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Objective Rotavirus is a highly infectious and prevalent ribonucleic acid (RNA) virus that causes fatal gastroenteritis in children. Despite vitamin D deficiency is associated with susceptibility to infections, the relationship between ferritin and vitamin B12 levels is not known. This study aimed to investigate and compare the effect of rotavirus on micronutrient levels, atopy, and the frequency of allergic diseases in children with rotavirus. Methods There were rotavirus gastroenteritis (RVG) (N = 92) and non-rotavirus (control) groups (N = 95). Serum micronutrient levels (B12, ferritin, and 25-hydroxyvitamin D [25-OH-D3]) were checked during the first control after gastroenteritis healed. Patients were also examined for allergic diseases on an average of 17 (14–32) months following rotavirus infection. Serum immunoglobulin E (IgE), eosinophil count, and percentage were analyzed. Skin tests and respiratory function tests were also performed on patients with allergic disease and asthma symptoms. Results Mean ferritin, B12, and 25-OH-D3 levels were lower in the RVG group compared with the control group. Allergic diseases in the RVG group were more frequent than in the control group. The prevalence of the allergic disease in the RVG group was 16.3%, as opposed to 5.2% in the control group (p = 0.014). The IgE level was significantly higher in the RVG group. Conclusion Children with rotavirus infection should be followed closely in terms of allergic diseases and micronutrient deficiency. Furthermore, rotavirus infection should be prevented in the society and early treatment should be made available via tests detecting micronutrient deficiency.

Aim The prevalence of congenital cerebral palsy (CP) worldwide ranges from 0.15 to 0.4%. CP causes several gastrointestinal complications that inhibit normal eating behavior. This single-center observational study aimed to determine the tolerability and benefits of percutaneous endoscopic gastrostomy (PEG) in pediatric CP patients with malnutrition. Materials and Methods The study included 41 pediatric CP patients with malnutrition. All patient data were retrospectively obtained from Bakırköy Dr. Sadi Konuk Research and Training Hospital, Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Istanbul, Turkey. In addition to baseline measurements of weight, height, triceps skinfold thickness, 1,25-hydroxyvitamin D3, folate, iron, zinc, vitamin B12, hemoglobin, and mean corpuscular volume, data analyzed included follow-up measurements recorded at 3 and 6 months of PEG (standard polymeric enteral supplementation as 1.0 kcal mL–1). Results There was significant improvement in both height, weight, and triceps skinfold thickness in all patients at 3 and 6 months of PEG (p Conclusion PEG significantly improves malnutrition in pediatric CP patients and does not cause any major complications. Based on these findings, we think PEG is a beneficial and cost-effective intervention with a high rate of tolerability in pediatric CP patients with malnutrition.

Cancer patients often face malnutrition, which negatively affects their response to cancer treatment. This study aims to analyze the effects of the COVID-19 pandemic on nutritional status and anxiety in cancer patients with different types and stages of cancer. This is a cross-sectional cohort study that includes 1,252 patients with varying cancer types from 17 radiation oncology centers. The nutritional risk scores (NRS-2002) and coronavirus anxiety scale (CAS) scores of all patients were measured. NRS-2002 >= 3 and CAS >= 5 were accepted as values at risk. Of all patients, 15.3% had NRS-2002 >= 3. Breast cancer was the most prevalent cancer type (24.5%) with the lowest risk of nutrition (4.9%, p < 0.001). Nutritional risk was significantly higher in patients with gastrointestinal cancer, head and neck cancer, and lung cancer (p < 0.005) and in patients with stage IV disease (p < 0.001). High anxiety levels (CAS >= 5) were significantly related to voluntary avoidance and clinical postponement of hospital visits due to the pandemic (p < 0.001), while clinical postponement was particularly frequent among patients with NRS-2002 < 3 (p = 0.0021). Fear and anxiety in cancer patients with COVID-19 cause hesitations in visiting hospitals, leading to disrupted primary and nutritional treatments. Thus, nutritional monitoring and treatment monitoring of cancer patients are crucial during and after radiotherapy., Nutricia Turkey, Funding for data analysis and medical writing has been provided by an independent third party and sponsored by Nutricia Turkey.

Aim: Malnutrition is a serious and frequently encountered condition affecting more than 900 million individuals worldwide. Its relationship with negative clinical outcome, bad prognosis and susceptibility to diseases has been demonstrated in numerous studies alongside with the importance of early nutritional intervention. The aim of this study was to define the beneficial influence of a hypercaloric enteral supplement on body mass index (BMI) z-score as well as ferritin, vitamin B12 and vitamin D micronutrients.Methods: This study is a retrospective observational study. Records of patients who were diagnosed with malnutrition via a physician by having height and weight scores below -2 standard deviation were collected from Gaziosmanpaşa Training and Resource Hospital, Istanbul, Turkey. A comparative statistical analysis was performed on 205 pediatric malnutrition patients (ages 1 to 16) by gathering their BMI, ferritin, b12 and vitamin D at baseline with their measurements at 2 follow-up visits after the administration of hypercaloric (1.5kcal/mL) enteral supplement over 6 months.Results: There was a significant inverse correlation between BMI z-scores and the duration of enteral supplement administration, reflected by a 33.2% reduction of the mean BMI z-scores from -2.11 to -0.7 over 6 months (Z=-12.4, P, Amaç: Malnutrisyon, dünya çapında 900 milyondan fazla insanı etkileyen ciddi ve sık karşılaşılan bir durumdur. Malnutrisyon; olumsuz klinik sonuç, kötü prognoz ve hastalıklara yatkınlık ile yakından ilişkilidir, bu yüzden erken müdahalenin öneminin altını çizen çok sayıda çalışma yapılmıştır. Bu çalışmanın amacı, hiperkalorik enteral beslenme tedavisinin vücut kitle indeksi (VKİ) z-skorunun yanı sıra ferritin, B12 vitamini ve D vitamini mikro-besinlerinin üzerindeki yararlı etkilerini tanımlamaktır.Yöntemler: Bu çalışma geriye dönük gözlemsel bir çalışmadır. Doktor tarafından boy ve kilo ölçümleri -2 standart deviasyonun altında olarak malnütrisyon tanısı almış hastaların kayıtları, Türkiye’nin İstanbul ilinde bulunan Gaziosmanpaşa Eğitim ve Araştırma Hastanesinden toplanmıştır. Toplamda 205 pediatrik malnutrisyon hastasının (1-16 yaş) ilk ziyaretine ait VKİ, ferritin, B12 vitamini ve D vitamini kayıtları, hiperkalorik (1,5 kcal/mL) müdahaleye başlandıktan 6 ay sonrasına kadar yapılan 2 vizite ölçümleri ile karşılaştırılarak istatistiksel olarak analiz edilmiştir. Bulgular: VKİ z-skorları ile enteral beslenme tedavisi uygulama süresi arasında görsel ve istatistiksel olarak ek hastalık durumları farketmeksizin anlamlı bir ters korelasyon görülmüştür (Z=-12,4, P

Objective: To analyze the rates and types of ongoing urological surgery clinical trials (CTs) in the Middle East (ME) and worldwide. Materials and Methods: The number of urological surgery CTs was identified via the ClinicalTrials.gov database. Studies were further analyzed using different filters present in ClinicalTrials.gov. Results: Vast majority of urological surgery CTs are progressing in North America and Europe with 71.53\%. The ME accounts for only 6.19\%. In the ME, only Turkiye hosts studies of pediatric urological surgery. Additionally, the vast majority of adult studies were also belongs to Turkiye with 64\%. Further, the large portion of conducted CTs in the ME is phase 3 studies and studies with no phase indicated. Similarly, all urological surgery CTs conducted in Turkiye are in later phases or with no phase indicated. Moreover, industry resources are not directed upon these studies in the ME. Few countries use the advantages of industry resources for conducting urological surgery CTs. Conclusion: The ME should be considered as a fertile land for adopting urological surgery CTs due to high population despite low ongoing studies. The lack of industry support in the ME is another problem, which may improve via rendering the ME more attractive for sponsors by adopting new regulatory guidelines for some of the countries.

To determine efficacies of fiber-containing isocaloric and hypercaloric enteral supplements generally used to treat undernutrition.Retrospective cohort study.Department of Pediatrics, Sanliurfa Halfeti State Hospital, Turkey from September 2019 to June 2020.Pediatric patients aged 1-19 years were diagnosed solely with primary undernutrition, were given fiber containing isocaloric or hypercaloric enteral supplements for six months based on their energy requirements. A comparative analysis of anthropometrical data was made with each formula. The analysis included baseline weight, height, BMI of patients, and important micro-nutrient levels at three and six months after intervention.BMI, weight and height z-scores (p0.001) were improved over six months. There were no differences in BMI and weight scores except for a significant improvement in height between baseline and third month, which was observed in patients who received hypercaloric formula unlike isocolaric formula. There was a two-tailed improvement in blood biochemistry values of both groups.Both isocaloric and hypercaloric supplementation had positive effects on anthropometry and blood biochemistry. These results show that both formulae are highly beneficial for children with primary undernutrition. Key Words: Pediatrics, Body mass index, Therapeutics, Gastroenterology, Undernutrition.

Background: Trastuzumab prolonged the overall survival in patients with advanced gastric cancer with human epidermal growth factor receptor 2 (HER2) overexpression in combination with chemotherapy. In this phase II open-label prospective study, the tolerability and safety of trastuzumab with chemotherapy, and chemoradiotherapy for curatively resected patients with HER2-positive gastric carcinoma was investigated. Methods: The patients with HER2-positive gastric, or gastroesophageal junction adenocarcinoma, after gastrectomy plus D2 dissection, were included. They received 3 cycles of oxaliplatin (100 mg/m(2) intravenously day 1) plus capecitabine (850 mg/m(2) orally days 1 to 14), trastuzumab (8 mg/kg intravenously day 1 in cycle 1, 6 mg/kg thereafter) every 21 days, followed by chemoradiotherapy. Trastuzumab was given for 1 year. Results: Of the 212 patients screened, 35 were eligible, and 34 were treated. The median age was 56 years (minimum to maximum: 35 to 75 y), male patients constituted 73.5% (n=25), and 33 (97.1%) had gastric adenocarcinoma. R0 resection was performed in 30 (88.2%). The majority (26, 61.7%) were in stage III disease. Most of the adverse events were grade I/II, the most frequent grade III side effects were nausea (3, 8.8%), vomiting (3, 8.8%), diarrhea (2, 5.9%), and weight loss (n=2, 5.9%). Two patients died during the first 3 cycles of chemotherapy and chemoradiotherapy; 1 secondary to pulmonary thromboembolism, and the other due to cerebral ischemia. After excluding 2 with early progression and 1 consent withdrawal, of the remaining 31 patients, 28 (90.3%) were able to complete the chemotherapy and chemoradiotherapy part of the trial. After the 25 months follow-up period, 21 patients (61.8%) were alive. Overall survival at 12 and 24 months was 75.0% and 58.0%, while disease-free survival at 12 and 24 months was 65.7% and 55.0%, respectively. Conclusions: Trastuzumab in combination with capecitabine, oxaliplatin following chemoradiotherapy as the adjuvant therapy for gastric or gastroesophageal junction adenocarcinoma was considered as safe and tolerable. The frequency of HER2 overexpression in curatively resected patients is comparable to that in patients with metastatic disease, Roche Pharmaceuticals Inc., Turkey, The study was fully sponsored by Roche Pharmaceuticals Inc., Turkey.

In this study, we investigated the relationship of demographic variables with mental disorders generally encountered by the caregivers. The cohort includes 109 caregivers (38.53 ± 9.62 year-old) of pediatric cerebral palsy patients (1-18 year-old) taken more than 3 months of caregiving. Data were obtained via face-to-face interviews and a 13-questioned survey followed by a statistical correlation with Zarit-Caregiver-Burden-Scale (Zarit-CBS), Beck Anxiety Inventory (BAI), and Beck Depression Inventory-II scores (BDI-II). BAI scores were lower in the case of collaborative caregiving (

Aims Coeliac disease (CD) is an autoimmune disorder with a prevalence ≤2% that causes an immune reaction to gluten. Growth retardation (GR) generally accompanies CD due to gastrointestinal complications and should be treated as early as possible along with initiation of a gluten-free diet. The aim of this study was to determine the indicators of GR in patients with CD. Methods This single-centre retrospective study included paediatric outpatients with CD. All patients were diagnosed with CD via serological analysis and upper gastrointestinal endoscopy if necessary. Patient records were obtained from Adana City Training and Research Hospital. Patients that were diagnosed with GR accompanying CD were given oral nutritional supplements and followed-up every 3-6 months. Statistical relationships between demographics, and anthropometric measurements, duration of breastfeeding, gluten contact time, diet duration, presenting complaints and serological findings were evaluated. Results This study included 169 paediatric outpatients between ages 1 and 18. Longer symptom duration and shorter breastfeeding duration were significantly correlated with GR accompanying CD (P = 0.007 and P = 0.029, respectively). Vomiting was the only symptom that was correlated with the presence of GR (P = 0.010). Helicobacter pylori infection was not correlated with the presence of GR (P = 0.277). Conclusions GR should be treated as early as possible to reduce the severity of CD and a 6 months sole breastfeeding followed by solid foods accompanied by breastfeeding for 2 years is crucial for preventing GR. Moreover, vomiting as a presenting complaint in patients with CD might be indicative of the presence of GR.

Aim: Febrile seizure is the most prevalent (~5%) convulsion in children between 3 to 60 months of age and has been related to iron deficiency. Thus, when it is combined with malnutrition, it may increase negative outcomes. In this study, we present the effects of hypercaloric (1.5 kcal mL-1) nutritional intervention on undernourished children with a history of febrile convulsions prior to the age of 6. Methods: A cohort of 44 patients between ages 1-6 years with a history of a febrile seizure was included in the study. Hypercaloric nutritional intervention was applied to all patients. Baseline patient records containing anthropometrical and micronutrient measurements were compared with the 3rd month and the 6th month visits. All patient records were retrospectively obtained from Istanbul Research and Training Hospital, İstanbul, Turkey. Results: There were significant improvements in the z-scores of weight (P=0.002) and body mass index (P, Amaç: Ateşli nöbet en yaygın olarak 3 ila 60 aylık çocuklarda görülen (~% 5) ve demir eksikliği ile ilişkilendirilen bir konvülsiyondur. Bu nedenle, yetersiz beslenme ateşli nöbetin olumsuz sonuçlarını artırabilir. Bu çalışmada, 6 yaşından önce ateşli konvülsiyon öyküsü olan yetersiz beslenen çocuklarda hiperkalorik (1,5 kcal/mL) beslenme müdahalesinin etkilerini sunulmaktadır.Yöntemler: Çalışma kohortu ateşli nöbet öyküsü olan 1-6 yaş arası 44 hastadan oluşmakta olup, tüm hastalara hiperkalorik beslenme müdahalesi uygulanmıştır. Hastaların ilk başvuruları sırasında kaydedilen antropometrik değerler ve mikronütrient ölçümleri, 3. ay ve 6. ay vizitleri ile karşılaştırılmıştır. Tüm hasta kayıtları, İstanbul, Türkiye İstanbul Eğitim ve Araştırma Hastanesi'nden geriye dönük olarak alınmıştır.Bulgular: Müdahale sonrasında ağırlık (P=0,002) ve vücut kitle indeksi (P

BackgroundTrastuzumab prolonged the overall survival in patients with advanced gastric cancer with HER2 overexpression in combination with chemotherapy. In this phase II open-label prospective study, the tolerability and safety of trastuzumab with chemotherapy, and chemoradiotherapy for curatively resected patients with HER2 + gastric carcinoma was investigated. MethodsThe patients with HER2-positive gastric, or gastroesophageal junction adenocarcinoma, after gastrectomy plus D2 dissection were included. They received 3 cycles of oxaliplatin (100 mg/m2 IV day 1) plus capecitabine (850 mg/m2 PO days 1-14), trastuzumab (8 mg/kg IV day 1 in cycle 1, 6 mg/kg thereafter) every 21 days, followed by chemoradiotherapy. Trastuzumab was given for 1 year.ResultsOf the 212 patients screened, 35 were eligible, and 34 were treated. The median age was 56 years (Min-max: 35-75), male patients constituted 73.5% (n=25), and 33 (97.1%) had gastric adenocarcinoma. R0 resection was performed in 30 (88.2%). The majority (26, 61.7%) were in stage III disease. Most of the AEs were grade I/II, the most frequent grade III side effects were nausea (3, 8.8%), vomiting (3, 8.8%), diarrhoea (2, 5.9%) and weight loss (N=2, 5.9%). Two patients died during the first 3 cycles of chemotherapy and chemoradiotherapy; 1 secondary to pulmonary thrombo-embolism, and the other due to cerebral ischemia. After excluding 2 with early progression and 1 consent withdrawal, of the remaining 31 patients, 28 (90.3%) were able to complete the chemotherapy and chemoradiotherapy part of the trial. After the 25 months follow up period, 21 patients (61.8%) were alive. Overall survival at 12 and 24 months was 75.0% and 65.7%, while disease-free survival at 12 and 24 months was 65.7% and 55.0%, respectively.ConclusionsTrastuzumab in combination with capecitabine, oxaliplatin and radiotherapy as the adjuvant therapy for gastric or gastroesophageal junction adenocarcinoma was considered safe and tolerable. The frequency of HER2 overexpression in curatively resected patients is comparable to that in patients with metastatic disease.

INTRODUCTION[|]The problem of the connection between theoretical knowledge and practical knowledge leads to the inadequate training of physicians that results in inaccurate prescriptions. Case-based learning (CBL) is a universal paradigm often used within the medical curriculum, and it encourages self-assessment while enabling the learner to generate analytical and diagnostic solutions to a real scenario. However, its applications are limited and more research is needed to test its compatibility with students with different learning styles. [¤]METHODS[|]CBL-based pharmacology courses have been integrated into the 3rd year curriculum of Bahcesehir University Faculty of Medicine. A 15-question questionnaire was filled out by 67 students who were informed in advance to evaluate the CBL-based lessons. In addition, 37 of the participants were asked to complete an approved VARK questionnaire. In this way, traditional education systems were evaluated in terms of learning styles with CBL.[¤]RESULTS[|]According to the majority of the students participating in the study, CBL is a very useful learning method compared to traditional learning methods by making it easier to direct real life cases. In addition, no significant difference was found between the answers of students with various preferences, such as multi-modal or single-modal learning styles, in terms of the evaluation of CBL. [¤]DISCUSSION AND CONCLUSION[|]The students' survey results showed that the CBL-based curriculum was a useful motivating method. This study shows that CBL is a teaching system that can be adapted to each type of student regardless of the learning style and it is a learning method that can be applied in other fields besides Clinical Pharmacology.[¤]

demirdal, tuna/0000-0002-9046-5666 WOS: 000440301200015 PubMed: 30249562 Background/Aims: The hepatitis C virus (HCV) infection is important cause of chronic hepatitis. Liver biopsy is considered the gold standard for assessment of fibrosis but this procedure is an invasive procedure. We aimed to evaluate the diagnostic efficiency of non-invasive serum biomarkers, separately and in combinations, on liver fibrosis in treatment-naive chronic hepatitis C (CHC) patients. Materials and Methods: Two hundred and sixteen treatment-naive CHC patients were enrolled from 32 locations across Turkey in this open-labelled, non-interventional prospective observational study. FibroTest (R), aspartate aminotransferase-to-platelet ratio index(A-PRI), aspartate aminotransferase and alanine aminotransferase ratio (AAR), fibrosis index based on four factors (FIB-4), Age-platelet(AP) index and Forns index were measured and compared with Metavir scores got from liver biopsies. Results: Data from 182 patients with baseline liver biopsy were suitable for analysis. One hundred and twenty patients (65.9%) had F0-F1 fibrosis and 62 patients (34.1%) had F2-F4 fibrosis. APRI 0.732 area under the curve(AUC) indicated advanced fibrosis with 69% sensitivity and 77% specificity. FIB-4 0.732 AUC and FibroTest 0.715 AUC indicated advanced fibrosis with 69% and 78.4% sensitivity, and 75% and 71.4% specificity, respectively. The combined use of tests also led to an increase in AUC and specificity. Combinations of FibroTest with APRI and/or FIB-4, and FIB-4 with APRI were optimal for the evaluation of liver fibrosis. Conclusion: Fibrotest, FIB-4, APRI, AP index and Forns index exhibit good diagnostic performance for determining liver fibrosis in CHC patients, and the use of at least two tests together will increase their diagnostic value still further. Roche PharmaceuticalsRoche Holding [ML21920] This study was financially supported by Roche Pharmaceuticals (Protocol No: ML21920).

Aim: To assess pediatric clinical nutrition research by analyzing clinical studies in the Middle East (ME) and globally. Methods: Using ClinicalTrials.gov, the numbers of clinical studies in the ME and globally were analyzed. Results: The majority of clinical nutrition trials are in North America and Europe. The ME accounts for 4% of all nutrition trials. The majority of pediatric nutrition studies in the ME are in the later phases or are observational and/or epidemiological studies with a focus on poor nutrition or nutrition disorders. Industry funding in the ME is mostly by regional or local companies; few major global companies are involved. Conclusion: The ME is not well represented in clinical nutrition studies involving children. Effort should be expended to rectify this., Lay abstract Nutritional disorders have become an important worldwide disease burden during the last several decades. The development of effective therapies for nutritional disorders requires clinical trials in the affected populations. Our results showed that although the Middle East currently has the highest proportion of children worldwide, it is not well represented in clinical trials on nutritional studies in children. Furthermore, there is suboptimal funding from the multinational nutrition industry. This analysis indicates that there is a reasonable rationale for inclusion of the Middle East in nutritional clinical research in children, and that there is an untapped opportunity for the expansion of clinical research in this region.

Background: We investigated the efficacy, safety and tolerability of once-monthly administration of C.E.R.A. in erythropoiesis stimulating agents (ESAs) naive predialysis patients with CKD for anemia treatment, Study Design: Single arm, open label study., Methods: A total of 75 patients (mean (SD) age was 52.8 (16.4) years, 76.0% were female) were included in this study conducted between 12 August 2008 and 30 October 2009 in 9 centers across Turkey. The mean change in Hb concentration (g/dL) between baseline (week 0) and the efficacy evaluation period (EEP) was the primary efficacy parameter evaluated in three consecutive periods including a dose titration period (DTP; with initial 1.2 mu g/kg dose of C.E.R.A., subcutaneously, 28 weeks), EEP (8 weeks) and a long-term safety period (16 weeks)., Results: Our analysis revealed an improvement in Hb levels from baseline value of 9.4 (0.4) g/dL to time adjusted average level of 11.4 (0.7) g/dL in EEP in the per protocol (PP) population and from 9.3 (0.5) g/dL to 11.1 (1.0) g/dL in intent-to-treat (ITT) population. Mean (SD) change in Hb levels from baseline to EEP was 2.0 (0.7) g/dl in the PP population (primary endpoint) and 1.7 (1.1) g/dL in the ITT population. The percentage of patients whose Hb concentrations remained within the target range of 10.0-12.0 g/dL throughout the EEP was 43.9% (95% CI: 28.5-60.3%) in the PP population and 38.7% (95% CI: 27.6% to 50.6%) in the ITP population. A total of 206 adverse events (AE) were reported in 77.0% of patients with hypertension (20%) as the most frequent AE., Conclusion: Once-monthly subcutaneous C.E.R.A. administration is effective and safe in the treatment of anemia in pre-dialysis patients with CKD, who are not currently treated with ESAs.

26 Background: We evaluated the safety and tolerability of trastuzumab (T) in combination with oxaliplatin (O), capecitabine (C) and chemo-radiotherapy in the adjuvant setting in operated, HER-2 positive gastric or gastroesophageal junction adenocarcinoma patients. Methods: We have screened 212 and enrolled 34 patients who were curatively resected (R0, R1 with partial or total gastrectomy, with D2 lymph node dissection) and were HER2-positive (IHC 2+/FISH+ or IHC 3+). The primary objectives were safety and tolerability of the treatment combination and secondary objectives were disease-free and overall survival rates. Patients received T 8 mg/kg intravenously (iv) on Day 1 of cycle 1 and 6 mg/kg iv on day 1 of every following 3-weekly cycle for 1 year as 17 cycles, O 100 mg/m2 iv on Day 1 of cycles 1-3 and C 850 mg/m2 orally twice daily on days 1-14 of cycles 1-3 and 5 days per week during chemo-radiotherapy. Radiotherapy was given at a total dose of 45 Gy divided into 25 doses 5 treatment days per week for 5 weeks starting from the 1st day of cycle 4. Results: The median age was 57 years and 73.5% were male, 97.0% had an ECOG PS score ≤ 1,33, 97.0% had D2 lymph node resection. Staging was 3A or higher at the time of diagnosis in 76.4% of patients. Patients had high rate of tolerability to the combination regimen (90.3%) and successfully completed 3 cycles of O+C+T plus chemoradiotherapy followed by continuation with T, achieving the primary goal of the study by showing a better tolerability rate as compared to tolerability reported for INT0116 study (p = 0.0068). After 25 months of follow-up confirmed through a telephone visit, 59.8% patients were still alive and median overall survival was not yet reached. Twelve patients died secondary to disease progression. There were no deaths due to toxicity and 6 dose reductions overall (1 for T, 2 for O and 3 for C). T was stopped in one patient; C was temporarily interrupted 11 times (mostly during radiotherapy) and stopped in 1 patient. Conclusions: T in combination with C, O and radiotherapy in the adjuvant setting for gastric or gastroesophageal junction adenocarcinoma seems safe and tolerable. Clinical trial information: NCT01748773.

WOS: 000352013300004, PubMed ID: 25096257, Background: One of the most important factors in breast cancer (BC) mortality is treatment delay. The primary goal of this survey was to identify factors affecting the total delay time (TDT) in Turkish BC patients. Methods: A total of 1031 patients with BC were surveyed using a uniform questionnaire. The time between discovering the first symptom and signing up for the first medical visit (patient delay time; PDT) and the time between the first medical visit and the start of therapy (system delay time; SDT) were modelled separately with multilevel regression. Results: The mean PDT, SDT and TDT were 4.8, 10.5 and 13.8 weeks, respectively. In all, 42% of the patients had a TDT >12 weeks. Longer PDT was significantly correlated with disregarding symptoms and having age of between 30 and 39 years. Shorter PDT was characteristic of patients who: had stronger self-examination habits, received more support from family and friends and had at least secondary education. Predictors of longer SDT included disregard of symptoms, distrust in success of therapy and medical system and having PDT in excess of 4 weeks. Shorter SDT was linked to the age of >60 years. Patients who were diagnosed during a periodic check-up or opportunistic mammography displayed shorter SDT compared with those who had symptomatic BC and their first medical examination was by a surgeon. Conclusion: TDT in Turkey is long and remains a major problem. Delays can be reduced by increasing BC awareness, implementing organized population-based screening programmes and founding cancer centres., Roche Mustahzarlari San. A.S., Istanbul, Turkey, This study was supported by a grant from Roche Mustahzarlari San. A.S., Istanbul, Turkey.

Phospholipase C-gamma-2 (PLCgamma2) activation is a key signaling event for many cell functions. In order to delineate the pathways that lead to PLCgamma2 activation, we devised a quick method for obtaining sufficient PLCgamma2. We obtained the full-length cDNA for human PLCgamma2 and expressed it in E. coli using the expression vector pT5T. To enhance the protein expression, tandem AGG-AGG arginine codons at the amino acid positions 1204-1205 were replaced by CGG-CGG arginine codons. The protein expression was detected in a Western blot analysis by both anti-PLCgamma2 antibodies and the antibodies that are raised against the tripeptide epitope (Glu-Glu-Phe) tag that are genetically-engineered to its carboxyl terminal. Crude lysates that were prepared from bacteria that express PLCgamma2 were found to catalyze the hydrolysis of phosphatidylinositol 4,5 bisphosphate. Similar to previous reports on PLCgamma2 that is isolated from mammalian tissue, the recombinant enzyme was Ca2+ dependent with optimal activity at 1-10 microM Ca2+.

WOS: 000341713400010, PubMed ID: 24752566, This study aimed to report the practice of managing breast cancer with bone metastasis in Turkey and to determine the adherence to the British Association of Surgical Oncology (BASO) guidelines. This multicenter, cross-sectional epidemiological survey was conducted in 38 centers across Turkey. Data from 1,026 breast cancer patients with bone metastases (mean age 54.0 +/- 11.9 years) were analyzed. Over 30 % of patients had a diagnosis of metastatic breast cancer (stage IV) at the time of primary diagnosis. The imaging modalities used for diagnosing bone metastases were bone scintigraphy (57.8 %), radiography (22.8 %), and bone survey (4.4 %). Tumor markers were detected in 94.9 %, and markers of bone metabolism were measured in 90.4 % of patients. A total of 3.5 % of patients underwent surgery for bone metastasis, 26.4 % underwent palliative chemotherapy (most commonly docetaxel + capecitabine), and 56.5 % endured radiotherapy. Most patients (96 %) also received bisphosphonate. Radiography, bone scintigraphy, and CT were the main imaging tools used for postoperative follow-up of bone metastasis. Our results were > 95 % in line with the BASO guidelines for the management of bone metastasis, except that interventional procedures, such as biopsy, were applied less frequently in our survey. The diagnosis and management practices of breast cancer with bone metastasis in Turkey were generally compatible with international guidelines. However, the awareness and knowledge of physicians on the current guidelines should be increased, and equipment for the appropriate interventional procedures should be provided in every clinic to obtain optimal and standard management of bone metastases., Roche, Turkey, This study was financially supported by Roche, Turkey.

e12518 Background: Breast cancer (BC) is the most common cancer in women in Turkey. Studies investigating the epidemiology of BC in Turkey are retrospective case series providing limited informatio...

Background This study was conducted to evaluate the efficacy and safety of once-monthly continuous erythropoietin receptor activator (CERA) for maintenance of stable haemoglobin (Hb) levels in adult chronic renal anaemia patients on dialysis according to local clinical judgment in Turkey. Methods This was a prospective, open-label, single-arm, multi-centre study conducted in 20 centres in Turkey. After a 4-week screening period, eligible patients receiving conventional erythropoiesis-stimulating agents were converted to monthly intravenous CERA and entered a 16-week CERA dose-titration period (DTP) followed by an 8-week efficacy evaluation period (EEP) and a 4-week safety follow-up. The primary endpoint was the proportion of patients whose Hb concentration remained stable within ±1.0 g/dL of their reference Hb and within the range of 10.0-12.0 g/dL during the EEP. Results A total of 173 patients were screened, 132 entered the DTP and 84 completed the study. Thirty-nine patients [46.4% (95% confidence interval: 35.5-57.7%)] maintained stable target Hb concentrations. The mean change in time-adjusted average Hb concentration was 0.29 ± 1.08 g/dL between baseline and the EEP. The mean CERA monthly dose was 112.4 ± 76.78 µg during the EEP, and the CERA dose was adjusted in 39 patients (36.4%). Eleven patients (8.4%) reported 13 treatment-related adverse events, the most frequent adverse events being infections and infestations, gastrointestinal and vascular disorders. Conclusions Once-monthly CERA maintains stable Hb concentrations in chronic renal anaemia patients on dialysis in Turkey. The study results confirm the known efficacy and safety profile of CERA. © © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA.

Background/Aims: To evaluate the association between insulin resistance and hepatic fibrosis in patients with chronic hepatitis C.Materials and Methods: A total of 104 chronic hepatitis C patients were included in this non-interventional, open-label, observational, multicenter, cross-sectional study conducted at 20 gastroenterology clinics in Turkey. The primary end point was the correlation between stage of hepatic fibrosis and insulin resistance evaluated via the homeostasis model of assessment-insulin resistance index. Confounders of hepatic fibrosis and insulin resistance were the secondary end points.Results: The mean age of patients was 52.8 years; 65.4% were female. Type 2 diabetes was present in 6.8% and insulin resistance noted in 38.0% of patients. Further, 45.7% of the patients had mild (A0/A1) and the remaining had moderate/severe (A2/A3) hepatic necroinflammatory activity. Patient distribution according to Metavir fibrosis stage was as follows: F0/F1 (57.0%); F2 (6.5%); F3 (23.7%); and F4 (12.9%). A univariate analysis revealed significant positive correlations between Metavir fibrosis stage and insulin resistance (r=0.297; p=0.007). Logistic regression analysis showed that significant predictors of insulin resistance were high alanine transaminase levels (odds ratio, 0.97; 95% confidence interval, 0.944-0.997) and liver fibrosis stage (odds ratio, 0.114; 95% confidence interval, 0.021-0.607).Conclusion: Our findings revealed significant associations between insulin resistance and hepatic fibrosis. © 2014 by The Turkish Society of Gastroenterology.

WOS: 000329268000003, PubMed ID: 24247559, Objective: It was the aim of this study to evaluate maintenance therapy with bevacizumab + capecitabine following induction with bevacizumab + capecitabine + oxaliplatin (XELOX) versus bevacizumab + XELOX until progression as first-line therapy in metastatic colorectal cancer (mCRC). Methods: Patients received either bevacizumab (7.5 mg/kg) + XELOX (capecitabine 1,000 mg/m(2) twice daily on days 1-14 + oxaliplatin 130 mg/m2 on day 1 every 3 weeks) until disease progression (arm A) or the same doses of bevacizumab + XELOX for 6 cycles followed by bevacizumab + capecitabine until disease progression (arm B). The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), objective response rate (ORR) and safety. Results: One hundred and twenty-three patients were randomized. Treatment compliance was similar in both groups. Median PFS was significantly longer for arm B than for arm A (11.0 vs. 8.3 months; p = 0.002). There was no significant difference between the two arms for ORR (66.7 vs. 59.0%; p = 0.861) or median OS (23.8 vs. 20.2 months; p = 0.100). Tolerability was acceptable in both treatment arms; the most frequent grade 3/4 treatment-related adverse events (arm B vs. arm A) were fatigue (6.6 vs. 16.1%), diarrhoea (3.3 vs. 11.3%), anorexia (3.3 vs. 11.3%), and neuropathy (1.6 vs. 8.1%). Conclusions: Maintenance therapy with bevacizumab + capecitabine can be considered an appropriate option following induction bevacizunnab + XELOX in patients with mCRC instead of continuation of bevacizumab + XELOX. (C) 2013 S. Karger AG, Basel, F. Hoffmann-La RocheHoffmann-La Roche, Funding for the study and support for third-party writing assistance for the manuscript were provided by F. Hoffmann-La Roche.

PubMedID: 23114743 OBJECTIVE: To evaluate the association of insulin resistance (IR), viral load, and adipokine levels with liver histology in patients with chronic hepatitis C (CHC). PATIENTS AND METHODS: In this noninterventional, multicenter study carried out at 11 infectious diseases clinics in Turkey, 103 CHC patients [mean (SD) age: 50.2 (11.0) years, 60 (58.3%) women] planned to be treated by ribavirin and peginterferon-?2a were included. Data on hepatic fibrosis and steatosis, IR, viral load, and hepatitis C virus-RNA genotyping, adipokine, and cytokine levels were collected. RESULTS: The mean (SD) Knodell score was 8.1 (3.6); grade I steatosis was evident in 46 (44.7%) patients and IR was identified in 56 (54.9%). There was a significant positive correlation of the homeostasis model assessment-IR index with Knodell fibrosis (r=0.235; P=0.027) and hepatic steatosis (r=0.435; P

Lilly is developing fasidotril, a diester prodrug of the active metabolite fasidotrilat, for the potential treatment of hypertension and congestive heart failure (CHF). Phase II trials to investigate the potential of fasidotril for the treatment of hypertension and CHF had commenced by the late 1990s, and were ongoing in July 2003 in the US and Europe.

Otsuka Pharmaceuticals in collaboration with Bristol-Myers Squibb is developing aripiprazole, a dual dopamine autoreceptor agonist and postsynaptic D2 receptor antagonist, for the potential treatment of psychoses including schizophrenia [281327], [340364]. A regulatory filing for schizophrenia in the US was submitted at the end of 2001 [340364]. The compound entered phase III trials in Japan in 1995 [192966]. Although presynaptic dopamine autoreceptor agonists may be efficacious in the treatment of schizophrenia, they may also potentially increase the risk for exacerbation of psychosis through stimulation of postsynaptic dopaminergic receptors [245791], [350478], [350479]. However, earlier neuropharmacology studies have shown that aripiprazole can act as a presynaptic D2 agonist while displaying an antagonistic effect at the postsynaptic D2 receptors [281327], [337126], [350479], [424587], [424588]. In animal models, aripiprazole inhibits the apomorphine-induced stereotypy, without causing catalepsy [281327], [337126]. Moreover, in contrast to classical antipsychotics that produce disabling movement disorders, aripiprazole does not cause an upregulation of D2 receptors or an increase in expression of the c-fos mRNA in the striatum, in agreement with the low risk for extrapyramidal side effects (EPS) during aripiprazole treatment [245781], [262096], [350481], [350483]. Collectively, aripiprazole is an important atypical antipsychotic candidate with a favorable safety profile. Moreover, the mechanism of action of aripiprazole differentiates it from both typical and atypical antipsychotics and hence, may provide important leads for pharmacotherapy of schizophrenia and other psychotic disorders. In January 2000, Lehman Brothers predicted peak sales of aripiprazole could reach US $500 million [357788]. In February 2001, Credit Suisse First Boston predicted sales of US $403 million in 2005 [399484].

49th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) -- MAY 31-JUN 04, 2013 -- Chicago, IL, WOS: 000335419604401, …, Amer Soc Clin Oncol

We examined whether a proposed spatial proximity between Asp114(2.50) and Asn332(7.49) affected the functional properties of the μ opioid receptor. The D114(2.50)N mutant had reduced binding affinities for morphine, DAMGO and CTAP, but not for naloxone and [3H]diprenorphine; this mutation also abolished agonist-induced increase in [35S]GTPγS binding. The N332(7.49)D mutation eliminated detectable binding of either [3H]diprenorphine or [3H]DAMGO. The combined D114(2.50)N-N332(7.49)D mutation restored high affinity binding for [3H]diprenorphine, CTAP and naloxone, and restored partially the binding affinities, potencies and efficacies of morphine and DAMGO. Thus, reciprocal mutations of Asp114(2.50) and Asn332(7.49) compensate for the detrimental effects of the single mutations, indicating that the residues are adjacent in space and that their chemical functionalities are important for ligand binding and receptor activation.