Predictive factors for decompensating events in patients with cirrhosis with primary biliary cholangitis under different lines of therapy.

BACKGROUND AND AIMS: The landscape in primary biliary cholangitis (PBC) has changed with the advent of second-line treatments. However, the use of obeticholic acid (OCA) and fibrates in PBC-related cirrhosis is challenging. We assessed the impact of receiving a second-line therapy as a risk factor for decompensated cirrhosis in a real-world population with cirrhosis and PBC, and identify the predictive factors for decompensated cirrhosis in these patients. APPROACH AND RESULTS: Multicenter study enrolling 388 patients with PBC-cirrhosis from the Spanish ColHai registry. Biopsy (20%), ultrasound (59%), or transient elastography (21%) defined cirrhosis, and the presence of varices and splenomegaly defined clinically significant portal hypertension (CSPH). Paris-II and PBC OCA international study of efficacy criteria determined the response to ursodeoxycholic acid (UDCA), fibrates (n=93), and OCA (n=104). The incidence of decompensated cirrhosis decreased for UDCA versus OCA or fibrates in the real-world population, but they were similar considering the propensity score-matched cohort (UDCA 3.77 vs. second-line therapy 4.5 100 persons-year, respectively), as patients on second-line therapy exhibited advanced liver disease. Consequently, GGT, albumin, platelets, clinically significant portal hypertension, and UDCA response were associated with a decompensating event. OCA response (achieved in 52% of patients) was associated with bilirubin (OR 0.21 [95% CI: 0.06-0.73]) and AST (OR 0.97 [95% CI: 0.95-0.99]), while fibrate response (achieved in 55% of patients) with AST [OR 0.96 (95% CI: 0.95-0.98]). In patients treated with OCA, drug response (sHR 0.23 [95% CI: 0.08-0.64]), diabetes (sHR 5.62 [95% CI: 2.02-15.68]), albumin (sHR 0.34 [95% CI: 0.13-0.89]), and platelets (sHR 0.99 [95% CI: 0.98-1.00]) were related to decompensation. In patients treated with fibrate, drug response (sHR 0.36 (95% CI: 0.14-0.95]), albumin (sHR 0.36 (95% CI: 0.16-0.81]), and clinically significant portal hypertension (sHR 3.70 (95% CI: 1.17-11.70]) were associated with decompensated cirrhosis. CONCLUSIONS: Advanced PBC, rather than OCA and fibrates, was found to be associated with decompensating events. Therefore, biochemical and clinical variables should be considered when making decisions about the management of these drugs. Moreover, a positive response to OCA and fibrates reduced the risk of decompensation.

Stent composition and immune response after long-term coronary angioplasty.

Background: There are limited data about the influence of stent composition on immune responses after percutaneous coronary intervention (PCI). Objective: The aim was to compare the effects of PCI with conventional cobalt-chromium bare metal stent (BMS) and drug-eluting stent (DES) implantation on the modulation of humoral and cellular immune responses. Methods: A randomised, single-centre, open pilot study involving patients with stable coronary artery disease eligible for PCI was performed. Blood samples were collected from the peripheral artery (PA) and the coronary sinus (CS) at baseline and 40 weeks following PCI. IgM and IgG autoantibodies (Abs), anti-oxLDL and anti-ApoB-D, as well as cytokine levels were evaluated by enzyme-linked immunosorbent assay. Results: A total of 30 patients of 60 years mean age were included, 68% of whom were men. At the nine-month follow-up, a modulation in the levels of cytokines and autoantibodies was observed in both stent type groups. However, no difference was observed in the modulation of these markers between stents. Conclusion: The stent type promotes modulations in cellular and humoral immune responses in the long-term, with differences in the magnitude of effects in specific immune responses.

Novel Approach for a Controlled Delivery of Essential Oils during Long-Term Maize Storage: Clove Bud and Pennyroyal Oils Efficacy to Control Sitophilus zeamais, Reducing Grain Damage and Post-Harvest Losses.

Maize grains represent a significant contribution for assuring food safety all over the globe. Sitophilus zeamais (Motschulsky) (Coleoptera: Curculionidae), also known as the maize weevil, is one of the most destructive pests in stored maize, causing qualitative and quantitative losses. To control S. zeamais populations in maize storage sites, synthetical chemical insecticides are applied. However, these are often used wastefully, have environmental implications, and can induce the development of resistant populations. In this work, the insecticidal and grain protecting efficacy of an innovative macro-capsule delivery device, loaded with essential oils from Clove bud and Pennyroyal, as well as their combined solutions, was tested against naturally S. zeamais-infested maize grains. The blend of both compounds incorporated in a controlled release device reduced losses by more than 45% over a long storage period of twenty weeks, diminishing the survivability of maize weevils by over 90%. The usage of the blend at a concentration of 370 µL⋅Lair-1 with an antioxidant showed the best results, however, by halving the concentration (185 µL⋅Lair-1), a significant control of S. zeamais populations was still achieved.

Preclinical and randomized phase I studies of plitidepsin in adults hospitalized with COVID-19.

Plitidepsin, a marine-derived cyclic-peptide, inhibits SARS-CoV-2 replication at nanomolar concentrations by targeting the host protein eukaryotic translation elongation factor 1A. Here, we show that plitidepsin distributes preferentially to lung over plasma, with similar potency against across several SARS-CoV-2 variants in preclinical studies. Simultaneously, in this randomized, parallel, open-label, proof-of-concept study (NCT04382066) conducted in 10 Spanish hospitals between May and November 2020, 46 adult hospitalized patients with confirmed SARS-CoV-2 infection received either 1.5 mg (n = 15), 2.0 mg (n = 16), or 2.5 mg (n = 15) plitidepsin once daily for 3 d. The primary objective was safety; viral load kinetics, mortality, need for increased respiratory support, and dose selection were secondary end points. One patient withdrew consent before starting procedures; 45 initiated treatment; one withdrew because of hypersensitivity. Two Grade 3 treatment-related adverse events were observed (hypersensitivity and diarrhea). Treatment-related adverse events affecting more than 5% of patients were nausea (42.2%), vomiting (15.6%), and diarrhea (6.7%). Mean viral load reductions from baseline were 1.35, 2.35, 3.25, and 3.85 log10 at days 4, 7, 15, and 31. Nonmechanical invasive ventilation was required in 8 of 44 evaluable patients (16.0%); six patients required intensive care support (13.6%), and three patients (6.7%) died (COVID-19-related). Plitidepsin has a favorable safety profile in patients with COVID-19.

Plitidepsin has a positive therapeutic index in adult patients with COVID-19 requiring hospitalization.

Plitidepsin is a marine-derived cyclic-peptide that inhibits SARS-CoV-2 replication at low nanomolar concentrations by the targeting of host protein eEF1A (eukaryotic translation-elongation-factor-1A). We evaluated a model of intervention with plitidepsin in hospitalized COVID-19 adult patients where three doses were assessed (1.5, 2 and 2.5 mg/day for 3 days, as a 90-minute intravenous infusion) in 45 patients (15 per dose-cohort). Treatment was well tolerated, with only two Grade 3 treatment-related adverse events observed (hypersensitivity and diarrhea). The discharge rates by Days 8 and 15 were 56.8% and 81.8%, respectively, with data sustaining dose-effect. A mean 4.2 log10 viral load reduction was attained by Day 15. Improvement in inflammation markers was also noted in a seemingly dose-dependent manner. These results suggest that plitidepsin impacts the outcome of patients with COVID-19. ONE-SENTENCE SUMMARY: Plitidepsin, an inhibitor of SARS-Cov-2 in vitro , is safe and positively influences the outcome of patients hospitalized with COVID-19.

Temperature Effects on the Fracture Dynamics and Elastic Properties of Popgraphene Membranes.

Popgraphene (PopG) is a new 2D planar carbon allotrope which is composed of 5-8-5 carbon rings. PopG is intrinsically metallic and possesses excellent thermal and mechanical stability. In this work, we report a detailed study of the thermal effects on the mechanical properties of PopG membranes using fully-atomistic reactive (ReaxFF) molecular dynamics simulations. Our results showed that PopG presents very distinct fracture mechanisms depending on the temperature and direction of the applied stretching. The main fracture dynamics trends are temperature independent and exhibit an abrupt rupture followed by fast crack propagation. The reason for this anisotropy is due to the fact that y-direction stretching leads to a deformation in the shape of the rings that cause the breaking of bonds in the pentagon-octagon and pentagon-pentagon ring connections, which is not observed for the x-direction. PopG is less stiff than graphene membranes, but the Young's modulus value is only 15 % smaller.

Development and application of Peptide Nucleic Acid Fluorescence in situ Hybridization for the specific detection of Listeria monocytogenes.

Listeria monocytogenes is one of the most important foodborne pathogens due to the high hospitalization and mortality rates associated to an outbreak. Several new molecular methods that accelerate the identification of L. monocytogenes have been developed, however conventional culture-based methods still remain the gold standard. In this work we developed a novel Peptide Nucleic Acid Fluorescence in situ Hybridization (PNA-FISH) method for the specific detection of L. monocytogenes. The method was based on an already existing PNA probe, LmPNA1253, coupled with a novel blocker probe in a 1:2 ratio. The method was optimized for the detection of L. monocytogenes in food samples through an evaluation of several rich and selective enrichment broths. The best outcome was achieved using One Broth Listeria in a two-step enrichment of 24 h plus 18 h. For validation in food samples, ground beef, ground pork, milk, lettuce and cooked shrimp were artificially contaminated with two ranges of inoculum: a low level (0.2-2 CFU/25 g or mL) and a high level (2-10 CFU/25 g or mL). The PNA-FISH method performed well in all types of food matrices, presenting an overall accuracy of ≈99% and a detection limit of 0.5 CFU/25 g or mL of food sample.

Scale Effects on the Ballistic Penetration of Graphene Sheets.

Carbon nanostructures are promising ballistic protection materials, due to their low density and excellent mechanical properties. Recent experimental and computational investigations on the behavior of graphene under impact conditions revealed exceptional energy absorption properties as well. However, the reported numerical and experimental values differ by an order of magnitude. In this work, we combined numerical and analytical modeling to address this issue. In the numerical part, we employed reactive molecular dynamics to carry out ballistic tests on single, double, and triple-layered graphene sheets. We used velocity values within the range tested in experiments. Our numerical and the experimental results were used to determine parameters for a scaling law. We find that the specific penetration energy decreases as the number of layers (N) increases, from ∼15 MJ/kg for N = 1 to ∼0.9 MJ/kg for N = 350, for an impact velocity of 900 m/s. These values are in good agreement with simulations and experiments, within the entire range of N values for which data is presently available. Scale effects explain the apparent discrepancy between simulations and experiments.

Determination of recombinant Interferon-α2 in E. coli periplasmic extracts by reversed-phase high-performance liquid chromatography.

Reversed-phase high-performance liquid chromatography (RP-HPLC) has been used to analyze Interferon α-2 (IFN-α2) as a pure protein or as a pharmaceutical preparation: a method for analyzing periplasmic IFN-α2 directly in osmotic shock extract has, however, never been reported. This work describes an RP-HPLC methodology for the qualitative and quantitative analysis of human IFN-α2a and IFN-α2b directly in bacterial periplasmic extracts or in purified preparations. The analytical method has been set up and validated for accuracy, precision, linearity, sensitivity and specificity. A recovery test indicated an average bias of ∼1%, intra-day and inter-day quantitative determinations presented relative standard deviations always≤5%, while the working sensitivity was of ∼0.3µg of IFN-α2 (RSD=5%). The method proved to be suitable for detecting and quantifying also glycosylated and oxidized forms and N-methionylated IFN-α2 molecules, it was, however, not able to distinguish between IFN-α2a and IFN-α2b. This rapid methodology allows the application of RP-HPLC as a powerful tool to monitor the production yield and quality of IFN-α2 in osmotic shock fluids, right after, or even during the fermentation process.

Identification of pathogenic bacteria in complex samples using a smartphone based fluorescence microscope.

Diagnostics based on fluorescence imaging of biomolecules is typically performed in well-equipped laboratories and is in general not suitable for remote and resource limited settings. Here we demonstrate the development of a compact, lightweight and cost-effective smartphone-based fluorescence microscope, capable of detecting signals from fluorescently labeled bacteria. By optimizing a peptide nucleic acid (PNA) based fluorescence in situ hybridization (FISH) assay, we demonstrate the use of the smartphone-based microscope for rapid identification of pathogenic bacteria. We evaluated the use of both a general nucleic acid stain as well as species-specific PNA probes and demonstrated that the mobile platform can detect bacteria with a sensitivity comparable to that of a conventional fluorescence microscope. The PNA-based FISH assay, in combination with the smartphone-based fluorescence microscope, allowed us to qualitatively analyze pathogenic bacteria in contaminated powdered infant formula (PIF) at initial concentrations prior to cultivation as low as 10 CFU per 30 g of PIF. Importantly, the detection can be done directly on the smartphone screen, without the need for additional image analysis. The assay should be straightforward to adapt for bacterial identification also in clinical samples. The cost-effectiveness, field-portability and simplicity of this platform will create various opportunities for its use in resource limited settings and point-of-care offices, opening up a myriad of additional applications based on other fluorescence-based diagnostic assays.

Ozonation and UV254nm radiation for the removal of microorganisms and antibiotic resistance genes from urban wastewater.

Conventional wastewater treatment has a limited capacity to reduce antibiotic resistant bacteria and genes (ARB&ARG). Tertiary treatment processes are promising solutions, although the transitory inactivation of bacteria may select ARB&ARG. This study aimed at assessing the potential of ozonation and UV254nm radiation to inactivate cultivable fungal and bacterial populations, and the selected genes 16S rRNA (common to all bacteria), intI1 (common in Gram-negative bacteria) and the ARG vanA, blaTEM, sul1 and qnrS. The abundance of the different microbiological parameters per volume of wastewater was reduced by ∼2 log units for cultivable fungi and 16S rRNA and intI1 genes, by∼3-4 log units, for total heterotrophs, enterobacteria and enterococci, and to values close or below the limits of quantification for ARG, for both processes, after a contact time of 30min. Yet, most of the cultivable populations, the 16S rRNA and intI1 genes as well as the ARG, except qnrS after ozonation, reached pre-treatment levels after 3days storage, suggesting a transitory rather than permanent microbial inactivation. Noticeably, normalization per 16S rRNA gene evidenced an increase of the ARG and intI1 prevalence, mainly after UV254nm treatment. The results suggest that these tertiary treatments may be selecting for ARB&ARG populations.

Photocatalytic ozonation of urban wastewater and surface water using immobilized TiO2 with LEDs: Micropollutants, antibiotic resistance genes and estrogenic activity.

Photocatalytic ozonation was employed for the first time in continuous mode with TiO2-coated glass Raschig rings and light emitting diodes (LEDs) to treat urban wastewater as well as surface water collected from the supply area of a drinking water treatment plant (DWTP). Different levels of contamination and types of contaminants were considered in this work, including chemical priority substances (PSs) and contaminants of emerging concern (CECs), as well as potential human opportunistic antibiotic resistant bacteria and their genes (ARB&ARG). Photocatalytic ozonation was more effective than single ozonation (or even than TiO2 catalytic ozonation) in the degradation of typical reaction by-products (such as oxalic acid), and more effective than photocatalysis to remove the parent micropollutants determined in urban wastewater. In fact, only fluoxetine, clarithromycin, erythromycin and 17-alpha-ethinylestradiol (EE2) were detected after photocatalytic ozonation, by using solid-phase extraction (SPE) pre-concentration and LC-MS/MS analysis. In surface water, this treatment allowed the removal of all determined micropollutants to levels below the limit of detection (0.01-0.20 ng L(-1)). The efficiency of this process was then assessed based on the capacity to remove different groups of cultivable microorganisms and housekeeping (16S rRNA) and antibiotic resistance or related genes (intI1, blaTEM, qnrS, sul1). Photocatalytic ozonation was observed to efficiently remove microorganisms and ARGs. Although after storage total heterotrophic and ARB (to ciprofloxacin, gentamicin, meropenem), fungi, and the genes 16S rRNA and intI1, increased to values close to the pre-treatment levels, the ARGs (blaTEM, qnrS and sul1) were reduced to levels below/close to the quantification limit even after 3-days storage of treated surface water or wastewater. Yeast estrogen screen (YES), thiazolyl blue tetrazolium reduction (MTT) and lactate dehydrogenase (LDH) assays were also performed before and after photocatalytic ozonation to evaluate the potential estrogenic activity, the cellular metabolic activity and the cell viability. Compounds with estrogenic effects and significant differences concerning cell viability were not observed in any case. A slight cytotoxicity was only detected for Caco-2 and hCMEC/D3 cell lines after treatment of the urban wastewater, but not for L929 fibroblasts.

Safety and efficacy of triple therapy with peginterferon, ribavirin and boceprevir within an early access programme in Spanish patients with hepatitis C genotype 1 with severe fibrosis: SVRw12 analysis.

BACKGROUND & AIMS: The addition of protease inhibitors (PIs) changed the hepatitis C virus (HCV) treatment standards and improved sustained viral response (SVR) rates in patients with genotype 1 HCV infection. METHODS: Prospective, multicentre, national registry that includes naïve and treatment-experienced patients with HCV genotype 1 infection, who had bridging fibrosis or cirrhosis and were treated with triple therapy (peginterferon alfa-2a or alfa-2b, ribavirin and boceprevir) as compassionate use, and in accordance with the Summary of Product Characteristics. RESULTS: Most of the patients (68.2%) were male, with a mean age of 53 years, 75% (n = 128) had HCV 1b genotype and baseline viral load of 6.2 log. According to prior treatment, 20% of patients were treatment-naïve and 80% had received prior treatment. Approximately 36.5% of patients (n = 62) reported at least one serious adverse events (SAEs) (total SAEs = 103). The most common SAEs were neutropenia (57.6%), anaemia (47.6%) and grade 3 thrombopenia (25.9%). Patients with albumin <3.5 g/dl and bilirubin >2 mg/dl had an increased relative risk (greater than one-fold) for SAEs, including infections and hepatic decompensation. In the intent-to-treat analysis (n = 170), the overall percentage of patients with SVRw12 was 46.5%. In patients with 1 log decrease at week 4 (lead-in phase), the overall SVRw12 rate was 67.0%. In the patients initiating triple therapy with boceprevir (n = 139), the global response rate was 56.4%. In a multivariate analysis, an increased probability of achieving SVR was associated with response to prior treatment (relapsers), >1 log decrease in viral load in the lead-in phase and baseline albumin >3.5 g/dl. CONCLUSIONS: Triple therapy in patients with severe fibrosis/cirrhosis is associated with a higher rate of SAE and a lower rate in comparison with patients with mild disease. However, for patients with intact liver function, it could be considered as a treatment option, when other alternatives would not be available.

Self-structuring of lamellar bridged silsesquioxanes with long side spacers.

Diurea cross-linked bridged silsesquioxanes (BSs) C(10)C(n)C(10) derived from organosilane precursors, including decylene chains as side spacers and alkylene chains with variable length as central spacers (EtO)(3)Si-(CH(2))(10)-Y-(CH(2))(n)-Y-(CH(2))(10)-Si(OEt)(3) (n = 7, 9-12; Y = urea group and Et = ethyl), have been synthesized through the combination of self-directed assembly and an acid-catalyzed sol-gel route involving the addition of dimethylsulfoxide (DMSO) and a large excess of water. This new family of hybrids has enabled us to conclude that the length of the side spacers plays a unique role in the structuring of alkylene-based BSs, although their morphology remains unaffected. All the samples adopt a lamellar structure. While the alkylene chains are totally disordered in the case of the C(10)C(7)C(10) sample, a variable proportion of all-trans and gauche conformers exists in the materials with longer central spacers. The highest degree of structuring occurs for n = 9. The inclusion of decylene instead of propylene chains as side spacers leads to the formation of a stronger hydrogen-bonded urea-urea array as evidenced by two dimensional correlation Fourier transform infrared spectroscopic analysis. The emission spectra and emission quantum yields of the C(10)C(n)C(10) materials are similar to those reported for diurea cross-linked alkylene-based BSs incorporating propylene chains as side spacers and prepared under different experimental conditions. The emission of the C(10)C(n)C(10) hybrids is ascribed to the overlap of two distinct components that occur within the urea cross-linkages and within the siliceous nanodomains. Time-resolved photoluminescence spectroscopy has provided evidence that the average distance between the siliceous domains and the urea cross-links is similar in the C(10)C(n)C(10) BSs and in oxyethylene-based hybrid analogues incorporating propylene chains as side spacers (diureasils), an indication that the longer side chains in the former materials adopt gauche conformations. It has also allowed us to demonstrate for the first time that the emission features of the urea-related component of the emission of alkylene-based BSs depend critically on the length of the side spacers.

Choice of calcineurin inhibitor may influence the development of de novo immune hepatitis associated with anti-GSTT1 antibodies after liver transplantation.

In 2004, we defined the genetic mismatch in the glutathione S-transferase T1 (GSTT1) gene positive donor/null recipient as a risk factor to develop de novo immune hepatitis (IH) after liver transplant (LT), which is always associated with production of donor-specific anti-GSTT1 antibodies. However, there are several unresolved questions, such as why some of these patients produce antibodies, why others do not and why not all of the patients with antibodies develop the disease. The aim of this study was to evaluate the influence of several variables in the production of anti-GSTT1 antibodies and/or de novo IH. The study group included 35 liver-transplanted patients. The number of patients not producing antibodies was significantly higher in the group treated with Tac-based immunosuppression compared with the CsA-based group (94.1% vs. 5.9%, p = 0.001). Additionally, a protective effect of the Tac-based therapy vs. the CsA-based therapy was observed with regard to development of de novo IH (80.8% vs. 19.2%, p = 0.003). In conclusion, the choice of calcineurin inhibitor may influence the development of de novo IH mediated by anti-GSTT1 antibodies.

Antibodies against glutathione S-transferase T1 in non-solid organ transplanted patients.

BACKGROUND: This article describes the presence of antibodies against glutathione S-transferase T1 (GSTT1) in a group of patients who never received a solid organ graft. These antibodies have been previously detected in liver and kidney transplant subjects with donor-recipient mismatch for this enzyme at the genetic level. In liver-grafted subjects, the appearance of these antibodies correlated with de novo immune hepatitis. STUDY DESIGN AND METHODS: To obtain some insights in this phenomenon, the clinical records of these patients were reviewed, and the possible causes leading to the production of these antibodies and possible clinical consequences were analyzed. RESULTS: The clinical situation of these patients was very heterogeneous, but they had in common the need for transfusions or a previous pregnancy. GSTT1 antigen is present in red blood cells, liver, kidney, and other tissues. Because the presence of the GSTT1-null allele in seven of these patients has been demonstrated, it can be hypothesized that both GSTT1-positive transfusions or pregnancy of a GSTT1-positive fetus could induce these antibodies. Because the recipient is allele-null, no adverse effects in the host are expected to occur. The longest follow-up (5 years) shows no antibody-derived diseases. CONCLUSION: It is concluded that anti-GSTT1 can appear in a context different from the previously published alloreactivity after liver and kidney transplantation, as a consequence of transfusions and pregnancies. So far, no adverse clinical outcomes in our patients have been observed.

A doença oncológica não deve ser um fator limitante para admissão na UTI de pacientes submetidos a cirurgias de alto risco / Cancer disease should not be a limitative factor for admission of high risk surgical patients to an intensive care unit

JUSTIFICATIVA E OBJETIVOS: A doença oncológica per se é uma condição que muitas vezes influencia no tratamento dispensado ao paciente. O objetivo do presente estudo foi comparar o desfecho hospitalar de pacientes oncológicos e não oncológicos submetidos à procedimentos cirúrgicos eletivos com alto risco de óbito. MÉTODO: Estudo de coorte prospectivo observacional, realizado em UTI de hospital terciário no período de 01 de abril a 31 de julho de 2005. Foram coletados dados demográficos, escore APACHE II, MODS, variáveis hemodinâmicas, laboratoriais e avaliadas complicações definidas como re-operação, necessidade de ventilação mecânica, transfusão sangüínea e uso de cateter de artéria pulmonar no pós-operatório desses pacientes. Todos foram acompanhados até alta ou o óbito hospitalar. Para variáveis numéricas foi utilizado o teste t de Student e Mann-Whitney, para variáveis categóricas o teste do Qui-quadrado sendo considerado significativo o valor de p < 0,05. RESULTADOS: Foram incluídos no estudo 119 pacientes, 43 não oncológicos e 76 oncológicos, 52,9 por cento eram do sexo feminino. A média de idade foi 65,1 ± 14,1 anos, o escore médio de APACHE II 16,5 ± 5,8 e a mediana do MODS de 3 (2-6). A duração mediana da intervenção cirúrgica foi de 5 (3,3-7) horas e a mortalidade na UTI e hospitalar foram 10,9 por cento e 25,2 por cento, respectivamente. Os pacientes oncológicos apresentaram maiores tempos de internação hospitalar e de internação antes da cirurgia, sendo estes resultados estatisticamente significativos. A mortalidade hospitalar dos pacientes oncológicos não foi superior a dos pacientes sem neoplasia (22,4 por cento versus 30,2 por cento, p = 0,32). CONCLUSÕES: Nesta observação os pacientes oncológicos, submetidos à procedimentos cirúrgicos de alto risco, apresentaram mortalidade semelhante aos pacientes não oncológicos com gravidade de doença similar.

BACKGROUND AND OBJECTIVES: Oncologic diseases are conditions that have influence in the treatment offered to affected patients. The aim of this study was to compare hospitalar outcome of oncologic and non oncologic patients submitted to high risk elective surgery. METHODS: Prospective, observational cohort study realized in an ICU of a tertiary hospital during the period between 04/01/2005 and 07/31/2005. Demographic data, APACHE II and MODS scores and laboratorial and hemodynamic variables were collected and complications like re-intervention need for mechanical ventilation, red blood cell transfusions and pulmonary artery catheter use during the post-operative period were evaluated. All patients were followed until hospital discharge or death. T student and Mann Whitney tests were used to compare numerical variables. Chi-square test was used to compare categorical variables. A p < 0.05 was considered as significant. RESULTS: 119 patients were included in the study. 43 were oncologic and 76 were non-oncologic. 52.9 percent were female. Mean age was 65.1 ± 14.1 years. Mean APACHE II score was 16.5 ± 5.8 and MODS median was 3 (2-6). Median length of surgery was 5 (3.3-7) hours and ICU and hospital mortality were 10.9 percent and 25.2 percent, respectively. Oncologic patients had greater length of hospital stay and length of stay before surgery. These results were statistically significant. Hospital mortality of oncologic patients was not greater than non-oncologic patients (22.4 percent versus 30.2 percent, p = 0.32). CONCLUSIONS: In this series, oncologic patients submitted to high risk surgery had the same mortality rate as non-onconlogic patients with similar disease severity.

[Cancer disease should not be a limitative factor for admission of high risk surgical patients to an intensive care unit]. / A doença oncológica não deve ser um fator limitante para admissão na UTI de pacientes submetidos a cirurgias de alto risco.

BACKGROUND AND OBJECTIVES: Oncologic diseases are conditions that have influence in the treatment offered to affected patients. The aim of this study was to compare hospitalar outcome of oncologic and non oncologic patients submitted to high risk elective surgery. METHODS: Prospective, observational cohort study realized in an ICU of a tertiary hospital during the period between 04/01/2005 and 07/31/2005. Demographic data, APACHE II and MODS scores and laboratorial and hemodynamic variables were collected and complications like re-intervention need for mechanical ventilation, red blood cell transfusions and pulmonary artery catheter use during the post-operative period were evaluated. All patients were followed until hospital discharge or death. T student and Mann Whitney tests were used to compare numerical variables. Chi-square test was used to compare categorical variables. A p < 0.05 was considered as significant. RESULTS: 119 patients were included in the study. 43 were oncologic and 76 were non-oncologic. 52.9% were female. Mean age was 65.1 ± 14.1 years. Mean APACHE II score was 16.5 ± 5.8 and MODS median was 3 (2-6). Median length of surgery was 5 (3.3-7) hours and ICU and hospital mortality were 10.9% and 25.2%, respectively. Oncologic patients had greater length of hospital stay and length of stay before surgery. These results were statistically significant. Hospital mortality of oncologic patients was not greater than non-oncologic patients (22.4% versus 30.2%, p = 0.32). CONCLUSIONS: In this series, oncologic patients submitted to high risk surgery had the same mortality rate as non-onconlogic patients with similar disease severity.

Glutathione S-transferase T1 mismatch constitutes a risk factor for de novo immune hepatitis after liver transplantation.

A new form of autoimmune hepatitis referred to as de novo, has been reported after liver transplantation during the past 5 years. The features are identical to those of classical autoimmune hepatitis (AIH), but the facts involved in the onset and outcome of this type of graft dysfunction are still unclear. The identification of antibodies directed to glutathione S-transferase T1 (GSTT1) in the sera of patients with de novo immune hepatitis led us to the description of an alloimmune reaction due to a GSTT1 genetic incompatibility between donor and recipient. We analyzed a cohort of 110 liver transplant patients treated in the liver transplant unit of our hospital during a period of 1 year, from September 2002 to October 2003. We found the following distribution of the GSTT1 genotypes (recipient/donor): +/+ = 66, +/- = 23, -/+ = 15, -/- = 6. Six of these patients were diagnosed with de novo immune hepatitis; all of them belong to the group of negative recipients with positive donors, and all produced anti-GSTT1 antibodies. This genetic combination is associated with a statistically significant increased risk of de novo immune hepatitis (IH) in liver transplant patients (P < .0001 by the Fisher exact test). In conclusion, our results clearly establish the importance of the GSTT1 genotype from donor and recipient of a liver transplant as a predictive marker for de novo IH. At the same time, we confirmed our initial results that only this particular donor/recipient combination triggers the anti-GSTT1 antibody production.