Pembrolizumab versus brentuximab vedotin in relapsed or refractory classical Hodgkin lymphoma (KEYNOTE-204): an interim analysis of a multicentre, randomised, open-label, phase 3 study.

BACKGROUND: PD-1 blockade via pembrolizumab monotherapy has shown antitumour activity and toxicity in patients with relapsed or refractory classical Hodgkin lymphoma. Here, we present interim analyses from the KEYNOTE-204 study evaluating pembrolizumab versus brentuximab vedotin for relapsed or refractory classical Hodgkin lymphoma. METHODS: In this randomised, open-label, phase 3 study, patients aged 18 years or older with relapsed or refractory classical Hodgkin lymphoma with measurable disease and an Eastern Cooperative Oncology Group performance status of 0 or 1 who were ineligible for or had relapsed after autologous haematopoietic stem-cell transplantation (HSCT) were enrolled at 78 hospitals and cancer centres in 20 countries and territories. Patients were randomly assigned (1:1) with an interactive voice response system to pembrolizumab 200 mg intravenously every 3 weeks or brentuximab vedotin 1·8 mg/kg intravenously every 3 weeks. Randomisation was stratified by previous autologous HSCT and status after front-line therapy. Results from the second interim analysis are presented here, with a database cutoff of Jan 16, 2020. The dual primary endpoints assessed in the intention-to-treat population were progression-free survival as assessed by blinded independent central review, and overall survival (not analysed at this interim analysis). Safety was assessed in all patients who received at least one dose of the study drug. This study is registered with ClinicalTrials.gov, NCT02684292. Recruitment for this trial is closed. FINDINGS: Between July 8, 2016, and July 13, 2018, 151 patients were randomly assigned to pembrolizumab and 153 to brentuximab vedotin. After a median time from randomisation to data cutoff of 25·7 months (IQR 23·4-33·0), median progression-free survival was 13·2 months (95% CI 10·9-19·4) for pembrolizumab versus 8·3 months (5·7-8·8) for brentuximab vedotin (hazard ratio 0·65 [95% CI 0·48-0·88]; p=0·0027). The most common grade 3-5 treatment-related adverse events were pneumonitis (six [4%] of 148 patients in the pembrolizumab group vs one [1%] of 152 patients in the brentuximab vedotin group), neutropenia (three [2%] vs 11 [7%]), decreased neutrophil count (one [1%] vs seven [5%]), and peripheral neuropathy (one [1%] vs five [3%]). Serious treatment-related adverse events occurred in 24 (16%) of 148 patients receiving pembrolizumab and 16 (11%) of 152 patients receiving brentuximab vedotin. One treatment-related death due to pneumonia occurred in the pembrolizumab group. INTERPRETATION: Pembrolizumab showed statistically significant and clinically meaningful improvement in progression-free survival compared with brentuximab vedotin, with safety consistent with previous reports. These data support pembrolizumab as the preferred treatment option for patients with relapsed or refractory classical Hodgkin lymphoma who have relapsed post-autologous HSCT or are ineligible for autologous HSCT. FUNDING: Merck Sharp & Dohme Corp (a subsidiary of Merck & Co, Inc, Kenilworth, NJ, USA).

Efficacy and safety of oral panobinostat plus subcutaneous bortezomib and oral dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma (PANORAMA 3): an open-label, randomised, phase 2 study.

BACKGROUND: Improved therapeutic options are needed for patients with relapsed or relapsed and refractory multiple myeloma. Subcutaneous bortezomib has replaced intravenous bortezomib as it is associated with a more favourable toxicity profile. We investigated the activity and safety of three different dosing regimens of oral panobinostat in combination with subcutaneous bortezomib and oral dexamethasone for this indication. METHODS: PANORAMA 3 is an open-label, randomised, phase 2 study being done at 71 sites (hospitals and medical centres) across 21 countries. Patients aged 18 years or older with relapsed or relapsed and refractory multiple myeloma (as per International Myeloma Working Group 2014 criteria), who had received one to four previous lines of therapy (including an immunomodulatory agent), and had an Eastern Cooperative Oncology Group performance status of 2 or lower, were randomly assigned (1:1:1) to receive oral panobinostat 20 mg three times weekly, 20 mg twice weekly, or 10 mg three times weekly, plus subcutaneous bortezomib and oral dexamethasone. All study drugs were administered in 21-day cycles. Randomisation was done by an interactive response technology provider, and stratified by number of previous treatment lines and age. The primary endpoint was overall response rate after up to eight treatment cycles (analysed in all randomly assigned patients by intention to treat). Safety analyses included all patients who received at least one dose of any study drug. No statistical comparisons between groups were planned. This trial is ongoing and registered with ClinicalTrials.gov, NCT02654990. FINDINGS: Between April 27, 2016, and Jan 17, 2019, 248 patients were randomly assigned (82 to panobinostat 20 mg three times weekly, 83 to panobinostat 20 mg twice weekly, and 83 to 10 mg panobinostat three times weekly). Median duration of follow-up across all treatment groups was 14·7 months (IQR 7·8-24·1). The overall response rate after up to eight treatment cycles was 62·2% (95% CI 50·8-72·7; 51 of 82 patients) for the 20 mg three times weekly group, 65·1% (53·8-75·2; 54 of 83 patients) for the 20 mg twice weekly group, and 50·6% (39·4-61·8; 42 of 83 patients) for the 10 mg three times weekly group. Grade 3-4 adverse events occurred in 71 (91%) of 78 patients in the 20 mg three times weekly group, 69 (83%) of 83 patients in the 20 mg twice weekly group, and 60 (75%) of 80 patients in the 10 mg three times weekly group; the most common (≥20% patients in any group) grade 3-4 adverse events were thrombocytopenia (33 [42%] of 78, 26 [31%] of 83, and 19 [24%] of 83 patients) and neutropenia (18 [23%], 13 [16%], and six [8%]). Serious adverse events occurred in 42 (54%) of 78 patients in the 20 mg three times weekly group, 40 (48%) of 83 patients in the 20 mg twice weekly group, and 35 (44%) of 83 patients in the 10 mg three times weekly group; the most common serious adverse event (≥10% patients in any group) was pneumonia (nine [12%] of 78, ten [12%] of 83, and nine [11%] of 80 patients). There were 14 deaths during the study (five [6%] of 78 patients in the 20 mg three times weekly group, three [4%] of 83 in the 20 mg twice weekly group, and six [8%] of 80 in the 10 mg three times weekly group); none of these deaths was deemed treatment related. INTERPRETATION: The safety profile of panobinostat 20 mg three times weekly was more favourable than in previous trials of this regimen with intravenous bortezomib, suggesting that subcutaneous bortezomib improves the tolerability of the panobinostat plus bortezomib plus dexamethasone regimen. The overall response rate was highest in the 20 mg three times weekly and 20 mg twice weekly groups, with 10 mg three times weekly best tolerated. FUNDING: Novartis Pharmaceuticals and Secura Bio.

Occupational Exposures and Risks of Non-Hodgkin Lymphoma: A Meta-Analysis.

Non-Hodgkin lymphoma (NHL) is a heterogeneous group with different types of diseases. It remains unclear as to what has led to an increase in incidences of NHL, however, chemical substance exposure is known to be one of the risk factors for the disease. Therefore, we performed a systematic review and meta-analysis including case-control, cohort, and cross-sectional observational epidemiological studies to verify the association between occupational exposure to carcinogens and NHL risk. Articles between the years 2000 and 2020 were collected. Two different reviewers performed a blind selection of the studies using the Rayyan QCRI web app. Post-completion, the selected articles were extracted and analyzed via the RedCap platform. Our review resulted in 2719 articles, of which 51 were included in the meta-analysis, resulting in an overall OR of 1.27 (95% CI 1.04-1.55). Furthermore, it was observed that the main occupation associated with the increased risk of NHL was that in which workers are exposed to pesticides. We therefore conclude that the evidence synthesis of the epidemiological literature supports an increased risk for NHL, regardless of subtype, considering occupational exposure to certain chemical compounds, mainly pesticides, benzene, and trichlorethylene, and certain classes of work, primarily in the field of agriculture.

Gram-negative bacilli bacteremia: a 7 year retrospective study in a referral Brazilian tertiary-care teaching hospital.

Introduction. Bloodstream infection is one of the most frequent and challenging hospital-acquired infections and it is associated with high morbidity, mortality and additional use of healthcare resources.Hypothesis/Gap Statement: Bloodstream infections have consequences for the patient, such as the evolution to mortality and inappropriate empirical antibiotic prescription, especially when caused by multidrug-resistant Gram-negative bacilli.Objective. To assess the impact of bloodstream infection and the status of multidrug resistance (MDR) in the evolution of patients who received inappropriate initial antibiotic therapy.Methods. A retrospective surveillance was conducted on nosocomial bloodstream infections caused by Gram-negative bacilli (GNB) from January 2012 to December 2018 in an adult intensive care unit of a Brazilian tertiary teaching hospital.Results. We identified 270 patients with GNB nosocomial bacteremia. Non-survivors were older (with an average age of 58.8 years vs 46.9 years, P=<0.0001), presented more severe illnesses, were immunosuppressed (73.7 vs 37.6%, P=<0.0001), were more likely to have septic shock (55.8 vs 22.4%, P=<0.0001) and had an increased usage of mechanical ventilators (98.6 vs 89.6%, P=0.0013) than survivors. In a logistic regression model, inappropriate empirical antibiotic therapy was not an independent predictor of mortality, different from mechanical ventilator (P=<0.0001; OR=28.0; 95% CI=6.3-123.6), septic shock (P=0.0051; OR=2.5; 95% CI=1.3-4.9) and immunosuppression (P=0.0066; OR=2.6; 95% CI=1.3-5.2). In contrast, in a separate model, MDR was strongly associated with the prescription of inappropriate initial antibiotic therapy (P=0.0030; OR=5.3; 95% CI=1.7-16.1). The main isolated pathogens were Acinetobacter baumannii (23.6 %) and Klebsiella pneumoniae (18.7 %). The frequency of MDR organisms was high (63.7 %), especially among non-fermenting bacilli (60.9 %), highlighting A. baumannii (81.6 %) and Pseudomonas aeruginosa (41.8 %).Conclusion. Illness severity (septic shock and immunosuppression) and mechanical ventilation were identified as predictors of mortality. Additionally, MDR was a major determinant of inappropriate antibiotic empirical therapy, but not associated with mortality, and both characteristics were not statistically associated with death.

High mortality by nosocomial infections caused by carbapenem-resistant P. aeruginosa in a referral hospital in Brazil: facing the perfect storm.

Introduction. Carbapenem-resistant Pseudomonas aeruginosa is responsible for increased patient mortality.Gap Statement. Five and 30 day in-hospital all-cause mortality in patients with P. aeruginosa infections were assessed, followed by evaluations concerning potential correlations between the type III secretion system (TTSS) genotype and the production of metallo-ß-lactamase (MBL).Methodology. This assessment comprised a retrospective cohort study including consecutive patients with carbapenem-resistant infections hospitalized in Brazil from January 2009 to June 2019. PCR analyses were performed to determine the presence of TTSS-encoding genes and MBL genes.Results. The 30-day and 5-day mortality rates for 262 patients were 36.6 and 17.9 %, respectively. The unadjusted survival probabilities for up to 5 days were 70.55 % for patients presenting exoU-positive isolates and 86 % for those presenting exo-negative isolates. The use of urinary catheters, as well as the presence of comorbidity conditions, secondary bacteremia related to the respiratory tract, were independently associated with death at 5 and 30 days. The exoS gene was detected in 64.8 % of the isolates, the presence of the exoT and exoY genes varied and exoU genes occurred in 19.3 % of the isolates. The exoU genotype was significantly more frequent among multiresistant strains. MBL genes were not detected in 92 % of the isolates.Conclusions. Inappropriate therapy is a crucial factor regarding the worse prognosis among patients with infections caused by multiresistant P. aeruginosa, especially those who died within 5 days of diagnosis, regardless of the genotype associated with TTSS virulence.

Association of Colistin-Resistant KPC Clonal Strains with Subsequent Infections and Colonization and Biofilm Production.

Carbapenemase-producing organisms are pandemic and a significant threat to public health. We investigated the clonal relatedness of colistin-resistant Klebsiella pneumoniae strains producing KPC-type carbapenemase (KPC-KP) causing subsequent infections or colonization. Moreover, we aimed to gain insight into the ability of biofilm production in K. pneumoniae strains producing carbapenemase. Twenty-two consecutive KPC-KP and one KPC-negative strain was identified from an adult intensive care unit in Brazil. Seventy-five percent of isolates that harbored the blaKPC gene exhibited genetic relatedness by pulsed-field gel electrophoresis, and none presented the plasmid-mediated mcr-1 and blaNDM genes. This study showed that the majority of repeated KPC infections in adults were caused by a clone that caused the previous infections/colonizations even after a long period of time and illustrates the capacity of multiple clones producing biofilms to coexist in the same patient at the same time, becoming a reservoir of KPC-KP in the hospital environment.

Hypervirulence and biofilm production in KPC-2-producing Klebsiella pneumoniae CG258 isolated in Brazil.

In this study, we describe the frequency of virulence genes in Klebsiella pneumoniae carbapenemase-2-producing Klebsiella pneumoniae (KPC-KP), including hypervirulent (hv) and hypermucoviscous (hm) strains by whole-genome sequencing. We also evaluate the capacity for biofilm formation by using phenotypic techniques. The occurrence of several virulence genes (fimABCDEFGHIK, mrkABCDFHJ, ecpA, wabG, entB, ugE, irp1, irp2, traT, iutA and ureADE) and a high frequency of hvhmKPC-KP isolates was found. Most hospital-associated lineages of KPC-KP belong to the international clonal group 258 (CG258). Biofilm formation was a constant feature among 90.9 % of KPC-KP strains. This report suggests a close relationship between ST437 and weak biofilm production, given that all weakly biofilm-producing strains belonged to this sequence type. This also supports the dissemination of KPC-KP containing numerous virulence determinants belonging to the biofilm-producing CG258 type in Brazil, including hv and hm strains. These factors allow this pathogen to cause infections, leading to its rapid expansion and persistence in hospital settings.

Molecular characterization and clonal dynamics of nosocomial blaOXA-23 producing XDR Acinetobacter baumannii.

The emergence of infections associated to new antimicrobial resistance in Acinetobacter baumannii (Ab) genotypes represents a major challenge. In this context, this study aimed to determine the diversity of resistance mechanisms and investigate clonal dissemination and predominant sequence types (STs) in multidrug-resistant Ab strains of clinical (tracheal aspirate, n = 17) and environmental (surface, n = 6) origins. Additionally, the major clones found in clinical (A) and environmental (H) strains had their complete genomes sequenced. All strains were submitted to polymerase chain reactions (PCR) for the detection of the ISAba1/blaOXA-51-like and ISAba1/blaOXA-23-like genes, while the expression of genes encoding the carO porin, AdeABC (adeB), AdeFGH (adeG), and AdeIJK (adeJ) efflux pumps was determined by real time PCR (qPCR). Most of the strains were characterized as extensively drug-resistant (XDR) with high minimal inhibitory concentrations (MICs) detected for tigecycline and carbapenems. Associations between ISAba1/OXA-51 and ISAba1/OXA-23 were observed in 91.3% and 52.2% of the strains, respectively. Only the adeB gene was considered hyper-expressed. Furthermore, most of the strains analyzed by the MuLtilocus Sequence-Typing (MLST) were found to belong to the clonal complex 113 (CC113). In addition, a new ST, ST1399, belonging to CC229, was also discovered herein. Strains analyzed by whole genome sequencing presented resistance genes linked to multidrug-resistance phenotypes and confirmed the presence of Tn2008, which provides high levels carbapenem-resistance.

Intervenções para perda auditiva sensorioneural: o que mostram as revisões sistemáticas Cochrane? / Interventions for hearing loss sensorineural: what do the Cochrane systematic reviews?

A perda auditiva sensorioneural é condição de elevada prevalência mundial, constituindo problema socioeconômico relevante e preocupante atualmente. Atrelada a muitos fatores de risco, os esforços voltam-se à redução de seu impacto para o futuro. Objetivos: Este estudo avaliou a efetividade das intervenções preventivas e terapêuticas para perda auditiva sensorioneural, segundo as revisões sistemáticas da Colaboração Cochrane. Métodos: Trata-se de overview de revisões sistemáticas Cochrane. Procedeu-se à busca na Cochrane Library (2022), sendo utilizado o termo MeSH "HEARING LOSS". Todos os estudos relacionados à prevenção e tratamento de perda auditiva sensorioneural foram incluídos. O desfecho primário de análise foi a melhora clínica. Resultados: Seis estudos foram incluídos, totalizando 26 ensaios clínicos randomizados (ECRs) (n = 2.139 participantes). Esteroides, antivirais, vasodilatadores, oxigenioterapia hiperbárica e prótese auditiva (aparelho de amplificação sonora individual, AASI) foram avaliados. Nenhuma intervenção medicamentosa mostrou efetividade. Apenas o uso de AASI mostrou melhora na qualidade de vida no que tange à audição. Discussão: Todos os estudos encontrados são de cunho terapêutico, não havendo análises de prevenção da perda auditiva. Em geral, trata-se de estudos com baixa amostragem e alta heterogeneidade, sendo que apenas o uso de AASI pode ser recomendado no momento. Sugere-se a realização de novos ECRs, de qualidade, para intervenções cuja efetividade é ainda incerta, seguindo-se as recomendações do CONSORT (Consolidated Standards of Reporting Trials) Statement. Conclusão: Apenas o uso de AASI apresenta evidência de melhora na qualidade de vida de pacientes com perda auditiva sensorioneural. Nenhuma intervenção medicamentosa apresenta evidência de efetividade atualmente para essa finalidade.

Carbapenem-resistant Pseudomonas aeruginosa: association with virulence genes and biofilm formation.

Pseudomonas aeruginosa is an opportunistic pathogen that causes frequently nosocomial infections, currently becoming more difficult to treat due to the various resistance mechanisms and different virulence factors. The purpose of this study was to determine the risk factors independently associated with the development of bacteremia by carbapenem-resistant P. aeruginosa, the frequency of virulence genes in metallo-ß-lactamases producers and to evaluate their ability to produce biofilm. We conducted a case-control study in the Uberlândia Federal University - Hospital Clinic, Brazil. Polymerase Chain Reaction was performed for metallo-ß-lactamases and virulence genes. Adhesion and biofilm assays were done by quantitative tests. Among the 157 strains analyzed, 73.9% were multidrug-resistant, 43.9% were resistant to carbapenems, 16.1% were phenotypically positive for metallo-ß-lactamases, and of these, 10.7% were positive for blaSPM gene and 5.3% positive for blaVIM. The multivariable analysis showed that mechanical ventilation, enteral/nasogastric tubes, primary bacteremia with unknown focus, and inappropriate therapy were independent risk factors associated with bacteremia. All tested strains were characterized as strongly biofilm producers. A higher mortality was found among patients with bacteremia by carbapenem-resistant P. aeruginosa strains, associated independently with extrinsic risk factors, however it was not evident the association with the presence of virulence and metallo-ß-lactamases genes.

Molecular epidemiological survey of bacteremia by multidrug resistant Pseudomonas aeruginosa: the relevance of intrinsic resistance mechanisms.

The bacterial factors associated with bacteremia by multidrug-resistant and extensively drug-resistant P. aeruginosa, including overexpression of efflux pumps, AmpC overproduction, and loss/alteration of the OprD porin in isolates that are non-Metallo-ß-Lactamase producing were analyzed in a retrospective study. Molecular analyses included strain typing by Pulsed Field Gel Electrophoresis and identification of key genes via qualitative and quantitative PCR-based assays. Previous use of carbapenems and tracheostomy was independently associated with the development of bacteremia by extensively drug-resistant and multidrug-resistant strains of P. aeruginosa. A high consumption of antimicrobials was observed, and 75.0% of the isolates contained amplicons with the blaSPM-1 and blaVIM genes. Of the 47 non-Metallo-ß-Lactamase isolates, none had another type of carbapenemase. However, the isolates exhibited high rates of hyperproduction of AmpC, loss of the OprD porin (71.4%) and the presence of MexABOprM (57.1%) and MexXY (64.3%). This study suggests that in non-Metallo-ß-Lactamase isolates, the association of intrinsic resistance mechanisms could contributes to the expression of multidrug-resistant/extensively drug-resistant phenotypes.

High frequency of the combined presence of QRDR mutations and PMQR determinants in multidrug-resistant Klebsiella pneumoniae and Escherichia coli isolates from nosocomial and community-acquired infections.

Plasmid-mediated quinolone resistance (PMQR) determinants combined with mutations in quinolone resistance-determining regions (QRDRs) and clonal dissemination were investigated in 40 fluoroquinolone-resistant Klebsiella pneumoniae and Escherichia coli isolates from nosocomial and community-acquired infections. We observed nucleotide substitutions in gyrA (Ser83Ile, Val37Leu, Lys154Arg, Ser171Ala, Ser19Asn, Ile198Val, Ser83Tyr, Ser83Leu, Asp87Asn and Asp87Gly) and parC genes (Ser80Ile, Glu84Lys, Ala129Ser, Val141Ala and Glu84Gly). Two novel substitutions were detected in the gyrA gene (Val37Leu and Ile198Val). The presence of PMQR genes predominated in community isolates (55.5 %). In addition to the frequent presence of the class 1 integron in isolates from community-acquired infections, the genetic similarity results obtained by PFGE showed high genomic diversity. This study suggests that management of multidrug-resistant Enterobacteriaceae isolates from the community are a possible source of genetic mobile elements that carry genes that confer resistance to fluoroquinolones. More attention should be paid to the surveillance of community-acquired infections.

Clinical and Molecular Epidemiology of Multidrug-Resistant P. aeruginosa Carrying aac(6')-Ib-cr, qnrS1 and blaSPM Genes in Brazil.

We described a comprehensive analysis of the molecular epidemiology of multidrug-resistant (MDR) P. aeruginosa. Molecular analysis included typing by Pulsed Field Gel Electrophoresis, identification of genes of interest through PCR-based assays and sequencing of target genes. Case-control study was conducted to better understand the prognostic of patients and the impact of inappropriate therapy in patients with bacteremia, as well as the risk factors of MDR infections. We observed a high rate of MDR isolates (40.7%), and 51.0% of them was independently associated with inappropriate antibiotic therapy. Bacteremia was detected in 66.9% of patients, and prolonged hospital stay was expressive in those resistant to fluoroquinolone. Plasmid-mediated quinolone resistance genes (PMQR), qnrS1 and aac(6')Ib-cr, were detected in two different nosocomial isolates (5.3%), and the aac(6')-Ib7 variant was detected at a high frequency (87.5%) in those negative to PMQR. The presence of mutations in gyrA and parC genes was observed in 100% and 85% of selected isolates, respectively. Isolates harboring PMQR genes or mutations in gyrA and parC were not closely related, except in those containing SPM (São Paulo metallo-ß-lactamase) clone. In addition, there is no study published in Brazil to date reporting the presence of Pseudomonas aeruginosa isolates harboring both qnrS1 and aac(6')Ib-cr genes, with alarming frequency of patients with inappropriate therapy.

Molecular epidemiological survey of the quinolone- and carbapenem-resistant genotype and its association with the type III secretion system in Pseudomonas aeruginosa.

This study evaluated the predictors of mortality and the impact of inappropriate therapy on the outcomes of patients with bacteraemia and ventilator-associated pneumonia (VAP). Additionally, we evaluated the correlation of the type III secretion system (TTSS) effector genotype with resistance to carbapenems and fluoroquinolones, mutations in the quinolone resistance-determining regions (QRDRs), metallo-ß-lactamase and virulence factors. A retrospective cohort was conducted at a tertiary hospital in patients with multidrug-resistant (MDR) P. aeruginosa bacteraemia (157 patients) and VAP (60 patients). The genes for blaIMP, blaVIM, blaSIM, blaGIM and blaSPM and virulence genes (exoT, exoS, exoY, exoU, lasB, algD and toxA) were detected; sequencing was conducted for QRDR genes on fluoroquinolone-resistant strains. The multivariate analyses showed that the predictors independently associated with death in patients with bacteraemia were cancer and inappropriate therapy. Carbapenem resistance was more frequent among strains causing VAP (53.3 %), and in blood we observed the blaSPM genotype (66.6 %) and blaVIM genotype (33.3 %). The exoS gene was found in all isolates, whilst the frequency was low for exoU (9.4 %). Substitution of threonine to isoleucine at position 83 in gyrA was the most frequent mutation among fluoroquinolone-resistant strains. Our study showed a mutation at position 91 in the parC gene (Glu91Lys) associated with a mutation in gyrA (Thre83Ile) in a strain of extensively drug-resistant P. aeruginosa, with the exoT(+)exoS(+)exoU(+) genotype, that has not yet been described in Brazil to the best of our knowledge. This comprehensive analysis of resistance mechanisms to carbapenem and fluoroquinolones and their association with TTSS virulence genes, covering MDR P. aeruginosa in Brazil, is the largest reported to date.

Carbapenem-resistant Pseudomonas aeruginosa: association with virulence genes and biofilm formation

Abstract Pseudomonas aeruginosa is an opportunistic pathogen that causes frequently nosocomial infections, currently becoming more difficult to treat due to the various resistance mechanisms and different virulence factors. The purpose of this study was to determine the risk factors independently associated with the development of bacteremia by carbapenem-resistant P. aeruginosa, the frequency of virulence genes in metallo-β-lactamases producers and to evaluate their ability to produce biofilm. We conducted a case–control study in the Uberlândia Federal University – Hospital Clinic, Brazil. Polymerase Chain Reaction was performed for metallo-β-lactamases and virulence genes. Adhesion and biofilm assays were done by quantitative tests. Among the 157 strains analyzed, 73.9% were multidrug-resistant, 43.9% were resistant to carbapenems, 16.1% were phenotypically positive for metallo-β-lactamases, and of these, 10.7% were positive for blaSPM gene and 5.3% positive for blaVIM. The multivariable analysis showed that mechanical ventilation, enteral/nasogastric tubes, primary bacteremia with unknown focus, and inappropriate therapy were independent risk factors associated with bacteremia. All tested strains were characterized as strongly biofilm producers. A higher mortality was found among patients with bacteremia by carbapenem-resistant P. aeruginosa strains, associated independently with extrinsic risk factors, however it was not evident the association with the presence of virulence and metallo-β-lactamases genes.

Risk factors for indications of intraoperative blood transfusion among patients undergoing surgical treatment for colorectal adenocarcinoma.

CONTEXT: Identification of risk factors for requiring transfusions during surgery for colorectal cancer may lead to preventive actions or alternative measures, towards decreasing the use of blood components in these procedures, and also rationalization of resources use in hemotherapy services. This was a retrospective case-control study using data from 383 patients who were treated surgically for colorectal adenocarcinoma at 'Fundação Pio XII', in Barretos-SP, Brazil, between 1999 and 2003. OBJECTIVE: To recognize significant risk factors for requiring intraoperative blood transfusion in colorectal cancer surgical procedures. METHODS: Univariate analyses were performed using Fisher's exact test or the chi-squared test for dichotomous variables and Student's t test for continuous variables, followed by multivariate analysis using multiple logistic regression. RESULTS: In the univariate analyses, height (P = 0.06), glycemia (P = 0.05), previous abdominal or pelvic surgery (P = 0.031), abdominoperineal surgery (P<0.001), extended surgery (P<0.001) and intervention with radical intent (P<0.001) were considered significant. In the multivariate analysis using logistic regression, intervention with radical intent (OR = 10.249, P<0.001, 95% CI = 3.071-34.212) and abdominoperineal amputation (OR = 3.096, P = 0.04, 95% CI = 1.445-6.623) were considered to be independently significant. CONCLUSION: This investigation allows the conclusion that radical intervention and the abdominoperineal procedure in the surgical treatment of colorectal adenocarcinoma are risk factors for requiring intraoperative blood transfusion.

Risk factors for indications of intraoperative blood transfusion among patients undergoing surgical treatment for colorectal adenocarcinoma / Fatores de risco para indicação de transfusão sanguínea intraoperatória em doentes operados por adenocarcinoma colorretal

CONTEXT: Identification of risk factors for requiring transfusions during surgery for colorectal cancer may lead to preventive actions or alternative measures, towards decreasing the use of blood components in these procedures, and also rationalization of resources use in hemotherapy services. This was a retrospective case-control study using data from 383 patients who were treated surgically for colorectal adenocarcinoma at "Fundação Pio XII", in Barretos-SP, Brazil, between 1999 and 2003. OBJECTIVE: To recognize significant risk factors for requiring intraoperative blood transfusion in colorectal cancer surgical procedures. METHODS: Univariate analyses were performed using Fisher's exact test or the chi-squared test for dichotomous variables and Student's t test for continuous variables, followed by multivariate analysis using multiple logistic regression. RESULTS: In the univariate analyses, height (P = 0.06), glycemia (P = 0.05), previous abdominal or pelvic surgery (P = 0.031), abdominoperineal surgery (P<0,001), extended surgery (P<0.001) and intervention with radical intent (P<0.001) were considered significant. In the multivariate analysis using logistic regression, intervention with radical intent (OR = 10.249, P<0.001, 95 percent CI = 3.071-34.212) and abdominoperineal amputation (OR = 3.096, P = 0.04, 95 percent CI = 1.445-6.623) were considered to be independently significant. CONCLUSION: This investigation allows the conclusion that radical intervention and the abdominoperineal procedure in the surgical treatment of colorectal adenocarcinoma are risk factors for requiring intraoperative blood transfusion.

OBJETIVO: Identificar fatores de risco de indicação de transfusão sanguínea intraoperatória em doentes submetidos a tratamento cirúrgico por adenocarcinoma colorretal. MÉTODOS: Estudo retrospectivo, tipo caso-controle, realizado na Fundação Pio XII, em Barretos, SP, utilizando-se base de dados de prontuários de 383 pacientes admitidos entre 1999 e 2003. Utilizou-se teste exato de Fischer ou qui ao quadrado para variáveis dicotômicas e t de Student para variáveis contínuas, na análise univariada, adotando-se nível de significância de 10 por cento (P<0,10); na análise multivariada foi aplicado o teste de regressão logística múltipla, com nível de significância de 5 por cento (P<0,05); as razões de chances e os respectivos intervalos de confiança de 95 por cento foram calculados. RESULTADOS: Nas análises univariadas foram consideradas significantes as variáveis altura (P = 0,06), glicemia (P = 0,05), antecedente de cirurgia abdominal ou pélvica (P = 0,031), operação abdominoperineal (P<0,001), cirurgia ampliada (P<0,001) e intervenção com intuito radical (P<0,001). Na análise multivariada por regressão logística foram considerados independentemente significantes, quando analisadas em conjunto, intervenção com intuito radical (OR = 10,249, P<0,001, IC95 por cento = 3,071-34,212) e amputação abdominoperineal (OR = 3,906, P = 0,04, IC95 por cento = 0,151-0,692). CONCLUSÃO: Esta investigação permitiu concluir que a intervenção radical e o procedimento abdominoperineal, no tratamento cirúrgico do adenocarcinoma colorretal, constituem fatores de risco independentes para a transfusão sanguínea intraoperatória.

Ascaridíase hepatobiliar complicada por pneumonia lipoídica / Hepatobiliary ascariasis complicated by lipoid pneumonia

OBJETIVO: Apresentar um caso de ascaridíase hepatobiliar complicado por pneumonia lipoídica e discutir as implicações anestésicas envolvidas. DESCRIÇÃO DO CASO: Menina de dois anos de idade com ascaridíase hepatobiliar complicada por pneumonia lipoídica por aspiração e desnutrição grave, advinda de família em condições sociais precárias em zona rural, com quatro irmãos. Foi tratada com sucesso por uma combinação de lavados broncopulmonares sucessivos e cirurgia. COMENTÁRIOS: Ascaridíase biliar corresponde a cerca de 10 por cento dos casos de complicações de ascaridíase. Apenas uma minoria precisa de tratamento cirúrgico. O uso de óleo mineral por via oral é um tratamento tradicional para a suboclusão intestinal pelo Ascaris lumbricoides, mas a broncoaspiração do óleo e a conseqüente pneumonia lipoídica representam um risco alto para o seu uso. Anestesia geral para laparotomia exploradora em pré-escolar desnutrido com pneumonia lipóide e ascaridíase biliar é uma situação pouco contemplada na literatura médica, o que exigiu um planejamento terapêutico específico.

OBJECTIVE: To present a case of hepatobiliary ascariasis complicated by exogenous lipoid aspirative pneumonia and the anesthetic implications involved. CASE DESCRIPTION: We present a case of hepatobiliary ascariasis complicated by exogenous lipoid aspirative pneumonia and severe undernourishment in a two-year-old female from a five-children poor family from the Brazilian rural area. She was successfully treated by the association of repeated bronchopulmonary lavage and surgery. COMMENTS: Biliary ascariasis corresponds roughly to 10 percent of complicated ascariasis cases. Only a minority requires surgery. Mineral oil is a traditional treatment for intestinal Ascaris lumbricoides subocclusion, but oil aspiration and lipoid pneumonia remain a highly morbid risk of this practice. General anesthesia and laparotomy in an undernourished small child with lipoid pneumonia and biliary ascariasis were rarely addressed in the medical literature. Therefore, the therapeutic planning of this case was difficult.