High frequency of transient congenital hypothyroidism among infants referred for suspected congenital hypothyroidism from the Turkish National screening program: thyroxine dose may guide the prediction of transients.

PURPOSE: We aimed to determine the frequency of transient congenital hypothyroidism (TCH) in 17 participating centers in Türkiye, evaluate the etiological distribution in permanent congenital hypothyroidism (PCH) cases, and investigate the role of laboratory and clinical findings in predicting TCH. METHODS: This retrospective observational multicenter study included patients from 17 pediatric endocrinology centers identified by "National Newborn Screening Program" (NNSP) who were born in 2015 and followed for 6 years. Demographic, clinical, and laboratory information of the cases were compiled through the database http://cedd.saglik-network.org (CEDD-NET). RESULTS: Of the 239 cases initially treated for CH, 128 (53.6%) were determined as transient in whom a trial of levothyroxine (LT4) withdrawal was performed at a median age of 36 (34-38) months. Among the patients with PCH (n = 111), thyroid dysgenesis was diagnosed in 39.6% (n = 44). The predictive factors for TCH were: LT4 dose at the withdrawal of treatment, and initial newborn blood screening (NBS)-TSH level. Based on the receiver operating characteristic (ROC) curve analysis to predict optimal cut-offs for TCH predictors, LT4 dose < 2.0 µg/kg/day at treatment discontinuation was predictive for TCH and was associated with 94.5% specificity and 55.7% sensitivity, with an area under the curve (AUC) of 0.802. The initial NBS-TSH level value < 45 µIU/mL was predictive for TCH with 93.1% specificity and 45.5% sensitivity, with an AUC of 0.641. In patients with eutopic thyroid gland only LT4 dose < 1.1 µg/kg/day at withdrawal time was predictive for TCH with 84.7% sensitivity and 40.4% specificity, with an AUC of 0.750. CONCLUSION: According to our national follow-up data, the frequency of TCH was 53.6%. We determined the LT4 dose < 2.0 µg/kg/day at discontinuation of treatment and the initial NBS-TSH level < 45 µIU/mL as the best cut-off limits to predict TCH.

Aromatase inhibitors: a useful additional therapeutic option for slowing down advanced bone age in boys with growth hormone deficiency.

INTRODUCTION: Aromatase inhibitors (AIs) have been used to slow down estrogen-dependent skeletal maturation in pubertal boys with short stature. In the literature, few data evaluate the effectiveness and safety of AIs in boys with growth hormone deficiency (GHD). This study aimed to evaluate the auxologic effects and short-term laboratory profiles of combined AI and rhGH therapy for 1 year in adolescent males with GHD. SUBJECTS AND METHODS: Male subjects between the ages of 10 and 16 with GHD from two different centers were included in the study. Patients were divided into two groups: (i) those who only used recombinant human growth hormone (rhGH) therapy (Group I; G-I) and (ii) those who also used AI therapy (anastrozole or letrozole) along with rhGH (Group II; G-II). RESULTS: Forty-one patients (G-I, 46%; G-II, 54%) were included in the study. All the subjects had isolated GHD. At the beginning of the treatment, the chronological ages (CAs) of the patients in the G-I and G-II groups were 11.8 (10.9-13.7) and 12.8 (12.0-14.3) years, respectively. The ratios of bone age (BA)/CA for the two groups were 0.8 (0.8-0.9) and 1.0 (0.9-1.1), respectively (p < 0.001). After the treatment, the height standard deviation (SD) scores and predicted adult height (PAH) significantly increased from baseline in all subjects in the G-I and G-II groups (p < 0.001; p < 0.001, respectively). There was no significant change in the ratio of BA/CA post-therapy in the G-I group (p = 0.1), while there was a significant decrease in the G-II group (p < 0.001). The growth velocities of the patients in the G-I and G-II groups were 9.1 (7.4-10.1) cm/year [1.5 (0.8-5.0) SD score] and 8.7 (7.5-9.9) cm/year [1.1 (0.3-3.1) SD score], respectively (p = 0.6). While post-therapy serum testosterone concentrations were seen to increase in the G-II group, none of the patients exhibited hematocrit above 50 percent, and the fasting glucose concentrations were normal. CONCLUSIONS: When used in addition to rhGH therapy in boys with GHD and advanced BA, AIs were observed to slow down the tempo of BA maturation after 1 year, compared to those who received rhGH treatment alone. AI therapy was found to be safe during the 1-year observation period and thus could be considered for preserving growth potential in these patients.

Long-term follow-up results and treatment outcomes of children and adults with resistance to thyroid hormone alpha.

PURPOSE: Resistance to thyroid hormone alpha (RTHα) is a rare entity and has no specific treatment. To date, mostly levothyroxine has been used, but there is a lack of knowledge about the long-term outcomes of this treatment. We aimed to evaluate the long-term follow-up results and treatment outcomes of children and their parents diagnosed with RTHα. METHODS: Four children [the median (minimum-maximum) age at diagnosis, 4.5 (1.4-9.5) years] and three adults [age at diagnosis, 31.7 (28.0-35.3) years] from two families were included in the study, who had RTHα and followed up between 2014 and 2021. RESULTS: The median duration of treatment was 6.7 (5.9-8.0) years, and the levothyroxine dose at the final visit was 1.4 (1.2-2.2) and 1.9 (1.2-2.4) mcg/kg/day for adults and pediatric patients, respectively. Treatment ameliorated constipation in all patients with this complaint (n = 5). Normal mental functions were achieved and IQ scores improved in most children except one (age at diagnosis, 9.5 years). At the final visit, creatine kinase levels relative to the reference upper limit were significantly lower compared to the pre-treatment ratios [0.9 (0.2-1.3) vs. 1.3 (0.5-1.6), p = 0.028]. Anemia was present in five patients at diagnosis, which resolved in one adult patient but occurred in one child despite treatment (p = 0.999). A minimal pericardial effusion persisted in one pediatric patient. CONCLUSIONS: We demonstrated that constipation was ameliorated, neuromotor development of some children was improved, and creatine kinase levels were diminished with levothyroxine treatment in patients with RTHα, while some features including anemia did not resolve.

What is the effect of subepithelial lesions of the esophagus on esophageal motility?

OBJECTIVE: Esophageal motility is regulated both by coordinated stimulation and inhibition of the circular and longitudinal muscle layers of the esophagus. Although there are many diseases known to have an effect on esophageal motility, the effect of subepithelial lesions (SELs) of the esophagus on esophageal motility, which is often detected incidentally, remains still unclear. The aim of this study is to reveal the effect of SELs of the esophagus on esophageal motility evaluating it by high-resolution manometry (HRM). PATIENTS AND METHODS: A total of 32 patients with SELs in the esophagus and 12 healthy individuals were included. All patients and controls included in the study underwent HRM using a Unisensor UniTip High Resolution catheter (Laborie, Amsterdam, Netherlands) and endosonographic examination. RESULTS: The mean age was 52.60±15.56 years (range: 23-79) and the average body mass index (BMI) was 26.63±4.71 kg/m2. Gender, height, weight, and BMI measurements, smoking status, alcohol use, and DM status did not statistically differ significantly between the groups (p>0.05). Of 32 patients with SELs, 65.6% (n=21) had lesions originating in the muscularis propria, while 34.4% had lesions originating in the submucosa. The rate of abnormal motility both in the supine and in upright positions of patients with SELs was found to be significantly higher than in the control group (p=0.001, p<0.01, respectively). In patients with SELs, the incidence of infective motility was higher than the normal group (p=0.001, p<0.01, respectively). As the size of the lesion increases (>2 cm), the probability of abnormal HRM results increased. CONCLUSIONS: SELs of the esophagus have pathological effects on esophageal motility, mainly ineffective esophageal motility disorder.

Is anterior segment OCT superior to slit-lamp biomicroscopic examination for Kayser Flesicher ring in Wilson's disease?

OBJECTIVE: Detection of the Kayser-Fleischer (KF) ring in the diagnostic scoring and treatment follow-up of Wilson's Disease (WD) is important. Slit lamp (SL) biomicroscopic examination has traditionally been used in the evaluation of the KF ring. The role of Anterior Segment Optical Coherence Tomography (AS-OCT), which is used in various corneal diseases, in the detection of KF rings has attracted attention in recent years. In our study, we tried to demonstrate the effectiveness of AS-OCT in detecting the KF ring by comparing it with SL biomicroscopic examination. PATIENTS AND METHODS: 64 of 356 patients followed in our outpatient clinic due to WD were included in the study in the order of their admission to the outpatient clinic. The KF ring was evaluated in both eyes by SL-biomicroscopic examination and AS-OCT. Ophthalmic examination, and findings were performed by the same physician. RESULTS: Age range was 18-67 years, mean 33.06±10.83 years, gender was 39.1% (n: 25) female. At the time of diagnosis, the mean age was 19.48 ± 9.36 years, range was minimum 5 years and maximum 51 years. Clinical presentation was mixed type involvement n: 18 (28.1%), hepatic involvement n: 32 (50%), neurological involvement n: 14 (21.9%). The follow-up period was 2-257 months (74.6±76.16). The presence of KF ring was evaluated together with both AS-OCT and slit-lamp examination, the presence of KF could be detected in both AS-OCT and SL biomicroscopic examination in 10 patients (15.6%), in 12 (18.8%) of the cases KF ring is positive in AS-OCT but was negative in Slit-lamp biomicroscopic examination, in 65.6 (n: 42) of the cases OCT and slit-lamp biomicroscopic examination results were negative. CONCLUSIONS: The sensitivity of AS-OCT in detecting the KF ring was higher than the slit-lamp biomicroscopic examination. AS-OCT can detect early stage of KF rings in Wilson's Disease patients, so that diagnosis and treatment accuracy can be evaluated effectively.

Is belching increasing after bariatric bypass surgery in the long term period?

BACKGROUND AND AIMS: Gastric bypass surgery effectively treats obesity; however, its association with belching, which occurs in other bariatric surgeries, remains unclear. Hence, we aimed to evaluate belching occurrence after gastric bypass surgery. METHODS: We enrolled 12 healthy volunteers and 17 patients (12 and 5 underwent Roux-en-Y gastric bypass and mini-gastric bypass surgeries 24 (18-54) months prior, respectively). Gastrointestinal symptoms were assessed. Gastroscopy was performed, followed by the 24-hour pH-impedance analysis. RESULTS: Age and sex were not statistically different between the two groups (P > 0.05). Patients had a significantly higher mean DeMeester score than the healthy controls (9.11 ± 19.40 vs. 6.04 ± 5.60, P = 0.048), but the pathologic acid reflux (DeMeester score > 14) rate was similar in both groups (11.8% vs. 8.3%). Regarding the impedance, symptom-association probability was positive in 11.8% of patients. The patients also had higher alkaline reflux rates (6% vs. 0%); additionally, 50% of them experienced belching based on the questionnaire, and 25% had esophagitis based on gastroscopy. Furthermore, patients had a significantly higher number of gas reflux (123.24 ± 80 vs. 37.2 ± 21.5, P = 0.001) and supragastric/ gastric belches (182 ± 64/228 ± 66.69 vs. 25.08 ± 15.20/12.17 ± 17.65, P = 0.001). Supragastric belching was more frequent than gastric belching in the controls, whereas gastric belching was more frequent in the patients. CONCLUSION: Belching increases after gastric bypass surgery in a long-term period. Gastric belching was more frequent than supragastric belching in these patients.

Assessment of prognostic and diagnostic value of some biomarkers in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is an increasing problem worldwide. Determining a prognosis is important for the management of HCC. AIM: We aimed to investigate the impact of interleukin (IL)-29, galectin-3, leptin, fibronectin and protease-activated receptor-1 on the prognosis and diagnosis of patients with HCC. MATERIALS AND METHODS: 60 HCC patients (75% male) and 20 healthy volunteers (70% male) were enrolled in this prospective study. Serum samples were obtained during the first admission before any adjuvant or metastatic treatments were administered. Serum biomarkers were determined using ELISA kits. RESULTS: All patients had cirrhosis, and the Child - Pugh stages were as follows: 61.5% Child - Pugh A, 35.9% Child - Pugh B and 2.6% Child - Pugh C (61.7% hepatitis B virus, 11.7% hepatitis C virus, 6.7% hepatitis B virus + hepatitis C virus, 11.7% alcoholic and 8.3% cryptogenic). Fifty-three percent of the HCC patients died within a median of 7.5 months. The mean serum level of IL-29 in patients with HCC was higher than that in the control group (32.55 pg/ml vs 11.46 pg/ml, p < 0.015). Galectin-3 levels were significantly higher in the HCC group (6.7 ng/ml vs 1.38 ng/ml, p < 0.001). Fibronectin levels were higher in the control group than in the HCC group (260 635 ng/ml vs 257 353 ng/ml). However, the mean protease-activated receptor-1 and leptin levels were similar between the two groups (p > 0.05). The biomarkers were divided into two groups according to their median level. In the log rank analysis, biomarkers had no effect on survival (p > 0.05). CONCLUSIONS: IL-29 and galectin-3 levels were significantly higher in HCC patients. Although IL-29 and galectin-3 can be used as diagnostic markers for HCC, they had no prognostic value in HCC patients.

Aortic stiffness in patients with wilson's disease.

AIM: Wilson's disease (WD) presents with different phenotypes. Neurologic and liver involvement in WD are well documented. Few reports demonstrated cardiac and vascular involvement. Several studies showed an association between serum copper levels and atherosclerosis. Although WD is the prototype disease of copper metabolism, atherosclerosis has not been studied yet. The aim of this study is to assess aortic stiffness in WD. MATERIALS AND METHODS: Aortic pulse wave velocity (PWV), augmentation pressure (AP), augmentation index (AIx), central aortic systolic, diastolic, mean, and pulse pressures were measured using SphygmoCor (AtCor Medical) device in 32 patients with WD and 24 healthy controls. RESULTS: Patients with WD and healthy controls were similar in terms of age sex, body mass index (BMI), and liver and kiney functions. However, patients with WD were anemic and thrombocytopenic. Echocardiographic parameters including left ventricular, atrial dimensions, and systolic and diastolic functions were similar between two groups. Patients with WD and healthy controls were compared. Baseline characteristics including age, sex, and BMI did not differ between groups. Central aortic systolic, diastolic, mean, and pulse pressures were similar between the groups. AP, AIx, and PWV did not differ between groups as well. CONCLUSION: Aortic stiffness in WD was similar in healthy controls.

Characteristics of Turkish children with Type 2 diabetes at onset: a multicentre, cross-sectional study.

AIMS: To describe the baseline clinical and laboratory findings and treatment modalities of 367 children and adolescents diagnosed with Type 2 diabetes in various paediatric endocrinology centres in Turkey. METHODS: A standard questionnaire regarding clinical and laboratory characteristics at onset was uploaded to an online national database system. Data for 367 children (aged 6-18 years) newly diagnosed with Type 2 diabetes at 37 different paediatric endocrinology centres were analysed. RESULTS: After exclusion of the children with a BMI Z-score < 1 SD, those with genetic syndromes associated with Type 2 diabetes, and those whose C-peptide and/or insulin levels were not available, 227 cases were included in the study. Mean age was 13.8 ± 2.2 (range 6.5-17.8) years, with female preponderance (68%). Family history of Type 2 diabetes was positive in 86% of the children. The mean BMI was 31.3 ± 6.5 kg/m2 (range 18.7-61) and BMI Z-score was 2.4 ± 0.8 (range 1-5). More than half (57%) of the children were identified by an opportunistic diabetes screening due to existing risk markers without typical symptoms of diabetes. Only 13% (n = 29) were treated solely by lifestyle modification, while 40.5% (n = 92) were treated with metformin, 13% (n = 30) were treated with insulin, and 33.5% (n = 76) were treated with a combination of insulin and metformin initially. Mean HbA1C levels of the insulin and combination of insulin and metformin groups were 98 (11.1%) and 102 mmol/mol (11.5%), respectively, and also were significantly higher than the lifestyle modification only and metformin groups mean HbA1C levels (70(8.6%) and 67 mmol/mol (8.3%), respectively). CONCLUSIONS: An opportunistic screening of children who are at high risk of Type 2 diabetes is essential, as our data showed that > 50% of the children were asymptomatic at diagnosis. The other important result of our study was the high rate of exclusion from the initial registration (38%), suggesting that accurate diagnosis of Type 2 diabetes in youth is still problematic, even for paediatric endocrinologists.

Radiological evaluation of the use of clay brick and pumice brick as a structural building material.

In this study, clay brick (CBRICK) and pumice brick (PBRICK) samples used as structural material in the construction of dwellings, schools, workplaces and factories in Turkey were compared with each other from a radiological viewpoint. The activity concentrations of 226Ra, 232Th and 40K naturally occurring in CBRICK and PBRICK samples collected from different regions of Turkey were determined by using a gamma-ray spectrometer with a high purity germanium detector (HPGe). The average activity concentrations of 226Ra, 232Th and 40K in CBRICK and PBRICK samples were found as 35.4 ±â€¯3.3, 37.5 ±â€¯2.4 and 593.7 ±â€¯42.7 Bq kg-1 and 81.9 ±â€¯2.5, 65.8 ±â€¯6.0 and 1066.0 ±â€¯46.6 Bq kg-1, respectively. The radon surface exhalation rate (EXS) and radon mass exhalation rate (EXM) of CBRICK and PBRICK samples were measured by using an active radon gas analyzer with an accumulation container. The average value of EXS and EXM of CBRICK and PBRICK samples found as 45.9 ±â€¯2.9 mBq m-2 h-1 and 3.7 ±â€¯2.9 mBq kg-1 h-1 and 100.9 ±â€¯4.7 mBq m-2 h-1 and 9.9 ±â€¯0.5 mBq kg-1 h-1, respectively. Radiological parameters related to external and internal exposure to members of the public such as the radiation protection index, alpha index, and indoor absorbed gamma radiation dose rate and the corresponding annual effective dose from external exposure, annual effective dose from inhalation of radon, and the lifetime cancer risk were estimated for CBRICK and PBRICK samples. The results were compared with each other and with the international recommended limits or criteria. The results reveal that the average values measured and estimated for CBRICK samples are approximately two times lower than those measured and estimated for PBRICK samples. Thus, from the radiological viewpoint, clay brick is preferable to pumice brick as a structural material in the building sector.

Effects of sunitinib on immunoreactivity of vimentin, E-cadherin and S100 in kidneys of streptozotocin induced diabetic mice.

Diabetes mellitus (DM) affects many organs including kidney. Tyrosine kinase can cause hypoglycemia and sunitinib is an inhibitor of tyrosine kinase. We investigated the possible effects of sunitinib on the kidney of streptozotocin (STZ) induced type 1 diabetic mice. We used 28 CD 1 type male mice divided into four groups of seven. Type 1 diabetes was induced by injection of STZ. Group 1 was the untreated control. Group 2 comprised non-diabetic mice + sunitinib. Both groups 1 and 2 exhibited normal blood glucose levels. Group 3 comprised STZ treated diabetic mice + saline. Group 4 were diabetic mice + sunitinib treatment. Kidneys were removed after 8 weeks. The immunoreactivities of vimentin, E-cadherin and S100 were assessed. Immunostaining of vimentin, E-cadherin and S100 was located in both the glomeruli and tubules of the kidney. We found that the number of vimentin and E-cadherin positive glomeruli and tubules were increased after sunitinib treatment compared to saline treated diabetic mice. The number of vimentin labeled tubules was decreased in the sunitinib treated group compared to diabetic + saline groups. Differences in the number of S100 positive tubules and glomeruli between groups 3 and 4 were not statistically significant. The effect of sunitinib on experimental diabetic mice appears to be related to levels of vimentin, E-cadherin and S100 in the glomeruli and tubules of the kidney, and sunitinib may protect against renal damage from DM.

Comparison of the effects of the L-dopa and insulin tolerance tests on cortisol secretion.

PURPOSE: The aims of the present study are to evaluate the effect of L-dopa on the secretion of cortisol and adrenocorticotropic hormone (ACTH) in short children and compare the performance of this test with the insulin tolerance test (ITT) in a large number of patients. METHODS: A total of 29 short but otherwise healthy children [mean age 9.5 ± 3.1 years (range 3.7-14.9 years)] who had inadequate growth hormone (GH) responses to ITT, which was performed as the first test, were consecutively enrolled in this study. GH, cortisol, and ACTH levels were measured just before administration of L-dopa and then at 30-min intervals afterward over a total time of 120 min. Peak concentrations of cortisol and ACTH exceeding 18 µg/dL (496 mmol/L) and 46 pg/mL (10.2 pmol/L), respectively, were defined as an adequate response. RESULTS: While the L-dopa test revealed that 26 of the 29 children (89.7%) had peak serum cortisol levels of > 18 µg/dL, the ITT revealed that only 23 children (79.3%) had adequate cortisol responses. The L-dopa test revealed normal ACTH responses (> 46 pg/mL) in 24 (82.8%) patients. Peak cortisol levels were higher in children with normal ACTH responses than in those with subnormal ACTH responses (25.6 ± 6.2 vs. 19.5 ± 6.4 µg/dL, p = 0.054), but the difference observed was statistically insignificant. CONCLUSION: The results of the current study confirm that the L-dopa test is a reliable test of cortisol secretion. As such, this test may be applicable to assessments of the hypothalamic-pituitary-adrenal axis.

Should we worry about incidental gastrointestinal tract involvement in positron emission tomography/computed tomography as gastroenterologist?

BACKGROUND AND AIM: Positron emission tomography/computed tomography(PET/CT) scans detects benign clinical conditions in addition to malignancy, and this leads to additional investigation and expenditure. The purpose of our study was to assess the endoscopic and histopathologic results of incidental 18F-FDG uptake in the GI tract. PATIENTS AND METHOD: We enrolled 110 patients who underwent gastroscopy/colonoscopy for incidental GI tract involvement in PET/CT. Histopathologic and endoscopic results were compared with FDG uptake level, pattern of uptake(diffuse/focal), and site of involvement. RESULTS: In our study, 52.7% of the patients were male and the mean age was 57±11 years. Among the participants, 47.3% and 52.7% of patients had upper GI tract and colorectal involvement in PET/CT, respectively. Gastritis and colonic polyps were the most common endoscopic diagnoses that caused FDG uptake in the upper and lower GI tract, respectively. Endoscopic evaluation was normal in 23.6% of patients with pathologic FDG involvement. The rates of adenomatous polyps, malignancy, and hyperplastic polyps were 18.5%, 13.6%, and 6.8%, respectively. The mean SUVmax were higher in malignant lesions than in non-malignant lesions (14.3±8.9 vs. 9.3±5.3)(p=0.02). Diffuse or focal FDG involvement patterns on PET/CT did not help to discriminate malignancy in the GI tract. CONCLUSION: Malignancy was detected in only 13.6% of patients with FDG involvement in the GI tract, and the involvement pattern(diffuse/focal) and SUVmax did not differentiate malignancy.

Preventive effect of intravesical ozone supplementation on n-methyl-n-nitrosourea-induced non-muscle invasive bladder cancer in male rats.

Although non-muscle invasive bladder cancer (NMIBC) is widely seen in men, most laboratory studies of new intravesical therapies to prevent NMIBC have been conducted on female animals. In addition, ozone (O3) has been shown to be a beneficial agent as an intravesical application in the treatment of various disorders. In the current study, we evaluated the immunohistopathological and oxidative-antioxidative effects of intravesical O3 treatment on n-methyl-n-nitrosourea (MNU)-induced NMIBC. Male Wistar-Albino rats (n=51) were divided into four groups: sham (n=6), O3 only (n=15), MNU only (n=15), and MNU+O3 (n=15). The MNU-only and MNU+O3 groups received MNU, and the O3-only group received saline every other week for 10 weeks. The MNU-only group received 1 ml saline in place of O3 treatment, whereas the O3-only and MNU+O3 groups were treated with 1 ml 25 µg/ml O3 between the 7th and 12th weeks. Rat bladders were collected in the 15th week for immunohistopathology and oxidant-antioxidant quantitation. Oxidant-antioxidant parameters were determined by ELISA. Although all surviving rats in the MNU-only group had preneoplastic (4/11, 36.4%) or neoplastic changes (7/11, 63.6%), a completely normal urothelium was observed in 2 rats (2/12, 16.7%) in the MNU+O3-group (P=0.478). More high-grade lesions were observed in the MNU-only group (4/11, 36.4%) than in the MNU+O3 group (1/12, 8.3%) (P=0.120). All oxidant-antioxidant parameters significantly increased (P<0.05) in the O3-only group compared with the sham group. However, only antioxidant superoxide dismutase was remarkably higher (178.9%, P=0.060) in the MNU+O3 group compared with the MNU-only group. This is the first methodologically and pathologically well-described male rat orthotopic bladder carcinogenesis model with intravesical MNU and administration of O3 in NMIBC.

Can Helicobacter pylori be eradicated with high-dose proton pump inhibitor in extensive metabolizers with the CYP2C19 genotypic polymorphism?

Proton pump inhibitors (PPI) metabolism and pharmacokinetics are regulated by cytochrome P450 enzymes in the liver. Cytochrome P450 2C19 (CYP2C19) polymorphism plays an import role in the metabolism of PPIs. The three possible genotypes for CYP2C19 each has a distinct effect on the pharmacodynamics of PPIs. Homozygote extensive metabolizers (HomEM) are the most frequent genotype and have two wild-types (non-mutant) (*1/*1) alleles. HomEM is associated with increased enzyme activity, which increases the rate of PPI metabolism. Intragastric pH, which is required for eradication, is lowest in HomEM. In HomEMs, an insufficient increase in intragastric pH results in decreased anti-Helicobacter pylori (HP) efficacy of the antibiotics and, therefore, lower eradication rates. We determined whether the HP eradication rate would increase after high-dose PPI treatment of extensive PPI metabolizers who had been treated unsuccessfully with a standard PPI dose. In our report, increasing the PPI dosage in patients with genotype polymorphisms may be effective on eradication rates. Eradication rates are directly affected by CYP2C19 polymorphisms, and eradication treatments should be planned considering such genotypic polymorphisms. Hence, CYP2C19 genotyping prior to treatment may facilitate determination of the optimum PPI dose to improve the therapeutic outcome. However, further researches are required to confirm this hypothesis.

Steroid-refractory inflammatory bowel disease is a risk factor for CMV infection.

OBJECTIVE: Patients with inflammatory bowel disease (IBD) show increased the prevalence of cytomegalovirus (CMV) infection due to the severity of the disease and the immunosuppressive treatments they receive. The aim of this study was to determine the prevalence of CMV infection in IBD patients and identify the risk factors for CMV infection with different demographic characteristics in IBD patients. PATIENTS AND METHODS: We enrolled 85 patients diagnosed with IBD (43 with ulcerative colitis (UC) and 42 with Crohn's disease (CD)) in this prospective study. The clinical disease activities of UC and CD were assessed using Truelove-Witts and Crohn's disease activity index (CDAI). CMV infection was assessed by detection of DNA using real-time polymerase chain reaction (PCR) in blood samples and quantitative PCR in colonic biopsy specimens and by detection of inclusion bodies using hematoxylin-eosin staining. RESULTS: Thirteen patients with IBD exhibited concomitant CMV infection. CMV infection was not detected in any of the patients in remission. Viral loads measured in the colonic mucosa of infected patients ranged from 800-7000 genome copies/mL total extracted DNA. The mean serum CMV DNA level was 1694 ± 910 copies/mL (range: 800-3800). The rate of steroid resistance in CMV-positive cases was significantly higher than that in CMV-negative cases (p = 0.001). CD with acute exacerbation was a risk factor for CMV disease (p = 0.04). All of the CMV-positive patients received immunosuppressive treatments. CONCLUSIONS: CMV infection should be suspected in steroid-resistant UC and CD. Antiviral treatment improved the clinical outcome in steroid-resistant IBD cases with serum CMV DNA levels above 1000 copies/mL.

Effect of cytochrome P450 2C19 polymorphisms on the Helicobacter pylori eradication rate following two-week triple therapy with pantoprazole or rabeprazole.

OBJECTIVE: Cytochrome P450 2C19 (CYP2C19) polymorphisms play an important role in the metabolism of proton pump inhibitors. Rabeprazole is primarily metabolized via non-enzymatic pathways. In this study, we determined whether rabeprazole- and pantoprazole-based eradication treatments were influenced by CYP2C19 polymorphisms. PATIENTS AND METHODS: A total of 200 patients infected with Helicobacter pylori were treated with either 40 mg of pantoprazole or 20 mg of rabeprazole plus 500 mg of clarithromycin, 1000 mg of amoxicillin twice daily for 2 weeks. CYP2C19 genotype status was determined by Polymerase Chain Reaction (PCR)-restriction-fragment-length polymorphism. The genotypes of cytochrome P450 2C19 were classified as homozigote extensive metabolizer (HomEM), heterozigote metabolizer (HetEM) and poor metabolizer (PM). The CYP2C19 genotype of all patients, the effectiveness of the treatment, the effect of the genotypic polymorphism on the treatment were assessed. RESULTS: The frequencies of HotEM, HetEM, PM were 78%, 19.5% and 2.5%, respectively. 48% (n = 96) of the patients received treatment with rabeprazole and 52% (n = 104) with pantoprazole. The eradication rate was 64.7% for HomEM, 79.4% for HetEM, 100% for PM (p = 0.06). In HetEM, PM, are considered as a single group, the eradication rates were higher in patients with the HetEM and PM (HetEM+PM) genotypes than in those with the wild-type genotype (81.8 vs. 64.7% p = 0.031). Among the patients treated with rabeprazole, the eradication rates were significantly lower in those with the HomEM genotype than in those with the HetEM+PM genotypes (60% vs. 85.7% p = 0.023). CONCLUSIONS: The genotypic polymorphism is effective on the rate of eradication. Eradication treatment rate with rabeprazole is influenced by CYP2C19 genotype.

Radiation dose and diagnostic accuracy of high-pitch dual-source coronary angiography in the evaluation of coronary artery stenoses.

PURPOSE: "Flash Spiral" imaging is a new prospective ECG-triggered spiral scan mode that uses a very high-pitch for coronary computed tomography angiography (CTA). This enables complete image acquisition within one cardiac cycle with a very low radiation exposure. The aim of this study was to investigate the diagnostic accuracy, image quality, and effective radiation dose of prospectively ECG-triggered high-pitch spiral method (Flash spiral mode) of coronary CTA using dual-source technology for the evaluation of coronary artery stenoses. MATERIAL AND METHODS: The study included 186 consecutive patients (115men, 71women; mean age: 53.37 years) who underwent coronary CTA. Coronary CTA was performed with a 128×2-slice dual-source CT (Somatom Definition Flash, Siemens, Germany) using a prospectively ECG-triggered high-pitch spiral mode. Patients were divided into three groups according to heart rate (≤65bpm, 66-75bpm, ≥76bpm) and body mass index (BMI) (20-24kg/m(2), 25-29kg/m(2), 30-34kg/m(2)) values. The correlation between heart rates, image quality and BMI values are investigated. A four-point scale (1=excellent, 4=poor/non-diagnostic) was used to rank the comparative image quality. Effective radiation doses were calculated. Also the correlation between radiation dose, sex and BMI values were investigated. In addition, diagnostic accuracy of CTA for detection of significant (≥50%) coronary artery stenoses was compared with invasive coronary angiography findings of 612vessel segments in 38patients. The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy rate were calculated. RESULTS: A total of 2976coronary artery segments were present. Of all coronary artery segments, 2381 (80%) had an image quality score of 1, and 1.5% segments were rated as "poor/non-diagnostic". When the correlation between heart rate and image quality is investigated, there was a significant difference between ≤65bpm and ≥76bpm groups. However, there was no significant difference between ≤65bpm and 66-75bpm groups. The mean effective dose was found as 1.3mSv (min: 0.5, max: 2.4mSv). The correlation between effective radiation dose and BMI was moderate. However, the correlation between gender and radiation dose was significant. Sensitivity, specificity, negative predictive value and accuracy of coronary CTA on a per-vessel segment were 90.1%, 97.4%, 98.6%, and 96.5%, respectively. CONCLUSIONS: Prospectively ECG-triggered high-pitch spiral mode coronary CTA provides high image quality and diagnostic accuracy, with very low radiation dose for evaluation and exclusion of coronary artery stenoses.

Neutrophil-to-lymphocyte ratio in inflammatory bowel disease - as a new predictor of disease severity.

BACKGROUND: The aims of this study were to investigate the utility of neutrophil-to-lymphocyte ratio (NLR) as a simple and readily available predictor for clinical disease activity in inflammatory bowel disease (IBD). METHODS: Sixty-six patients (22 CD, 44 UC) and 41 healthy controls were enrolled in the study. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels and complete blood count (CBC) were measured. The neutrophil and lymphocyte counts were recorded and NLR was calculated. The patients with active or inactive UC and CD were classified according to the severity of the disease. RESULT: The serum NLR values of active CD patients were significantly higher than those of inactive ones and controls (p = 0.000, p = 0.000, respectively). NLR values of active UC patients were significantly higher than those of inactive ones and controls (p = 0.000, p = 0.000, respectively. The optimum NLR cut-off point for active CD and UC was 3.2 and 3.1. CONCLUSION: This study demonstrates that NLR in subjects with IBD is strongly associated with active disease and correlated with clinical and laboratory indices (Tab. 5, Fig. 2, Ref. 31).

Infliximab in inflammatory bowel disease: attention to adverse events.

OBJECTIVE: To assess the efficacy and adverse effects of infliximab in patients with Crohn's disease and ulcerative colitis who are resistant to conventional therapy or having fistulising type Crohn's disease. PATIENTS AND METHODS: The patients with a diagnosis of inflammatory bowel disease received infliximab between 2007 and 2009 were followed-up prospectively. Infliximab 5 mg/kg was given at week 0, 2, 6, and every 8 weeks thereafter. Early and late adverse events occurring during the treatment were recorded for each patient. RESULTS: There were 36 patients [mean age 35±12, 17 male] included in the study. Thirty-two (88%) patients were receiving concomitant long-term immunosuppressive therapy. Complete or partial response was obtained in 75% of all patients. At least one adverse event was observed in 10 (28%) patients. Anaphylaxis was seen in 2 (6%) patients, mild acute infusion reaction in 2 (6%) patients, hypotension in 2 (6%) patients, respiratory distress in 2 (6%) patients, skin rash and eruptions in 2 (6%) patients, one hypertension (3%) and one (3%) tightness in the chest. Treatment was continued in all except patients with anaphylaxis. No infection, tumour or cases of death were observed. CONCLUSIONS: Several adverse events might be observed in patients who receive infliximab. Care should be given to patients whom treatment was restarted after a break in regard to anaphylaxis. No serious adverse event was observed during infliximab treatment except allergic events.