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Molecular insights into clinical trials for immune checkpoint inhibitors in colorectal cancer:Unravelling challenges and future directions

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World Journal of Gastroenterology 2024年第13期30卷 1815-1835页

作者： Samantha Sharma Naresh Singh Anita Ahmed turk Isabella Wan Akshay Guttikonda Julia Lily Dong Xinna Zhang Mateusz Opyrchal Department of Medical and Molecular Genetics Indiana University School of MedicineIndianapolisIN 46202United States Division of Hematology/Oncology Department of MedicineIndiana University School of MedicineIndianapolisIN 46202United States Melvin and Bren Simon Comprehensive Cancer Center Indiana University School of MedicineIndianapolisIN 46202United States

Colorectal cancer(CRC)is a complex disease with diverse etiologies and clinical *** considerable progress in development of CRC therapeutics,challenges remain regarding the diagnosis and management of advanced stage metastatic CRC(mCRC).In particular,the five-year survival rate is very low since mCRC is currently rarely *** the past decade,cancer treatment has significantly improved with the introduction of cancer immunotherapies,specifically immune checkpoint *** aimed at blocking immune checkpoints such as PD-1,PD-L1,and CTLA-4 target inhibitory pathways of the immune system,and thereby enhance anti-tumor *** therapies thus have shown promising results in many clinical trials alone or in *** efficacy and safety of immunotherapy,either alone or in combination with CRC,have been investigated in several clinical *** trials,including KEYNOTE-164 and CheckMate 142,have led to Food and Drug Administration approval of the PD-1 inhibitors pembrolizumab and nivolumab,respectively,for the treatment of patients with unresectable or metastatic microsatellite instability-high or deficient mismatch repair ***,these drugs benefit only a small percentage of patients,with the benefits of immunotherapy remaining elusive for the vast majority of CRC *** this end,primary and secondary resistance to immunotherapy remains a significant issue,and further research is necessary to optimize the use of immunotherapy in CRC and identify biomarkers to predict the *** review provides a comprehensive overview of the clinical trials involving immune checkpoint inhibitors in *** underlying rationale,challenges faced,and potential future steps to improve the prognosis and enhance the likelihood of successful trials in this field are discussed.

关键词： Colorectal cancer Immune checkpoint inhibitors Clinical trials Immunotherapy Microsatellite instability Microsatellite stability DNA mismatch repair

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Giant saccular aneurysm of the left main coronary artery

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Journal of Geriatric Cardiology 2013年第1期10卷 110-112页

作者： Esref Tuncer ugur Onsel turk Emin Alioglu Department of Cardiology Central Hospital 2/2 Bayrakli Izmir 35050 Turkey

Coronary aneurysms represent anomalies identified in 0.15%–4.9%of patients undergoing coronary angiography. At present, there is no uniform definition of this pathology. Aneurysms of the left main coronary artery (LMCA) are extremely uncommon, with an incidence of 0.1%. It has been demonstrated that atherosclerosis is the main cause of these anomalies in adults, and Kawasaki disease in children and adolescents. Other causes include connective tissue disorders, trauma, vasculitis, congenital, mycotic, and idiopathic. These dilated sections of the coronary artery are not benign pathology because they are subject to spasm, thrombosis, and subsequent distal embolism, spontaneous dissection and rupture. Treatment options include anticoagulation, custom-made covered stents, reconstruction, resection, and exclusion with bypass. Our report on an old case illustrates the giant saccular LMCA aneurysm leading to myocardial ischemia due to coronary steal phenomenon.

关键词： Coronary aneurysm Coronary angiography Coronary artery disease

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Deep neck infections mortal complications:Intrathoracic complications and necrotising fasciitis

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World Journal of Clinical Cases 2024年第30期12卷 6383-6390页

作者： Kemal Koray Bal Can Aslan Harun Gür Seda turk Bal Recep Okan Ustun Murat Unal Department of Otorhinolaryngology Mersin UniversityMersin 33160Türkiye Department of Emergency Medicine Tarsus State HospitalMersin 33460Türkiye Department of Aestetic Division of Plastic and Reconstructive SurgeryUniversity of Health Sciences Mersin City HospitalMersin 33230Türkiye

BACKGROUND We planned this study considering that complications of deep neck infections can be seriously life *** To raise awareness that introthoracic complications and necrotizing fasciitis are causes of serious mortality and *** This study was carried out with the participation of 188 patients who were treated at Mersin University Department of Otorhinolaryngology and Head and Neck Surgery at January 1,*** the patient files were retrospectively examined,16 of 188 patients(8.5%)were included in the study because they were observed to have necrotizing fasciitis and/or intrathoracic *** There were a total of 16 patients in this study,9 males(56.25%)and 7 females(43.75%).All patients were adults(>18 years)and the mean age was 50.37 years±15.37 *** patients had a mean age of 40.42 years±13.38 years,whereas for male patients was 58.11 years±12.44 *** Patients with necrotizing fasciitis and/or intrathoracic complications require more complicated and serious surgeries,intensive care unit monitoring,and mechanical ventilator *** rates of morbidity and mortality should be expected in Bal KK et *** neck infections mortal complications WJCC https://*** 6384 October 26,2024 Volume 12 Issue 30 these patients who are hospitalized for longer periods of time.

关键词： Deep neck infection Necrotising fasciitis Mediastinitis Complications Mortality

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A new device for paravalvular leak closure

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Journal of Geriatric Cardiology 2015年第2期12卷 187-188页

作者： Ertugrul Ercan Istemihan Tengiz ugur.turk Ferhat Ozyurtlu Emin Alioglu Department of Cardiology &mir University Yeni Girne Bulvari 1825 Sok. No.12 Karsiyaka lzmir Turkey Department qf Cardiology Central Hospital 1644 Sok. No:2 Bayrakli Izmir Turkey

Percutaneous closure of a prosthetic paravalvular leak （PVL） is a challenging procedure. Operators must use devices constructed for other applications. We present the use of a device which is specifically designed f... 详细信息

关键词： Device Paravalvular leak Percutaneous intervention Prosthetic valve

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Metabolic syndrome and the urinary microbiome of patients undergoing percutaneous nephrolithotomy

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Asian Journal of Urology 2024年第2期11卷 316-323页

作者： Ryan A.Dornbier Chirag P.Doshi Shalin C.Desai Petar Bajic Michelle Van Kuiken Mark Khemmani Ahmer V.Farooq Larissa Bresler Thomas M.T.turk Alan J.Wolfe Kristin G.Baldea Loyola University Medical Center Department of UrologyMaywoodILUSA Loyola University Chicago Department of Microbiology and ImmunologyMaywoodILUSA

Objective:To identify possible stone-promoting microbes,we compared the profiles of microbes grown from stones of patients with and without metabolic syndrome(MetS).The association between MetS and urinary stone disease is well established,but the exact pathophysiologic relationship remains *** evidence suggests urinary tract dysbiosis may lead to increased nephrolithiasis ***:At the time of percutaneous nephrolithotomy,bladder urine and stone fragments were collected from patients with and without *** sample types were subjected to expanded quantitative urine culture(EQUC)and 16 S ribosomal RNA gene ***:Fifty-seven patients included 12 controls(21.1%)and 45 MetS patients(78.9%).Both cohorts were similar with respect to demographics and non-MetS *** controls had uric acid stone *** EQUC,bacteria were detected more frequently in MetS stones(42.2%)compared to controls(8.3%)(p=0.041).Bacteria also were more abundant in stones of MetS patients compared to *** validate our EQUC results,we performed 16 S ribosomal RNA gene *** 12/16(75.0%)sequence-positive stones,EQUC reliably isolated at least one species of the sequenced *** were detected in both“infectious”and“non-infectious”stone ***:Bacteria are more common and more abundant in MetS stones than control *** findings support a role for bacteria in urinary stone disease for patients with MetS regardless of stone composition.

关键词： Nephrolithiasis Urolithiasis Metabolic syndrome Urinary microbiome Percutaneous nephrolithotomy

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Digoxin intoxication： An old enemy in modern era

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Journal of Geriatric Cardiology 2012年第3期9卷 237-242页

作者： Bahadir Kirilmaz Serkan Saygi Hasan Gungor ugur Onsel turk Emin Alioglu Serdar Akyuz Fatih Asgun Istemihan Tengiz Ertugrul Ercan Department of Cardiology Canakkale Onsekiz Mart University Medical Faculty Canakkale 17100 Turkey Department of Cardiology Odemis State Hospital Izmir 35750 Turkey Department of Cardiology Central Hospital Izmir 35580 Turkey Department of Cardiology Yunus Emre State Hospital Eskisehir 26190 Turkey Department of Cardiovascular Surgery Canakkale Onsekiz Mart University Medical Faculty Canakkale 17100 Turkey

Objectives Although development of new treatment modalities limited digoxin usage, digoxin intoxication is still an important issue which could be easily overlooked. In this report, we analyzed a case series definitively diagnosed as digoxin intoxication in the modern era. Methods We analyzed 71 patients hospitalized with digoxin intoxication confirmed by history, complaints, clinical and electrocardiograph （ECG） findings, and serum digoxin levels 〉 2.0 ng/mL, during a five year period. The demographic and clinical data, indications for digoxin use, digoxin dosage, concurrent medications, laboratory data, hospital monitoring, and ECG findings were obtained from all patients. Results Thirty-eight of 71 patients （53.5%） had symptoms of heart failure during admission or later. Sixty-four percent of patients were older than 75 years. The percentage of females was 67%. Atrial fibrillation, hypertension and gastrointestinal complaints were more frequent in the females （64% in females, 30% in males, P = 0.007; 81% in female, 52% in males, P = 0.01; 50% in female, 17.3% in males, P = 0.008, respectively）. The mortality rate during the hospital course was 7%. Conclusions This report demonstrated the reduced mortality rates in patients with digoxin intoxication over the study period. Gastrointestinal complaints are the most common symptoms in this population.

关键词： Digoxin intoxication Digitalis Heart failure Arrhythmia

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Last Interglacial-Glacial Cycle and an Attempt to Reconstruct Würmian Paleohumidity of the European Alps

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Journal of Mountain Science 2012年第3期9卷 322-330页

作者： Janez turk Karst Research Institute ZRC SAZU Postojna 6230 Slovenia

A lot of paleoenvironmental surveys have been carried out in the Alpine region to elucidate glacier extension during the Last Glacial or the Würmian (115 - 12 ka BP). However, the evidence of past glaciations differs greatly between Western and Eastern Alps, while contrast between Southern and Northern Alps is not evident. The main purpose of this paper is to interpret variability of humidity during the last interglacial-glacial cycle in the Alpine region, based on results of various surveys performed in the Alpine region. Results show that distribution of moisture throughout the Alps was most even during the Late Würmian, while precipitation was mainly concentrated in the (North)Western Alps during the Early Würmian and in the (North)Western and along all the Southern Alps during the Middle Würmian. The Eastern Alps were rather dry during both episodes. Such moisture distribution can be explained by paths of prevailing winds. Moisture distribution is directly linked with atmospheric and oceanic circulation.

关键词： Alps Wuermian glaciers Humidity Paleoclimate Atmospheric circulation

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Radiation associated coronary occlusion: Overlooked as trastuzumab-induced cardiomyopathy

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Open Journal of Internal Medicine 2013年第1期3卷 1-2页

作者： ugur.turk Veysel Yavuz Nurullah Cetin Department of Cardiology Celal Bayar University Manisa Turkey Department of Cardiology Central Hospital Izmir Turkey

Trastuzumab is an agent used for receptor-positive breast cancer. Up to a third of patients treated with trastuzumab might develop cardiomyopathy. Many patients with breast cancer have taken pre- or co-administration of mediastinal radiotherapy. Both of treatment modalities have toxic effects on myocardium. It may result with diagnostic confusion between radiation-induced CAD (riCAD) and trastuzumab cardiomyopathy in the case with dilated cardiomyopathy. TTE may offer clues of differential diagnosis.

关键词： Cardiomyopathy Trastuzumab Radiation

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Breast Cancer Diagnosis Using Feature Selection Approaches and Bayesian Optimization

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Computer Systems Science & Engineering 2023年第5期45卷 1017-1031页

作者： Erkan Akkur Fuat turk Osman Erogul Department of Biomedical Engineering TOBB University of Economics and TechnologyAnkara06560Turkey Deparment of Computer Engineering Karatekin UniversityÇankırı18100Turkey

Breast cancer seriously affects many *** breast cancer is detected at an early stage,it may be *** paper proposes a novel classification model based improved machine learning algorithms for diagnosis of breast cancer at its initial *** has been used by combining feature selection and Bayesian optimization approaches to build improved machine learning *** Vector Machine,K-Nearest Neighbor,Naive Bayes,Ensemble Learning and Decision Tree approaches were used as machine learning *** experiments were tested on two different datasets,which are Wisconsin Breast Cancer Dataset(WBCD)and Mammographic Breast Cancer Dataset(MBCD).Experiments were implemented to obtain the best classification ***,Least Absolute Shrinkage and Selection Operator(LASSO)and Sequential Forward Selection were used to determine the most relevant features,*** machine learning models were optimized with the help of Bayesian optimization approach to obtain optimal hyperparameter *** results showed the unified feature selection-hyperparameter optimization method improved the classification performance in all machine learning *** the various experiments,LASSO-BO-SVM showed the highest accuracy,precision,recall and F1-score for two datasets(97.95%,98.28%,98.28%,98.28%for MBCD and 98.95%,97.17%,100%,98.56%for MBCD),yielding outperforming results compared to recent studies.

关键词： Breast cancer machine learning Bayesian optimization feature selection

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The Bivariate Transmuted Family of Distributions:Theory and Applications

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Computer Systems Science & Engineering 2021年第1期36卷 131-144页

作者： Jumanah Ahmed Darwish Lutfiah Ismail Al turk Muhammad Qaiser Shahbaz Department of Statistics Faculty of ScienceKing Abdulaziz UniversityJeddahSaudi Arabia

The bivariate distributions are useful in simultaneous modeling of two random *** distributions provide a way to model *** bivariate families of distributions are not much widely explored and in this article a new family of bivariate distributions is *** new family will extend the univariate transmuted family of distributions and will be helpful in modeling complex joint *** properties of the new family of distributions are explored which include marginal and conditional distributions,conditional moments,product and ratio moments,bivariate reliability and bivariate hazard rate *** maximum likelihood estimation(MLE)for parameters of the family is also carried *** proposed bivariate family of distributions is studied for the Weibull baseline distributions giving rise to bivariate transmuted Weibull(BTW)*** new bivariate transmuted Weibull distribution is explored in *** properties of the new BTW distribution are studied which include the marginal and conditional distributions,product,ratio and conditional *** hazard rate function of the BTW distribution is *** estimation of the BTW distribution is also ***,real data application of the BTW distribution is *** is observed that the proposed BTW distribution is a suitable fit for the data used.

关键词： Transmuted Distributions (T-X)family of distributions bivariate transmuted family of distributions Weibull distribution maximum likelihood estimation

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