The Effect of Etrasimod on Fecal Calprotectin and High-sensitivity C-reactive Protein: Results From the ELEVATE UC Clinical Program.

BACKGROUND: Biomarkers offer potential alternatives to endoscopies in monitoring ulcerative colitis (UC) progression and therapeutic response. This post hoc analysis of the ELEVATE UC clinical program assessed potential predictive values of fecal calprotectin (fCAL) and high-sensitivity C-reactive protein (hsCRP) as biomarkers and associated responses to etrasimod, an oral, once-daily, selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active UC, in 2 phase 3 clinical trials. METHODS: In ELEVATE UC 52 and ELEVATE UC 12, patients were randomized 2:1 to 2 mg of etrasimod once daily or placebo for 52 or 12 weeks, respectively. Fecal calprotectin/hsCRP differences between responders and nonresponders for efficacy end points (clinical remission, clinical response, endoscopic improvement-histologic remission [EIHR]) were assessed by Wilcoxon P-values. Sensitivity and specificity were presented as receiver operating characteristics (ROC) curves with area under the curve (AUC). RESULTS: In ELEVATE UC 52 and ELEVATE UC 12, 289 and 238 patients received etrasimod and 144 and 116 received placebo, respectively. Baseline fCAL/hsCRP concentrations were generally balanced. Both trials had lower week-12 median fCAL levels in week-12 responders vs nonresponders receiving etrasimod for clinical remission, clinical response, and EIHR (all P < .001), with similar trends for hsCRP levels (all P < .01). For etrasimod, AUCs for fCAL/hsCRP and EIHR were 0.85/0.74 (week 12; ELEVATE UC 52), 0.83/0.69 (week 52; ELEVATE UC 52), and 0.80/0.65 (week 12; ELEVATE UC 12). CONCLUSIONS: Fecal calprotectin/hsCRP levels decreased with etrasimod treatment; ROC analyses indicated a prognostic correlation between fCAL changes during induction and short-/long-term treatment response.

We show associations between fecal calprotectin (fCAL) and high-sensitivity C-reactive protein (hsCRP) levels with efficacy outcomes among patients receiving 2 mg of etrasimod once daily, and that fCAL levels may be an early indicator of the achievement of long-term efficacy end point achievement.

Role of Pernicious Anemia in Patients Admitted to Internal Medicine with Vitamin B12 Deficiency and Oral Replacement Therapy as a Treatment Option.

BACKGROUND: To determine the role of vitamin B12 deficiency in pernicious anemia and the efficacy of oral vitamin B12 replacement therapy given regardless of the etiology, and to compare the endoscopic and pathological findings in patients diagnosed with vitamin B12 deficiency. METHODS: The study included 216 patients, aged 18 - 65 years, diagnosed with vitamin B12 level < 200 pg/mL between May 2015 and May 2016. Evaluation was made of the demographic characteristics of the patients, diseases, drugs used, dietary habits, previous use of vitamin B12 replacement therapy, family history of vitamin B12 deficiency, laboratory test values, and neurological symptoms present at the time of presentation. Endoscopy was applied to all the patients included in the study. Anti-parietal cell antibody (APCA) and anti-intrinsic factor antibody (AIFA) analyses were applied to all patients. RESULTS: Evaluation was made of a total of 216 patients diagnosed with vitamin B12 deficiency, comprising 145 (67.1%) females and 71 (32.9%) males. The mean vitamin B12 level of the patients was determined as 127 pg/mL at the time of presentation and 334 pg/mL after treatment. APCA positivity was determined in 40 (18.5%) patients, and AIFA positivity in 5 (2.3%) patients. Atrophy was determined endoscopically in 53 (24.5%) patients and pathologically in 90 (41.7%). Helicobacter pylori positivity was determined in 196 (90.7%) patients. A diagnosis of pernicious anemia (PA) was made in 4 (1.9%) patients (patients with AIFA positivity or APCA accompanied by corpus atrophy). APCA positivity was determined but not corpus atrophy in 36 (16.7%) patients and these cases were accepted as suspected pernicious anemia. In this study of 216 patients with vitamin B12 deficiency, stomach pathologies which could cause vitamin B12 deficiency (atrophic gastritis, HP, PA) and the responses to oral replacement therapy were investigated. As vitamin B12 absorption plays a role in the pathogenesis. Vitamin B12 deficiency can lead to atrophic gastritis, and this was determined with biopsy in 41.7% of the patients. APCA positivity was determined in 18.5% of the patients investigated with respect to autoimmune atrophic gastritis (pernicious anemia) and AIFA positivity in 2.3%. A diagnosis of PA was made in 4 (1.9%) patients from autoimmune marker positivity and the presence of corpus atrophic gastritis. HP was determined in 90.7% of the patients with vitamin B12 deficiency, and although no correlation was determined between HP and atrophy, HP positivity was determined in 84 (93.3%) of the patients with pathological atrophy. From the time of diagnosis, the patients in the study were prescribed 1,000 µg/day vitamin B12. At the 40-day follow-up examination, a significant increase was observed in the vitamin B12 levels of 92.5% of the patients. At the end of the study, as oral replacement therapy was seen to be effective to a great extent, even in patients with PA, it was concluded that for patients not responding to oral replacement therapy, it would be appropriate to apply parenteral vitamin B12 treatment. CONCLUSIONS: In developing countries such as Turkey, the role of HP infection in vitamin B12 deficiency must be kept in mind. The incidence of atrophic gastritis and pernicious anemia is higher than expected in vitamin B12 deficiency. Thus, it can be concluded that it is appropriate to investigate patients with vitamin B12 deficiency with respect to atrophic gastritis and PA, and oral replacement therapy should be the first stage in the treatment of vitamin B12 deficiency.

Pre-Diabetics with Hypovitaminosis D Have Higher Risk for Insulin Resistance.

BACKGROUND: Various studies have been reported on the relationship between vitamin D, whose deficiency has been identified in a pandemic way, and metabolic-endocrine diseases, including insulin resistance. Insulin resistance is an important public health issue since it is a common cause of death as it transforms into metabolic syndrome and type 2 diabetes mellitus (DM). In this study, the aim is to investigate the relationship between the level of serum 25 hydroxy vitamin D (25(OH)D) and insulin resistance. METHODS: A retrospective study was carried out including 2,008 patients aged between 18 - 67 chosen from among the patients who had applied to Saglik Bilimleri University Antalya Training and Research Hospital. Patients were divided into three groups as non-diabetic, pre-diabetic, and diabetic according to their blood glucose profile and into three categories according to their 25(OH)D levels. The relationship between serum vitamin D levels and insulin resistance was compared between the groups. Individuals with homeostasis model assessment of insulin re-sistance (HOMA-IR) > 2.5 were considered to have insulin resistance. RESULTS: The study was composed of 2,008 patients, 1,614 were female (80.4%). Of the participants, 216 (10.6%) were diabetics, 849 (42.3%) were pre-diabetics, and 943 (47.1%) were non-diabetics. It was identified that age, fasting blood glucose, HbA1c, triglyceride (Tg), very-low-density lipoprotein cholesterol (VLDL-C), fasting insulin, and HOMA-IR levels were significantly higher in diabetic patients than in pre-diabetic patients (all p < 0.001) and similarly higher in pre-diabetics than in non-diabetics. Tg, VLDL, fasting insulin, and HOMA-IR levels were significantly lower in the group with 25(OH)D ≥ 30 ng/mL. Especially in pre-diabetic individuals, a significant negative correlation was observed between the 25(OH)D level and HbA1c (p = 0.020), Tg (p = 0.001), VLDL-C (p = 0.001), fasting insulin (p < 0.001) and HOMA-IR (p < 0.001). While high HOMA-IR was positively associated with fasting blood glucose and total cholesterol values (all p < 0.001), it was negatively associated with age (p < 0.001), LDL-cholesterol (p < 0.001), HDL-cholesterol (p < 0.001) and 25(OH)D (p = 0.001). CONCLUSIONS: Diabetic subjects have lower plasma 25(OH)D levels and pre-diabetics with hypovitaminosis D have higher risk for insulin resistance. Thus, HOMA-IR must be well evaluated in pre-diabetic individuals with vitamin D deficiency/insufficiency, if there is associating abdominal obesity.

Could Insulin and Hemoglobin A1c Levels be Predictors of Hunger- Related Malnutrition/Undernutrition Without Disease?

BACKGROUND: Malnutrition results in functional changes in the liver and pancreas that negatively affect carbohydrate metabolism. The aim of this study was to evaluate whether insulin hormone and glycated hemoglobin A1c (HbA1c) could serve as predictors of hunger-related malnutrition/undernutrition without disease in adults. METHODS: The Malnutrition Universal Screening Tool (MUST) was used to assess malnutrition in this single-center, cross-sectional study. The malnourished group (n = 67) comprised patients with a MUST score of ≥ 2, and the control group (n = 31) included subjects with a MUST score of 0 - 1. Serum albumin, prealbumin, C-reactive protein (CRP), fasting glucose, fasting insulin, hemoglobin and HbA1c levels, body mass index (BMI), and homoeostatic model for insulin resistance (HOMA-IR) scores were compared between the two groups. RESULTS: No significant difference was determined between the control and malnourished groups in respect of age or gender. HbA1c [5.5% (5 - 6.2) vs. 5.2% (3.9 - 6.7), p = 0.001], insulin levels [7.37 (2.36 - 52.16) vs. 3.91(1.17 - 30.08) µIU/mL, p < 0.001], and BMI [21.7 (14.1 - 34.0) vs. 17.8 (12.0 - 26.6) kg/m2, p < 0.001] were significantly lower in the malnourished group. Logistic regression analysis revealed that BMI was the only significant parameter (odds ratio [95% confidence interval] 0.680 [0.543 - 0.852]). CONCLUSIONS: Plasma insulin and HbA1c levels were significantly decreased in young adult malnourished patients without disease who had normal fasting glucose levels. These two parameters are known to be unaffected by inflammatory states, and therefore warrant further research on larger and different age sub-populations to assess if they might be early predictors of hunger-related malnutrition without disease.

Short-Term Effect of High-Dose Pantoprazol on Serum and Urinary Magnesium Levels.

BACKGROUND: Proton pump inhibitor (PPI) induced hypomagnesemia is a completely unexplained issue and cases are still being reported. Long-term use is the main factor, but there are a few articles stating that it may also emerge with short-term use. We aimed to evaluate the changes of serum and urine magnesium levels during shortterm high dose pantoprazol treatment. METHODS: The serum and 24-hour urine magnesium levels of 58 patients were evaluated during the course of 2 days. Of 58 patients, 25 were allowed oral intake on the 3rd day of hospitalization and thus, 24-hour urine for 3 days was collected from 33 patients. RESULTS: There were no significant differences in the mean levels of serum magnesium and the median levels of urine magnesium. When the magnesium levels were evaluated by age over and under 60 years, the baseline serum magnesium level was significantly higher than the 1st level in patients aged ≥ 60 years (p = 0.029). The 3rd day serum magnesium level was significantly higher than the baseline and 1st day levels in those aged < 60 years (p = 0.049). CONCLUSIONS: We showed that plasma levels and urinary excretion of magnesium did not change significantly during high-dose pantoprazol treatment. It can be hypothesized that magnesium levels are not affected by PPIs in short-term usage. Age and other contributing factors may have more impact on PPI induced hypomagnesemia. Patients aged over 60 years might be handled carefully under proton pump inhibitors treatment.

The Frequency of Primary Sjogren's Syndrome and Fibromyalgia in Irritable Bowel Syndrome.

OBJECTIVE: To determine the frequency of sicca complex, Sjogren's Syndrome (SS) and Fibromyalgia (FM) in patients with Irritable Bowel Syndrome (IBS). METHODS: Seventy seven IBS patients who fulfilled the Rome-III criteria were included in the study. All patients were assessed for FM according to the American College of Rheumatology (ACR) 2010 criteria. After examination for objective evidence of sicca complex by Schirmer test, TBUT and Ocular Staining Score (OSS), serological tests were performed. And the diagnosis of SS was made according to the American College of Rheumatology (ACR) classification criteria for SS - 2012. RESULTS: Thirteen (16.9%) of IBS patients had FM. Dry eye was detected in 20(26.0%), 7(9.1%) and 29(37.7%) patients by OSS, Schirmer test and TBUT, respectively. Of 77 patients with IBS, the diagnosis of SS was established in two patients (2.6%). CONCLUSION: The frequency of Sjogren's Syndrome among patients with IBS is relatively higher than the general population. All IBS patients should be questioned for dryness of the mouth and eyes, and if necessary, should be evaluated for SS.