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Both resistive index (RI) and pulsatility index (PI) estimate vascular resistance within an artery. But, there are only few studies reporting normal values of the renal RI and PI in healthy cats but no study could be found with regard to Turkish Angora breed of cats. So, we decided to determine the normal values of intra-renal RI and PI in non-sedated, non-hypertensive clinically normal Turkish Angora breed cats. For this purpose 20 each of mixed-breed and Turkish Angora breed, different ages and sex healthy cats constituted the study groups. At the result of the pulsed wave doppler ultrasonographic examinations mean values for RI and PI were 0.61±0.04 and 0.97±0.17 for mixed-breed cats; 0.60±0.07 and 1.16±0.34 for Turkish Angora breed cats were recorded, respectively. No significant differences were noted between the groups. At the result, we determined that, they were in normal limits as previously described in clinically healthy Turkish Angora breed of cats.

Background: The aim of this study was to determine the bacterial species recovered from 61 cats with lower urinary tract infection (LUTI), and their susceptibility to cefovecin in vitro. Results: The clinical signs and final clinical diagnosis for cats with confirmed LUTI were also reported. After physical examination of the cats, urine samples including ≥5-6 leucocytes in microscopic evaluation were cultured using bacteriological techniques. The isolates were identified by conventional microbiological methods and tested for in vitro susceptibility using the Kirby-Bauer disc diffusion method recommended by the Clinical Laboratory Standards Institute. Bacterial growth was observed in 16 of 61 urine samples. Antimicrobial susceptibility tests showed that 13 of 16 (81%) isolates were susceptible to cefovecin. The most frequently isolated bacterium from cats with signs of lower urinary tract infection, was Escherichia coli. Conclusion: Cefovecin was found to be effective in cats with LUTI. Because cefovecin is a new antimicrobial agent in veterinary medicine, there are only few studies about urine culture of cats with LUTI. It is the first study on in vitro activity of cefovecin against bacterial isolates from cats with lower urinary infections in Istanbul, Turkey. [ABSTRACT FROM AUTHOR]

Deals with a study which determined the diagnostic importance of erythrocyte glutathione peroxidase activity in lambs with white muscle disease and the changes in some serum parameters in healthy and white muscle diseased lambs. Materials and methods; Results; Conclusion.

Historical mapping of landscapes shows the characteristics of the relationship between man and landscape in certain chronosections and gives the opportunity to analyze and reconstruct the dynamics of nature management, environmental situations and the anthropogenic evolution of landscapes. An analysis of the development of the relationship between man and specific landscapes, studies of the dynamics of nature management of the old habitable territories are currently impossible without landscape-historical mapping with the use of GIS technologies. These technologies make it possible to carry out more quickly and efficiently a cross-spectrum analysis of multi-temporal and multi-scale historical maps and to quantitatively describe the dynamics of land use of specific landscape complexes of various taxonomic ranks, up to such types as tracts and sub-tracts, at certain historical intervals. The new landscapehistorical geographic information system that we are creating allows us to get a clear picture of the functioning of territories in different historical periods, on the basis of a landscape-historical analysis of the territory, involving the study of the dynamics of the landscape and economic activity within it, and the compilation of a series of maps for various chronosections. The use of GIS technology allows you to simulate the dynamics of the human-landscape interaction in a specific territory of a particular region. This is achieved by displaying changes in settlement systems and environmental management systems against the background of landscape conditions characteristic of the reflected period. The main subjects of such research are not only natural landscape or natural-anthropogenic complexes, but also landscapeeconomic systems and landscape-historical complexes, reflecting the economic or spiritual activity of man in specific landscape conditions in specific historical periods. These key areas for research are justified by the historical value and significance of the territory, the diversity of natural conditions and the presence of an almost complete set of landscape complexes of different hierarchical levels characteristic of the forest zone of the Russian Plain. The selection of the key areas for the research is justified by the historical value and significance of the territory, the diversity of natural conditions and the presence of an almost complete set of landscape complexes of different hierarchical levels characteristic of the forest zone of the Russian Plain. Such territories are: the historical center of Moscow - the Kremlin, State Borodino War and History Museum and Reserve, the museum-reserves "Kolomenskoye" and "Tsaritsyno", the vicinity of ancient cities and settlements: Rurikovo Ancient Town, Gnezdovo, Radonezh, the historical centers of Smolensk and Veliky Novgorod and many others. The work was carried out at several hierarchical levels: local level for key areas, and regional level for the forest areas of the Russian Plain. A series of landscape-historical maps were compiled, including the actual landscape maps, maps of landscape-economic systems, of nature management, and of settlement systems. Landscape-historical GIS, including a series of maps of different times for the key areas, clearly reflect the economic activity at a certain historical stage in the specific natural conditions in which this activity took place. At the same time, all maps are compiled on a single scale, which makes it possible to produce not only a qualitative assessment, but also a quantitative analysis of the processes taking place. The most important result of multi-scale landscape-historical mapping of territories of a regional level may be the compilation of electronic landscape-historical atlases. Success has already been achieved in creating such an atlas for the territory of the Moscow region. Such an electronic landscape-historical atlas is regional in scope, comprehensive, thematic in content; its purpose is diverse: its individual blocks can be considered as scientific-reference, local historical, educational, tourist information resources. It is the first time that several hierarchical levels of mapping and analysis of depicted objects are presented in an atlas. [ABSTRACT FROM AUTHOR]

Copyright of Kafkas Universitesi Veteriner Fakultesi Dergisi is the property of University of Kafkas, Faculty of Veterinary Medicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The article presents information on a study which investigated the cardiac problems observed in hepatic or renal insufficiency in dogs. It discusses cardiac insufficiencies that can occur as a result of hepatic and renal insufficiency. Several clinical and laboratory examinations were conducted to determine hepatic and renal insufficiency in dogs. It reveals the hematological, biochemical and cardiac changes in dogs with hepatic and renal insufficiency. Changes in the blood pressure were determined oscilloscopically and the effects of these changes on cardiac performance were observed electrocardiographically.

Primary cutaneous infection by Aspergillus spp. is an uncommon form of aspergillosis in patients with severe immunosuppression, e.g. patients with HIV infection or hematological malignancies. Disruption of the dermal integrity by trauma or maceration, followed by colonization of the wound by Aspergillus spp. creates a suitable environment for cutaneous infection. Despite aggressive therapy with amphotericin, primary cutaneous aspergillosis can lead to disseminated disease with fatal consequences. Tuberculosis is another rare infection in patients with hematological malignancies, but when present it is usually disseminated. We present a 46-year-old woman with acute myeloid leukemia who developed concomitantly Mycobacterium tuberculosis and Aspergillus niger infection. Cutaneous aspergillosis was diagnosed during neutropenia after induction therapy, which later became disseminated disease during antifungal therapy. Tuberculosis infection was diagnosed in a scalene lymph node biopsy specimen. The patient achieved remission of her underlying disease and responded very well to antituberculous and antifungal therapy.Copyright © 2003 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The article reports on a study of the impact of the clinical application of Minerasol, which is a hypertonic infusion solution that contains phosphate, calcium, sodium salts, magnesium, potassium, zinc trace elements, cobalt, iron and iodine. The study was conducted on 25 healthy cows in Istanbul, Turkey. Results indicated that there was a significant rise in levels of zinc and iron. On the other hand, there was no change in the levels of calcium, magnesium and copper, and in the hemogram parameters.

An abstract of the research paper "Peritoneal Tuberculosis Mimicking Ovarian Cancer," by M. Erman Akar and colleagues is presented.

Background: In this study, we reported the real-life results of data from impaired renal patients with urothelial carcinoma who were treated with ICTs., Methods: The patients were categorized into 3 different groups GFR ≥60mL/min (normal), 60mL/min-30mL/min (low), and less than 30 mL/min (very low) based on GFR. The primary endpoints were the overall response rate (ORR), overall survival (OS), duration of response with ICT, and safety. Median follow-up and OS were estimated by using the Kaplan-Meier method., Results: One hundred-five (60.3%) of patients were GFR normal, 26.4% were GFR low with 30mL/min-60mL/min, and 13.2% were very low group. ORR for GFR normal, low and very low groups were 36% (n = 38), 26% (n = 12) and %31 (7); P = .2, respectively. The median duration of response for GFR normal, low and very low groups were 47.2 months (95% CI, 24.5-51.4), 33.1 months (95% CI, 26.9-47), and 23.5 months (95% CI, 12.2-43.7); P = .01, respectively. The Median OS rate for GFR normal, low and very low groups were 11.9 (7.2-16.5) months, 4.7 (1.8-7.7) and 6.8 (1.1-13.6) months, P = .015, respectively. In addition, GFR <60 ml/min HR = 1.6; 95% CI 1.12-1.80; P = .02, maintained a significant association with OS in multivariate analysis., Conclusions: Long-term follow-up of real-world data confirms that the overall survival rate and durable response rate with ICT were higher in patients with GFR >60mL/min. On the other hand, we demonstrated that ICT was effective and a durable response seen in a group of patients with renal inpairement who did not have an effective systemic treatment option., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Heavy metals in the marine environment are significant contaminants that readily bioaccumulate in the tissues of aquatic organisms, particularly in filter-feeding animals such as bivalve molluscs. Human exposure to elevated concentrations of heavy metals, including essential elements such as Fe, Cu, and Zn, through the consumption of seafood can lead to various pathological effects. Research has demonstrated that among bivalve molluscs, mussels are the most effective indicators for monitoring marine pollution. Consequently, this study focused on the species Mytilus galloprovincialis to evaluate the levels of Al, As, Cd, Cr, Cu, Fe, Mg, Ni, Pb, and Zn in the two primary harvesting areas of Albania and to assess the associated human health risks from mussel consumption. The results revealed a concerning situation, particularly for Pb and Cd, with average concentrations of 2.15 μg/g and 4.14 μg/g, respectively, significantly exceeding the limits established by Regulation (EC) No. 915/2023. The levels of the other investigated elements also raised concerns, as only half of them were within the dietary intake values recommended by scientific authorities for weekly consumption of 250 g of mussels., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Invasive mucinous adenocarcinoma (IMA) is a rare histological subtype of lung invasive adenocarcinoma with unique clinical, radiological, histopathological, and genomic characteristics. There have been limited studies on the effectiveness of systemic therapy for lung IMA, with conflicting results reported., Methods: We retrospectively investigated the medical records of patients diagnosed with lung IMA. Patients who were ≥ 18 years of age and received at least 1 course of treatment for metastatic or locally advanced inoperable disease were included in the study. Archive records of 113 patients diagnosed with IMA were screened for the study., Results: A total of 41 patients with lung IMA were included. The targetable mutation rate was 20.6% (in 6 of 29 patients). Most patients (83.1%) had received platinum-based chemotherapy as a first-line treatment. The objective response rate (ORR) was 25.7%, and median progression-free survival (PFS) and overall survival (OS) were 8.1 months (95% CI, 5.02-11.2) and 17.5 months (95% CI, 11.7-23.3 months), respectively, in the patients who received chemotherapy. The median PFS and ORR were 20.6 (95% CI, 18.9-66.5) and 66.6%, respectively, in epidermal growth factor receptor (EGFR) mutation-positive patients (n = 3) with relevant targeted therapy. Only 1 patient used oxaliplatin and capecitabine combination (XELOX) as chemotherapy in the second-line treatment and achieved a partial response (PR) at 7.2 months., Conclusion: Platinum-based chemotherapies moderately enhance IMA patients' survival rates. Anti-EGFR-targeted drugs are seen as potentially effective in patients with EGFR driver mutation positive. Large, prospective studies are needed to confirm our findings., Competing Interests: Disclosure Young Kwang Chae COI Research Grant: Abbvie, BMS, Biodesix, Freenome, Predicine Honoraria/Advisory Boards: Roche/Genentech, AstraZeneca, Foundation Medicine, Neogenomics, Guardant Health, Boehringher Ingelheim, Biodesix, Immuneoncia, Lilly Oncology, Merck, Takeda, Lunit, Jazz Pharmaceutical, Tempus, BMS, Regeneron, NeoImmunTech, Esai All other authors do not have competing interests., (Published by Elsevier Inc.)

Background: Despite initial dramatic responses, metastatic small cell lung cancer (SCLC) invariably recurs. Irinotecan is one of the active agents for patients with recurrent SCLC. In the second line, weekly or three-weekly irinotecan regimens have been adopted, however, the optimal dose and schedule is not defined. In our institution, we use a bi-weekly regimen of irinotecan. In this study, we aimed to investigate the safety and efficacy of the bi-weekly irinotecan in the second- or third-line treatment of SCLC patients., Methods: The study population consisted of advanced stage SCLC patients who were followed at Hacettepe University Cancer Institute between January 2007 and March 2021 and received salvage irinotecan 180 mg/m 2 every two weeks, following progression after platinum-etoposide treatment., Results: One hundred patients were included. At diagnosis, nineteen patients (19%) had limited stage and 81 patients (81%) had extensive stage SCLC. Objective response rates (ORR) were 44.6% and 46.2% for patients who received irinotecan treatment in second line, and in third line, respectively. Seventeen percent of all the patients had grade 3 and above adverse events during irinotecan treatment. In our study, 45.8% of patients were able to complete at least 6 cycles of irinotecan treatment and 69.8% were able to receive at least 3 cycles of irinotecan treatment without any dose interruption or reduction., Conclusions: Irinotecan 180 mg/m 2 every two weeks appears to be safe and effective in the 2nd- and 3rd-line treatment of advanced stage SCLC. Bi-weekly administration allows G-CSF prophylaxis in between doses, leading to an uninterrupted administration., (© 2024. The Author(s).)

Background: This study aimed to evaluate the utility of RECIST criteria-based objective response rate (ORR) as a potential surrogate endpoint for long-term overall survival (OS) in patients with metastatic urothelial carcinoma who were treated with immune checkpoint inhibitors (ICIs)., Methods: The primary endpoint was overall ORR and OS, duration of treatment (DoR) with ICIs. ORR was analyzed using Fisher's exact test. Median follow-up and OS were estimated by using the Kaplan-Meier method., Results: The median follow-up was 58 (1.15-71) months. Progression developed in 94 (47%) patients during the first 3 months of ICIs therapy. The treatment response to ICIs included complete response (CR), partial response (PR) and stable disease in 10% (n = 20), 23% (n = 46), and 20% (n = 41) of patients, respectively. The responder and nonresponder groups differed in terms of certain baseline characteristics, such as Bellmunt risk factors, and neutrophil-to-lymphocyte ratio (NLR). The 5-year OS rates for patients with CR and PR were 73% and 23%, respectively. The median DoR for CR, PR, and SD were 51.8 months (44.5-59.1), 20.7 months (16.7-24.6), and 8.8 months (5.5-12.1), respectively. Overall, 16(80%) patients with CR and 14(30%) patients with PR had an ongoing response at the time of the analysis. In the univariate analysis, NLR > 3, liver metastases, ECOG PS ≥ 1, and hemoglobin levels < 10 mg/dl, as well as the PR and CR, were all significantly associated with OS. In multivariate analysis, presence of liver metastases (HR 2.3; 95% CI, 1.3-4.2; P < .004) was found to be an independent determinant of short OS, while PR (HR 0.3; 95% CI, 0.15-0.5; P < .001) and CR (HR 0.06; 95% CI, 0.014-0.27; P < .001) were associated with improved OS., Conclusions: In conclusion, this 5-year analysis of real-world data in the setting of metastatic urothelial cancer indicated a significant correlation between ORR, especially CR, and OS in patients who received ICIs. Therefore, identifying a potential surrogate marker for survival in patients treated with ICIs would represent an important advance in the early identification of patients' response or resistance to ICIs., Competing Interests: Disclosure No conflict of interest exists in the submission of this manuscript, and the manuscript is approved by all authors for publication. I would like to declare on behalf of my co-authors that the work described was original research that has not been published previously, and is not under consideration for publication elsewhere, in whole or in part. All the authors listed have approved the manuscript that is enclosed. All authors have contributed to the collection of the data, analysis, and writing of the article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Pandemics like COVID-19 have illuminated the significant disparities in the performance of national healthcare systems (NHCSs) during rapidly evolving crises. The challenge of comparing NHCS performance has been a difficult topic in the literature. To address this gap, our study introduces a bi-criteria longitudinal algorithm that merges fuzzy clustering with Data Envelopment Analysis (DEA). This new approach provides a comprehensive and dynamic assessment of NHCS performance and efficiency during the early phase of the pandemic. By categorizing each NHCS as an efficient performer, inefficient performer, efficient underperformer, or inefficient underperformer, our analysis vividly represents performance dynamics, clearly identifying the top and bottom performers within each cluster of countries. Our methodology offers valuable insights for performance evaluation and benchmarking, with significant implications for enhancing pandemic response strategies. The study's findings are discussed from theoretical and practical perspectives, offering guidance for future health system assessments and policy-making., (© 2024. His Majesty the King in Right of Canada, as represented by the National Research Council of Canada, and Adel Guitouni, Loubna Benabbou, Belaid Moa, Munire Erman, Halim Abdul 2024.)

Non-clear cell renal cell carcinoma (non-ccRCC) is a highly heterogeneous disease group, accounting for approximately 25% of all RCC cases. Due to its rarity and especially heterogeneity, phase III trial data is limited and treatment options generally follow those of clear cell RCC. In the literature, there exists a number of studies with sunitinib, cabozantinib, and everolimus, but data on the efficacy of pazopanib are limited. Our aim in this study was to compare the efficacy of pazopanib and sunitinib, in a multicenter retrospective cohort of non-ccRCC patients. Our study included patients diagnosed with non-ccRCC who received pazopanib or sunitinib treatment as first-line therapy from 22 tertiary hospitals. We compared the progression-free survival (PFS), overall survival (OS), and response rates of pazopanib and sunitinib treatments. Additionally, we investigated prognostic factors in non-ccRCC. PFS and response rates of sunitinib and pazopanib were found to be similar, while a numerical difference was observed in OS. Being 65 years and older, being in the intermediate or poor risk group according to the International Metastatic Renal Cell Carcinoma Database Consortium, having liver metastases, presence of a sarcomatoid component, and having de novo metastatic disease were found to be significantly associated with shorter PFS. Pazopanib treatment appears to have similar efficacy in the treatment of non-ccRCC compared to sunitinib. Though randomized controlled trials are lacking and will probably be never be available, we suggest that pazopanib could be a preferred agent like sunitinib and cabozantinib.

Background: Immunotherapy-based combinations have emerged as standard therapies for patients with metastatic renal cell carcinoma (mRCC). Pembrolizumab, a PD-1 inhibitor, combined with epacadostat, an indoleamine 2,3-deoxygenase 1 selective inhibitor, demonstrated promising antitumor activity in a phase 1 study in advanced solid tumors, including mRCC., Methods: KEYNOTE-679/ECHO-302 was a randomized, open-label, parallel-group, multicenter, phase 3 study (NCT03260894) that compared pembrolizumab plus epacadostat with sunitinib or pazopanib as first-line treatment for mRCC. Eligible patients had histologically confirmed locally advanced or metastatic clear cell RCC and had not received systemic therapy. Patients were randomly assigned 1:1 to pembrolizumab 200 mg IV every 3 weeks plus epacadostat 100 mg orally twice daily versus sunitinib 50 mg orally once daily (4 weeks on treatment followed by 2 weeks off treatment) or pazopanib 800 mg orally once daily. Original dual primary end points were progression-free survival and overall survival. Enrollment was stopped when a phase 3 study in melanoma of pembrolizumab plus epacadostat compared with pembrolizumab monotherapy did not meet its primary end point. This protocol was amended, and primary end point was changed to investigator-assessed objective response rate (ORR) per RECIST 1.1., Results: One-hundred-twenty-nine patients were randomly assigned to receive pembrolizumab plus epacadostat (n = 64) or sunitinib/pazopanib (n = 65). Median (range) follow-up, defined as time from randomization to data cutoff, was 10.3 months (2.2-14.3) and 10.3 months (2.7-13.8) in the pembrolizumab plus epacadostat and sunitinib/pazopanib arms, respectively. ORRs were similar between pembrolizumab plus epacadostat (31.3% [95% CI 20.2-44.1] and sunitinib/pazopanib (29.2% [18.6-41.8]). Grade 3-5 treatment-related adverse events occurred in 34.4% and 42.9% of patients in the pembrolizumab plus epacadostat and sunitinib/pazopanib arms, respectively. One patient in the sunitinib/pazopanib arm died of septic shock (not treatment-related). Circulating kynurenine levels decreased in the pembrolizumab plus epacadostat arm, but not to levels observed in healthy subjects., Conclusions: ORRs were similar between pembrolizumab plus epacadostat and sunitinib/pazopanib as first-line treatment in patients with mRCC. Safety and tolerability appeared similar between treatment arms; no new safety concerns were identified. Antitumor responses observed in patients with RCC receiving pembrolizumab plus epacadostat may be driven primarily by pembrolizumab., Clinical Trial Registration: ClinicalTrials.gov; NCT03260894 ., (© 2023. The Author(s).)

Purpose: This study aimed to assess the effects of concurrent opioid analgesic (OA) use with immune checkpoint inhibitors (ICIs) on progression-free survival (PFS) and overall survival (OS)., Methods: In this observational retrospective study, we included advanced cancer patients who received ICIs at Hacettepe University Hospital's Department of Medical Oncology between June 2018 and January 2023., Results: Our study included 375 recurrent or metastatic cancer patients treated with ICIs in the first, second line, or beyond. There were no significant differences between the OA-treated and OA-untreated groups regarding median age, age group, gender, primary tumor location, ICI type, or the presence of baseline liver and lung metastases. However, the OA-treated group exhibited a significantly higher proportion of patients who had received three or more prior treatments before initiating ICIs (p = 0.015). OA-Untreatment was significantly correlated with prolonged mPFS (6.83 vs. 4.30 months, HR 0.59, 95% CI 0.44-0.79, p < 0.001) and mOS (17.05 vs. 7.68 months, HR 0.60, 95% CI 0.45-0.80, p < 0.001)., Conclusions: Our study demonstrates an association between the concurrent use of OAs and reduced OS and PFS in patients treated with ICIs. While OA treatment serves as a surrogate marker for higher disease burden, it may also suggest a potential biological relationship between opioids and immunotherapy efficacy., (© 2024. The Author(s).)

Introduction: Adrenocortical carcinoma (ACC) is a rare yet highly malignant tumor associated with significant morbidity and mortality. This study aims to delineate the clinical features, survival patterns, and treatment modalities of ACC, providing insights into the disease's prognosis., Materials and Methods: A retrospective analysis of 157 ACC patients was performed to assess treatment methodologies, demographic patterns, pathological and clinical attributes, and laboratory results. The data were extracted from the hospital's database. Survival analyses were conducted using the Kaplan-Meier method, with univariate and multivariate analyses being performed through the log-rank test and Cox regression analyses., Results: The median age was 45, and 89.4% had symptoms at the time of diagnosis. The median tumor size was 12 cm. A total of 117 (79.6%) patients underwent surgery. A positive surgical border was detected in 26 (24.1%) patients. Adjuvant therapy was administered to 44.4% of patients. The median overall survival for the entire cohort was 44.3 months. Median OS was found to be 87.3 months (95% confidence interval [CI] 74.4-100.2) in stage 2, 25.8 (95% CI 6.5-45.1) months in stage 3, and 13.3 (95% CI 7.0-19.6) months in stage 4 disease. Cox regression analysis identified age, Ki67 value, Eastern Cooperative Oncology Group performance status, and hormonal activity as significant factors associated with survival in patients with nonmetastatic disease. In metastatic disease, only patients who underwent surgery exhibited significantly improved overall survival in univariate analyses., Conclusion: ACC is an uncommon tumor with a generally poor prognosis. Understanding the defining prognostic factors in both localized and metastatic diseases is vital. This study underscores age, Ki67 value, Eastern Cooperative Oncology Group performance status, and hormonal activity as key prognostic determinants for localized disease, offering critical insights into the complexities of ACC management and potential avenues for targeted therapeutic interventions., Competing Interests: Disclosure The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

To evaluate radiological and clinical features in metastatic anaplastic lymphoma kinase+ non-small cell lung cancer patients and crizotinib efficacy in different lines. This national, non-interventional, multicenter, retrospective archive screening study evaluated demographic, clinical, and radiological imaging features, and treatment approaches in patients treated between 2013-2017. Totally 367 patients (54.8% males, median age at diagnosis 54 years) were included. Of them, 45.4% were smokers, and 8.7% had a family history of lung cancer. On radiological findings, 55.9% of the tumors were located peripherally, 7.7% of the patients had cavitary lesions, and 42.9% presented with pleural effusion. Pleural effusion was higher in nonsmokers than in smokers (37.3% vs. 25.3%, P = .018). About 47.4% of cases developed distant metastases during treatment, most frequently to the brain (26.2%). Chemotherapy was the first line treatment in 55.0%. Objective response rate was 61.9% (complete response: 7.6%; partial response: 54.2%). The highest complete and partial response rates were observed in patients who received crizotinib as the 2nd line treatment. The median progression-free survival was 14 months (standard error: 1.4, 95% confidence interval: 11.2-16.8 months). Crizotinib treatment lines yielded similar progression-free survival (P = .078). The most frequent treatment-related adverse event was fatigue (14.7%). Adrenal gland metastasis was significantly higher in males and smokers, and pleural involvement and effusion were significantly higher in nonsmokers-a novel finding that has not been reported previously. The radiological and histological characteristics were consistent with the literature data, but several differences in clinical characteristics might be related to population characteristics., Competing Interests: OUD and BA are the employees of Pfizer Biopharmaceuticals Group, Istanbul, Türkiye. BOU reports research support for clinical trials through institution from Novartis, GSK, Astra Zeneca; honoraria from BMS, Amgen, Novartis, Pfizer, Astra Zeneca, Roche, MSD; support for attending meetings from Roche, Pfizer, Novartis and is on the advisory boards of Takeda, Roche, Astra Zeneca, MSD, Novartis, Amgen, Gilead. ME has support funding for medical writing from Pfizer, provides lectures for Pfizer, Novartis, Roche, Astellas, Janssen, MSD, Gen, Nobel, Deva, Eczacibasi, BMS, Takeda, Astra Zeneca, has support for attending meetings from Roche, has participation on advisory board of Novartis, Pfizer, Roche, Astellas, MSD, Deva, Astra Zeneca. The remaining authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: The advances in immune checkpoint inhibitors (ICIs) were relatively slow in rare tumors. Therefore, we conducted a multi-center study evaluating the efficacy of ICI monotherapy and the combination of ICIs with chemotherapy (CT) in patients with advanced rare tumors., Methods: In this retrospective cohort study, we included 93 patients treated with ICIs for NCI-defined rare tumors from the 12 cancer centers in Turkey. The primary endpoints were the overall response (ORR) and disease control rate (DCR)., Results: The cohort's median age was 56, and 53.8% of the patients were male. The most frequent diagnosis was sarcoma (29%), and 81.7% of the patients were previously treated with at least one line of systemic therapy in the advanced stage. The ORR and DCR were 36.8% and 63.2%, respectively. The germ cell tumors had the lowest ORR (0%), while the Merkel cell carcinoma had the highest ORR to ICIs (57.1%). Patients treated with ICI + ICI or ICI plus chemotherapy combinations had higher ORR (55.2% vs. 27.6%, p = 0.012) and DCR (82.8% vs. 53.4%, p = 0.008). The median OS was 13.47 (95% CI: 7.79-19.15) months, and the six and 12-month survival rates were 71% and 52%. The median duration of response was 16.59 months, and the 12-month progression-free survival rate was 66% in responders. The median time-to-treatment failure was 5.06 months (95% CI: 3.42-6.71). Three patients had high-grade irAEs with ICIs (grade 3 colitis, grade 3 gastritis, and grade 3 encephalitis in one patient each)., Conclusion: We observed over 30% ORR and a 13-month median OS in patients with rare cancers treated with ICI monotherapy or ICI plus CT combinations. The response rates to ICIs or ICIs plus CT significantly varied across different tumor types. Responding patients had over 2 years of survival, highlighting a need for further trials with ICIs for patients with rare tumors., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Introduction: Although immune checkpoint inhibitors (ICIs) are widely used in cancer treatment, identifying factors that predict treatment response remains a challenge in clinical practice. There is a need for biomarkers to identify patients who may not benefit from these treatments. It is crucial to identify a simple and cost-effective biomarker that can be easily incorporated into clinical practice. This study aims to investigate the mean platelet volume to lymphocyte ratio (MPVLR), as measured by a hemogram test, and median overall survival (mOS) in patients with cancer treated with nivolumab., Methods: A total of 131 adult patients with metastatic cancer, including malignant melanoma (MM), renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC), and head and neck cancer (HNC), were included in this study. Baseline demographics, ECOG (Eastern Cooperative Oncology Group) performance status, tumor type, and blood count parameters were recorded. Univariate and multivariate analyses were conducted to evaluate potential risk factors., Results: The median age of the patients was 59.87 ± 11.97 years, and the median follow-up period was 20.20 months (IQR, 12.80-27.60). RCC (43.5%) and MM (25.9%) were the most common diagnoses. Patients with ECOG scores of 0-1 had a longer mOS than those with scores of 2-3 (mOS: 20.60 months [95% CI, 14.94-25.29] vs. 5.24 months [95% CI, 0-16.42], p < 0.001). Additionally, patients with lactate dehydrogenase (LDH) levels within the normal range had a longer mOS than those with high LDH levels (mOS: 24.54 months [95% CI, 14.13-34.96] vs. 13.10 months [95% CI, 4.49-21.72], p = 0.038). Patients with low MPVLR also had a longer mOS than those with high MPVLR (mOS: 33.70 months [95% CI, 25.99-41.42] vs. 11.07 months [95% CI, 6.89-15.24], p < 0.001). In the multivariate Cox regression analysis, high MPVLR, ECOG score of 2-3, and high LDH level were associated with shorter mOS ( p < 0.001, p = 0.001, and p = 0.046, respectively)., Conclusion: This study demonstrates that MPVLR could serve as a novel biomarker for predicting response to nivolumab treatment. Incorporating MPVLR into clinical practice may aid in identifying patients who are less likely to benefit from the treatment., Competing Interests: Source of Support: None. Conflict of Interest: None

Purpose: Anaplastic lymphoma kinase (ALK) mutations occurs in approximately 3-5% of patients with non-small cell lung cancer (NSCLC). Pleural involvement/effusion is common in ALK-positive patients with NSCLC at baseline. The aim of the study was to evaluate the characteristics of ALK-positive patients who have Ple-I/E., Methods: In this multicenter study, patients with ALK-positive NSCLC who have Ple-I/E were retrospectively analyzed. Clinical and demographic characteristics of the disease, response rates, median progression-free survival (PFS), and overall survival (OS) were evaluated in 362 ALK-positive patients with NSCLC., Results: Of the patients, 198 (54.7%) were male. The median age at the time of diagnosis was 54 (range 21-85) years. All patients' histology was adenocarcinoma (100%). At baseline, 57 (15.7%) patients had Ple-I/E. There was no association between Ple-I/E and gender, lung metastasis, or distant lymphadenopathy (LAP) metastasis. The frequencies of liver, brain, and bone metastases were significantly higher in ALK-positive patients without Ple-I/E compared to those with Ple-I/E (respectively 18.2% vs 4.8%, p = 0.008; 19.1% vs 4.8%, p = 0.001; 20.6% vs 8.9%, p = 0.002). The median PFS was longer in ALK-positive patients who had Ple-I/E (18.7 vs 10.6 months, p = 0.017). Similarly, the median OS was longer in ALK-positive patients who had Ple-I/E (44.6 vs 22.6 months, p = 0.051)., Conclusion: Brain, liver, and bone metastases were lower in ALK-positive patients with Ple-I/E. Patients presented with Ple-I/E were prone to have better PFS and OS., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Chronic kidney disease (CKD) is associated with a state of chronic inflammation. This study aimed to investigate effects of Ramadan fasting on the markers of chronic inflammation and gut bacterial endotoxin levels in maintenance hemodialysis., Method: A prospective self-controlled observational study included 45 patients. Serum levels of High Sensitive CRP (hsCRP), indoxyl sulfate, and trimethylamine-n-levels were measured within a week before and a week after Ramadan fasting., Results: Twenty-seven patients have fasted more than 15 days (29 ± 2.2 days). The levels of high sensitive C-reactive protein (hsCRP) (median of 62 mg/L vs. 91 mg/L), trimethylamine-n-oxide (TMAO) (median of 4.5 μmoL/L vs. 17 μmoL/L), platelet-to-lymphocyte ratio (PLR) (mean of 98.9 mg/L vs. 111.8 mg/L) and neutrophil-to-lymphocyte ratio (NLR) (median of 1.56 vs. 1.59) were significantly lower after Ramadan fasting with p < 0.001, p < 0.001, p < 0.001, and p = 0.04, respectively., Conclusion: A beneficial effect of Ramadan fasting on levels of bacterial endotoxins and markers of chronic inflammation in hemodialysis patients was observed., (© 2023 International Society for Apheresis and Japanese Society for Apheresis.)

Objective: Treatment beyond progression (TBP) with immune checkpoint inhibitors (ICIs) is an evolving field due to the limitations of conventional imaging in response evaluation. However, real-life data on the benefit of TBP is scarce, especially from the limited resource settings and patients treated in the later lines. Therefore, we aimed to investigate the survival benefit of TBP with ICIs in patients with advanced tumors from a limited resource setting., Methods: For this multi-center retrospective cohort study, we included 282 patients treated with ICIs and had radiological progression according to RECIST 1.1 criteria. We evaluated post-progression survival according to the use of TBP (TBP and non-TBP groups) with univariate and multivariate analyses., Results: The cohort's median age was 61, and 84.4% were treated in the second or later lines. 82 (29.1%) of 282 patients continued on ICIs following the initial progression. In multivariate analyses, patients in the TBP group had improved post-progression survival compared to non-TBP (13.18 vs. 4.63 months, HR: 0.500, 95% CI: 0.349-0.717, p < 0.001). The benefit of the TBP was independent of the tumor type, treatment line, and age. Furthermore, TBP with ICIs remained associated with improved post-progression survival (HR: 0.600, 95% CI: 0.380-0.947, p = 0.028) after excluding the patients with no further treatment after progression in the non-TBP arm., Conclusions: In this study, we observed that patients receiving ICIs beyond progression had considerably longer survival. Continuation of ICIs after progression should be considered a reasonable management option for patients with advanced cancer, specifically for patients with limited alternative options., (© 2022. Crown.)

Recent observational studies reported acute kidney injury (AKI) events in over 10% of the patients treated with immune checkpoint inhibitors (ICIs). However, these studies included patients treated in high-resource settings and earlier lines. Therefore, we aimed to assess the AKI rates and predisposing factors in ICI-treated patients from a limited resource setting. We evaluated 252 patients with advanced cancer for this retrospective cohort study. AKI events were defined by Kidney Disease Improving Global Outcomes criteria. The median age was 59 years. The melanoma (18.3%), non-small cell lung cancer (14.7%) and renal cell carcinoma (22.6%) patients comprised over half of the cohort. During the follow-up, 45 patients (17.9%) had at least one AKI episode. In multivariable analyses, patients with chronic kidney disease (CKD) [odds ratio (OR), 3.385; 95% confidence interval (CI), 1.510-7.588; P  = 0.003], hypoalbuminemia (OR, 2.848; 95% CI, 1.225-6.621; P  = 0.015) or renin-angiotensin-aldosterone system (RAAS) inhibitor use (OR, 2.236; 95% CI, 1.017-4.919; P  = 0.045) had increased AKI risk. There was a trend towards increased AKI risk in patients with diabetes (OR, 2.042; 95% CI, 0.923-4.518; P  = 0.78) and regular proton pump inhibitors use (OR, 2.024; 95% CI, 0.947-4.327; P  = 0.069). In this study, we observed AKI development under ICIs in almost one in five patients with cancer. The increased AKI rates in CKD, hypoalbuminemia or RAAS inhibitor use pointed out a need for better onco-nephrology collaboration and efforts to improve the nutritional status of ICI-treated patients., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Metastatic castration-resistant prostate cancer (mCRPC) is characterized by heterogeneity among patients as well as therapy responses due to diverse genetic, epigenetic differences, and resistance mechanisms. At this stage of the disease, therapy modalities should be individualized in light of the patients' clinical state, symptoms, and genetic characteristics. In this prospective study, we aimed to evaluate the outcome of patients with mCRPC treated with 177 Lutetium labeled PSMA-617 therapy (PSMA-RLT), as well as baseline and therapy-related parameters associated with survival., Methods: This prospective study included 52 patients who received two to six cycles of PSMA-RLT. Primary endpoints were overall survival (OS) and prostate-specific antigen (PSA)-progression-free survival (PFS). 18 F-Fluorodeoxyglucose (FDG) and 68 Ga-PSMA (PSMA) Positron Emission Tomography/Computer Tomography (PET/CT) scans were performed for a comprehensive assessment of tumor burden and heterogeneity. Biochemical, imaging, clinical, and therapy-related parameters were analyzed with the Kaplan-Meier, log-rank, and Cox regression analyses to predict OS and PFS., Results: Median OS and PSA-PFS were 17.7 (95% confidence interval [CI]: 15.2-20.2) and 6.6 months (95% CI: 4.5-8.8), respectively. Primary resistance to PSMA-RLT (hazard ratio [HR]: 12.57, 95% CI: 2.4-65.2, p: 0.003), <30% PSA response rate after first cycle of PSMA-RLT (HR: 1.016, 95% CI: 1.006-1.03, p: 0.003), FDG > PSMA disease (HR: 4.9, 95% CI: 1.19-20.62, p: 0.03), PSA doubling time (PSA DT) of ≤2.4 months (HR: 15.7, 95% CI: 3.7-66.4, p: <0.0001), and low hemoglobin levels (HR: 0.59, 95% CI: 0.41-0.83, p: 0.003) were correlated with poor OS in the multivariate analysis. Bone scintigraphy >  PSMA disease (HR: 5.6; 95% CI: 1.8-17, p: 0.002) and high C-reactive protein (HR: 1.4, 95% CI: 1.1-1.7, p: 0.001) were significant predictive biomarkers for PFS in the multivariate analysis., Conclusion: PSA response rate and pattern to PSMA-RLT are the most important predictors of survival in patients receiving PSMA-RLT. Being a strong predictive biomarker, combined FDG and PSMA PET can be helpful for the decision of PSMA-RLT eligibility., (© 2023 The Authors. The Prostate published by Wiley Periodicals LLC.)

Background: In this study, we report real-world results from the 5-year follow-up data of urothelial carcinoma patients treated with immune checkpoint blockade therapies (ICTs)., Patients and Methods: Metastatic urothelial carcinoma patients treated with at least one course of ICT were included in the study. The primary endpoint was overall response rate (ORR), and secondary endpoints were overall survival (OS), progression-free survival (PFS), duration of treatment with ICT, and safety. Median follow-up, PFS, and OS were estimated by using the Kaplan-Meier method., Results: Data of 201 eligible patients were analyzed. The median age of the patients was 66 (37-86) years, and 156 (84.3%) were male. The majority of patients (94.6%) had Eastern Cooperative Oncology Group (ECOG) PS scores of 0 to 1 and primary tumor in the bladder was predominant (87.5%). The median follow-up time was 54 (1.15-65) months. The rate of complete response (CR) to ICT, partial response (PR) rate, and ORR were 10.4% (n = 21), 22.4% (n = 45), and 32.4% (n = 66), respectively. The median duration of response (DOR) was 34.8 months (95% confidence interval [CI], 29.2-42.1). Of the 66 patients who responded to treatment, 28 (42%) had an ongoing response at the time of the analysis. Median PFS and OS were 3.8 (2.6-5.8) months and 9.4 (7.4-11.4) months, respectively. The 5-year PFS and OS rates were 9.8% and 12.8%, respectively. Fifty-eight percent of patients experienced a treatment-related adverse event of any grade, and 33 (16.4%) patients had a grade 3 to 4 adverse event., Conclusion: This 5-year analysis of real-world data confirms the durable response and long-term survival with ICT in metastatic urothelial carcinoma patients., (Copyright © 2022 Elsevier Inc. All rights reserved.)

We aimed to evaluate the seroconversion rates after two doses of inactive COVID-19 vaccine (CoronaVac) and the benefit of a third dose mRNA vaccine booster in patients with cancer receiving active treatment. Patients with solid tumors receiving active treatment (n = 101) and patients with no-cancer (n = 48) as the control group were included in the study. All the patients and controls had received two doses of CoronaVac and a third booster dose of the mRNA vaccine (Bnt162b2). Anti-SARS-CoV-2 Spike Receptor Binding Domain IgG antibody levels after the second and third dose were measured with quantitative ELISA. The median age of the patients was 66 (IQR 60-71). 79% of the patients were receiving chemotherapy, and 21% were receiving immunotherapy at the time of vaccination. Antibody levels measured after two doses of CoronaVac were significantly lower in patients with cancer than in the control group (median 0 μg/ml [IQR 0-1.17 μg/ml] vs median 0.91 μg/ml [IQR 0-2.24 μg/ml], respectively, P = .002). Seropositivity rates were 46.5% in patients with cancer and 72.9% in the control group (P = .002). Antibody measurement was performed in 26 patients after the third dose. Seroconversion rate increased from 46.5% to 88.5% (P < .001), and the antibody titers significantly increased with the third-dose booster (median 0 μg/ml [IQR 0-1.17 μg/ml] after two doses vs 12.6 μg/ml [IQR 1.8-69.1 μg/ml] after third booster dose, P < .001). Immunogenicity of CoronaVac is low in patients with cancer receiving active treatment, and administering a third dose of an mRNA vaccine is effective in terms of improving seroconversion rates., (© 2022 UICC.)

Introduction: NEPTUNE, a phase 3, open-label study, evaluated first-line durvalumab plus tremelimumab versus chemotherapy in metastatic NSCLC (mNSCLC)., Methods: Eligible patients with EGFR and ALK wild-type mNSCLC were randomized (1:1) to first-line durvalumab (20 mg/kg every 4 weeks until progression) plus tremelimumab (1 mg/kg every 4 weeks for up to four doses) or standard chemotherapy. Randomization was stratified by tumor programmed death-ligand 1 expression (≥25% versus <25%), tumor histologic type, and smoking history. The amended primary end point was overall survival (OS) in patients with blood tumor mutational burden (bTMB) greater than or equal to 20 mutations per megabase (mut/Mb). Secondary end points included progression-free survival (PFS) in patients with bTMB greater than or equal to 20 mut/Mb and safety and tolerability in all treated patients., Results: As of June 24, 2019, 823 patients were randomized (intention-to-treat [ITT]); 512 (62%) were bTMB-evaluable, with 129 of 512 (25%) having bTMB greater than or equal to 20 mut/Mb (durvalumab plus tremelimumab [n = 69]; chemotherapy [n = 60]). Baseline characteristics were balanced in the intention-to-treat. Among patients with bTMB greater than or equal to 20 mut/Mb, OS improvement with durvalumab plus tremelimumab versus chemotherapy did not reach statistical significance (hazard ratio 0.71 [95% confidence interval: 0.49-1.05; p = 0.081]; median OS, 11.7 versus 9.1 months); the hazard ratio for PFS was 0.77 (95% confidence interval, 0.51-1.15; median PFS, 4.2 versus 5.1 months). In the overall safety population, incidence of grade 3 or 4 treatment-related adverse events was 20.7% (durvalumab plus tremelimumab) and 33.6% (chemotherapy)., Conclusions: NEPTUNE did not meet its primary end point of improved OS with durvalumab plus tremelimumab versus chemotherapy in patients with mNSCLC and bTMB greater than or equal to 20 mut/Mb. Despite the amended study design, with a resultant small primary analysis population, therapeutic activity was aligned with expectations based on mechanistic biology and previous studies., (Copyright © 2022 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Purpose: With the widespread use of immunotherapy agents, we encounter treatment responses such as hyperprogression disease (HPD) that we have not seen with previous standard chemotherapy and targeted therapies. It is known that survival in patients with HPD is shorter than in patients without HPD. Therefore, it is important to know the factors that will predict HPD. We aimed to identify HPD-related factors in patients treated with immunotherapy. Methods: A total of 121 adult metastatic cancer patients treated with immunotherapy for any cancer were included. Baseline demographics, the ECOG performance status, type of tumors and baseline blood count parameters were recorded. Possible predisposing factors were evaluated with univariate and multivariate analyses. Results: The median age was 62.28 (interquartile range (IQR) 54.02−67.63) years, and the median follow-up was 12.26 (IQR 5.6−24.36) months. Renal cell carcinoma (33%) and melanoma (33.8%) were the most common diagnoses. Twenty patients (16.5%) had HPD. A high LDH level (p: 0.001), hypoalbuminemia (p: 0.016) and an NLR > 5 (p: 0.007) were found to be associated with hyperprogression. Sex (female vs. male, p: 0.114), age (>65 vs. <65, p: 0.772), ECOG (0 vs. 1−4, p: 0.480) and the line of treatment (1−5, p: 0.112) were not found to be associated with hyperprogression. Conclusions: In this study, we observed HPD in 16.5% of immunotherapy-treated patients and increased HPD risk in patients with a high LDH level (p: 0.001), hypoalbuminemia (p: 0.016) and an NLR > 5 (p: 0.007).

Dynamic changes in the blood-based biomarkers could be used as a prognostic biomarker in patients treated with immune checkpoint inhibitors (ICIs), although the data are limited. We evaluated the association between the neutrophil−lymphocyte ratio (NLR) and early NLR changes with survival in ICI-treated patients. We retrospectively evaluated the data of 231 patients with advanced-stage cancer. We recorded baseline clinical characteristics, baseline NLR and fourth-week NLR changes, and survival data. A compound prognostic score, the NLR2-CEL score, was developed with the following parameters: baseline NLR (<5 vs. ≥5), ECOG status (0 vs. ≥1), Charlson Comorbidity Index (CCI, <9 vs. ≥9), LDH (N vs. ≥ULN), and fourth-week NLR change (10% or over NLR increase). In the multivariable analyses, higher NLR (HR: 1.743, p = 0.002), 10% or over NLR increase in the fourth week of treatment (HR: 1.807, p = 0.001), higher ECOG performance score (HR: 1.552, p = 0.006), higher LDH levels (HR: 1.454, p = 0.017), and higher CCI (HR: 1.400, p = 0.041) were associated with decreased OS. Compared to patients with the lowest scores, patients in the highest score group had significantly lower OS (HR: 7.967, 95% CI: 3.531−17.979, p < 0.001) and PFS. The composite score had moderate success for survival prediction, with an AUC of 0.702 (95% CI: 0.626−0.779, p < 0.001). We observed significantly lower survival in patients with higher baseline NLR values and increased NLR values under treatment.

Background: The association of thrombospondin type 1 domain-containing 7A (THSD7A) expression, a novel angiogenesis-related marker, with survival outcomes of tumors including renal cell carcinoma (RCC) remains to be clarified. Therefore, we investigated the impact of THSD7A on outcomes of metastatic RCC (mRCC) patients treated with targeted therapy., Methods: A total of 86 mRCC patients were included. The expression of THSD7A in nephrectomy material of the patients was assessed by immunohistochemistry and expression patterns were categorized into two groups: negative (no staining) and positive. Univariable and multivariable Cox regression models evaluated the impact of THSD7A expression on progression free survival (PFS) and overall survival (OS) of the patients., Results: THSD7A expression was determined in 77.9% of the patients. Kaplan-Meier analyses showed that while the patients with THSD7A expression had significantly inferior OS times than those with negative THSD7A expression (19.9 months vs. 52.2 months, P = 0.024, respectively), there was no association between THSD7A expression and PFS. The univariate analyses demonstrated that the significant variables in predicting OS were presence of bone metastasis (P = 0.030), THSD7A expression (P = 0.028), and International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) scoring system (P < 0.001). However, applying multivariate analyses, the independent variables in predicting OS were THSD7A expression (HR: 2.639, P = 0.037) and IMDC scoring system (P < 0.001)., Conclusion: We revealed that THSD7A expression was associated with OS of mRCC patients treated with targeted therapy. There might be an important link between THSD7A expression and resistance to targeted therapy., (© 2021. Royal Academy of Medicine in Ireland.)