Two novel phages, Klebsiella phage GADU21 and Escherichia phage GADU22, from the urine samples of patients with urinary tract infection.

Phages are found in a wide variety of places where bacteria exist including body fluids. The aim of the present study was to isolate phages from the urine samples of patients with urinary tract infection. The 10 urine samples were cultured to isolate bacteria and also used as phage sources against the isolated bacteria. From 10 urine samples with positive cultures, 3 phages were isolated (33%) and two of them were further studied. The Klebsiella phage GADU21 and Escherichia phage GADU22 phages infected Klebsiella pneumonia and Escherichia coli, respectively. Among the tested 14 species for host range analysis, the Klebsiella phage GADU21 was able to infect two species which are Klebsiella pneumonia and Proteus mirabilis, and Escherichia phage GADU22 was able to infect four species which are Shigella flexneri, Shigella sonnei and Escherichia coli. Among different isolates of the indicator bacteria for each phage, GADU21 infected half of the tested 20 Klebsiella pneumonia isolates while GADU22 infected 85% of the tested 20 E. coli isolates. The genome sizes and GC ratios were 75,968 bp and 44.4%, and 168,023 bp and 35.3% for GADU21 and GADU22, respectively. GADU21 and GADU22 were both lytic and had no antibiotic resistance and virulence genes. GADU21 was homologue with Klebsiella phage vB_KpP_FBKp27 but only 88% of the genome was covered by this phage. The non-covered parts of the GADU21 genome included genes for tail-fiber-proteins and HNH-endonuclease. GADU22 had 94.8% homology with Escherichia phage vB_Eco_OMNI12 and had genes for immunity proteins. Phylogenetic analysis showed GADU21 and GADU22 were members of Schitoviridae family and Efbeekayvirus genus and Straboviridae family and Tevenvirinae genus, respectively. VIRIDIC analysis classified these phages in new species clusters. Our study demonstrated the possibility to use infected body fluids as phage sources to isolate novel phages. GADU21 is the first reported Klebsiella phage isolated from human body fluid. The absence of virulence and antibiotic resistance genes in their genomes makes the phages a potential therapeutic tool against infections.

Could PD-L1 positivity be associated with venous thrombosis in patients with non-small cell lung cancer?

The risk of venous thromboembolism (VTE) is increased in non-small cell lung cancer (NSCLC), and defining at-risk patients is important. Thus, we aimed to assess the association between programmed cell death ligand 1 (PD-L1) expression and VTE [pulmonary embolism (PE), deep venous thrombosis (DVT)] in NSCLC. In this retrospective, observational multicentre study, 369 patients with NSCLC who had PD-L1 immunohistochemistry based on biopsies taken between January 2017 and December 2019, were divided as PD-L1-positive (n = 181) and -negative (n = 188) groups, and low-positive (n = 99) and high-positive (n = 82) PD-L1 groups. Among all population, 12.5% of them developed a VTE during a median follow-up of 474 days. The rates of DVT, PE, and PE + DVT were 5.7%, 6% and 0.8%, respectively. VTE (15.5% vs. 9.5%) and DVT (3.8% vs. 7.4%) were similar between two groups, while PE was significantly higher in PD­L1-positive group than those in PD-L1-negative group (11.1% vs 1%, p < 0.001). There were no significant differences between low- and high-positive groups in terms of VTE (14.1% vs. 17%), PE (12.1% vs. 9.8%), and DVT (2% vs. 6.1%). In the multivariate analysis, multiple metastases (Hazard ratio [HR] 4.02; 95% confidence interval [Cl] 1.18-13.63; p = 0.07) and PD-L1 positivity was associated with an increased PE risk (HR 8.39; 95% Cl 2.07-34.07; p = 0.003). In conclusion, PD-L1 positivity may be of important role in predicting the increased risk of PE in patients with NSCLC and thereby may be used to define patients likely to benefit from thromboprophylaxis.

Importance of Histopathological Grading for Treatment Selection in Malignant Mesothelioma.

BACKGROUND: Complexities in TNM staging in epithelioid malignant pleural mesothelioma (MPM) may lead to errors in treatment selection, leading to major surgical interventions in patients with low survival expectations. METHODS: Sixty-nine stage I epithelioid MPM patients, including 27 patients treated with pleurectomy/decortication (P/D) and multimodal therapy (MMT) (the P/D [MMT] group), and 42 patients treated with chemotherapy or chemoradiotherapy (the CRT group), were included in the study. After an initial evaluation of overall survival, all patients were grouped in terms of histopathological parameters and treatment types, and then, a secondary survival evaluation was performed for the groups. RESULTS: Forty-one patients were male, the mean age was 61.8 years. The median survival time was 26 months in the P/D (MMT) group, and 19.6 months in the CRT group, but the difference was not statistically significant. After grouping according to pathological criteria, a median survival time of 32.4 ± 2.9 months in the P/D (MMT) group and 21.9 ± 3.2 months in the CRT group was obtained among patients with histopathological low-grade tumors. Among patients with high-grade tumors, the median survival time was 18.3 ± 2.6 months in the P/D (MMT) group and 17 ± 4.4 months in the CRT group. Among patients with low-grade tumors, the P/D (MMT) group had longer survival. Median survival times were similar among patients with high-grade tumors. CONCLUSION: In epithelioid MPM, histopathological grading by video-assisted thoracic surgery pleural biopsy can prove accurate in selecting patients for P/D and MMT.

Small cell lung cancer stem cells display mesenchymal properties and exploit immune checkpoint pathways in activated cytotoxic T lymphocytes.

Small cell lung cancer (SCLC) is an aggressive tumor type with early dissemination and distant metastasis capacity. Even though optimal chemotherapy responses are observed initially in many patients, therapy resistance is almost inevitable. Accordingly, SCLC has been regarded as an archetype for cancer stem cell (CSC) dynamics. To determine the immune-modulatory influence of CSC in SCLC, this study focused on the characterization of CD44+CD90+ CSC-like subpopulations in SCLC. These cells displayed mesenchymal properties, differentiated into different lineages and further contributed to CD8+ cytotoxic T lymphocytes (CTL) responses. The interaction between CD44+CD90+ CSC-like cells and T cells led to the upregulation of checkpoint molecules PD-1, CTLA-4, TIM-3, and LAG3. In the patient-derived lymph nodes, CD44+ SCLC metastases were also observed with T cells expressing PD-1, TIM-3, or LAG3. Proliferation and IFN-γ expression capacity of TIM-3 and LAG3 co-expressing CTLs are adversely affected over long-time co-culture with CD44+CD90+ CSC-like cells. Moreover, especially through IFN-γ secreted by the T cells, the CSC-like SCLC cells highly expressed PD-L1 and PD-L2. Upon a second encounter with immune-experienced, IFN-γ-stimulated CSC-like SCLC cells, both cytotoxic and proliferation capacities of T cells were hampered. In conclusion, our data provide evidence for the superior potential of the SCLC cells with stem-like and mesenchymal properties to gain immune regulatory capacities and cope with cytotoxic T cell responses. With their high metastatic and immune-modulatory assets, the CSC subpopulation in SCLC may serve as a preferential target for checkpoint blockade immunotherapy .

Evaluation of Exudative Pleural Effusions: A Multicenter, Prospective, Observational Study.

PURPOSE: The aim of this study is to determine the diagnostic performances of pleural procedures in undiagnosed exudative pleural effusions and to evaluate factors suggestive of benign or malignant pleural effusions in tertiary care centers. METHODS: This was a multicenter prospective observational study conducted between January 1 and December 31, 2018. A total of 777 patients with undiagnosed exudative pleural effusion after the initial work-up were evaluated. The results of diagnostic procedures and the patients' diagnoses were prospectively recorded. Sensitivity, specificity, and accuracy estimates with 95% confidence intervals were used to examine the performance of pleural procedures to detect malignancy. RESULTS: The mean age ± SD of the 777 patients was 62.0 ± 16.0 years, and 68.3% of them were male. The most common cause was malignancy (38.3%). Lung cancer was the leading cause of malignant pleural effusions (20.2%). The diagnostic sensitivity and accuracy of cytology were 59.5% and 84.3%, respectively. The diagnostic sensitivity of image-guided pleural biopsy was 86.4%. The addition of image-guided pleural biopsy to cytology increased diagnostic sensitivity to more than 90%. Thoracoscopic biopsy provided the highest diagnostic sensitivity (94.3%). The highest diagnostic sensitivity of cytology was determined in metastatic pleural effusion from breast cancer (86.7%). CONCLUSION: The diagnostic performance increases considerably when cytology is combined with image-guided pleural biopsy in malignant pleural effusions. However, to avoid unnecessary interventions and complications, the development of criteria to distinguish patients with benign pleural effusions is as important as the identification of patients with malignant pleural effusions.

The clinical utility of the LENT score in patients with malignant pleural mesothelioma.

Introduction: In malignant pleural mesothelioma (MPM), useful tools are needed to predict survival. Thus, we aimed to evaluate the LENT score, and demonstrate the performance of the LENT score in predicting survival in patients with MPM. Materials and Methods: This was a retrospective, observational single-center study. Sixty-nine patients diagnosed with MPM who had pleural effusion (March 2009-December 2020) were divided into groups according to their LENT score and compared. Median survivals were estimated and compared according to the LENT score and parameters of the LENT score. Result: Fifty-four patients were in the low-LENT score group, 15 patients were in the moderate-LENT score group, and there were no patients in the highLENT score group. The two groups had similar characteristics in terms of age, gender, and histological subtype distribution. There were no patients with ECOG-PS 0 in the moderate-LENT score group. Serum neutrophil-tolymphocyte ratio (NLR), pleural lactate dehydrogenase (LDH), patients with serum NLR> 9, and patients with pleural LDH> 1500 were significantly higher in the moderate-LENT score group (p= 0.002, 0.001, <0.01, <0.01, respectively). Fifty patients had died during a median follow-up of 38.6 ± 6.5 (95% CI= 25.84-51.41) months. The median survival for all patients was 28.63 ± 3.2 (95% CI= 22.33-34.92) months, higher than the original study. It was 30.97 ± 2 months in the low-LENT score group, and 20.7 ± 3.4 months in the moderate-LENT score group (p= 0.98). The median survival for patients with pleural LDH<1500 was significantly higher than for patients with pleural LDH> 1500 (p= 0.006) (30.97 vs. 16.73 months), while ECOG-PS (0 vs. 1) and NLR (<9 vs. >9) showed no differences. Conclusions: The survival in our resultant groups was higher than those reported in the original study, and the LENT score had no discriminatory ability for predicting survival in patients with MPM. We nevertheless believe that before reaching more definite conclusions, further large-scale multicenter prospective studies are needed to better define the clinical utility of the LENT score.

Clinical management of lung cancer patients with respiratory symptoms during the COVID-19 pandemic.

OBJECTIVE: There are many clinical conditions, such as lung cancer, that need to be followed up and treated during a pandemic. Providing health care for patients who are immune-suppressive requires extra care. METHOD: Among 108 lung cancer patients who had been hospitalized during the COVID-19 pandemic, 18 with respiratory symptoms were evaluated retrospectively. RESULTS: The patients' median age was 64 ± 9.4 with a male predominance (male n = 16, female n = 2). Thirteen had non-small cell lung cancer (NSCLC), and 5 had small cell lung cancer (SCLC). Nine (50%) patients were receiving chemotherapy. The most common symptom was shortness of breath (n = 14, 77.8%), followed by fever (n = 10, 55.6%). The findings confirmed on computed thorax tomography (CTT) were as follows: consolidation (n = 8, 44.4%), ground glass opacities (n = 8, 44.4%) and thoracic tumour/mediastinal-hilar lymphadenopathy (n = 3, 16.7%). Hypoxia was seen in 11 patients (61.1%), twelve patients had an elevated LDH (median = 302 ± 197) and lymphopenia (median = 1055 ± 648) and 5 (27.7%) were highly suspected of having contracted COVID-19. None of their nasopharyngeal swaps was positive. Two of these 5 patients received COVID-19 specific treatment even though they thrice had negative reverse transcription polymerase chain reaction (RT-PCR) results. The two patients responded well to both clinical and radiological treatments. For one case with SCLC receiving immunotherapy, methylprednisolone was initiated for radiation pneumonitis after excluding COVID-19. CONCLUSION: In line with a country's health policies and the adequacy of its health system, the necessity of a multidisciplinary approach in the management and treatment of complications in patients with lung cancer has become even more important during the COVID-19 pandemic.

The success of non-invasive mechanical ventilation in lung cancer patients with respiratory failure.

INTRODUCTION AND AIM: Despite the improvement in survival among patients with lung cancer as a result of the development of novel treatment options, acute respiratory failure (ARF), which may occur because of the disease itself, comorbidities or complications in treatment may be life threatening. The most commonly utilised treatment option in cancer patients with ARF is invasive mechanical ventilation (IMV). The prognosis of lung cancer patients admitted to the intensive care unit is poor. The use of non-invasive mechanical ventilation (NIMV) in the setting of ARF not only supports the respiratory muscles and facilitates alveolar ventilation and airway patency, but also reduces the risk of serious complications of IMV, such as ventilator-associated pneumonia. NIMV treatment in the event of respiratory failure has been associated with a high rate of mortality in recently diagnosed or progressive lung cancer with organ failure. However, studies in this regard are limited, and the role of NIMV has yet to be investigated in patients in hospital wards. Accordingly, the present study investigates retrospectively the success of NIMV among patients with lung cancer (including all stages and histopathological types) in a hospital ward setting and the influential factors. MATERIAL AND METHOD: The data of 42 patients with lung cancer and respiratory failure who were admitted to the palliative care service and received NIMV between 2014 and 2018 were reviewed retrospectively. Demographic features, comorbidities, respiratory failure types, rate of withdrawal from NIMV, frequencies of tracheostomy and intubation, bacteriologic examination of the airway samples, rate of discharge from hospital and any history of NIMV/USOT use at home were recorded. NIMV success was defined as the discharge of the patient from the hospital, with or without a respiratory support device. The primary end-point of the study was NIMV success, while the secondary end-point was NIMV success with respect to the underlying diagnosis and respiratory failure type. RESULTS: A total of 42 patients (38 males and 4 females) were included in the study, with a mean age of 67.4 ± 9.5 years. The rate of discharge from hospital was 71% across the entire study population, among which, 13 (31%) were discharged with USOT and 16 (38.1%) with NIMV. Among the 12 patients under palliative supportive treatment, 8 were discharged from the hospital. The success rates of NIMV in the respiratory failure aetiological subgroups were: 66% (12 patients) in the pneumonia subgroup and 71.4% (15 patients) in the COPD subgroup. The difference between these subgroups was not significant (P = .841). The success rate of NIMV in the hypercapnic and hypoxaemic respiratory failure subgroups was 72.7% (24 patients) and 66.6% (6 patients), respectively. There were no significant differences between the type of respiratory failure subgroups (P = .667). The success rate of NIMV was similar in patients with a positive airway sample microbiology (71.4%, n = 14) and those with no growth identified in the culture (70.3%, n = 28) (P = .834). CONCLUSION: In lung cancer patients with no contraindication, NIMV can be used to reduce or postpone the need for ICU admission, independent of disease stage, cellular type and underlying cause.

Characteristics of hospitalised COVID-19 patients and parameters associated with severe pneumonia.

BACKGROUND: After the first case of coronavirus disease 2019 (COVID-19) was reported in China in December 2019, it caused a global pandemic, including Turkey. OBJECTIVES: The aim of this study was to analyse the characteristics of hospitalised COVID-19 patients and assess the parameters related to severe pneumonia. METHODS: Included in the study were hospitalised COVID-19 patients with positive naso-oropharyngeal swabs. Patients' demographics, admission symptoms, laboratory and radiological findings were recorded retrospectively. RESULTS: Of 1013 patients, 583 were males (57.6%) and 430 were females (42.4%), with a mean age of 53.7 ± 17.9. More than half of the patients had at least one comorbidities, the most common of which were hypertension and diabetes mellitus. Cough (59.8%), fatigue (49.5%) and fever (41.2%) were the most common presenting symptoms. Of the hospitalised COVID-19 patients, 84.9% had pneumonia and 83.5% had typical radiological COVID-19 appearances (94.5%: ground-glass areas). The most common laboratory findings were high C-reactive protein (CRP) (73.6%) and lactate dehydrogenase (LDH) (46.2%) levels, as well as lymphopenia (30.1%). Severe pneumonia was present in 28.1% of COVID-19 patients. Multivariate logistic regression analysis indicated that advanced age, hypotension, anaemia and elevated CRP and LDH serum levels were independent risk factors for the severity of COVID-19 pneumonia (P = .011, .006, .017, .003 and .001, respectively). CONCLUSION: This study, as one of the first multicentre studies about characteristics of COVID-19 in Turkey, may guide about disease-related parameters and severity of pneumonia. Age, blood pressure, complete blood count and routine biochemical tests (including CRP and LDH) would appear to be important parameters for the evaluation of the severity of COVID-19 pneumonia.

[Immunotherapy and multidisciplinary approach to treatment in lung cancer]. / Akciger kanserinde immünoterapi ve tedavide multidisipliner yaklasim.

Lung cancer remains as the main cause of cancer-related deaths worldwide. Over the last two decades, information about biology and pathogenesis of cancer has increased, immune checkpoint inhibitors (ICIs) have been introduced, and thus a significant period has started in treatment of solid cancers. This review discussed lung cancer in the framework of innovations in treatment, immunotherapy, and multidisciplinary approach to treatment. Non-small cell lung cancer (NSCLC) was the focal point of this article as it is the most frequent lung cancer type and the type of lung cancer which can ideally benefit from ICI treatment due to its characteristics. This review is the first review in Turkish language, which aimed to raise the multidisciplinary awareness about immunotherapy approach in lung cancer treatment in all branches, primarily in chest diseases, and to provide information about its management. Moreover, this review has importance as it presents the remarkable results of recent clinical trials on the use of ICIs in NSCLC treatment. Immunotherapy has initiated a new era in cancer treatment; the specific mechanism of action of ICIs has resulted in a group of some new adverse events, among which pneumonitis is particularly important and when necessary, patients are needed to be consulted with relevant specialties about adverse events. Lung cancer treatment should be planned specific to each patient by considering patient characteristics, histological features, and genetic status and specialty areas of chest diseases, thoracic surgery, medical oncology, radiation oncology, pathology, and radiology should collaborate together for diagnostic evaluation and optimal treatment of a lung cancer patient. Moreover, family physicians may have an important role in early diagnosis of lung cancer and in preventing lung cancer by encouraging their patients regarding tobacco cessation. Moreover, screening studies for lung cancer should be targeted to create awareness in society and for early diagnosis.

The association of clinicopathologic features and peripheral blood parameters with high PD-L1 expression in non-small cell lung cancer.

INTRODUCTION: Programmed death ligand 1 (PD-L1) is a marker that widely used for prediction of response to immunotherapy. Dynamic alteration of PD-L1 expression are the major problems for reflection of the actual status of the PD-L1. So, we aimed to investigate the factors that may be associated with PD-L1 expression in lung cancer. MATERIALS AND METHODS: The patients diagnosed with non-small cell lung cancer were enrolled, retrospectively. The patients were stratified according to PD-L1 expression level as ≥ 50% and < 50%. RESULT: Totally, 217 patients were enrolled. The clinicopathologic features were similar between two groups, except the amount of cigarette consumption. Neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, and systemic immune-inflammmotry index were found significantly lower in PD-L1 ≥ 50% (p< 0.001, p= 0.006 and p= 0.003, respectively) and also negatively correlated with PD-L1 level (rho= -0.255, p< 0.001; rho= -0.17, p= 0.013; rho= - 0.185, p= 0.006, respectively). CONCLUSIONS: According to the results of our study, peripheral blood parameters can be used to the prediction of the high PD-L1 expression and can be used for reflection of current PD-L1 expression.

EGFR, KRAS, and BRAF mutational profiles of female patients with micropapillary predominant invasive lung adenocarcinoma

Background/aim: This study aimed to analyze EGFR, KRAS, and BRAF mutations in females with micropapillary predominant invasive lung adenocarcinoma and their relationships with immunohistochemical and clinicopathological patterns.Materials and methods: A total of 15 females with micropapillary lung adenocarcinoma were selected. Mutational analysis of the EGFR, KRAS, and BRAF genes was carried out. Information regarding the demographic data, tumor size, treatment, and survival time for each patient was collated, and the predominant cell type, secondary architectural growth patterns, psammoma bodies, necrosis, and visceral pleural and angiolymphatic invasions were evaluated.Results: We identified EGFR mutation in six cases, KRAS mutation in three cases, and BRAF mutation in one case. EGFR, c-kit, VEGFR, and bcl-2 positivity was observed in ten, seven, four, and six cases, respectively. All cases were positive for VEGF (strong positivity in 11 cases and weak positivity in four cases) and bcl-2 (strong positivity in nine cases and weak positivity in six cases). Seven (46.6%) cases were positive for c-kit and 10 (66.6%) cases were positive for EGFR. Conclusion: EGFR mutation occurred at a higher incidence rate in micropapillary predominant invasive adenocarcinoma than has previously been found in conventional lung adenocarcinomas. KRAS mutation was observed as having a similar frequency to what was previously observed, but the frequency of BRAF mutation was lower than previously reported.

[Serological evaluation of Bordetella pertussis infection in adults with prolonged cough]. / Uzamis öksürügü olan eriskinlerde Bordetella pertussis enfeksiyonunun serolojik olarak degerlendirilmesi.

Pertussis is a vaccine-preventable disease that is transmitted from infected to susceptible individuals by respiratory route. Bordetella pertussis infection may occur at any age as neither vaccine nor natural infection induced immunity lasts life-long. This study was planned to demonstrate the serological evidence of infection among adults, to raise awareness among clinicians and to provide data for the development of strategies to protect vulnerable infants. A total of 538 patients (345 female, 193 male) ages between 18-87 years who had a complain of prolonged cough for more than two weeks were included in the study. Anti-pertussis toxin (PT) IgG and anti-filamentous hemagglutinin (FH) IgG levels from single serum samples were measured by an in-house ELISA test which was standardized and shown to be efficient previously. Anti-PT IgG antibody levels of ≥ 100 EU/ml were considered as acute/recent infection with B.pertussis. In our study, 9.7% (52/538) of the patients had high levels of anti-PT IgG (≥ 100 EU/ml) and among those patients 43 (43/52; 82.7%) also had high (≥ 100 EU/ml) anti-FHA IgG levels. There were no statistically significant differences in terms of age, gender, education level, DPT (diphtheria-pertussis-tetanus) vaccination history, smoking history or average daily cigarette consumption (p> 0.05) between the cases with high antibody levels (n= 52). When the symptoms and the presence of cases with high antibody levels were evaluated, it was detected that no one parameter was significantly different from others, except that 24.1% of the cases with inspiratory whooping had high anti-PT levels. There was also no statistically significant difference between high anti-PT levels ≥ 100 EU/ml and the patients with risk factors [smoking (21/200; 10.5%), presence of disease that cause chronic cough and/or drug usage (19/171; %11.1), and whole factors which cause chronic cough (32/306; %10.5)] and without risk factors (p= 0.581; p= 0.357; p= 0.249, respectively). The distribution of anti-PT IgG geometric mean titer (GMT) according to the age groups, was as follows; 32.41 in 18-30 years; 36.28 in 31-50 years; 36.82 in 51-70 years and 31.15 in ≥ 71 years. Our results indicated that B.pertussis infections are also present among adult population with a frequency not to be underestimated (9.7%) and the results also emphasized that since typical whooping cough symptoms may not be seen in adults, pertussis infection should be considered as a differential diagnosis in adults with prolonged cough, even if there are some other underlying factors of cough. The data obtained from this study was also considered to be helpful in the development of adult vaccination policies for the protection of infants who have not completed the vaccination schedule yet.

Potential role of pre-treatment bone marrow SUVmean to liver SUVmean ratio (BM/L) and comparison of primary tumour FDG uptake with brain FDG uptake in predicting survival in limited-stage lung cancers.

INTRODUCTION: The survival rates of patients with limited-stage small-cell lung cancer are low despite curative treatment. Accordingly, we investigated the disease prognosis by comparing the pre-treatment bone marrow mean standardised uptake values (SUVmean) / liver SUVmean ratio (BM/L) and primary tumour FDG uptake and brain FDG uptake to prognosis. MATERIALS AND METHODS: This was an observational, retrospective, single-centre study of patients with limited-stage small-cell lung cancer. Maximum standardised uptake values before treatment SUVmax, mean SUV (SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG), liver (KC) SUVmean, bone marrow SUVmean, BM/L ratio (grouped as BM/L <1 and BM/L<1), FDG uptake level of the primary tumour are higher than brain FDG uptake. The association of low prevalence with overall survival (OS) and progression-free survival (PFS) was evaluated. DISCUSSION: A total of 125 patients were included in the study. The risk of death was found to be two times higher in patients with primary tumour FDG uptake higher than brain FDG uptake compared to those with less brain involvement. The risk of death in patients with BM/L>1 was found to be 1.6 times higher than in patients with BM/L<1. CONCLUSION: Comparison of BM/L, FDG uptake of the primary tumour and brain FDG uptake as new prognostic parameters can be guiding in the classification of patients with LD-SCLC with a higher risk of death or progression and in planning new treatment strategies.

Evaluation of the efficacy and safety of nivolumab in the second- or later-line treatment of patients with locally advanced/metastatic non-small cell lung cancer in Türkiye: a retrospective multicenter non-interventional registry study.

OBJECTIVE: To evaluate the efficacy and safety of nivolumab in the second-line (2L) or later-line (LL) treatment of patients with locally advanced/metastatic non-small cell lung cancer (NSCLC) in real-life setting in Türkiye. METHODS: This study was designed as a national, multi-center, retrospective study. The study population was evaluated in two groups for the line of nivolumab therapy: those receiving nivolumab in the 2L (Group 2L) and third-line (3L) or LL (Group 3L/LL). Efficacy was evaluated based on one-year overall survival (OS) and progression-free survival (PFS). Safety was evaluated based on treatment-related adverse events (AEs) and nivolumab discontinuation rate. RESULTS: Of 244 patients, 52.9% were in Group 2L and 47.1% were in Group 3L/LL. Demographic and clinical characteristics did not differ between the groups. In Group 2L and Group 3L/LL, one-year OS and PFS rates were 60.8% and 61.4% (p = 0.592) and 31.2% and 21.3% (p = 0.078), respectively. The objective response rate (ORR) was 34.7% in Group 2L and 27.3% in Group 3L/LL (p = 0.262). The percentage of patients reporting at least one AE in Groups 2L and 3L/LL was 34.9% and 43.5%, respectively (p = 0.169). Fatigue was the most common (16.4%) treatment-related AE in each group. The groups were comparable regarding the AE frequency. Nivolumab was discontinued in 61 patients in Group 2L and 53 patients in Group 3L/LL, with the most common reason being disease progression (57.4% and 66.0%, respectively). CONCLUSION: Nivolumab is safe and effective in the 2L or 3L/LL treatment of locally advanced/metastatic NSCLC and associated with acceptable AEs in real-life setting.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer (around 85% of all lung cancers). Patients with NSCLC are usually diagnosed at advanced or metastatic stages. When cancer cells spread to other areas from where they first formed, it is called metastatic cancer. Surgery may not be a treatment option for such patients. Currently, immunotherapeutic agents are used in the treatment of NSCLC. Nivolumab is one of the approved immunotherapeutic agents in the treatment of patients with metastatic NSCLC, who have failed after receiving chemotherapy. Our study explored the efficacy and safety of nivolumab in real-life setting in Türkiye. Nivolumab effectiveness was evaluated by overall survival (OS) and progression-free survival (PFS) rates. OS indicates the proportion of patients who are still alive at a given time after diagnosis or treatment initiation. PFS refers to "the length of time during and after cancer treatment that a person lives with the disease but does not get worse." In the present study, one-year OS for 244 patients who received nivolumab was 61.1% and one-year PFS was 26.4%. Nivolumab safety was evaluated based on the frequency of adverse events observed during nivolumab therapy. Of the patients 38.9% had at least one side effect, with fatigue being the most common (16.4%). Our results support the earlier studies and showed that nivolumab was a safe and effective agent and is associated with acceptable side effects.

Evolutionary engineering and transcriptomic analysis of nickel-resistant Saccharomyces cerevisiae.

Increased exposure to nickel compounds and alloys due to industrial development has resulted in nickel pollution and many pathological effects on human health. However, there is very limited information about nickel response, transport, and tolerance in eukaryotes. To investigate nickel resistance in the model eukaryote Saccharomyces cerevisiae, evolutionary engineering by batch selection under gradually increasing nickel stress levels was performed. Nickel hyper-resistant mutants that could resist up to 5.3 mM NiCl2 , a lethal level for the reference strain, were selected. The mutants were also cross-resistant against iron, cobalt, zinc, and manganese stresses and accumulated more than twofold higher nickel than the reference strain. Global transcriptomic analysis revealed that 640 upregulated genes were related to iron homeostasis, stress response, and oxidative damage, implying that nickel resistance may share common mechanisms with iron and cobalt resistance, general stress response, and oxidative damage.

Synthesis, characterization and microwave-promoted catalytic activity of novel N-phenylbenzimidazolium salts in Heck-Mizoroki and Suzuki-Miyaura cross-coupling reactions under mild conditions.

A number of novel benzimidazolium salts having aryl substituents such as N-phenyl, 4-chlorophenyl and various alkyl substituents were synthesized. Their microwave-assisted catalytic activities were evaluated in Heck-Mizoroki and Suzuki-Miyaura cross-coupling reactions using a catalytic system consisting of Pd(OAc)(2)/K(2)CO(3) in DMF/H(2)O under mild reaction conditions with consistent high yields, except those of 2-bromopyridine.

Microwave assisted Suzuki-Miyaura and Ullmann type homocoupling reactions of 2- and 3-halopyridines using a Pd(OAc)2/benzimidazolium salt and base catalyst system.

A number of novel benzimidazole derivatives 1-4 were synthesized and the catalytic activity of these compounds in a catalytic system consisting of a benzimidazolium salt/Pd(OAc)2/K2CO3 were investigated in the Suzuki-Miyaura and Ullmann type homocoupling reactions under microwave irradiation. We obtained both cross coupling and homocoupling products of pyridine and some side products such as dimethylaminopyridine and unsubstituted pyridine.

The efficacy of 18F-FDG PET/CT in monitoring disease progression in malignant pleural mesothelioma.

OBJECTIVE: In the event of suspicion of malignant pleural mesothelioma (MPM) progression, imaging plays an important role. We aimed to evaluate the efficacy of 18F-FDG PET/CT in monitoring disease progression by comparing it with CT, and estimate median overall survival (OS) according to progression status with CT and 18F-FDG PET/CT. MATERIALS AND METHODS: This was an observational, retrospective, single-institution study with MPM patients who had both 18F-FDG PET/CT and CT for monitoring disease progression from March 2009 to February 2020. Clinical features, radiological findings, and progression status according to CT [radiologic progression negative (RPN), radiologic progression positive (RPP)] and 18F-FDG PET/CT [metabolic progression negative (MPN), metabolic progression positive (MPP)] were recorded. The discrepancies and concordance between two methods were evaluated. The OS was estimated using the Kaplan-Meier method. RESULTS: A total of 56 patients were included. There were thirty-one (55.3%) RPN and 25 (44.7%) RPP, while there were 26 (46.5%) MPN and 30 (53.5%) MPP. All RPP patients were also found to be MPP, however, among RPN, 5 patients (8.9% of all patients) were evaluated as MPP. The concordance between two methods in monitoring disease progression was very good (K = 0.423; p < 0.01). The OS was 26 ±â€¯2.6 months in all patients. Kaplan-Meier curves between RPN and RPP, and between MPN and MPP did not show statistically significant differences (p = 0.56 and p = 0.25, respectively). CONCLUSIONS: Both methods are equally acceptable in monitoring disease progression in MPM, even though 18F-FDG PET/CT detected more progression than CT did.