EFFECT OF OBESITY AND ROUX-EN-Y GASTRIC SURGERY ON OMEPRAZOLE PHARMACOKINETICS

Background: The prevalence of obesity is increasing globally. Objectives: To evaluate whether gastric bypass surgery modifies the bioavailability and pharmacokinetic (PK) parameters of Omeprazole. Setting: Hospital Clínico San Carlos, Madrid, Spain. Methods: Controlled, open-label, bioavailability clinical trial in patients undergoing Roux-en-Y gastric bypass (RYGB). Healthy patients with obesity (BMI>35) were included and assessed for Omeprazole PK before RYGB and after (1 and 6 months). PK sampling was done at baseline and several times up to 12 h after drug dosing. Pre- and post-surgery parameters were compared using paired ANOVA or Wilcoxon tests, and Control vs. Cases using ANOVA or Mann Whitney tests. Given the post-surgery change in body weight, parameters were corrected by dose/body-weight. Results: Fourteen Case and 24 Control subjects were recruited, 92% were women (N= 35/38). In patients who underwent RYGB, Cmax was significantly reduced at 1 and 6 months after surgery compared with pre-surgery values (p=0.001). Regarding the AUC, the values are lower at 1 and 6 months after surgery than at baseline (p<0.001).The drug clearance was also increased in the first month after surgery. No differences were found between patients 6 months after surgery and Controls. Cmax and AUC corrected by dose/body-weight were significantly different between the baseline surgery subjects and Controls. Conclusions: Omeprazole bioavailability is reduced in patients with obesity at 1 and 6 months after RYGB. However, Omeprazole PK parameters 6 months after RYGB are similar to control subjects, and thus no dose correction is required after RYGB for a given indication.

Utility of Continuous Glucose Monitoring vs. Meal Study in Detecting Hypoglycemia After Gastric Bypass

Context Gastric bypass (GB) increases postprandial glucose excursion, which in turn can predispose to the late complication of hypoglycemia. Diagnosis remains challenging and requires documentation of symptoms associated with low glucose, and relief of symptom when glucose is normalized (Whipple’s triad). Objective To compare the yield of mixed meal test (MMT) and continuous glucose monitoring system (CGMS) in detecting hypoglycemia after gastric bypass surgery (GB). Setting The study was conducted at General Clinical Research Unit, Cincinnati Children’s Hospital (Cincinnati, OH, United States). Methods Glucose profiles were evaluated in 15 patients with documented recurrent clinical hypoglycemia after GB, 8 matched asymptomatic GB subjects, and 9 healthy weight-matched non-operated controls using MMT in a control setting and CGMS under free-living conditions. Results Patients with prior GB had larger glucose variability during both MMT and CGMS when compared to non-surgical controls regardless of their hypoglycemic status. Sensitivity (71 vs. 47 %) and specificity (100 vs. 88 %) of MMT in detecting hypoglycemia was superior to CGMS. Conclusions Our findings indicate that a fixed carbohydrate ingestion during MMT is a more reliable test to diagnose GB-related hypoglycemia compared to CGMS during free-living state.

Biliary reflux after laparoscopic modified antireflux monoanastomotic gastric bypass surgery

Aim. Determination of biliary reflux in patients with morbid obesity after a single-anastomotic gastric bypass operation performed in the clinic's modification and according to the classical Roux-en-Y gastric bypass technique. Development of diagnostic criteria for biliary reflux Materials and methods. The results of treatment of 36 patients with morbid obesity who underwent bypass surgery were studied. The patients are divided into two groups. Clinically modified laparoscopic monoanastomotic gastric bypass surgery was performed in 25 patients (main group). The control group included 11 patients after the standard technique of Roux-en-Y laparoscopic gastric bypass. Inclusion criteria were: persons of both sexes aged 18-60 years with morbid obesity and a body mass index of 40 or more, as well as 35 or more in the presence of comorbid diseases (type 2 diabetes mellitus, arterial hypertension, dyslipidemia, sleep apnea syndrome). In both groups, impedance pH measurements were performed in the postoperative period. Statistical processing was performed using the Statistica 13.0 software package using parametric and nonparametric statistical methods. Results: Clinical manifestations of the enterogastric biliary reflex were found in both groups; in addition, clinical manifestations of the corresponding symptoms were noted by patients of both groups. The analysis of daily pH-metry in the studied groups showed that in the esophagus the time with pH <4 in the main group 2.83 (1.55; 3.95)% 3.00 (2.30; 3.50)% in the control group, time with pH 4-6.9 (physiological for the esophagus) 92.40 (90.65; 94.20)% and 94.10 (89.80; 95.50)%, respectively, time with pH> 7 (weak alkaline) was 4.80 (3.45; 5.85)% and in the control group 2.90 (1.20; 7.20)%. There was no statistically significant difference in these indicators (p> 0.05). Conclusions. Monoanastomotic gastric bypass surgery in the modification of the clinic has the same positive properties as the Rouen-Wye technique, allowing you to avoid the risks associated with possible pathological reflux of bile into the esophagus. Patients who have undergone mini-gastric bypass surgery require a thorough examination with fibrogastroscopy in combination with pH impedance measurement at least 1 time per year in order to determine biliary reflux and morphological changes both in the lumen of the esophagus and in the stomach stump. The level of quality of life of patients after surgery in the control group and the main group does not significantly differ, as evidenced by the results of the questionnaire survey using the GERG Q questionnaire, which indicates the effectiveness of the methodology of laparoscopic monoanastomotic gastric bypass surgery modified in the clinic. Key words: morbid obesity, gastric bypass surgery, surgical treatment, mini-gastric bypass, biliary reflux.

European Respiratory Society guideline on non-CPAP therapies for obstructive sleep apnoea

Treatment of obstructive sleep apnoea (OSA) in adults is evolving, as new therapies have been explored and introduced in clinical practice, while other approaches have been refined or reconsidered. In this European Respiratory Society (ERS) guideline on non-continuous positive airway pressure (CPAP) therapies for OSA, we present recommendations determined by a systematic review of the literature. It is an update of the 2011 ERS statement on non-CPAP therapies, advanced into a clinical guideline. A multidisciplinary group of experts, including pulmonary, surgical, dentistry and ear–nose–throat specialists, methodologists and patient representatives considered the most relevant clinical questions (for both clinicians and patients) relating to the management of OSA. Eight key clinical questions were generated and a systematic review was conducted to identify published randomised clinical trials that answered these questions. We used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to assess the quality of the evidence and the strength of recommendations. The resulting guideline addresses gastric bypass surgery, custom-made dual-block mandibular advancement devices, hypoglossal nerve stimulation, myofunctional therapy, maxillo-mandibular osteotomy, carbonic anhydrase inhibitors and positional therapy. These recommendations can be used to benchmark quality of care for people with OSA across Europe and to improve outcomes.

Acquired Hyperzincaemia Due to Zinc-Laden Denture Adhesives Leading to Hypocupraemia as a Cause of Neutropenia

Introduction: Copper deficiency or hypocupraemia is a rare cause of anaemia and neutropenia. Case description: We hereby present the case of a 34-year-old female with gastric bypass surgery who presented with neutropenic fever, abdominal pain and diarrhoea, later found to have extended-spectrum beta-lactamase resistant Escherichia coli urinary tract infection and small bowel bacterial overgrowth syndrome, with her anaemia and neutropenia being caused by copper deficiency due to hyperzincaemia induced by using zinc denture adhesive cream. Discussion: Various causes of copper deficiency have been recognized including, but not limited to, malnutrition, gastrectomy, gastric bypass surgery, protein-losing enteropathies (coeliac disease, tropical sprue), Wilson disease and Menkes syndrome. Copper deficiency caused by zinc overuse is not very prevalent. The haematologic abnormalities associated with copper deficiency are neutropenia, sideroblastic anaemia and/or pancytopenia. Conclusion: Because of its low prevalence and nonspecific haematologic and clinical manifestations, the diagnosis of zinc-induced copper deficiency (ZICD) can be missed.

Fetal Growth and Adipose Fat Tissue Trajectories in Twin Pregnancies after Gastric Bypass Surgery

Introduction: Previous studies demonstrated a continues decline in fetal growth throughout singleton pregnancy after bariatric surgery. However, intrauterine growth in twin pregnancy is subjected to further underlying processes. This study was to investigate the longitudinal assessment of fetal biometry and abdominal fat thickness of twin pregnancies conceived after gastric bypass surgery and compare them to BMI-matched and obese controls. Materials and methods: We retrospectively assessed ultrasound data of 30 women with dichorionic-diamniotic twin pregnancy (11 women after gastric bypass surgery, 9 obese mothers with pregestational BMI ≥ 30 kg/m² and 10 BMI and age matched controls). We assessed fetal growth parameters including fetal subcutaneous adipose tissue thickness (FSCTT) as well as newborn biometry after delivery. Patient characteristics were obtained from the medical records. Results: The rise in FSCTT curves was markedly slower in twin offspring of women with history of gastric bypass as compared to offspring of obese mothers and offspring of BMI matched controls. Hence, FSCTT was significantly decreased in gastric bypass offspring as compared to both control groups at 34 weeks of gestation. Also, growth curves of abdominal circumference were decreased in offspring of gastric bypass patients as compared to obese mothers. Infants of mothers with history of gastric bypass showed significantly lower birth weight percentiles compared to newborns of obese mothers (27.2 vs 48.8 pct, p=0.025). There was no significant difference in inter twin birth weight difference between offspring of gastric bypass (median: 9.9%, IQR: 6.5 to 20.0) vs. obese (median: 14.6%, IQR: 8.2 to 21.6) and BMI matched controls (median: 9.0%, IQR: 6.3 to 12.6, p=0.714). Conclusions: In summary, intrauterine growth delay in twin pregnancies after GB is assumed to be a multifactorial event with altered metabolism as the most important factor. However, special attention must be paid to the particularity of twin pregnancies as they seem to be subject to other additional mechanism.