adjuvant nivolumab than with placebo in the intention-to-treat population and among patients with a PD-L1 expression level of 1% or more. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 274 ClinicalTrials.gov number, NCT02632409.).

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is often a sequel of venous thromboembolism with fatal natural history; however, many cases can be cured by pulmonary endarterectomy. The clinical characteristics and current management of patients enrolled in an international CTEPH registry was investigated. METHODS AND RESULTS: The international registry included 679 newly diagnosed (≤6 months) consecutive patients with CTEPH, from February 2007 until January 2009. Diagnosis was confirmed by right heart catheterization, ventilation-perfusion lung scintigraphy, computerized tomography, and/or pulmonary angiography. At diagnosis, a median of 14.1 months had passed since first symptoms; 427 patients (62.9%) were considered operable, 247 (36.4%) nonoperable, and 5 (0.7%) had no operability data; 386 patients (56.8%, ranging from 12.0%- 60.9% across countries) underwent surgery. Operable patients did not differ from nonoperable patients relative to symptoms, New York Heart Association class, and hemodynamics. A history of acute pulmonary embolism was reported for 74.8% of patients (77.5% operable, 70.0% nonoperable). Associated conditions included thrombophilic disorder in 31.9% (37.1% operable, 23.5% nonoperable) and splenectomy in 3.4% of patients (1.9% operable, 5.7% nonoperable). At the time of CTEPH diagnosis, 37.7% of patients initiated at least 1 pulmonary arterial hypertension-targeted therapy (28.3% operable, 53.8% nonoperable). Pulmonary endarterectomy was performed with a 4.7% documented mortality rate. CONCLUSIONS: Despite similarities in clinical presentation, operable and nonoperable CTEPH patients may have distinct associated medical conditions. Operability rates vary considerably across countries, and a substantial number of patients (operable and nonoperable) receive off-label pulmonary arterial hypertension-targeted treatments.

OBJECTIVES: Acute renal failure is a complication in critically ill patients that has been associated with an excess risk of hospital mortality. Whether this reflects the severity of the disease or whether acute renal failure is an independent risk factor is unknown. The aim of this study was to analyze severity of illness and mortality in a group of critically ill patients with acute renal failure requiring renal replacement therapy in a number of Austrian intensive care units. DESIGN: Prospective, multicenter cohort study. PATIENTS AND SETTING: A total of 17,126 patients admitted consecutively to 30 medical, surgical, and mixed intensive care units in Austria over a period of 2 yrs. MEASUREMENTS AND MAIN RESULTS: Analyzed data included admission data, Simplified Acute Physiology Score, Logistic Organ Dysfunction system, Simplified Therapeutic Intervention Scoring System, length of intensive care unit stay, intensive care unit mortality, and hospital mortality. Of the admitted patients, 4.9% (n = 839) underwent renal replacement therapy because of acute renal failure (renal replacement therapy patients). These patients had a significantly higher hospital mortality (62.8% vs. 15.6%, p<.001), which remained significantly higher even when renal replacement therapy patients were matched with control subjects for age, severity of illness, and treatment center. Since univariate analysis demonstrated further intensity of treatment to be an additional predictor for outcome, a multivariate model including therapeutic interventions was developed. Five interventions were associated with nonsurvival (mechanical ventilation, single vasoactive medication, multiple vasoactive medication, cardiopulmonary resuscitation, and treatment of complicated metabolic acidosis/alkalosis). In contrast, the use of enteral nutrition predicted a favorable outcome. CONCLUSIONS: The results of our study suggest that acute renal failure in patients undergoing renal replacement therapy presents an excess risk of in-hospital death. This increased risk cannot be explained solely by a more pronounced severity of illness. Our results provide strong evidence that acute renal failure presents a specific and independent risk factor for poor prognosis.

The fifth edition of the World Health Organization (WHO) classification of urogenital tumours (WHO "Blue Book"), published in 2022, contains significant revisions. This review summarises the most relevant changes for renal, penile, and testicular tumours. In keeping with other volumes in the fifth edition series, the WHO classification of urogenital tumours follows a hierarchical classification and lists tumours by site, category, family, and type. The section "essential and desirable diagnostic criteria" included in the WHO fifth edition represents morphologic diagnostic criteria, combined with immunohistochemistry and relevant molecular tests. The global introduction of massive parallel sequencing will result in a diagnostic shift from morphology to molecular analyses. Therefore, a molecular-driven renal tumour classification has been introduced, taking recent discoveries in renal tumour genomics into account. Such novel molecularly defined epithelial renal tumours include SMARCB1-deficient medullary renal cell carcinoma (RCC), TFEB-altered RCC, Alk-rearranged RCC, and ELOC-mutated RCC. Eosinophilic solid and cystic RCC is a novel morphologically defined RCC entity. The diverse morphologic patterns of penile squamous cell carcinomas are grouped as human papillomavirus (HPV) associated and HPV independent, and there is an attempt to simplify the morphologic classification. A new chapter with tumours of the scrotum has been introduced. The main nomenclature of testicular tumours is retained, including the use of the term "germ cell neoplasia in situ" (GCNIS) for the preneoplastic lesion of most germ cell tumours and division from those not derived from GCNIS. Nomenclature changes include replacement of the term "primitive neuroectodermal tumour" by "embryonic neuroectodermal tumour" to separate these tumours clearly from Ewing sarcoma. The term "carcinoid" has been changed to "neuroendocrine tumour", with most examples in the testis now classified as "prepubertal type testicular neuroendocrine tumour".

PURPOSE: To evaluate whether capecitabine plus oxaliplatin (XELOX) is noninferior to fluorouracil. folinic acid, and oxaliplatin (FOLFOX-4) as first-line therapy in metastatic colorectal cancer (MCRC). PATIENTS AND METHODS: The initial design of this trial was a randomized, two-arm, noninferiority, phase III comparison of XELOX versus FOLFOX-4. After patient accrual had begun, the trial design was amended in 2003 after bevacizumab phase III data became available. The resulting 2 x 2 factorial design randomly assigned patients to XELOX versus FOLFOX-4, and then to also receive either bevacizumab or placebo. We report here the results of the analysis of the XELOX versus FOLFOX-4 arms. The analysis of bevacizumab versus placebo with oxaliplatin-based chemotherapy is reported separately. The prespecified primary end point for the noninferiority analysis was progression-free survival. RESULTS: The intent-to-treat population comprised 634 patients from the original two-arm portion of the study, plus an additional 1,400 patients after the start of the amended 2 x 2 design, for a total of 2,034 patients. The median PFS was 8.0 months in the pooled XELOX-containing arms versus 8.5 months in the FOLFOX-4-containing arms (hazard ratio [HR], 1.04; 97.5% CI, 0.93 to 1.16). The median overall survival was 19.8 months with XELOX versus 19.6 months with FOLFOX-4 (HR, 0.99; 97.5% CI, 0.88 to 1.12). FOLFOX-4 was associated with more grade 3/4 neutropenia/granulocytopenia and febrile neutropenia than XELOX, and XELOX with more grade 3 diarrhea and grade 3 hand-foot syndrome than FOLFOX-4. CONCLUSION: XELOX is noninferior to FOLFOX-4 as a first-line treatment for MCRC, and may be considered as a routine treatment option for appropriate patients.

In this report, which is an update of a guideline published in 2002 (Bandelow et al. 2002, World J Biol Psychiatry 3:171), recommendations for the pharmacological treatment of anxiety disorder, obsessive-compulsive disorder (OCD) and post-traumatic stress disorder (PTSD) are presented. Since the publication of the first version of this guideline, a substantial number of new randomized controlled studies of anxiolytics have been published. In particular, more relapse prevention studies are now available that show sustained efficacy of anxiolytic drugs. The recommendations, developed by the World Federation of Societies of Biological Psychiatry (WFSBP) Task Force for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-traumatic Stress Disorders, a consensus panel of 30 international experts, are now based on 510 published randomized, placebo- or comparator-controlled clinical studies (RCTs) and 130 open studies and case reports. First-line treatments for these disorders are selective serotonin reuptake inhibitors (SSRIs), serotonin-noradrenaline reuptake inhibitors (SNRIs) and the calcium channel modulator pregabalin. Tricyclic antidepressants (TCAs) are equally effective for some disorders, but many are less well tolerated than the SSRIs/SNRIs. In treatment-resistant cases, benzodiazepines may be used when the patient does not have a history of substance abuse disorders. Potential treatment options for patients unresponsive to standard treatments are described in this overview. Although these guidelines focus on medications, non-pharmacological were also considered. Cognitive behavioural therapy (CBT) and other variants of behaviour therapy have been sufficiently investigated in controlled studies in patients with anxiety disorders, OCD, and PTSD to support them being recommended either alone or in combination with the above medicines.

PURPOSE: To establish a process to evaluate and standardize a state-of-the-art nomenclature for reporting neovascular age-related macular degeneration (AMD) data. DESIGN: Consensus meeting. PARTICIPANTS: An international panel of retina specialists, imaging and image reading center experts, and ocular pathologists. METHODS: During several meetings organized under the auspices of the Macula Society, an international study group discussed and codified a set nomenclature framework for classifying the subtypes of neovascular AMD and associated lesion components. MAIN OUTCOME MEASURES: A consensus classification of neovascular AMD. RESULTS: The study group created a standardized working definition of AMD. The components of neovascular AMD were defined and subclassified. Disease consequences of macular neovascularization were delineated. CONCLUSIONS: The framework of a consensus nomenclature system, a definition of AMD, and a delineation of the subtypes of neovascular AMD were developed. Establishing a uniform set of definitions will facilitate comparison of diverse patient groups and different studies. The framework presented is modified and updated readily, processes that are anticipated to occur on a periodic basis. The study group suggests that the consensus standards outlined in this article be used in future reported studies of neovascular AMD and clinical practice.