Brazil-TNT: A Randomized Phase 2 Trial of Neoadjuvant Chemoradiation Followed by FOLFIRINOX Versus Chemoradiation for Stage II/III Rectal Cancer.

BACKGROUND: Neoadjuvant radiation and oxaliplatin-based systemic therapy (total neoadjuvant therapy-TNT) have been shown to increase response and organ-preservation rates in localized rectal cancer. However, trials have been heterogeneous regarding treatment protocols and few have used a watch-and-wait (WW) approach for complete responders. This trial evaluates if conventional long-term chemoradiation followed by consolidation of FOLFIRINOX increases complete response rates and the number of patients managed by WW. METHODS: This was a pragmatic randomized phase II trial conducted in 2 Cancer Centers in Brazil that included patients with T3+ or N+ rectal adenocarcinoma. After completing a long-course 54 Gy chemoradiation with capecitabine patients were randomized 1:1 to 4 cycles of mFOLFIRINOX (Oxaliplatin 85, irinotecan 150, 5-FU 2400)-TNT-arm-or to the control arm, that did not include further neoadjuvant treatment. All patients were re-staged with dedicated pelvic magnetic resonance imaging and sigmoidoscopy 12 weeks after the end of radiation. Patients with a clinical complete response were followed using a WW protocol. The primary endpoint was complete response: clinical complete response (cCR) or pathological response (pCR). RESULTS: Between April 2021 and June 2023, 55 patients were randomized to TNT and 53 to the control arm. Tumors were 74% stage 3, median distance from the anal verge was 6 cm, 63% had an at-risk circumferential margin, and 33% an involved sphincter. The rates of cCR + pCR were (31%) for TNT versus (17%) for controls (odds ratio 2.19, CI 95% 0.8-6.22 P = .091) and rates of WW were 16% and 9% (P = ns). Median follow-up was 8.1 months and recurrence rates were 16% versus 21% for TNT and controls (P = ns). CONCLUSIONS: TNT with consolidation FOLFIRINOX is feasible and has high response rates, consistent with the current literature for TNT. This trial was supported by a grant from the Brazilian Government (PROADI-SUS - NUP 25000.164382/2020-81).

Is physical inactivity and sedentary behavior associated with tumor stage in breast cancer patients? A cross-sectional study of Brazilian women.

OBJECTIVE: A comparative analysis of the association between sedentary behavior versus physical activity levels and tumor staging in women with breast cancer. METHODS: The present research adopted a cross-sectional study design to recruit a total of 55 adult and elderly women newly diagnosed with breast cancer for data collection and analysis. Inclusion criteria involved patients in procession of a formal approval for participation in the study by the treating physician and those not hitherto subjected to the first cycle of chemotherapy. RESULTS: Physical activity levels did not influence the pathological stage of breast cancer (p=0.26) or histological tumor grade (p=0.07) in the analyzed subjects. However, there was a significant association between physical activity levels and responsiveness to hormones (epidermal growth factor receptor (HER2), p<0.05) in the analyzed subjects. Significant difference was detected in the histological tumor grade in relation to the mean time spent sitting during the weekend (p<0.05). However, sedentary behavior had no influence on the tumor stage (p>0.05). CONCLUSION: Physical activity levels did not influence the tumor stage and histological tumor grade. Sedentary behavior had a significant influence on the histological tumor grade.

Is physical inactivity and sedentary behavior associated with tumor stage in breast cancer patients? A cross-sectional study of Brazilian women

ABSTRACT Objective A comparative analysis of the association between sedentary behavior versus physical activity levels and tumor staging in women with breast cancer. Methods The present research adopted a cross-sectional study design to recruit a total of 55 adult and elderly women newly diagnosed with breast cancer for data collection and analysis. Inclusion criteria involved patients in procession of a formal approval for participation in the study by the treating physician and those not hitherto subjected to the first cycle of chemotherapy. Results Physical activity levels did not influence the pathological stage of breast cancer (p=0.26) or histological tumor grade (p=0.07) in the analyzed subjects. However, there was a significant association between physical activity levels and responsiveness to hormones (epidermal growth factor receptor (HER2), p<0.05) in the analyzed subjects. Significant difference was detected in the histological tumor grade in relation to the mean time spent sitting during the weekend (p<0.05). However, sedentary behavior had no influence on the tumor stage (p>0.05). Conclusion Physical activity levels did not influence the tumor stage and histological tumor grade. Sedentary behavior had a significant influence on the histological tumor grade.

Systematic review and meta-analysis of docetaxel perioperative chemotherapy regimens in gastric and esophagogastric tumors.

FLOT regimen became the standard perioperative treatment in several centers around the world for esophagogastric tumors despite concerns about toxicity. In addition, FLOT has never been compared with other docetaxel-based regimens. To address this question, we conducted a systematic review of PubMed, Embase and Web of Science including prospective or retrospective studies of docetaxel based perioperative regimen in gastric and esophagogastric tumors. Data regarding chemotherapy regimens, efficacy and toxicity were extracted. Outcomes were compared using a random effects model. Of 548 abstracts, 16 were considered eligible. Comparing the studies with meta-analysis we can see that the regimens are similar in terms of pathological complete response, resection rate, progression free survival and overall survival in one year, without significant heterogeneity. The meta-regression of docetaxel dose failed to show any association with dose ranging between 120-450 mg/m². Regarding the toxicity of the regimens it is noted that the regimens are quite toxic (up to 50-70% of grade 3-4 neutropenia). The results of this meta-analysis with a combined sample size of more than 1,000 patients suggest that docetaxel perioperative regimens are equivalent in outcomes. Prospective trials addressing modified regimens should be performed to provide less toxic strategies and be applicable to all patients.

Meta-analysis of Modified FOLFIRINOX Regimens for Patients With Metastatic Pancreatic Cancer.

BACKGROUND: We performed a meta-analysis of previous reports evaluating the effect of mFIO (modified FOLFIRINOX; leucovorin, 5-fluorouracil, irinotecan, oxaliplatin) regimens in advanced pancreatic cancer. MATERIALS AND METHODS: We performed a meta-analysis of reported studies in PubMed, Scopus, and Web of Science (1950-2016) in December 2016. The inclusion criteria were randomized trials, prospective or retrospective cohorts, patients with metastatic pancreatic adenocarcinoma, the use of mFIO or FOLFIRINOX (FIO) chemotherapy, and available information for ≥ 1 efficacy endpoint (response rate, progression-free survival, and/or overall survival). The outcomes were compared according to the chemotherapy regimen using a random effects model. We also performed a meta-regression analysis to evaluate the effect of dose reductions on outcomes. RESULTS: Of 2525 abstracts, 32 were considered eligible. Modifications in the FIO regimen included omission of the 5-fluorouracil bolus and/or dose reductions in infusional 5-fluorouracil, irinotecan, and/or oxaliplatin. mFIO was not associated with inferior response rates (32% vs. 33%; P = .879), lower rates of survival at 11 months (47% vs. 50%; P = .38), or lower 6-month progression-free survival rates (47% vs. 53%; P = .38). The meta-regression of the percentage of dose reduction failed to show any association. CONCLUSION: The results of the present meta-analysis with a combined sample size of 1461 patients suggest that it is reasonable to consider mFIO regimens for patients with metastatic pancreatic adenocarcinoma.

Incidental Findings in Reduction Mammoplasty Specimens in Patients with No Prior History of Breast Cancer. An Analysis of 783 Specimens.

Breast reduction surgery is a common procedure and the rate of incidental findings in the removed specimens varies between 0% and 4.6%. There are no guidelines about pathological evaluation of breast reduction surgery. We reviewed all pathology reports of patients undergoing breast reduction surgery in a single tertiary institution in Brazil from January 2008 to August 2014. Exclusion criteria were a personal history of breast cancer, unclear reason for mastectomy and incomplete data on the pathology report. We considered "relevant findings" flat epithelial atypia, atypical hyperplasia, carcinomas in situ and invasive carcinoma. Of 1672 specimens from breast reduction surgery, 783 met inclusion criteria. Median patient age was 40 (8-77), 91% underwent bilateral mastectomy and 57% of the specimens weighted less than 200 g. In 55% of cases, 4 or more paraffin blocks were sampled. There were 40 (5.1%) relevant findings and the most common was atypical lobular hyperplasia (16-2%). There were 3 invasive carcinomas (0.38%). In multivariate analysis, the only variables associated with a higher odds of relevant pathological findings were patient age ≥ 40 (OR 4.73 CI95% 1.98-11.3 p < 0.001) and sampling of ≥4 paraffin blocks from each specimen (OR 6.69 95% CI 2.25-19.9 p < 0.001). The incidence of pre-malignant and malignant lesions in specimens from breast reduction surgery is around 5%, but this risk is significantly higher for patients older than 40 years-old. Sampling at least 4 paraffin blocks from each specimen significantly increases detection rates.

Does Time-to-Chemotherapy Impact the Outcomes of Resected Ovarian Cancer? Meta-analysis of Randomized and Observational Data.

OBJECTIVES: This study is a meta-analysis of prior publications evaluating the impact of time-to-chemotherapy (TTC) on disease recurrence and survival 3 years after the original surgery. METHODS: We performed a meta-analysis of studies published in PubMed (1950-2016) as of April 2016. Inclusion criteria were as follows: randomized controlled trials and prospective or retrospective cohorts that included patients with ovarian cancer who had undergone surgery with curative intent and use of adjuvant chemotherapy. We compared rates of disease recurrence and death according to the TTC ("early" vs "delayed") using a random-effects model and performed a metaregression to evaluate the impact of covariates on these outcomes. RESULTS: Of 239 abstracts in the original search, 12 were considered eligible. The cutoffs used for TTC were between 20 and 40 days. All studies used a platinum-based chemotherapy, and the rates of patients with suboptimal resection varied from 33% to 70%. A longer TTC was not associated with higher rates of disease recurrence (odds ratio, 0.89; 95% confidence interval, 0.63-1.24) or death at 3 years (odds ratio, 1.06; 95% confidence interval, 0.9-1.24). There was no evidence of significant publication bias (Egger test P = 0.472), but data were heterogeneous (I = 64.3%). Metaregression showed that the percentage of patients with suboptimal surgery and values used as cutoff to define "delayed" chemotherapy combined were a significant source of bias (residual I = 0%). CONCLUSIONS: In our analysis, TTC after surgery for ovarian cancer with curative intent was not associated with higher risk of disease recurrence or death. However, this association was influenced by the rate of optimal debulking and definition of "late" initiation of chemotherapy, so we must be careful when applying these data to patients with complete resection.

Clinical features and overall survival among elderly cancer patients in a tertiary cancer center.

OBJECTIVE: To evaluate the epidemiological profile and overall survival of a large population of elderly individuals diagnosed with solid tumors in a tertiary hospital. METHODS: This retrospective study included patients aged >65 years, diagnosed with solid tumors between January 2007 and December 2011, at Hospital Israelita Albert Einstein, São Paulo, Brazil. The medical records were reviewed to obtain information about clinical variables and overall survival. RESULTS: A total of 806 patients were identified, and 58.4% were male. Mean age was 74 years (65 to 99 years). The most common types were prostate (22%), colorectal (21%), breast (19%), and lung cancer (13%), followed by bladder (8%), pancreas (6%), and other types (11%). The majority of patients were diagnosed at early stage disease. After a median follow-up of 27 months (15 to 45 months), 29% of the patients (234/806) died, predominantly in the group older than 70 years. For the entire cohort, the median 2-year survival rate was 71%. Median overall survival was not reached within the study period. In a multivariate analysis, age (HR: 1.35; 95%CI: 1.25-1.45; p<0.001) and disease stage (HR: 1.93; 95%CI: 1.75-2.14; p<0.001) were independent negative predictors of poor survival. CONCLUSION: The most prevalent tumors were prostate, colorectal, breast, and lung cancer, with the larger proportion diagnosed at initial stages, reflecting the great number of patients alive at last follow-up.

Clinical features and overall survival among elderly cancer patients in a tertiary cancer center / Características clínicas e de sobrevida global em pacientes oncológicos idosos num centro oncológico terciário

ABSTRACT Objective To evaluate the epidemiological profile and overall survival of a large population of elderly individuals diagnosed with solid tumors in a tertiary hospital. Methods This retrospective study included patients aged >65 years, diagnosed with solid tumors between January 2007 and December 2011, at Hospital Israelita Albert Einstein, São Paulo, Brazil. The medical records were reviewed to obtain information about clinical variables and overall survival. Results A total of 806 patients were identified, and 58.4% were male. Mean age was 74 years (65 to 99 years). The most common types were prostate (22%), colorectal (21%), breast (19%), and lung cancer (13%), followed by bladder (8%), pancreas (6%), and other types (11%). The majority of patients were diagnosed at early stage disease. After a median follow-up of 27 months (15 to 45 months), 29% of the patients (234/806) died, predominantly in the group older than 70 years. For the entire cohort, the median 2-year survival rate was 71%. Median overall survival was not reached within the study period. In a multivariate analysis, age (HR: 1.35; 95%CI: 1.25-1.45; p<0.001) and disease stage (HR: 1.93; 95%CI: 1.75-2.14; p<0.001) were independent negative predictors of poor survival. Conclusion The most prevalent tumors were prostate, colorectal, breast, and lung cancer, with the larger proportion diagnosed at initial stages, reflecting the great number of patients alive at last follow-up.

RESUMO Objetivo Avaliar o perfil epidemiológico e a sobrevida global em uma grande população de indivíduos idosos diagnosticados com tumores sólidos, em um hospital terciário. Métodos Estudo retrospectivo que incluiu pacientes com idade >65 anos, diagnosticados com tumores sólidos entre janeiro de 2007 e dezembro de 2011, no Hospital Israelita Albert Einstein, São Paulo, Brasil. Os prontuários médicos foram revisados para se obterem informações sobre variáveis clínicas e sobrevida global. Resultados Foi identificado um total de 806 pacientes, sendo 58,4% deles do sexo masculino. A média de idade foi de 74 anos (65 a 99 anos). Os tipos mais comuns de câncer foram de próstata (22%), colorretal (21%), de mama (19%) e de pulmão (13%), seguidos pelos de bexiga (8%), pâncreas (6%) e outros tipos (11%). A maioria dos pacientes foi diagnosticada em estágios iniciais. Depois de um seguimento médio de 27 meses (15 a 45 meses), 29% (234/806) estavam mortos, predominantemente no grupo com idade >70 anos. Para toda a coorte, a mediana de taxa de sobrevida em 2 anos foi 71%. A mediana de sobrevida global não foi alcançada dentro do período de estudo. Em análise multivariada, idade (HR: 1,35; IC95%: 1,25-1,45; p<0,001) e estadiamento (HR: 1,93; IC95%: 1,75-2,14; p<0,001) foram preditores negativos independentes de pior sobrevida. Conclusão Os tumores mais prevalentes foram de próstata, colorretal, mama e pulmão, com uma grande proporção diagnosticada em estádios iniciais, o que reflete em um grande número de pacientes vivos até o último seguimento.

Prevalence of renal insufficiency in elderly cancer patients in a tertiary cancer center.

OBJECTIVE: To estimate the prevalence of abnormal glomerular filtration rate in elderly patients with solid tumors. METHODS: A retrospective study with patients aged >65 years diagnosed with solid tumors between January 2007 and December 2011 in a cancer center. The following data were collected: sex, age, serum creatinine at the time of diagnosis and type of tumor. Renal function was calculated using abbreviated Modification of Diet in Renal Disease (MDRD) formulae and then staged in accordance with the clinical practice guidelines published by the Working Group of the National Kidney Foundation. RESULTS: A total of 666 patients were included and 60% were male. The median age was 74.2 years (range: 65 to 99 years). The most prevalent diagnosis in the study population were colorectal (24%), prostate (20%), breast (16%) and lung cancer (16%). The prevalence of elevated serum creatinine (>1.0mg/dL) was 30%. However, when patients were assessed using abbreviated MDRD formulae, 66% had abnormal renal function, stratified as follows: 45% with stage 2, 18% with stage 3, 3% with stage 4 and 0.3% with stage 5. CONCLUSION: To the best of our knowledge, this was the first study to estimate the frequency of renal insufficiency in elderly cancer patients in Brazil. The prevalence of abnormal renal function among our cohort was high. As suspected, the absolute creatinine level does underestimate renal function impairment and should not be used as predictor of chemotherapy metabolism, excretion and consequent toxicity.

Prevalence of renal insufficiency in elderly cancer patients in a tertiary cancer center / Prevalência de insuficiência renal em pacientes idosos com câncer em um centro de tratamento oncológico

Objective To estimate the prevalence of abnormal glomerular filtration rate in elderly patients with solid tumors. Methods A retrospective study with patients aged >65 years diagnosed with solid tumors between January 2007 and December 2011 in a cancer center. The following data were collected: sex, age, serum creatinine at the time of diagnosis and type of tumor. Renal function was calculated using abbreviated Modification of Diet in Renal Disease (MDRD) formulae and then staged in accordance with the clinical practice guidelines published by the Working Group of the National Kidney Foundation. Results A total of 666 patients were included and 60% were male. The median age was 74.2 years (range: 65 to 99 years). The most prevalent diagnosis in the study population were colorectal (24%), prostate (20%), breast (16%) and lung cancer (16%). The prevalence of elevated serum creatinine (>1.0mg/dL) was 30%. However, when patients were assessed using abbreviated MDRD formulae, 66% had abnormal renal function, stratified as follows: 45% with stage 2, 18% with stage 3, 3% with stage 4 and 0.3% with stage 5. Conclusion To the best of our knowledge, this was the first study to estimate the frequency of renal insufficiency in elderly cancer patients in Brazil. The prevalence of abnormal renal function among our cohort was high. As suspected, the absolute creatinine level does underestimate renal function impairment and should not be used as predictor of chemotherapy metabolism, excretion and consequent toxicity. .

Objetivo Estimar a prevalência de taxa de filtração glomerular alterada em pacientes idosos diagnosticados com tumores sólidos. Métodos Estudo retrospectivo de pacientes com mais de 65 anos de idade, diagnosticados com tumores sólidos entre janeiro de 2007 e dezembro de 2011 em um centro de tratamento oncológico. Foram coletados dados sobre sexo, idade, creatinina sérica à época do diagnóstico e tipo de tumor. A função renal foi calculada utilizando a versão simplificada da equação MDRD (Modification of Diet in Renal Disease) e depois estratificada de acordo com as diretrizes de prática clínica do Working Group of the National Kidney Foundation. Resultados Foram incluídos 666 pacientes, sendo 60% do sexo masculino. A idade mediana foi 74,2 anos (variação de 65 a 99 anos), e os diagnósticos mais prevalentes na população do estudo foram câncer colorretal (24%), de próstata (20%), mama (16%) e pulmão (16%). A prevalência de creatinina sérica elevada (>1,0mg/dL) foi 30%. No entanto, quando os pacientes foram avaliados utilizando a forma abreviada da equação MDRD, 66% tinham uma função renal anormal assim estratificada: 45% em estádio 2, 18% em estádio 3, 3% em estádio 4 e 0,3% em estádio 5. Conclusão Até onde sabemos, este foi o primeiro estudo a estimar a frequência de insuficiência renal em pacientes idosos com câncer no Brasil. A prevalência de função renal alterada na coorte estudada foi alta. Como suspeitávamos, o nível absoluto de creatinina subestima a alteração na função renal e não deve ser usado como preditor de metabolismo, excreção e consequente toxicidade dos agentes quimioterápicos. .

Impact of Plasma-Lyte pH 7.4 on acid-base status and hemodynamics in a model of controlled hemorrhagic shock.

OBJECTIVE: Intravenous infusion of crystalloid solutions is a cornerstone of the treatment of hemorrhagic shock. However, crystalloid solutions can have variable metabolic acid-base effects, perpetuating or even aggravating shock-induced metabolic acidosis. The aim of this study was to compare, in a controlled volume-driven porcine model of hemorrhagic shock, the effects of three different crystalloid solutions on the hemodynamics and acid-base balance. METHODS: Controlled hemorrhagic shock (40% of the total blood volume was removed) was induced in 18 animals, which were then treated with normal saline (0.9% NaCl), Lactated Ringer's Solution or Plasma-Lyte pH 7.4, in a blinded fashion (n = 6 for each group). Using a predefined protocol, the animals received three times the volume of blood removed. RESULTS: The three different crystalloid infusions were equally capable of reversing the hemorrhage-induced low cardiac output and anuria. The Lactated Ringer's Solution and Plasma-Lyte pH 7.4 infusions resulted in an increased standard base excess and a decreased serum chloride level, whereas treatment with normal saline resulted in a decreased standard base excess and an increased serum chloride level. The Plasma-Lyte pH 7.4 infusions did not change the level of the unmeasured anions. CONCLUSION: Although the three tested crystalloid solutions were equally able to attenuate the hemodynamic and tissue perfusion disturbances, only the normal saline induced hyperchloremia and metabolic acidosis.

Meta-análise Cochrane: teicoplanina versus vancomicina para infecções suspeitas ou confirmadas / Cochrane meta-analysis: teicoplanin versus vancomycin for proven or suspected infection

Objective: To compare efficacy and safety of vancomycin versus teicoplanin in patients with proven or suspected infection. Methods: Data Sources: Cochrane Renal Group's Specialized Register, CENTRAL, MEDLINE, EMBASE, nephrology textbooks and review articles. Inclusion criteria: Randomized controlled trials in any language comparing teicoplanin to vancomycin for patients with proven or suspected infection. Data extraction: Two authors independently evaluated methodological quality and extracted data. Study investigators were contacted for unpublished information. A random effect model was used to estimate the pooled risk ratio (RR) with 95% confidence interval (CI). Results: A total of 24 studies (2,610 patients) were included. The drugs had similar rates of clinical cure (RR: 1.03; 95%CI: 0.98-1.08), microbiological cure (RR: 0.98; 95%CI: 0.93-1.03) and mortality (RR: 1.02; 95%CI: 0.79-1.30). Teicoplanin had lower rates of skin rash (RR: 0.57; 95%CI: 0.35-0.92), red man syndrome (RR: 0.21; 95%CI: 0.08-0.59) and total adverse events (RR: 0.73; 95%CI: 0.53-1.00). Teicoplanin reduced the risk of nephrotoxicity (RR: 0.66; 95%CI: 0.48-0.90). This effect was consistent for patients receiving aminoglycosides (RR: 0.51; 95%CI: 0.30-0.88) or having vancomycin doses corrected by serum levels (RR: 0.22; 95%CI: 0.10-0.52). There were no cases of acute kidney injury needing dialysis. Limitations: Studies lacked a standardized definition for nephrotoxicity. Conclusions: Teicoplanin and vancomycin are equally effective; however the incidence of nephrotoxicity and other adverse events was lower with teicoplanin. It may be reasonable to consider teicoplanin for patients at higher risk for acute kidney injury.

Objetivo: Comparar eficácia e toxicidade da teicoplanina e da vancomicina em pacientes com infecção suspeita ou confirmada. Métodos: Fontes de dados: Cochrane Renal Group's Specialized Register, CENTRAL, MEDLINE, EMBASE, livros de referência e artigos de revisão. Critérios de inclusão: Ensaios clínicos controlados randomizados em qualquer idioma, comparando teicoplanina e vancomicina em pacientes com infecção suspeita ou confirmada. Extração de dados: Dois autores avaliaram a qualidade metodológica dos estudos e extraíram os dados de forma independente. Tentou-se obter dados não publicados diretamente com os autores de cada trabalho. Usou-se um modelo de efeito aleatório para estimar a razão de risco (RR) combinada, com um intervalo de confiança (IC) de 95%. Resultados: Foram incluídos 24 estudos (2.610 pacientes). As drogas tiveram taxas semelhantes de cura clínica (RR: 1,03; IC95%: 0,98-1,08), cura microbiológica (RR: 0,98; IC95%: 0,93-1,03) e mortalidade (RR: 1,02; IC95%: 0,79-1,30). A teicoplanina apresentou menores incidências de rash cutâneo (RR: 0,57; IC95%: 0,35-0,92), síndrome do homem vermelho (RR: 0,21; IC95%: 0,08-0,59) e eventos adversos em geral (RR: 0,73; IC95%: 0,53-1,00). A teicoplanina reduziu o risco de nefrotoxicidade (RR: 0,66; IC95%: 0,48-0,90). Esse efeito foi consistente em todos os subgrupos, inclusive aqueles com pacientes recebendo aminoglicosídeos concomitantes (RR: 0,51; IC95%: 0,30-0,88) oucom dosagens de vancomicina corrigidas pelo nível sérico (RR: 0,22; IC95%: 0,10-0,52). Não foi encontrado nenhum caso de injúria renal que necessitasse de diálise. Limitações: Os estudos não seguiram uma definição padrão de nefrotoxicidade. Conclusões: Teicoplanina e vancomicina têm eficácia semelhante; no entanto, o risco de nefrotoxicidade e outros eventos adversos foi menor com teicoplanina. É razoável considerar o uso de teicoplanina para pacientes em risco de desenvolver injúria renal aguda.

Is Gilbert syndrome a new risk factor for breast cancer?

Patients with Gilbert syndrome have an impaired function of the enzyme UGT1A1, responsible for the degradation of 4-OH-estrogens. These elements are produced by the degradation of estrogens and are well-known carcinogens. In theory, patients with Gilbert syndrome accumulate 4-OH-estrogens and, therefore, might have a higher risk for breast cancer, especially when exposed to higher levels of estrogens. If this theory is true, a new risk group for breast cancer would be described, producing new insights in breast carcinogenesis.

Cochrane meta-analysis: teicoplanin versus vancomycin for proven or suspected infection.

OBJECTIVE: To compare efficacy and safety of vancomycin versusteicoplanin in patients with proven or suspected infection. DATA SOURCES: Cochrane Renal Group's Specialized Register, CENTRAL, MEDLINE, EMBASE, nephrology textbooks and review articles. INCLUSION CRITERIA: Randomized controlled trials in any language comparing teicoplanin to vancomycin for patients with proven or suspected infection. DATA EXTRACTION: Two authors independently evaluated methodological quality and extracted data. Study investigators were contacted for unpublished information. A random effect model was used to estimate the pooled risk ratio (RR) with 95% confidence interval (CI). RESULTS: A total of 24 studies (2,610 patients) were included. The drugs had similar rates of clinical cure (RR: 1.03; 95%CI: 0.98-1.08), microbiological cure (RR: 0.98; 95%CI: 0.93-1.03) and mortality (RR: 1.02; 95%CI: 0.79-1.30). Teicoplanin had lower rates of skin rash (RR: 0.57; 95%CI: 0.35-0.92), red man syndrome (RR: 0.21; 95%CI: 0.08-0.59) and total adverse events (RR: 0.73; 95%CI: 0.53-1.00). Teicoplanin reduced the risk of nephrotoxicity (RR: 0.66; 95%CI: 0.48-0.90). This effect was consistent for patients receiving aminoglycosides (RR: 0.51; 95%CI: 0.30-0.88) or having vancomycin doses corrected by serum levels (RR: 0.22; 95%CI: 0.10-0.52). There were no cases of acute kidney injury needing dialysis. LIMITATIONS: Studies lacked a standardized definition for nephrotoxicity. CONCLUSIONS: Teicoplanin and vancomycin are equally effective; however the incidence of nephrotoxicity and other adverse events was lower with teicoplanin. It may be reasonable to consider teicoplanin for patients at higher risk for acute kidney injury.

Impact of Plasma-Lyte pH 7.4 on acid-base status and hemodynamics in a model of controlled hemorrhagic shock

OBJECTIVE: Intravenous infusion of crystalloid solutions is a cornerstone of the treatment of hemorrhagic shock. However, crystalloid solutions can have variable metabolic acid-base effects, perpetuating or even aggravating shock-induced metabolic acidosis. The aim of this study was to compare, in a controlled volume-driven porcine model of hemorrhagic shock, the effects of three different crystalloid solutions on the hemodynamics and acid-base balance. METHODS: Controlled hemorrhagic shock (40 percent of the total blood volume was removed) was induced in 18 animals, which were then treated with normal saline (0.9 percent NaCl), Lactated Ringer's Solution or Plasma-Lyte pH 7.4, in a blinded fashion (n = 6 for each group). Using a predefined protocol, the animals received three times the volume of blood removed. RESULTS: The three different crystalloid infusions were equally capable of reversing the hemorrhage-induced low cardiac output and anuria. The Lactated Ringer's Solution and Plasma-Lyte pH 7.4 infusions resulted in an increased standard base excess and a decreased serum chloride level, whereas treatment with normal saline resulted in a decreased standard base excess and an increased serum chloride level. The Plasma-Lyte pH 7.4 infusions did not change the level of the unmeasured anions. CONCLUSION: Although the three tested crystalloid solutions were equally able to attenuate the hemodynamic and tissue perfusion disturbances, only the normal saline induced hyperchloremia and metabolic acidosis.

Antibiotic management of sepsis: current concepts.

BACKGROUND: The development of guidelines for sepsis management has improved disease survival and reduced treatment costs. Adequate antibiotic therapy is the cornerstone of sepsis treatment. Specific rules should be established in every institution according to its profiles. OBJECTIVES: To review the current knowledge about the best drugs to be used as empiric treatment for sepsis based on their clinical efficacy and costs. METHODS: Medline 1950 - 2008 was searched using the following terms: sepsis, organ failure, system failure, SIRS, septic shock, antibiotic, pneumonia, urinary tract infection, urosepsis, catheter-related infection, bloodstream, abdominal infection, and surgical wound. RESULTS/CONCLUSION: For most septic shock patients, monotherapy is adequate and treatment should be initiated in the first hour after first sepsis-induced organ dysfunction. The drug of choice varies in different situations and choosing the right antibiotic enables better survival, fewer complications and shorter stays in intensive care.