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INTRODUCTION: Resistance to immune checkpoint inhibitors (ICI) is a significant issue in metastatic renal cell carcinoma (mRCC), as it is in the majority of cancer types. An important deficiency in immunooncology today is the lack of a predictive factor to identify this patient group. Myeloid-derived suppressor cells (MDSC) are a type of cell that contributes to immunotherapy resistance by inhibiting T cell activity. While it accumulates in the tumor microenvironment and blood, it can also accumulate in lymphoid organs such as the spleen and cause splenomegaly. Therefore we aimed to evaluate the effect of increase in splenic volume, which can be considered as an indirect indicator of increased MDSC cells, on survival outcomes in mRCC patients. METHODS: We analyzed 45 patients with mRCC who received nivolumab as a second-line or subsequent therapy. Splenic volume was analyzed from baseline imaging before starting nivolumab and from control imaging performed within the first 6 months of treatment initiation. Additionally, we analyzed how patients' body mass index (BMI), IMDC risk score, ECOG performance status, nephrectomy status, neutrophil-lymphocyte ratio (NLR), Platelet-to-lymphocyte ratio (PLR) and sites of metastasis. RESULTS: Median splenic volume change was 10% (ranging from - 22% to + 117%) during follow-up. Change in splenic volume was found to be associated with overall survival (OS) and progression-free survival (PFS) (p = 0.025, 0.04). The median PFS in patients with increased splenic volume was 5 months, while it was 17 months in patients without increased splenic volume. (HR 2.1, 95% CI (1-4), p = 0.04). The median OS in patients with increased splenic volume was 9 months, while it was 35 months in patients without increased splenic volume (HR 2.7, 95% CI (1.1-6.2), p = 0.025). In four patients with decreased splenic volume, neither PFS nor OS could reach the median value. Log-rank p value in respectively (0.015, 0.035), The group in which an increase in volume was accompanied by a high NLR had the shortest survival rate. Basal splenic volume was analyzed separately. However, neither PFS nor OS differed significantly. CONCLUSION: Our findings suggest that the change in splenic volume throughout immunotherapy regimens may be utilized to predict PFS and OS in mRCC patients undergoing treatment.
Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/tratamento farmacológico , Nivolumabe/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Baço/patologia , Imunoterapia , Estudos Retrospectivos , Microambiente TumoralRESUMO
INTRODUCTION: To evaluate biosimilar understanding and preference trends of medical oncologists in Turkey. METHODS: A survey consisting of 24 multiple-choice questions with checkbox answers was conducted among medical oncologists. The questionnaire was divided into five parts to some intentions: demographic characteristics, general knowledge about biosimilars, knowledge about local approval and reimbursement issues, individual preference trends, and ranking the knowledge of their own. All answers were analyzed as whole cohort, specialists and fellows. RESULTS: Fellows (n = 47) consisted 42%, and academic clinicians (n = 37) consisted 35% of the participants. In the whole cohort, the overall rate of correct answers was 55.1% in the general knowledge about the biosimilars part, and 26.7% in the local approval and reimbursement issues part. At all, 57.7% of the participants declared that they object to switch from a reference product to a biosimilar product. The rate of those who defined themselves as extremely knowledgeable decreased from 8.1% to 2.7% in the whole cohort at the end of the survey. CONCLUSION: The need for more accurate and clarified local regulations and education emerging in the biotechnology era must be met.
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Medicamentos Biossimilares , Oncologistas , Medicamentos Biossimilares/uso terapêutico , Humanos , Inquéritos e Questionários , TurquiaRESUMO
Post-pandemic inflationist pressures, climate changes and extremes, regional conflicts, and soaring food prices caused the food crisis to increase rapidly worldwide. This global problem directs producers and researchers to use oils used as feedstock in biodiesel production effectively. In this context, it is important to assay the transesterification parameters and conduct new optimization studies to increase biodiesel yield. In this study, methyl ester was produced from hemp oil by transesterification using sodium hydroxide (NaOH). Next, classical optimization study was carried out to determine the effects of catalyst amount, alcohol:oil molar ratio, reaction temperature, and reaction time variables on biodiesel yield. Secondly, the cubic spline mathematical model (CSMM) and polynomial regression mathematical model (PRMM) were applied to the first data of this optimization. Among these optimization methods, the utmost biodiesel yield registered was 96.115% at hemp seed oil (HSO):methanol molar ratio of 5.59:1, catalyst concentration of 0.531 wt%, reaction temperature of 42.5 °C, reaction time of 62.1 min, and agitation intensity of 600 rpm at PRMM. Some vital fuel properties obtained from HSO biodiesels as a result of three optimizations satisfied the EN 14214 standard. The results illustrated that the optimal yields from CSMM and PRMM are 0.765% and 1.065% higher, respectively, according to the maximum efficiency obtained from the classical optimization. The outcomes showed that CSMM and PRMM are cost-effective, easy to handle, and promising new approaches.
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Biocombustíveis , Cannabis , Biocombustíveis/análise , Óleos de Plantas , Esterificação , Modelos Teóricos , CatáliseRESUMO
The current new technology in the automotive sector depends on the primary energy source because the power source is from the secondary energy source. Besides, the interest in biofuels is increasing due to the weaknesses of fossil fuels that have been voiced for years. The feedstock is important in biodiesel production and its use in the engine. Mustard oil is non-edible, high mono-unsaturated fatty acid value, conveniences in cultivation conditions, and worldwide use that offer significant advantages to biodiesel producers. The presence of erucic acid, which forms the basis of mustard biodiesel, makes itself felt in the prevention of the fuel-food debate, its effect on biodiesel fuel properties, and its relationship to engine performance and exhaust emissions. Along with the minuses of mustard biodiesel in kinematic viscosity and oxidation ability, the problems experienced in engine performance and exhaust emissions compared to diesel fuel offer new studies to policymakers, industrialists and researchers. Accordingly, this review focuses on the recent finding in fuel properties, engine performance and emission characteristic of mustard seed biodiesel as well as its types, geographical distribution, and biodiesel production. It can be stated that this study will be an important supplementary reference to the above-mentioned groups.
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Biocombustíveis , Mostardeira , Gasolina , Emissões de Veículos , SementesRESUMO
INTRODUCTION: Immune checkpoint inhibitors (ICI) have transformed treatments for patients with metastatic renal cell carcinoma (mRCC). Although some patients benefit greatly from ICI treatments, an effective marker to determine which patients will benefit from these treatments is lacking. Moreover, chronic inflammation and sarcopenia have been associated with poor survival rates among cancer patients. Accordingly, in this study, we investigated how the cachexia index (CXI), used as a combined score for sarcopenia and chronic inflammation, affects the survival outcomes of patients with mRCC receiving ICI. METHODS: We retrospectively screened data from 52 mRCC patients who had followed up between October 2010 and October 2021 after receiving ICI as a second-line or later treatment. Patients' respective basal CXI score were calculated according to the following formula, based on their L3 vertebral skeletal musculoskeletal area (SMI), neutrophil-lymphocyte ratio (NLR), and albumin (Alb) levels: CXIâ¯=â¯(SMI x Alb) / NLR. Additionally, we analyzed how patients' subcutaneous adipose tissue (SAT), body mass index (BMI), ECOG performance status, The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk score, nephrectomy status, sites of metastasis, and histological subtypes affected survival outcomes. RESULTS: Our univariate analysis significantly associated CXI score, NLR, nephrectomy status, and patient age with overall survival (OS). However, only CXI scores' significance was confirmed through multivariate analysis. The median OS (mOS) was 7 months for patients whose CXI score < the median value and 48 months for patients with a CXI score ≥ the median value. (HR 4.5, 95% CI [1.9-11], pâ¯=â¯0.001). Only CXI was significantly associated with progression-free survival (PFS) outcomes. The median progression-free survival (mPFS) was 4 months for patients whose CXI score < the median value and 17 months for patients with a CXI score ≥ the median value. (HR 2.6, 95% CI [1.3, 5.3], pâ¯=â¯0.007). Sarcopenia, sarcopenic obesity, and sarcopenia combined with NLR were not found to significantly affect OS. CONCLUSION: Our findings suggest that CXI score, a combined indicator of sarcopenia and chronic inflammation parameters, may serve as a useful marker in predicting the outcomes of ICI-based treatments for mRCC patients.
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Carcinoma de Células Renais , Neoplasias Renais , Sarcopenia , Humanos , Carcinoma de Células Renais/complicações , Carcinoma de Células Renais/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Renais/complicações , Neoplasias Renais/tratamento farmacológico , Sarcopenia/etiologia , Caquexia/etiologia , Estudos Retrospectivos , Prognóstico , Inflamação , AlbuminasRESUMO
BACKGROUND: The relationship of the ABO blood group system with the immune response is known, but its relationship with immune checkpoint inhibitors (ICIs) has not been clearly investigated until now. OBJECTIVE: In this study, the relationship between different blood groups and nivolumab treatment response in patients with advanced malignant melanoma was investigated. METHODS: The data of patients who used nivolumab for advanced malignant melanoma between April 2018 and April 2021 were retrospectively reviewed. RESULTS: A total of 73 patients were included in the study. In the progression-free survival (PFS) analysis according to blood groups, it was 3.9 months, 16.1 months, 20.0 months and 3.0 months for A, B, AB and O, respectively (p= 0.1). Overall survival (OS) analysis according to blood groups was 5.1 months, 25.0 months, 20.0 months and 9.3 months for A, B, AB and O, respectively (p= 0.1). The B antigen group (B or AB) had significantly longer PFS and OS than the non-B antigen group (A or O) (16.1 vs. 3.5 months for PFS, respectively, p= 0.03; 20.0 vs. 7.4 months for OS, respectively, p= 0.02). CONCLUSIONS: The presence of B antigen provides a significant advantage in terms of survival in patients using ICIs for advanced melanoma.
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Inibidores de Checkpoint Imunológico , Melanoma , Sistema ABO de Grupos Sanguíneos/uso terapêutico , Humanos , Melanoma/patologia , Nivolumabe/uso terapêutico , Prognóstico , Estudos Retrospectivos , Neoplasias Cutâneas , Melanoma Maligno CutâneoRESUMO
Penicillin binding protein 2a/2' (PBP2a/PBP2') which is encoded by the mecA gene, is responsible for the methicillin resistance in staphylococci. Detection of methicillin resistance with phenotypic methods is still a problem especially because of heterogenous expression of mecA gene. Although mecA gene determination by polymerase chain reaction is considered as the gold standard method, molecular tests are not easily applied in all routine laboratories. Thus, for the rapid and accurate diagnosis of MRSA strains, easy and practical phenotypic tests are still required. This study was conducted to compare the oxacillin (OX), cefoxitin (CFX), ceftizoxime (CZX), and moxolactam (MOX) susceptibility testing by disk diffusion method for the detection of methicillin resistance in staphylococci. A total of 247 staphylococci (125 Staphylococcus aureus and 122 coagulase-negative staphylococci; CNS) isolated from various clinical specimens (114 wound and soft tissue materials, 51 urine, 48 blood, 30 respiratory tract, and four other samples) of inpatients and outpatients, were included in this study. PBP2a latex agglutination test was used as the reference method for the recognition of methicillin resistance; four antibiotic disks tested and sensitivity, specificity, positive and negative predictive values (PPV and NPV) were determined for each of them. According to PBP2a latex agglutination test 66 (54.1%) of CNS and 53 (42.4%) of S.aureus isolates were found methicillin- resistant. OX and MOX disks detected 113 (63 CNS and 50 S.aureus) methicillin-resistant strain out of 119 PBP2a positive isolates, where CFX and CZX disks detected 110 (60 CNS and 50 S.aureus) of them. Among 128 PBP2a negative isolates, 123 (52 CNS and 71 S.aureus) were detected as susceptible with OX, 127 (55 CNS and 72 S.aureus) with CFX and CZX, 126 (54 CNS and 72 S.aureus) with MOX. According to these results, the sensitivities and specificities of OX, CFX, CZX, and MOX disks were; 95.4% and 92.8%, 90.9% and 98.2%, 90.9% and 98.2%, 95.4% and 96.4%, respectively for CNS and 94.3% and 98.6%, 94.3% and 100%, 94.3% and 100%, 94.3% and 100%, respectively for S.aureus. The difference between sensitivities and specificities of tested antibiotic disks were not found statistically significant. In conclusion, due to the problems in detection of methicillin resistance with phenotypic methods, the use of different mecA gene-inducing antibiotic disks at the same time, and utilization of molecular methods as reference method might be suggested, when a discordance is observed between the antibiotic disks.
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Antibacterianos/farmacologia , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão/métodos , Meticilina/farmacologia , Staphylococcus/efeitos dos fármacos , Cefoxitina/farmacologia , Ceftizoxima/farmacologia , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão/normas , Humanos , Testes de Fixação do Látex , Moxalactam/farmacologia , Oxacilina/farmacologia , Proteínas de Ligação às Penicilinas , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Infecções Estafilocócicas/microbiologiaAssuntos
Antineoplásicos Imunológicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Antígeno B7-H1/genética , Antineoplásicos Imunológicos/efeitos adversos , Biomarcadores Tumorais , Mutação , ImunoterapiaAssuntos
Antineoplásicos , Neoplasias do Colo do Útero , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Feminino , Humanos , Inibidores de Checkpoint Imunológico , Neoplasias do Colo do Útero/tratamento farmacológicoRESUMO
BACKGROUND/AIMS: We aimed to search the effects of two different drugs in bacterial translocation, both in combination and alone: ursodeoxycholic acid, the effectiveness of which was evidenced previously, and ciprofloxacin, which had not been used before, in an experimental obstructive jaundiced rat model. METHODS: Fifty Wistar Albino rats were divided into five groups: sham group (A), control group (B), ciprofloxacin group (C), ursodeoxycholic acid group (D), and ciprofloxacin + ursodeoxycholic acid group (E). Except in Group A animals, the common bile ducts in all animals were ligated. Hematological, microbiological and histopathological changes were compared between the groups. RESULTS: White blood cell counts were elevated in all common bile duct-ligated test subjects. The median white blood cell count in Group B was significantly higher than that in Group D and Group E (p=0.022 and p=0.037, respectively). There was no significant difference between the control group and the study groups in terms of biochemical changes. Blood cultures were negative in Group A and Group E. The positive blood culture rate in Group B was significantly higher than in Groups A and E (p<0.05). Positive mesenteric lymph node culture rate was significantly lower in Group E than in the control group (p=0.026). In the histopathological evaluation, there was no difference in the morphology of the terminal ileum between the groups, but Group E animals had significantly less inflammatory cells in the intestinal wall compared to Group C and D animals. CONCLUSIONS: Ciprofloxacin and ursodeoxycholic acid have a synergic effect on prevention of bacterial translocation in obstructive jaundice.