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An increased number of patients is at risk of Candida spp. bloodstream infection (CBSI) in modern medicine. Moreover, the rising of antifungal resistance (AR) was recently reported. All consecutive CBSI occurred in our Hospital (consisting of 1,370 beds) between 2015 and 2018, were reviewed. For each case, Candida species, AR pattern, ward involved and demographic data of patients were recorded. Overall, 304 episodes of CBSI occurred, with a median (q1:first-,q3:third quartile) of 77 (71-82) CBSI/year. Over the years, a significant increase of CBSI due to C. albicans compared to non-albicans strains was recorded in medical wards (from 65% to 71%, p=0.030), while this ratio remained stable in others. An increase of resistant strains to multiple antifungals such as C. guillermondii was noticed in recent years (from 0% to 9.8%, p=0.008). Additionally, from 2015 to 2018 an increase in fluconazole-resistance was recorded in our Hospital (from 7.4% to 17.4%, p=0.025) and a slight increase in voriconazole-resistance (from 0% to 7% in 2018, p=0.161) was observed, while resistance to echinocandin and amphotericin B remained firmly below 2%.This study suggests a rapid spread of antifungal resistance in our Hospital; therefore, an appropriate antifungal stewardship programs is urgently warranted.  相似文献   
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Breast Cancer Research and Treatment - Preclinical evidence suggests that natural killer cell (NK-cell) function and myokines facilitate the protective effects of exercise for breast cancer...  相似文献   
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Variation in drug disposition genes might contribute to susceptibility to toxicities and interindividual differences in clinical management on chemotherapy for epithelial ovarian cancer (EOC). This study was designed to explore the association of GST and ABCB1 genetic variation with hematologic and neurologic toxicity, changes in chemotherapy, and disease prognosis in Brazilian women with EOC. A total of 112 women with a confirmed histological diagnosis of EOC treated with carboplatin/paclitaxel were enrolled (2014–2019). The samples were analyzed by multiplex polymerase chain reaction (PCR) for the deletion of GSTM1 and GSTT1 genes. GSTP1 (c.313A>G/rs1695) and ABCB1 (c.1236C>T/rs1128503; c.3435C>T/rs1045642; c.2677G>T>A/rs2032582) single nucleotide polymorphisms (SNPs) were detected by real‐time PCR. Subjects with the GSTP1 c.313A>G had reduced risk of anemia (odds ratio (OR): 0.17, 95% confidence interval (CI): 0.04–0.69, P = 0.01, dominant model) and for thrombocytopenia (OR: 0.27, 95% CI: 0.12–0.64, P < 0.01; OR 0.18, 95% CI 0.03–0.85, P = 0.03, either dominant or recessive model), respectively. The GSTP1 c.313A>G AG genotype was associated with a lower risk of dose delay (OR: 0.35, 95% CI: 0.13–0.90, P = 0.03). The ABCB1 c.1236C>T was associated with increased risk of thrombocytopenia (OR: 0.15, 95% CI: 0.03–0.82, P = 0.03), whereas ABCB1 c.3435C>T had increased risk of grade 2 and 3 neurotoxicity (OR: 3.61, 95% CI: 1.08–121.01, P = 0.03) in recessive model (CC + CT vs. TT). This study suggests that GSTP1 c.313A>G, ABCB1 c.1236C>T, and c.3435C>T SNP detection is a potential predictor of hematological toxicity and neurotoxicity and could help predict the clinical management of women with EOC.

Study Highlights
  • WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?
Variation in drug disposition genes encoding drug‐metabolizing enzymes and transporters might contribute to susceptibility to toxicities and interindividual differences in clinical management such as the need to delay, reduce, or discontinue treatment.
  • WHAT QUESTION DID THIS STUDY ADDRESS?
We studied the association of GST and ABCB1 genetic variation with hematologic and neurologic toxicity, clinical management, and disease prognosis in Brazilian women with epithelial ovarian carcinoma (EOC) who undergo carboplatin and paclitaxel‐based chemotherapy.
  • WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?
GSTP1 c.313A>G is a potential predictor of anemia and thrombocytopenia and associated with a lower risk of dose delay during chemotherapy. In addition, ABCB1 c.1236C>T and c.3435C>T is associated with a higher risk of thrombocytopenia and neurotoxicity.
  • HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?
The polymorphism detection could be a strategy to careful monitoring of patients at increased risk of toxicity and appropriate supportive therapy could decrease the need for changes in treatment, thus improving the likelihood of a beneficial treatment response in women with EOC.

Epithelial ovarian cancer (EOC) is the most common cause of gynecological cancer death, largely due to the advanced stage of the disease at the time of diagnosis. 1 Standard first‐line treatment is cytoreductive surgery and subsequent chemotherapy using a combination of carboplatin and paclitaxel or neoadjuvant chemotherapy and residual tumor resection. 2 Despite a high response rate to chemotherapy, ~ 70% of the women have a relapse within the subsequent 3 years. 3 Platinum and taxane‐based chemotherapy are often associated with severe hematological toxicities, such as anemia, neutropenia, leukopenia, and thrombocytopenia. 4 In addition, neuropathy is a dose‐limiting side effect of paclitaxel. 5 , 6 Interindividual differences in carboplatin and paclitaxel toxicity may be associated with polymorphisms in genes encoding drug‐metabolizing enzymes and transporters, including GSTs and ATP‐binding cassette (ABC) efflux transporters like ABCB1. 4 , 7 , 8 , 9 The GSTs are a family of phase II enzymes involved in detoxification of xenobiotics by conjugation reactions between glutathione and endogenous and exogenous electrophilic compounds, such as chemotherapeutic drugs, including the platinum agents. The GST family consists of several gene subfamilies of which GSTM1, GSTT1, and GSTP1 are the most relevant for drug metabolism. 10 , 11 Functional GSTM1 and GSTT1 enzymes are directly related with the presence of the intact genes, because the absence of activity is the result of a 15 kb and 54 kb deletions that span the entire GSTM1 and GSTT1 genes (GSTM1‐null and GSTT1‐null genotypes), respectively. Consequently, individuals homozygous for the GSTM1 or GSTT1‐null allele have a complete absence of GSTM1 and GSTT1 activity, whereas individuals with two copies of the GSTM1 or GSTT1 genes have reference protein levels. 12 , 13 There is some evidence that these deletion genotypes may play a role in toxicity, response to treatment, and survival in some cancers, 14 , 15 , 16 including cancer of the ovary. 8 In contrast to the commonly studied GSTM1 and GSTT1 genotypes, the GSTP1 c.313A>G (rs1695) is an exonic single nucleotide polymorphism (SNP) that causes an amino acid substitution and results in an isoleucine to valine (Ile > Val) change at codon 105 of the enzyme. The highest level of GSTP1 activity is seen in individuals with the AA genotype (Ile/Ile) and is associated with increased toxicity in different carcinomas, but there are discordant results regarding the effect of GSTP1 c.313A>G on treatment outcomes. 9 , 17 , 18 , 19 , 20 Polymorphisms in ABCB1 or multidrug resistance 1 may affect the function of P‐glycoprotein, a critical transporter for efflux of paclitaxel from cells. 21 , 22 Three SNPs in the coding region of ABCB1 (c.1236C>T, rs1128503; c.3435C>T, rs1045642; and c.2677G>T>A, rs2032582) have been extensively studied. 23 , 24 These common ABCB1 SNPs have been associated with toxicity during carboplatin and paclitaxel‐based chemotherapy, including increased risk of anemia in carriers of the c.1236C>T SNP, a more pronounced neutrophil decrease in patients carrying the c.3435C>T and c.2677G>T>A SNPs and increased risk of peripheral neuropathy associated with the c.3435C>T SNP. 18 , 25 , 26 Similar to studies of GST polymorphisms, the associations of ABCB1 genetic variation with treatment outcomes is inconsistent across studies. 27 , 28 Patients developing severe toxicities often require dose reduction, dose delay, or treatment interruption that require clinical interventions and may affect the disease prognosis. 4 However, no study has been found so far focus on regarding the utility of polymorphisms in the management of chemotherapy and toxicities for ovarian cancer. The current study was designed to examine the association of GST and ABCB1 genetic variants with hematologic and neurologic toxicities, clinical management on chemotherapy, and disease prognosis in Brazilian women with EOC.  相似文献   
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BackgroundHeart Failure with mid-range Ejection Fraction (HFmEF) was recently described by European and Brazilian guidelines on Heart Failure (HF). The ejection fraction (EF) is an important parameter to guide therapy and prognosis. Studies have shown conflicting results without representative data from developing countries.ObjectiveTo analyze and compare survival rate in patients with HFmEF, HF patients with reduced EF (HFrEF), and HF patients with preserved EF (HFpEF), and to evaluate the clinical characteristics of these patients.MethodsA cohort study that included adult patients with acute HF admitted through the emergency department to a tertiary hospital, reference in cardiology, in south Brazil from 2009 to 2011. The sample was divided into three groups according to EF: reduced, mid-range and preserved. A Kaplan-Meier curve was analyzed according to the EF, and a logistic regression analysis was done. Statistical significance was established as p < 0.05.ResultsA total of 380 patients were analyzed. Most patients had HFpEF (51%), followed by patients with HFrEF (32%) and HFmEF (17%). Patients with HFmEF showed intermediate characteristics related to age, blood pressure and ventricular diameters, and most patients were of ischemic etiology. Median follow-up time was 4.0 years. There was no statistical difference in overall survival or cardiovascular mortality (p=.0031) between the EF groups (reduced EF: 40.5% mortality; mid-range EF 39.7% and preserved EF 26%). Hospital mortality was 7.6%.ConclusionThere was no difference in overall survival rate between the EF groups. Patients with HFmEF showed higher mortality from cardiovascular diseases in comparison with HFpEF patients. (Arq Bras Cardiol. 2021; 116(1):14-23)  相似文献   
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Statement of problemRemovable partial dentures (RPDs) are traditionally made by casting, a complex, error-prone, and time-consuming process. Computer-aided design and computer-aided manufacturing (CAD-CAM) RPD systems may simplify the clinical steps and minimize errors; however, the accuracy of CAD-CAM RPD systems is unclear.PurposeThe purpose of this systematic review was to determine whether CAD-CAM systems are accurate for the manufacturing of RPD frameworks.Material and methodsA literature search was conducted through Medline-PubMed, Scopus, Lilacs, Web of Science, and Cochrane Library databases using specific keywords for articles published up to November 2019. Three reviewers obtained data and compared the results. All studies evaluated the framework accuracy or fit of prostheses fabricated with conventional and digital techniques.ResultsA total of 7 articles, 2 clinical studies, and 5 in vitro studies that complied with the inclusion criteria were evaluated. One in vitro study compared indirect (extraoral) and direct (intraoral) scanning for partially edentulous ridges and shows that digital scans were better than conventional impressions in terms of trueness. In the other studies included, although the frameworks analyzed had clinically acceptable discrepancies (<311 μm), the material influenced the fit. Polyetheretherketone (PEEK) showed better fit than traditional metal cast RPDs. Co-Cr alloy RPDs produced by rapid prototyping exhibited the highest discrepancies when produced by sintering laser melting.ConclusionsThe results show that the digital technique for RPD frameworks is accurate. In the studies included, the analyzed frameworks had clinically acceptable gaps, but the results were heterogeneous among studies because the articles used different measurement methods with small sample sizes. Few studies discussed the long-term clinical performance. The digital technique for RPD frameworks was accurate because the misfits and mismatches found in in vitro and clinical studies were within the acceptable clinical limit for RPDs.  相似文献   
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Journal of Muscle Research and Cell Motility - Acute metabolic and molecular response to exercise may vary according to exercise’s intensity and duration. However, there is a lack regarding...  相似文献   
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Anthropomorphic measures among type 1 diabetic patients are changing as the obesity epidemic continues. Excess fat mass may impact bone density and ultimately fracture risk. We studied the interaction between bone and adipose tissue in type 1 diabetes subjects submitted to two different clinical managements: (I) conventional insulin therapy or (II) autologous nonmyeloablative hematopoietic stem-cell transplantation (AHST). The study comprised 3 groups matched by age, gender, height and weight: control (C = 24), type 1 diabetes (T1D = 23) and type 1 diabetes treated with AHST (T1D-AHST = 9). Bone mineral density (BMD) and trabecular bone score (TBS) were assessed by dual X-ray absorptiometry (DXA). 1H Magnetic resonance spectroscopy was used to assess bone marrow adipose tissue (BMAT) in the L3 vertebra, and abdominal magnetic resonance imaging was used to assess intrahepatic lipids (IHL), visceral (VAT) and subcutaneous adipose tissue (SAT). Individuals conventionally treated for T1D were more likely to be overweight (C = 23.8 ± 3.7; T1D = 25.3 ± 3.4; T1D-AHST = 22.5 ± 2.2 Kg/m2; p > 0.05), but there was no excessive lipid accumulation in VAT or liver. Areal BMD of the three groups were similar at all sites; lumbar spine TBS (L3) was lower in type 1 diabetes (p < 0.05). Neither SAT nor VAT had any association with bone parameters. Bone marrow adipose tissue (BMAT) lipid profiles were similar among groups. BMAT saturated lipids were associated with cholesterol, whereas unsaturated lipids had an association with IGF1. Overweight and normal weight subjects with type 1 diabetes have normal areal bone density, but lower trabecular bone scores. Adipose distribution is normal and BMAT volume is similar to controls, irrespective of clinical treatment.  相似文献   
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