Therapeutic drug monitoring of methotrexate in patients with Crohn's disease.

BACKGROUND: Therapeutic drug monitoring (TDM) has the potential to improve efficacy and diminish side effects. Measuring methotrexate-polyglutamate (MTX-PG) in erythrocytes might enable TDM for methotrexate in patients with Crohn's disease (CD). AIM: To investigate the relationship between MTX-PGs and methotrexate drug survival, efficacy and toxicity METHODS: In a multicentre prospective cohort study, patients with CD starting subcutaneous methotrexate without biologics were included and followed for 12 months. Primary outcome was subcutaneous methotrexate discontinuation or requirement for step-up therapy. Secondary outcomes included faecal calprotectin (FCP), Harvey Bradshaw Index (HBI), hepatotoxicity and gastrointestinal intolerance. Erythrocyte MTX-PGs were analysed at weeks 8, 12, 24 and 52 or upon treatment discontinuation. RESULTS: We included 80 patients with CD (mean age 55 ± 13y, 35% male) with a median FCP of 268 µg/g (IQR 73-480). After the 12-month visit, 21 patients (26%) were still on subcutaneous methotrexate monotherapy. Twenty-one patients stopped because of disease activity, 29 because of toxicity, and four for both reasons. Five patients ended study participation or stopped methotrexate for another reason. A higher MTX-PG3 concentration was associated with a higher rate of methotrexate drug survival (HR 0.86, 95% CI 0.75-0.99), lower FCP (ß -3.7, SE 1.3, p < 0.01) and with biochemical response (FCP ≤250 if baseline >250 µg/g; OR 1.1, 95% CI 1.0-1.3). Higher MTX-PGs were associated with less gastrointestinal intolerance. There was no robust association between MTX-PGs and HBI or hepatotoxicity. CONCLUSIONS: Higher MTX-PG3 concentrations are related to better methotrexate drug survival and decreased FCP levels. Therefore, MTX-PG3 could be used for TDM if a target concentration can be established.

Thoracic and abdominal pain in a 28-year-old woman with a failing kidney transplant.

This case report describes a young, immunocompromised patient who presented with thoracic pain. After an extensive workup, she was diagnosed with a varicella zoster virus infection with involvement of the gastric mucosa, pancreas and lungs for which she was treated with acyclovir. Although the viral load decreased significantly, the patient had persistent postherpetic neuralgia and nausea.

Fast-track bariatric surgery improves perioperative care and logistics compared to conventional care.

BACKGROUND: Due to the increased incidence of morbid obesity, the demand for bariatric surgery is increasing. Therefore, the methods for optimising perioperative care for the improvement of surgical outcome and to increase efficacy are necessary. The aim of this prospective matched cohort study is to objectify the effect of the fast-track surgery (FTS) programme in patients undergoing primary Laparoscopic Roux-en-Y Gastric Bypass (LRYGB) surgery compared to conventional perioperative care (CPC). METHODS: This study compared the perioperative outcome data of two groups of 75 consecutive morbid obese patients who underwent a primary LRYGB according to international guidelines in the periods January 2011-April 2011 (CPC group) and April 2012-June 2012 (FTS group). The two groups were matched for age and sex. Primary endpoints were surgery and hospitalisation time, while secondary endpoints were intraoperative medication use and complication rates. RESULTS: Baseline patient characteristics for age, sex, weight and ASA classification were similar (p > 0.05) for CPC and FTS patients. BMI and waist circumference were significantly lower (p < 0.05) in the FTS compared to CPC. The total time from arrival at the operating room to the arrival at the recovery was reduced from 119 to 82 min (p < 0.001). Surgery time was reduced from 80 to 56 min (p < 0.001); mean hospital stay was reduced from 65 to 43 h (p < 0.001). Major complications occurred in 3 versus 4 % in the FTS and CPC, respectively. CONCLUSIONS: The introduction of a fast-track programme after primary LRYGB improves short-term recovery and may reduces direct hospital-related resources.

Optimization of vitamin suppletion after Roux-en-Y gastric bypass surgery can lower postoperative deficiencies: a randomized controlled trial.

Iron, vitamin B12, and folic acid deficiencies are among the most common deficiencies occurring after laparoscopic Roux-en-Y gastric bypass (LRYGB). The present study evaluates the effectiveness of a specially designed multivitamin supplement (WLS Forte, FitForMe, Rotterdam, the Netherlands) specifically developed for LRYGB patients.A triple-blind, randomized, 12-month study was conducted comparing WLS forte with a standard multivitamin supplement (sMVS) containing approximately 100% of the recommended daily allowance (RDA) for iron, vitamin B12, and folic acid. WLS Forte contains vitamin B12 14000% RDA, iron 500% RDA, and folic acid 300% RDA.In total, 148 patients (74 in each group) underwent a LRYGB procedure. Baseline characteristics were similar for both groups. Per protocol analysis demonstrated that sMVS treatment was associated with a decline in ferritin (-24.4 ±â€Š70.1 µg/L) and vitamin B12 (-45.9 ±â€Š150.3 pmol/L) over 12 months, whereas in WLS Forte patients, ferritin remained stable (+3.2 ±â€Š93.2 µg/L) and vitamin B12 increased significantly (+55.1 ±â€Š144.2 pmol/L). The number of patients developing ferritin or vitamin B12 deficiency was significantly lower with WLS Forte compared with sMVS (P < 0.05). Iron deficiency (ID) was reduced by 88% after WLS Forte compared with sMVS. Adverse events related to supplement use did not occur.An optimized multivitamin supplement is safe and reduces the development of iron and vitamin B12 deficiencies after LRYGB.

Revisional surgery after failed gastric banding: results of one-stage conversion to RYGB in 195 patients.

BACKGROUND: The most performed restrictive bariatric procedure is the laparoscopic adjustable gastric band (LAGB). With many patients still receiving a LAGB in Europe and the United States, inevitably, the number of complications also increases. For many complications revisional bariatric surgery is necessary. In this study, the outcomes of one-stage LAGB conversion to a Roux-en-Y gastric bypass (RYGB) at our institution are presented. The objective of this study was to investigate the safety and efficiency of RYGB performed as a one-stage procedure after failed LAGB. METHODS: Patients were retrospectively selected using a prospectively collected database. The gastric band had to be in situ for at least 1 year and minimum postoperative follow-up was 12 months. The revisional RYGB had to be performed as a 1-step procedure. RESULTS: A total of 195 patients were included while 3 were lost to follow up. Overall, 178 (91%) procedures were performed without perioperative complications, and only 8 (4%) patients required reoperation within 30 days. The mean follow-up was 40 months (±24) after RYGB. Mean excess weight loss (EWL) increased from 25% (±26/-50- 120%) to 60% (±21.2/0- 130), 65% (±23.5/0- 131), 63% (±24.2/2- 132), 60% (±24.1/0- 111) and 53% (±28.7/-39- 109) in the first 5 postoperative years. CONCLUSION: Converting a gastric band to a RYGB in a one-stage procedure is safe and feasible, with acceptable complication rates when performed in a specialized institution. The RYGB conversion results in a good EWL of 65% after 2 years. However, proper patient selection is of the utmost importance.

What happens after gastric band removal without additional bariatric surgery?

BACKGROUND: The laparoscopic adjustable gastric band (LAGB) is widely used for the treatment of morbid obesity. Many patients benefit from this procedure initially, but experience complications after a few years. The treatment for many complications is revisional bariatric surgery. A number of patients, however, request only band removal without secondary bariatric surgery. The aim of this study was to assess the perioperative and medium term outcomes of patients who had their LAGB removed without secondary bariatric surgery. METHODS: Patients were retrospectively selected using a prospectively collected database. The LAGB had to be in situ for at least 1 year, and minimum postoperative follow-up had to be 12 months. RESULTS: Thirty-eight patients who had their LAGB laparoscopically removed between 2000 and 2010 were included. Median follow-up after LAGB removal was 3.0 (1.4 to 8.9) years. Only 2 complications (5%) and no mortality occurred perioperatively. In the 21 patients who did not undergo additional bariatric surgery, the median excess weight loss (EWL) decreased from 41% (-12% to -100%) at band removal to 9% (-10% to 90%), 0% (-20% to 78%), and -11% (-12% to 56%) after 1, 2, and 5 years, respectively. Percentage weight loss (%WL) was 17% (-54% to -5%), 4% (-47% to -9%), 0% (-41% to 11%), and -5% (-29% to 9%) after these same time intervals, respectively. After a median 2.1 (.5 to 9.9) years, 17 patients underwent either a Roux-en-Y gastric bypass (14 patients) or a Scopinaro (3 patients) all because of weight regain. The current EWL and %WL in these patients is 67% (24% to 113%) and 30% (12% to 53%), respectively compared with -11% (-33% to 57%) and -4% (-14% to 34%) in patients without a secondary bariatric procedure (P< .001). CONCLUSION: Patients who have their LAGB removed are guaranteed to suffer from weight regain. It is inadvisable to only remove the LAGB without performing an additional bariatric procedure when deemed technically feasible and safe. In this study, no patient was able to maintain the weight loss achieved with the LAGB after its removal.

Duodenal-jejunal bypass liner implantation provokes rapid weight loss and improved glycemic control, accompanied by elevated fasting ghrelin levels.

BACKGROUND AND STUDY AIMS: Endoscopic implantation of a duodenal-jejunal bypass liner (DJBL) is a novel bariatric technique to induce weight loss and remission of type 2 diabetes mellitus. Placement of the DJBL mimics the bypass component of the Roux-en-Y gastric bypass (RYGB) procedure. In this observational study, we evaluated improvement of glycemic control and weight loss in the course of the treatment (0 - 24 weeks after DJBL implantation) and analyzed accompanying gut hormone responses. PATIENTS AND METHODS: 12 obese individuals with type 2 diabetes were selected for DJBL implantation. Body weight, fat mass, and fasting plasma levels of glucose, insulin, C-peptide, and glycated hemoglobin (HbA1c), were analyzed at 0, 1, 4 and 24 weeks post-implant. Fasting ghrelin, gastric inhibitory peptide (GIP), and glucagon-like peptide (GLP-1) were determined at 0, 1 and 4 weeks post-implant. RESULTS: Besides significant weight loss, fat mass, fasting insulin, and homeostasis model assessment-estimated insulin resistance (HOMA-IR) index were also significantly decreased after DJBL implantation and a 42 % reduction was found in diabetes medication (P < 0.05). The fasting GLP-1 response in the first 4 weeks post-implant was significantly correlated with the fasting insulin and HOMA-IR response. Fasting ghrelin was found to be significantly elevated, in contrast to the decrease in ghrelin that is found after RYGB surgery. CONCLUSIONS: DJBL implantation provoked significant weight loss, a decrease in fat mass, and an early remission of type 2 diabetes, comparable to results seen after RYGB surgery. Gut hormone analyses revealed a potential role of fasting GLP-1 in early remission of type 2 diabetes. Interestingly, the DJBL-induced elevation of ghrelin contradicts the suggested role of reduced ghrelin levels after RYGB in improvement of glycemic control.