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Öğe Comprehensive tumor molecular profle analysis in clinical practice(PMC, 2021) Ozdogan, Mustafa; Papadopoulou, Eirini; Tsoulos, Nikolaos; Tsantikidi, Aikaterini; Mariatou, Vasiliki?Metaxa; Cakir, OkanBackground: Tumor molecular profle analysis by Next Generation Sequencing technology is currently widely applied in clinical practice and has enabled the detection of predictive biomarkers of response to targeted treatment. In parallel with targeted therapies, immunotherapies are also evolving, revolutionizing cancer therapy, with Pro? grammed Death-ligand 1 (PD-L1), Microsatellite instability (MSI), and Tumor Mutational Burden (TMB) analysis being the biomarkers employed most commonly. Methods: In the present study, tumor molecular profle analysis was performed using a 161 gene NGS panel, containing the majority of clinically signifcant genes for cancer treatment selection. A variety of tumor types have been analyzed, including aggressive and hard to treat cancers such as pancreatic cancer. Besides, the clinical utility of immunotherapy biomarkers (TMB, MSI, PD-L1), was also studied. Results: Molecular profle analysis was conducted in 610 cancer patients, while in 393 of them a at least one bio? marker for immunotherapy response was requested. An actionable alteration was detected in 77.87% of the patients. 54.75% of them received information related to on-label or of-label treatment (Tiers 1A.1, 1A.2, 2B, and 2C.1) and 21.31% received a variant that could be used for clinical trial inclusion. The addition to immunotherapy biomarker to targeted biomarkers’ analysis in 191 cases increased the number of patients with an on-label treatment recommenda? tion by 22.92%, while an option for on-label or of-label treatment was provided in 71.35% of the cases. Conclusions: Tumor molecular profle analysis using NGS is a frst-tier method for a variety of tumor types and provides important information for decision making in the treatment of cancer patients. Importantly, simultaneous analysis for targeted therapy and immunotherapy biomarkers could lead to better tumor characterization and ofer actionable information in the majority of patients. Furthermore, our data suggest that one in two patients may be eli? gible for on-label ICI treatment based on biomarker analysis. However, appropriate interpretation of results from such analysis is essential for implementation in clinical practice and accurate refnement of treatment strategy.Öğe Prevalence of human pseudocholinesterase (butyrylcholinesterase) deficiency in central Anatolian people: a cross-sectional study(DergiPark, 2020) Gencer, Muzaffer; Göçmen, Ayşe YeşimAim: Human pseudocholinesterase (PChE) is an enzyme responsible for hydrolysis of the muscle relaxant drugs like succinylcholine and mivacurium. PChE deficiency, which may lead to prolonged apnea, may occur due to hereditary or acquired causes. In our study, we aimed to investigate the prevalence of human pseudocholinesterase (PChE) enzyme deficiency around the central Anatolia region and present our results in light of the literature. Methods: This cross-sectional study included 936 patients (age 18-70 years) who underwent any elective surgery under general anesthesia between August 2015 and September 2019. Human PChE level, plasma PChE activity, the human PChE activity/albumin, serum liver and kidney function tests were analyzed from blood samples. Human PChE enzyme deficiency and possible association of the PChE deficiency with other values was also investigated. The normal value of PChE was considered to range from 4650 U/L to 10,440 U/L. Results: PChE activity was decreased in 19 (1.9%) of the 936 patients (442 males and 494 females). There was no statistically significant difference between the PChE levels in terms of gender (P=0.236). The mean human PChE activity of all patients was 7.490 (0.980). The PChE activity of 22 (2.35%) and 58 patients (6.4%) were below 5.000 U/ml and 6.000 U/, respectively. A statistically significant difference was found between serum urea, creatinine and human PChE levels (P=0.034, P=0.236, respectively). However, PChE deficiency had no correlation with liver function tests such as AST and ALT (P=0.432, P=0.022, respectively). Conclusion: PChE deficiency can be observed in preoperatively evaluated patients and may cause serious life-threatening conditions, including respiratory failure and prolonged apnea.Öğe A study comparing the effect of premedication with intravenous midazolam or dexmedetomidine on ketamine-fentanyl sedoanalgesia in burn patients: a randomized clinical trial(Elsevier Ltd, 2021) Gencer, Muzaffer; Sezen, Ozlem K.Introduction: Dressing changes and wound care-debridement procedures often cause fear and anxiety in burn patients, as these processes are quite painful. In order to determine the best method for alleviating pain during these procedures, the current study compared the efficacy and safety of intravenous dexmedetomidine and midazolam for premedication prior to these painful burn care procedures. Methods: This comparative and randomized study included patients who had a burn size of 1563%, were aged 1870 years, were diagnosed with the American Society of Anesthesiologists physical status (ASA I–II), and who underwent painful burn care procedures. Patients were intravenously administered either 1 mcg/kg dexmedetomidine (Group 1) or 0.03 mg/kg midazolam (Group 2) prior to the burn care procedure. Recorded at predetermined time points for each patient were heart rhythm (HR), mean arterial pressure (MAP), peripheral oxygen saturation (SpO2), standard bispectral index (BIS), and Ramsay Sedation Scale (RSS). Results: In the dexmedetomidine group, HR and MAP measurements of patients ??at the 3rd, 5th, and 10th mins during sedation were significantly lower than the baseline values (p < 0.05). A significant decrease in SpO2 was observed in both groups at the 10th min during sedation, but the decline was higher in the midazolam group (p < 0.05). BIS measurements of the patients in both groups were significantly lower at 10 min. during sedation and at 15th and 60th mins during the procedure (p < 0.05). However, there was no significant difference between the group (p > 0.05). The RSS scales of both groups in during the sedation were higher in the 3rd, 5th and 10th mins than the baseline values (p < 0.05), but there was no significant difference between the groups (p > 0.05). The RSS scales of groups in during the burn procedure were significantly higher at 15 th min than the 0 th values, while the RSS scales of both groups were significantly lower in the 45th and 60th mins (p < 0.05). Conclusion: Results of this study indicate that dexmedetomidine causes hemodynamic alterations while midazolam causes respiratory depression. However, these effects are not severe, and we conclude that both agents are safe and effective to ensure sedation prior to painful burn-care procedures.Öğe The relationship between the level of ?-opioid receptor (?ORs) and postoperative analgesic use in patients undergoing septoplasty: a prospective randomized controlled trial(NLM (Medline), 2020) Gencer, Muzaffer; Gocmen, Ayse YesimBACKGROUND: In this study, the ?-Opioid receptor activity was assessed pre-operatively for its association with postoperative pain level and second analgesic requirement in patients undergoing septoplasty. METHODS: In our prospective study, 120 adult patients underwent septoplasty from June 2015 to January 2019 were randomly divided into 2 pre-operative groups. The first group (n?=?60) was patients given tramadol (1-2?mg/kg) for post-operative analgesia, and the second group (control group) (n?=?60) was initially prescribed only fentanyl (1??g/ kg-i.v.) in the induction. Acetaminophen with codeine analgesic 325/30?mg (p.o.) was used as an rescue painkiller in the post-operative period. The ?-Opioid receptor activity was investigated in pre-operative blood samples and compared to post-operative pain level and time required for second round of analgesic administration. The visual analogue score (VAS) was used to evaluate the post-operative pain degree (0 no pain; 10 worst pain). The patients' post-operative VAS scores were evaluated upon arrival to recovery room, and at the 1st, 3rd, 7th, 10th, and 24th hour post-operative period. RESULTS: Demographic data and peri-operative variables were similar in both study group (p?Öğe Changes in various hormone levels in The rabbit traumatic facial nerve injury model(Deomed Publ, Istanbul, 2018) Kapusuz Gencer, Zeliha; Özkiriş, Mahmut; Gencer, Muzaffer; Göçmen, Ayşe Yeşim; Dağlıoğlu, Yusuf KenanObjectives: We aimed to look into potential associations between specific biomarkers and trauma to Cranial Nerve VII (CNVII) in a rabbit model, focusing on whether endocrine studies have potential as biomarkers in this context. Methods: 30 adult New Zealand rabbits with intact facial muscles were used for the research. Each animal underwent identical surgery by the same surgeon. The facial nerve divisions were exposed by incising below the level of the mandible. After dissection of the skin and subcutaneous layers, the buccal division of CNVII was located with the nerve stimulator and microscopic dissection and a section of nerve 10mm long was excised in each case from the buccal branch of CNVII. Blood samples were drawn 8 weeks and 12 weeks after nerve injury had been surgically induced. The samples from day 1, week 4 and week 8 were tested for the following levels: Testosterone, oestrogen, progesterone, free T3 and T4, Cancer antigen 19-9 (Ca19-9), folate, TPSA, FPSA, FSH, LH, CA15.3, CAE, AFP and prolactin. Results: The levels of free T3 and T4 as well as testosterone, were down at 4th week, but at 8 weeks each had increased. Ca19-9 levels were also above the baseline. At 4 weeks, whilst oestrogen had markedly risen, progesterone had fallen. The statistical significance of the change in levels of free T3 and T4, testosterone, oestrogen, progesterone and FPSA was evaluated. For the group of animals with induced paralysis, the association between the lesion and testosterone, oestrogen, progesterone, free T3 and T4, Ca19-9, and folate levels were strong and at the level of statistical significance. Conclusion: There were statistically significant alterations in the serum levels of free T3 and T4, testosterone, oestrogen, progesterone and FPSA at the 4 and 8 week intervals post surgically-induced CNVII injury. It is likely that rabbit pathophysiology resembles human pathophysiology in nervous injury, hence these six biomarkers may be of value in managing trauma or idiopathic degeneration of CNVII in humans. The authors hope this study will pave the way for future research in this area.Öğe Objective response rate assessment in oncology: current situation and future expectations(Baishideng Publishing Group Inc, 2020) Aykan, Nuri Faruk; Özatlı, TahsinThe tumor objective response rate (ORR) is an important parameter to demonstrate the efficacy of a treatment in oncology. The ORR is valuable for clinical decision making in routine practice and a significant end-point for reporting the results of clinical trials. World Health Organization and Response Evaluation Criteria in Solid Tumors (RECIST) are anatomic response criteria developed mainly for cytotoxic chemotherapy. These criteria are based on the visual assessment of tumor size in morphological images provided by computed tomography (CT) or magnetic resonance imaging. Anatomic response criteria may not be optimal for biologic agents, some disease sites, and some regional therapies. Consequently, modifications of RECIST, Choi criteria and Morphologic response criteria were developed based on the concept of the evaluation of viable tumors. Despite its limitations, RECIST v1.1 is validated in prospective studies, is widely accepted by regulatory agencies and has recently shown good performance for targeted cancer agents. Finally, some alternatives of RECIST were developed as immune-specific response criteria for checkpoint inhibitors. Immune RECIST criteria are based essentially on defining true progressive disease after a confirmatory imaging. Some graphical methods may be useful to show longitudinal change in the tumor burden over time. Tumor tissue is a tridimensional heterogenous mass, and tumor shrinkage is not always symmetrical; thus, metabolic response assessments using positron emission tomography (PET) or PET/CT may reflect the viability of cancer cells or functional changes evolving after anticancer treatments. The metabolic response can show the benefit of a treatment earlier than anatomic shrinkage, possibly preventing delays in drug approval. Computer-assisted automated volumetric assessments, quantitative multimodality imaging in radiology, new tracers in nuclear medicine and finally artificial intelligence have great potential in future evaluations.
