Browsing by Author "Keskin, Ö"
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Item Perceptions of Parents and Physicians Concerning the Childhood Asthma Control TestSoyer, ÖU; Öztürk, F; Keskin, Ö; Asilsoy, S; Altinel, N; Karaman, Ö; Yazicioglu, M; Sapan, N; Zeyrek, D; Kuyucu, S; Özmen, S; Reisli, I; Aydogan, M; Altintas, DU; Orhan, F; Yüksel, H; Boz, AB; Gürkan, F; Tahan, F; Cevit, Ö; Sekerel, BEBackground. The Childhood Asthma Control Test (C-ACT) has been proposed to be a simple, patient-based test that is able to reflect the multidimensional nature of asthma control. In this analysis, the aim was to evaluate the perceptions of physicians and caregivers concerning C-ACT and its predictive value for future asthma-related events. Method. In a multicenter prospective design, 368 children aged 4-11 years with asthma who were either well-or not well-controlled were included in the study. The study participants were evaluated during three visits made at 2-month intervals and the Turkish version of C-ACT was completed each month. Parents completed questionnaires concerning their perception of asthma (before and after the study) and the C-ACT (after the study). Physicians completed a survey about their perception of a control-based approach and the C-ACT. Results. The C-ACT scores increased from visit 1 to visit 3, with improvement seen in all domains of the test. At the end of the study period, the parents more strongly agreed that asthma could be controlled completely and that asthma attacks and nocturnal awakenings due to asthma were preventable (p < .05). Most of the parents reported that the C-ACT helped them to determine asthma treatment goals for their children and also that the C-ACT improved communication with their physicians. The physicians indicated that a control-centered approach was more convenient (95%) and simpler (94.5%) thana severity-centered approach and provided better disease control (93.4%). A higher C-ACT score was associated with a decreased risk of asthma attack and emergency department admittance in the 2 months following the administration of C-ACT. Conclusion. Our findings indicated that the C-ACT improved both parental outlook on asthma control and the communication between the physician and parents. There was a good correlation between the C-ACT score and the level of asthma control achieved, as described by the physician. Additionally the C-ACT score was predictive of future asthma-related events. These findings suggest that the C-ACT may have an important role in asthma management in the future.Item Comparison of refugee patients with cystic fibrosis and their counterpart children from Turkey during the warYilmaz, AI; Pekcan, S; Eyüboglu, TS; Hangül, M; Arslan, H; Kilinç, AA; Çokugras, H; Arik, E; Keskin, Ö; Özdemir, A; Ersoy, M; Ersoy, A; Köse, M; Özsezen, B; Ünal, G; Ercan, Ö; Girit, S; Oksay, SC; Gökdemir, Y; Karadag, B; Sen, V; Çakir, E; Yüksel, H; Tekin, MN; Aslan, ATSince the outbreak of the Syrian civil war in 2011, the population of Arab refugees in Turkey has rapidly increased. While cystic fibrosis (CF) is believed to be rare among Arabs, recent studies suggest it is underdiagnosed. This study aims to present the demographic, clinical, and genetic characteristics of CF patients among Arab refugees in Turkey. Additionally, a comparison is made between the findings in the National CF Registry 2021 in Turkey (NCFRT) and the refugee CF patient group. The study included refugee patients between the ages of 0 and 18 years who were diagnosed with CF and received ongoing care at pediatric pulmonology centers from March 2011 to March 2021. The study examined demographic information, age at diagnosis, age of diagnosis of patients through CF newborn screening (NBS), presenting symptoms, CF transmembrane conductance regulator (CFTR) mutation test results, sputum culture results, weight, height, and body mass index (BMI) z score. Their results were compared with the NCFRT results. The study included 14 pediatric pulmonology centers and 87 patients, consisting of 46 (52.9%) boys and 41 (47.1%) girls. All of the patients were Arab refugees, with 80 (92%) being Syrian. All the patients were diagnosed in Turkey. The median age at diagnosis of patients was 22.33 (interquartile range, 1-258) months. The median age of diagnosis of patients through NBS was 4.2 (interquartile range, 1-12) months. The median age of older patients, who were unable to be included in the NBS program, was 32.3 (interquartile range, 3-258) months. Parental consanguinity was observed in 52 (59.7%) patients. The mutation that was most frequently found was F508del, which accounted for 22.2% of the cases. It was present in 20 patients, constituting 32 out of the total 144 alleles. There was a large number of genetic variations. CFTR genotyping could not be conducted for 12 patients. These patients had high sweat tests, and their genetic mutations could not be determined due to a lack of data. Compared to NCFRT, refugee patients were diagnosed later, and long-term follow-up of refugee CF patients had significantly worse nutritional status and pseudomonas colonization. Conclusion: Although refugee CF patients have equal access to NBS programs and CF medications as well as Turkish patients, the median age at diagnosis of patients, the median age of diagnosis of patients through NBS, their nutritional status, and Pseudomonas colonization were significantly worse than Turkish patients, which may be related to the difficulties of living in another country and poor living conditions. The high genetic heterogeneity and rare mutations detected in the refugee patient group compared to Turkish patients. Well-programmed NBS programs, thorough genetic studies, and the enhancement of living conditions for refugee patients in the countries they relocate to can have several advantages such as early detection and improved prognosis.What is Known:center dot Children who have chronic diseases are the group that is most affected by wars.center dot The outcome gets better with early diagnosis and treatment in patients with Cystic Fibrosis (CF).What is New:center dot Through the implementation of a newborn screening program, which has never been done in Syria previously, refugee patients, the majority of whom are Syrians were diagnosed with cystic fibrosis within a duration of 4 months. center dot Despite equal access to the newborn screening program and CF medications for both Turkish patients and refugee patients, the challenges of living in a foreign country have an impact on refugees.Item Evaluation of factors affecting bone mineral density in CF patients through CF registry of TurkeySoydas, SSA; Tugcu, GD; Gençoglu, MY; Cinel, G; Emiralioglu, N; Yalçin, E; Kiper, N; Sen,; Altintas, DU; Çokugras, H; Kilinç, AA; Yazan, H; Ünal, G; Yilmaz, A; Çaglar, HT; Damadoglu, E; Irmak, I; Demir, E; Öztürk, GK; Bingöl, A; Basaran, E; Sapan, N; Aslan, AT; Asfuroglu, P; Harmanci, K; Köse, M; Hangül, M; Özdemir, A; Özcan, G; Gayretli, ZG; Keskin, Ö; Yüksel, H; Özdogan, S; Topal, E; Çaltepe, G; Can, D; Ekren, PK; Kiliç, M; Eyüboglu, TS; Pekcan, S; Çobanoglu, N; Çakir, E; Özçelik, U; Dogru, DItem Patients with cystic fibrosis who could not receive the CFTR modulator treatment: What did they lose in 1 year?Uytun, S; Cinel, G; Polat, SE; Tabakçi, SO; Kiper, N; Yalçin, E; Tural, DA; Özsezen, B; Sen, V; Sen, HS; Altintas, DU; Çokugras, H; Kilinç, AA; Baskan, AK; Yazan, H; Çollak, A; Uzuner, S; Ünal, G; Yilmaz, AI; Çaglar, HT; Damadoglu, E; Irmak, I; Demir, E; Öztürk, GK; Bingöl, A; Basaran, E; Sapan, N; Canitez, Y; Aslan, AT; Asfuroglu, P; Harmanci, K; Köse, M; Hangül, M; Özdemir, A; Çobanoglu, N; Özcan, G; Keskin, Ö; Yüksel, H; Özdogan, S; Topal, E; Çaltepe, G; Can, D; Ekren, PK; Kiliç, M; Emiralioglu, N; Eyüboglu, TS; Pekcan, S; Çakir, E; Özçelik, U; Dogru, DBackgroundCystic fibrosis (CF) is an autosomal recessive disorder caused by CF transmembrane conductance regulator (CFTR) genetic variants. CFTR modulators improve pulmonary function and reduce respiratory infections in CF. This study investigated the clinical and laboratory follow-up parameters over 1 year in patients with CF who could not receive this treatment. MethodsThis retrospective cohort study included 2018 and 2019 CF patient data from the CF registry of Turkey. Demographic and clinical characteristics of 294 patients were assessed, who had modulator treatment indications in 2018 but could not reach the treatment. ResultsIn 2019, patients younger than 18 years had significantly lower BMI z-scores than in 2018. During the 1-year follow-up, forced expiratory volumes (FEV1) and FEV1 z-scores a trend toward a decrease. In 2019, chronic Staphylococcus aureus colonization, inhaled antipseudomonal antibiotic use for more than 3 months, oral nutritional supplement requirements, and oxygen support need increased. ConclusionsPatients who had indications for modulator treatments but were unable to obtain them worsened even after a year of follow-up. This study emphasized the importance of using modulator treatments for patients with CF in our country, as well as in many countries worldwide.Item Evaluation of respiratory function at 6 years of age in patients with cystic fibrosis with frequent pulmonary exacerbations in the first 2 years of lifeTabakci, SO; Cinel, G; Uytun, S; Polat, SE; Yalçin, E; Kiper, N; Erdal, MA; Sen, V; Savas, S; Çelebi, Ö; Altintas, DU; Serbes, M; Kilinç, AA; Çokugras, H; Arslan, H; Yazan, H; Kafi, HM; Çollak, A; Ünal, G; Yilmaz, AI; Çaglar, HT; Irmak, I; Damadoglu, E; Öztürk, GK; Demir, E; Basaran, E; Bingöl, A; Canitez, Y; Çekiç, S; Asfuroglu, P; Aslan, AT; Harmanci, K; Kiliç, G; Köse, M; Ersoy, A; Hangül, M; Özdemir, A; Özcan, G; Çobanoglu, N; Aydin, ZGG; Keskin, Ö; Yüksel, H; Özdogan, S; Topal, E; Çaltepe, G; Can, D; Ekren, PK; Kiliç, M; Eyüboglu, TS; Pecan, S; Çakir, E; Emiralioglu, N; Özçelik, U; Ersöz, DDItem The efficacy of inhaled hypertonic saline in children with cystic fibrosis who receive daily DNase.Gencoglu, MY; Tugcu, GD; Soydas, SSA; Cinel, G; Emiralioglu, N; Yalçin, E; Kiper, N; Sen,; Altintas, DU; Çokugras, H; Kilinç, AA; Yazan, H; Ünal, G; Yilmaz, A; Çaglar, HT; Damadoglu, E; Irmak, I; Demir, E; Öztürk, G; Bingöl, A; Basaran, E; Sapan, N; Aslan, AT; Asfuroglu, P; Harmanci, K; Köse, M; Hangül, M; Özdemir, A; Özcan, G; Gayretli, ZG; Keskin, Ö; Yüksel, H; Özdogan, S; Topal, E; Çaltepe, G; Can, D; Ekren, PK; Kiliç, M; Eyüboglu, TS; Pekcan, S; Çobanoglu, N; Çakir, E; Özçelik, U; Dogru, DItem Cystic Fibrosis Patients Eligible for Modulator Drugs: Data from Cystic Fibrosis Registry of TurkeyÇobanoglu, FN; Ersöz, DD; Çakir, E; Eyüboglu, TS; Pekcan, S; Cinel, G; Yalçin, E; Kiper, N; Sen, V; Sen, HS; Ercan, Ö; Keskin, Ö; Eltan, SB; Al Shadfan, LM; Yazan, H; Altintas, DU; Sasihüseyinoglu, S; Sapan, N; Çekiç, S; Çokugras, H; Atabek, AA; Gürsoy, TR; Aslan, AT; Bingöl, A; Basaran, AE; Özdemir, A; Köse, M; Hangül, M; Emiralioglu, N; Tugcu, G; Yuksel, H; Yilmaz, Ö; Orhan, F; Aydin, ZGG; Topal, E; Tamay, Z; Süleyman, A; Can, D; Bal, CM; Çaltepe, G; Özçelik, UItem Cystic fibrosis in Turkey: First data from the national registryDogru, D; Çakir, E; Sismanlar, T; Çobanoglu, N; Pekcan, S; Cinel, G; Yalçin, E; Kiper, N; Sen, V; Sen, HS; Ercan, Ö; Keskin, Ö; Eltan, SB; Al Shadfan, LM; Yazan, H; Altintas, DU; Sasihüseyinoglu, S; Sapan, N; Çekiç, S; Çokugras, H; Kilinç, AA; Gürsoy, TR; Aslan, AT; Bingöl, A; Basaran, AE; Özdemir, A; Köse, M; Hangül, M; Emiralioglu, N; Tugcu, G; Yüksel, H; Yilmaz, Ö; Orhan, F; Gayretli Aydin, ZG; Topal, E; Tamay, Z; Süleyman, A; Can, D; Bal, CM; Çaltepe, G; Özçelik, UBackground Cystic fibrosis (CF) care has been implemented in Turkey for a long time; however, there had been no patient registry. For this purpose, the Turkish National CF Registry was established. We present the first results of registry using data collected in 2017. Methods The data were collected using a data-entry software system, which was accessed from the internet. Demographic and annually recorded data consisted of 15 and 79 variables, respectively. Results There were 1170 patients registered from 23 centers; the estimated coverage rate was 30%. The median age at diagnosis was 1.7 years (median current age: 7.3 years); 51 (4.6%) patients were aged over 18 years. Among 293 patients who were under 3 years of age, 240 patients (81.9%) were diagnosed through newborn screening. Meconium ileus was detected in 65 (5.5%) patients. Genotyping was performed in 978 (87.4%) patients and 246 (25.2%) patients' mutations were unidentified. The most common mutation was deltaF508 with an allelic frequency of 28%, followed by N1303K (4.9%). The median FEV1% predicted was 86. Chronic colonization with Pseudomonas aeruginosa was seen in 245 patients. The most common complication was pseudo-Bartter syndrome in 120 patients. The median age of death was 13.5 years in a total of 15 patients. Conclusions Low coverage rate, lack of genotyping, unidentified mutations, and missing data of lung functions are some of our greatest challenges. Including data of all centers and reducing missing data will provide more accurate data and help to improve the CF care in Turkey in the future.Item One-Year Follow-Up of Cystic Fibrosis Patients Who Cannot Reach the Modulator Therapies Although Having Indications: What are Their Losses?Uytun, S; Polat, SE; Tabakçi, SÖ; Cinel, G; Emiralioglu, N; Yalçin, E; Kiper, N; Sen,; Altintas, DU; Çokugras, H; Kilinç, AA; Yazan, H; Çollak, A; Uzuner, S; Ünal, G; Yilmaz, A; Çelik, S; Damadoglu, E; Irmak, I; Demir, E; Öztürk, G; Basaran, E; Bingöl, A; Sapan, N; Aslan, AT; Asfuroglu, P; Harmanci, K; Köse, M; Hangül, M; Özdemir, A; Özcan, G; Gayretli, ZG; Keskin, Ö; Yüksel, H; Özdogan, S; Topal, E; Çaltepe, G; Can, D; Ekren, PK; Kiliç, M; Süleyman, A; Eyüboglu, TS; Pekcan, S; Çobanoglu, N; Çakir, E; Özçelik, U; Dogru, DItem CFTR mutations unidentified in CFTR2 database and their phenotypic characteristics: Data from cystic fibrosis registry of TurkeyCinel, G; Dogru, D; Çakir, E; Eyüboglu, TS; Çobanoglu, N; Pekcan, S; Yalçin, E; Kiper, N; Sen, V; Sen, HS; Ercan, Ö; Keskin, Ö; Eltan, SB; Al Shadfan, LM; Yazan, H; Altintas, DU; Sasihüseyinoglu, S; Sapan, N; Çekiç, S; Çokugras, H; Atabek, AA; Gürsoy, TR; Aslan, AT; Bingöl, A; Basaran, AE; Özdemir, A; Köse, M; Hangül, M; Emiralioglu, N; Tugcu, G; Yüksel, H; Yilmaz, Ö; Orhan, F; Aydin, ZGG; Topal, E; Tamay, Z; Can, D; Bal, CM; Çaltepe, G; Özçelik, UItem Atezolizumab in Patients with Metastatic Urothelial Carcinoma Who Have Progressed After First-line Chemotherapy: Results of Real-life ExperiencesTural, D; Ölmez, ÖF; Sümbül, AT; Artaç, M; Özhan, N; Akar, E; Çakar, B; Köstek, O; Ekenel, M; Erman, M; Coskun, HS; Selçukbiricik, F; Keskin, Ö; Türköz, FP; Oruç, K; Bayram, S; Yglmaz, U; Bilgetekin, I; Ygldgz, B; Sendur, MAN; Paksoy, N; Dirican, A; Erdem, D; Selam, M; Tanrgverdi, Ö; Paydas, S; Urakçg, Z; Atag, E; Güncan, S; Ürün, Y; Alkan, A; Kaya, AO; Özyükseler, DT; Taskaynatan, H; Ygldgrgm, M; Sönmez, M; Basoglu, T; Gündüz, S; Kglgçkap, SBackground: Atezolizumab (ATZ) has demonstrated antitumor activity and manageable safety in previous studies in patients with locally advanced or metastatic platinum resistant urothelial carcinoma. Objective: To compare the real-life experience and data of clinical trials on ATZ treatment in metastatic urothelial carcinoma. Design, setting, and participants: Patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy from an expanded access program were retrospectively studied. Data of patients were obtained from their files and hospital records. Safety was evaluated for patients treated with at least one cycle of ATZ. Outcome measurements and statistical analysis: The primary endpoint was objective response rate (ORR). The secondary endpoints are overall survival (OS), progression-free survival (PFS), duration of response, and safety profile of patients. Kaplan-Meier methods were used to calculate median follow-up and estimate PFS and OS. Results and limitations: Data of 115 enrolled patients were analyzed. Most of the patients (92.3%, n = 106) had received chemotherapy regimen only once prior to ATZ. The median follow-up duration was 23.5 mo. The complete response rate, partial response rate, and ORR were 8.7% (n = 10), 20.0% (n = 23), and 28.7% (n = 33), respectively. The median duration of response was 20.4 mo (95% confidence interval [CI], 6.47-28.8). Of the 33 patients who responded to treatment, 60% (n = 20) had an ongoing response at the time of the analysis. PFS and OS with ATZ were 3.8 mo (95% CI, 2.25-5.49) and 9.8 mo (95% CI, 6.7-12.9), respectively. All-cause and any-grade adverse events were observed in 113 (98%) patients. Of the patients, 64% experienced a treatment-related adverse event of any grade and 24 (21.2%) had a grade 3-4 treatment-related adverse event. Limitations of the study included its retrospective design, and determination of treat-ment response based on clinical notes and local radiographic studies. Conclusions: In these real-life data, ATZ was effective and well tolerated in patients with metastatic urothelial carcinoma who have progressed with platinum-based first-line chemotherapy. ATZ is an effective and tolerable treatment for patients with locally advanced or metastatic platinum-resistant urothelial carcinoma in our study, similar to previously reported trials. Patient summary: Atezolizumab is effective and well-tolerated in patients with meta-static urothelial cancer who progressed with first-line chemotherapy, consistent with the outcomes of the previous clinical trials in this setting. (c) 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.Item Comparison of clinical features of cystic fibrosis patients eligible but not on CFTR modulators to ineligible for CFTR modulatorsBüyüksahin, HN; Emiralioglu, N; Yalçin, E; Sen, V; Sen, HS; Arslan, H; Baskan, AK; Çakir, FB; Koray, CF; Yilmaz, AI; Ercan, F; Altintas, DU; Serbes, M; Keskin, Ö; Arik, E; Gülen, F; Barlik, M; Karcioglu, O; Damadoglu, E; Köse, M; Ersoy, A; Bingöl, A; Basaran, E; Çakir, EP; Aslan, AT; Canitez, Y; Korkmaz, M; Özdemir, A; Harmanci, K; Soydas, SS; Hangül, M; Yüksel, H; Özcan, G; Korkmaz, P; Kiliç, M; Aydin, ZGG; Çaltepe, G; Can, D; Dogru, S; Öztürk, GK; Süleyman, A; Topal, E; Özsezen, B; Hizal, M; Demirdögen, E; Ogun, H; Börekçi, S; Yazan, H; Çakir, E; Eyüboglu, TS; Çobanoglu, N; Cinel, G; Pekcan, S; Özçelik, U; Dogru, DIntroduction: Cystic fibrosis transmembrane conductance regulator (CFTR) modulator drugs target the underlying defect and improve CFTR function. They are a part of standard care in many countries, but not all patients are eligible for these drugs due to age and genotype. Here, we aimed to determine the characteristics of non-eligible patients for CFTR modulators in the CF registry of Turkey (CFRT) to highlight their clinical needs. Methods: This retrospective cohort study included CF patient data from the CFRT in 2021. The decision of eligibility for the CFTR modulator was determined according to the 'Vertex treatment-Finder' on the Vertex (R) website. Demographic and clinical characteristics of patients were compared between eligible (group 1) and ineligible (group 2) groups for CFTR modulators. Results: Among the study population (N = 1527), 873 (57.2%) were in group 1 and 654 (42.8%) were in group 2. There was no statistical difference between groups regarding sex, meconium ileus history, diagnoses via newborn screening, FEV1 z-score, CF-associated complications, organ transplant history, and death. Patients in group 2 had a higher incidence of pancreatic insufficiency (87.7% vs. 83.2%, p = .010), lower median height z-scores (-0.87 vs. -0.55, p < .001), lower median body mass index z-scores (-0.65 vs. -0.50, p < .001), longer days receiving antibiotics due to pulmonary exacerbation (0 [interquartile range, IQR: 0-2] vs. 0 [IQR: 0-7], p = 0.001), and more non-invasive ventilation support (2.6% vs. 0.9%, p = 0.008) than patients in group 1. Conclusion: The ineligible group had worse clinical outcomes than the eligible group. This highlights their need for life-changing drugs to improve clinical outcomes.Item Prognostic factors in patients with metastatic urothelial carcinoma who have treated with AtezolizumabTural, D; Ölmez, ÖF; Sümbül, AT; Özhan, N; Çakar, B; Köstek, O; Ekenel, M; Erman, M; Coskun, HS; Selçukbiricik, F; Keskin, Ö; Türköz, FP; Oruç, K; Bayram, S; Bilgetekin, I; Yildiz, B; Sendur, MAN; Paksoy, N; Dirican, A; Erdem, D; Selam, M; Tanriverdi, Ö; Paydas, S; Urakçi, Z; Atag, E; Güncan, S; Ürün, Y; Alkan, A; Kaya, AO; Özyükseler, DT; Taskaynatan, H; Yildirim, M; Sönmez, M; Basoglu, T; Gündüz, S; Kiliçkap, S; Artaç, MBackground Atezolizumab (ATZ) has demonstrated antitumor activity and manageable safety in previous studies of patients with metastatic platinum-resistant urothelial carcinoma. However, the response rate of Atezolizumab was modest. In the current study, we evaluated the pretreatment prognostic factors for overall survival in patients with metastatic urothelial carcinoma who have progressed after first-line chemotherapy in the Expanded-Access Program of Atezolizumab. Patients and methods In this study, we present a retrospective analysis of 113 patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy. Data of the patients was obtained from patient files and hospital records. Eligible patients included metastatic urothelial carcinoma patients treated with at least one course of ATZ. Univariate analysis was used to identify clinical and laboratory factors that significantly impact OS. Variables were retained for multivariate analysis if they had a statistical relationship with OS (p < 0.1), and then included a final model of p < 0.05. Results The median follow-up duration was 23.5 months. Of the patients, 98 (86.7%) were male and 13.3% were female. The median age was 65 years of age (37-86). In univariate analysis, primary tumor location in the upper tract, increasing absolute neutrophil count (ANC), increasing absolute lymphocyte count, neutrophil-to-lymphocyte ratio (NLR) > 3, liver metastases, baseline creatinine clearance less (GFR) than 60 ml/min, Eastern Cooperative Oncology Group (ECOG) performance status (1 >=), and hemoglobin levels below 10 mg/dl were all the significantly associated with OS. Three of the five adverse prognostic factors according to the Bellmunt criteria were independent of short survival: liver metastases HR 3.105; 95% CI 1.673-5.761; p < (0.001), ECOG PS (1 >=) HR 2.184; 95% CI 1.120-4.256; p = 0.022, and Hemoglobin level below 10 mg/dl HR 2.680; 95% CI 1.558-4.608; p < (0.001). In addition, NLR > 3 hazard ratio [HR] 2.092; 95% CI 1.031-4.243; p = 0.041 and GFR less than 60 ml/min HR 1.829; 95% CI 1.1-3.041; p = 0.02, maintained a significant association with OS in multivariate analysis. Conclusions This model confirms the Bellmunt model with the addition of NLR > 3 and GFR less than 60 ml/min and can be associated with clinical trials that use immunotherapy in patients with bladder cancer.