Diogo Diniz Gomes Bugano

Effect of Tight Blood Glucose Control Versus Conventional Control in Patients with Type 2 Diabetes Mellitus: A Systematic Review with Meta-Analysis of Randomized Controlled Trials.

Tight control of blood glucose reduces cardiovascular events and total mortality is conflicting. To summarize clinical effects of tight versus conventional glucose control in patients with type 2 diabetes. We systematically searched MEDLINE, EMBASE, Cochrane Library, and ISI Web of Knowledge with no limits of language and time. Further trials were searched from the reference lists of identified studies. We included randomized controlled comparing different levels of blood glucose control intensity in type 2 diabetic patients. Two independent reviewers extracted data of eligible studies using standard case report forms. We investigated total mortality, cardiovascular and microvascular events, and hypoglycemia in patients with type 2 diabetes. We used random-effects models to obtain relative risks (RR) with 95% confidence intervals (CI). We included 6 trials involving 27,654 patients. There was no significant effect of tight blood glucose control on all-cause mortality (RR 1.03; 95% CI 0.90-1.17) or cardiovascular mortality (RR 1.04; 95% CI 0.83-1.29). Tight glucose control reduced the risk for nonfatal MI (RR 0.85; 95% CI 0.76-0.95), although had no effect on the incidence of nonfatal stroke (RR 1.02; 95% CI 0.88-1.17). For microvascular events, tight glucose control reduced the risk progression of retinopathy (RR 0.80; 95% CI 0.71-0.91), incidence of peripheral neuropathy (RR 0.94; 95% CI 0.89-0.99), and progression of nephropathy (RR 0.55; 95% CI 0.37-0.80), but had not significant effect on the incidence of nephropathy (RR 0.69; 95% CI 0.42-1.14). The risk of severe hypoglycemia increased with tight glucose control (RR 2.39; 95% CI 1.79-3.18). Tight blood glucose control reduces the risk for some macrovascular and microvascular events, without effect on all-cause mortality and cardiovascular mortality. Tight glucose control increases the risk of severe hypoglycemia.

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 Ringers 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 Ringers 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.

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.

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 (I2 = 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 I2 = 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

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.

Association of glucocorticoid receptor polymorphisms with clinical and metabolic profiles in polycystic ovary syndrome

OBJECTIVES: We aimed to investigate whether glucocorticoid receptor gene polymorphisms are associated with clinical and metabolic profiles in patients with polycystic ovary syndrome. Polycystic ovary syndrome is a complex endocrine disease that affects 5-8% of women and may be associated with metabolic syndrome, which is a risk factor for cardiovascular disease. Cortisol action and dysregulation account for metabolic syndrome development in the general population. As glucocorticoid receptor gene (NR3C1) polymorphisms regulate cortisol sensitivity, we hypothesized that variants of this gene may be involved in the adverse metabolic profiles of patients with polycystic ovary syndrome. METHOD: Clinical, metabolic and hormonal profiles were evaluated in 97 patients with polycystic ovary syndrome who were diagnosed according to the Rotterdam criteria. The alleles of the glucocorticoid gene were genotyped. Association analyses were performed using the appropriate statistical tests. RESULTS: Obesity and metabolic syndrome were observed in 42.3% and 26.8% of patients, respectively. Body mass index was positively correlated with blood pressure, triglyceride, LDL-c, total cholesterol, glucose and insulin levels as well as HOMA-IR values and inversely correlated with HDL-c and SHBG levels. The BclI and A3669G variants were found in 24.7% and 13.4% of alleles, respectively. BclI carriers presented a lower frequency of insulin resistance compared with wild-type subjects. CONCLUSION: The BclI variant is associated with a lower frequency of insulin resistance in women with polycystic ovary syndrome. Glucocorticoid gene polymorphism screening during treatment of the syndrome may be useful for identifying subgroups of at-risk patients who would benefit the most from personalized treatment.

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

Micro‐Abstract: Chemotherapy is the currently recommended first‐line treatment for metastatic pancreatic cancer; however, few patients are eligible for aggressive treatment. We performed a meta‐analysis with a combined sample size of 1461 patients and found that mFIO (modified FOLFIRINOX; leucovorin, 5‐fluorouracil, irinotecan, oxaliplatin) regimens are associated with outcomes similar to those with regular FOLFIRINOX. The analysis results suggest that it is reasonable to consider mFIO for patients with metastatic pancreatic adenocarcinoma, increasing the patient population eligible for this regimen. 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.

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. METHODS DATA SOURCES Cochrane Renal Groups 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.