Measuring Small Bowel Length in Bariatric Surgery: An Ex Vivo Laparoscopic Training Experiment.

INTRODUCTION: Determining limb length in gastric bypass procedures is a crucial step to ensure significant weight loss without risking malnutrition. This study investigated the effect of ex vivo training on the skills needed to determine limb lengths. MATERIALS AND METHODS: This was a single-center ex vivo training experiment in a teaching hospital in the Netherlands. We designed a training exercise with marked ropes in a laparoscopic trainer box. All ten surgical residents participated and practiced the skill of estimating limb length. Before and after the two-week period their results on a 150-centimeter limb length task were evaluated. RESULTS: Before training, 10 surgical residents estimated 150 centimeters of small bowel with an absolute deviation of 21% [range 9-30]. After the training experiment, the residents measured with 8% [2-20] deviation (P = .17). The 8 residents who trained sufficiently improved statistically significantly to an absolute deviation of 5% [2-17] (P = .012). Over 70% of the participants felt their skills had improved. CONCLUSIONS: With sufficient training, surgical residents' skills in measuring small bowel length improved when tested in an ex vivo model. Residents became more confident in their laparoscopic measurement skills. This ex vivo training model is a alternative and addition to on-site training.

Medical and surgical treatment of postbariatric hypoglycaemia: Retrospective data from daily practice.

AIM: To evaluate medical and surgical treatment of postbariatric hypoglycaemia (PBH) in daily practice. MATERIALS AND METHODS: Retrospective data were extracted from medical records from four hospitals. PBH was defined by neuroglycopenic symptoms together with a documented glucose <3.0 mmol/L in the postprandial setting after previous bariatric surgery. Data were scored semiquantitatively on efficacy and side effects by two reviewers independently. Duration of efficacy and of use were calculated. RESULTS: In total, 120 patients were included with a median follow-up of 27 months with a mean baseline age of 41 years, total weight loss of 33% and glucose nadir 2.3 mmol/L. Pharmacotherapy consisted of acarbose, diazoxide, short- and long-acting octreotide and glucagon-like peptide-1 receptor agonist analogues (liraglutide and semaglutide) with an overall efficacy in 45%-75% of patients. Combination therapy with two drugs was used by 30 (25%) patients. The addition of a second drug was successful in over half of the patients. Long-acting octreotide and the glucagon-like peptide-1 receptor agonist analogues scored best in terms of efficacy and side effects with a median duration of use of 35 months for octreotide. Finally, 23 (19%) patients were referred for surgical intervention. Efficacy of the surgical procedures, pouch banding, G-tube placement in remnant stomach and Roux-en-Y gastric bypass reversal, pooled together, was 79% with a median duration of initial effect of 13 months. CONCLUSIONS: In daily practice, pharmacotherapy for PBH was successful in half to three quarters of patients. Combination therapy was often of value. One in five patients finally needed a surgical procedure, with overall good results.

Altered bile acid kinetics contribute to postprandial hypoglycaemia after Roux-en-Y gastric bypass surgery.

BACKGROUND/OBJECTIVES: Bile acids (BA) act as detergents in intestinal fat absorption and as modulators of metabolic processes via activation of receptors such as FXR and TGR5. Elevated plasma BA as well as increased intestinal BA signalling to promote GLP-1 release have been implicated in beneficial health effects of Roux-en-Y gastric bypass surgery (RYGB). Whether BA also contribute to the postprandial hypoglycaemia that is frequently observed post-RYGB is unknown. METHODS: Plasma BA, fibroblast growth factor 19 (FGF19), 7α-hydroxy-4-cholesten-3-one (C4), GLP-1, insulin and glucose levels were determined during 3.5 h mixed-meal tolerance tests (MMTT) in subjects after RYGB, either with (RYGB, n = 11) or without a functioning gallbladder due to cholecystectomy (RYGB-CC, n = 11). Basal values were compared to those of age, BMI and sex-matched obese controls without RYGB (n = 22). RESULTS: Fasting BA as well as FGF19 levels were elevated in RYGB and RYGB-CC subjects compared to non-bariatric controls, without significant differences between RYGB and RYGB-CC. Postprandial hypoglycaemia was observed in 8/11 RYGB-CC and only in 3/11 RYGB. Subjects who developed hypoglycaemia showed higher postprandial BA levels coinciding with augmented GLP-1 and insulin responses during the MMTT. The nadir of plasma glucose concentrations after meals showed a negative relationship with postprandial BA peaks. Plasma C4 was lower during MMTT in subjects experiencing hypoglycaemia, indicating lower hepatic BA synthesis. Computer simulations revealed that altered intestinal transit underlies the occurrence of exaggerated postprandial BA responses in hypoglycaemic subjects. CONCLUSION: Altered BA kinetics upon ingestion of a meal, as frequently observed in RYGB-CC subjects, appear to contribute to postprandial hypoglycaemia by stimulating intestinal GLP-1 release.

The association of low muscle mass with prevalence and incidence of type 2 diabetes in different BMI classes.

OBJECTIVE: The aim of this study is to investigate whether muscle mass is associated with the prevalence and incidence of type 2 diabetes and whether this association differs within men and women of normal weight, overweight or obesity. METHODS: Adult participants were included from the Lifelines cohort study. Low muscle mass was defined as < -1SD of the gender-stratified creatinine excretion rate (CER). Multivariate logistic regression analysis was used to assess the association between muscle mass and the prevalence and incidence of type 2 diabetes. RESULTS: Muscle mass was associated with the prevalence of type 2 diabetes both in men and in women (OR 1.51 [95 %CI 1.32-1.72]; P < 0.001 and OR 1.53 [1.36 - 1.73]; P < 0.001). Incident type 2 diabetes was associated with a decreased muscle mass for both men and women (male; OR 1.22 [1.05 - 1.43]; P = 0.01 and female; OR 1.36 [1.17 - 1.59]; P < 0.001), and remained significant after adjustments in normal weight women (OR 1.77 [1.16-2.70]; P = 0.008). CONCLUSIONS: Both a low muscle mass and loss of muscle mass are associated with the prevalence and incidence of diabetes in the general population. This association is strongest in people with normal weight, and weakens in people within higher BMI subgroups.

[Hypoglycaemia after bariatric surgery]. / Hypoglykemie na een bariatrische operatie.

BACKGROUND: The beneficial effects of bariatric surgery on type 2 diabetes can come at a price : the development of postprandial hypoglycaemia, also called post-bariatric hypoglycaemia (PBH). PBH is to some extend present in almost all patients after bariatric surgery but can sometimes lead to serious hypoglycaemia. CASE DESCRIPTION: A 53 year old woman experienced periods with reduced consciousness eventually leading to a fall from the stairs with fracturing of her shoulder and ankle. On further evaluation she had frequent periods of postprandial hypoglycaemia without noticing these. Eventually dietary advice and 3 different medications were needed to control her hypoglycaemic episodes. CONCLUSION: Due to lack of classic hypoglycaemic symptoms PBH is often not recognized as such. Consequently, loss of consciousness can have serious consequences. Treatment consists of dietary advice, sometimes supplemented with medication which is not always successful. Surgical intervention is then the next option, however without guarantees for success.

Tailoring limb length based on total small bowel length in one anastomosis gastric bypass surgery (TAILOR study): study protocol for a randomized controlled trial.

BACKGROUND: The one anastomosis gastric bypass (OAGB) is being performed by an increasing number of bariatric centers over the world. However, the optimal length of the biliopancreatic (BP) limb remains a topic of discussion. Retrospective studies suggest the benefit of tailoring BP-limb length; however, randomized trials are lacking. The aim of this study is to investigate whether tailoring the length of the BP-limb based on total small bowel length (TSBL) leads to better results in terms of weight loss, vitamin deficiencies, and bowel movements compared to a fixed BP-limb length. METHODS: The TAILOR study is a double-blind single-center randomized controlled trial. Patients scheduled for primary OAGB surgery will be randomly allocated either to a standard BP-limb of 150 cm or to a BP-limb length based on their TSBL: TSBL < 500 cm, BP-limb 150 cm; TSBL 500-700 cm, BP-limb 180 cm; TSBL > 700 cm, BP-limb 210 cm. The primary outcome is to compare the percent total weight loss (%TWL) at 5 years between the two groups. Secondary outcomes include nutritional deficiencies, remission of comorbidities, symptoms of dumping, quality of life, and daily bowel movements. The study includes a total of 212 patients and is designed to detect a 5% difference in the primary endpoint. DISCUSSION: The TAILOR study will provide new insights into the effect of different BP-limb lengths and the role of the TSBL in the OAGB. The study is designed to provide guidance for bariatric surgeons to determine the optimal BP-limb length in the OAGB. TRIAL REGISTRATION: Dutch Trial Register NL7945. Prospectively registered on 08 September 2019. NTR (trialregister.nl ).

Laparoscopic Small Bowel Length Measurement in Bariatric Surgery Using a Hand-Over-Hand Technique with Marked Graspers: an Ex Vivo Experiment.

INTRODUCTION: Tailoring limb length in bariatric surgery is a subject of many studies. To acquire the optimal limb length, accurate measurement of the small bowel length is essential. OBJECTIVE: To assess the intra- and inter-individual variability of laparoscopic bowel length measurement using a hand-over-hand technique with marked graspers. METHOD: Four bariatric surgeons and four surgical residents performed measurements on cadaver porcine intestine in a laparoscopic box using marked graspers. Each participant performed 10 times a measurement of three different lengths: 150, 180, and 210 cm. Acceptable percentage deviation from the goal lengths was defined as less than 10%, while unacceptable deviations were defined as more than 15%. RESULTS: The bariatric surgeons measured the 150-, 180-, and 210-cm tasks with 4% (CI 0.4, 9), - 6% (CI - 11, - 0.8), and 1% (CI - 4, 6) deviation, respectively. In total, the bariatric surgeons estimated 58 out of 119 times (49%) between the margins of 10% deviation and 36 times (30%) outside the 15% margin. Considerable inter-individual differences were found between the surgeons. The surgical residents underestimated the tasks with 12% (CI - 18, - 6), 16% (CI - 19, - 13), and 18% (CI - 22, - 13), respectively. CONCLUSION: Bariatric surgeons estimated bowel length with on average less than 10% deviation. However, this still resulted in 30% of the measurements with more than 15% deviation. There were considerable inter-individual differences between the surgeons and residents structurally underestimated the bowel length. Ascertainment of measurement accuracy and adequate training is essential for bariatric procedures in which limb length is of importance.

Long-term Effect of Bariatric Surgery on the Use of Levothyroxine and Thyroid Levels.

BACKGROUND: The aim of this study was to evaluate the effect of bariatric surgery on the defined daily dose of levothyroxine (DDD LT4), thyroid-stimulating hormone (TSH), and free thyroxine (fT4) in female patients with hypothyroidism until 48 months after surgery. METHODS: A retrospective observational study of hypothyroid patients who underwent bariatric surgery. Changes in DDD LT4, TSH, and fT4 over a 48 month period after surgery were analyzed. RESULTS: Thirty-seven patients were included: 27 Roux-en-Y gastric bypass (RYGB), 6 sleeve gastrectomy (SG), 3 adjustable gastric band, and 1 one anastomosis gastric bypass. The median DDD LT4 decreased from 125 µg at baseline to 100 µg 12 months after surgery. From 24 to 48 months after surgery, the median DDD LT4 was stable at 125 µg. Most dose adjustments occurred during the first 24 months after surgery. In the time period of 24-48 months after surgery, the dose remained stable in 73.1% of the RYGB patients and in 60.0% of the SG patients. After 48 months in the RYGB group, no significant change in TSH and fT4 levels was observed. CONCLUSIONS: Bariatric surgery led to frequent dose adjustments during the first 2 years after surgery. However, 24-48 months after surgery in the majority of patients, the dosage remained stable. No significant change in TSH and fT4 was observed 48 months after RYGB. In the first 2 years after surgery, clinicians should frequently monitor TSH and fT4 for individual dose adjustment of levothyroxine. Thereafter, the frequency of monitoring may be decreased.

Dumping Syndrome and Postbariatric Hypoglycemia: Supporting Evidence for a Common Etiology.

BACKGROUND: Dumping syndrome (DS) and postbariatric hypoglycemia (PBH) are frequent complications of bariatric surgery. Previously known as "early and late dumping," these complications have been separated due to differences in their onset and behaviors. OBJECTIVES: To investigate a potentially common etiology of DS and PBH using an analysis of a mixed meal test (MMT) study. SETTING: A large teaching hospital in the Netherlands. METHODS: From all patients who underwent bariatric surgery in 2008-2011, a random selection completed an MMT (n = 47). Patients scored complaints related to DS and PBH with a standardized questionnaire at several time intervals. The groups were divided into patients with (DS+; n = 22) and without (DS-; n = 25) an increase in DS symptoms after the start of the MMT. Glucose and gut hormone levels were compared. Hypoglycemia was defined as a blood glucose level below 3.3 mmol/L. RESULTS: The DS+ group had lower blood glucose values compared to the DS- group, which reached significance at 90 and 120 minutes (P < .05). For the DS+ group, glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and satiety were higher at various time intervals (P < .05) compared to the DS- group. No differences were found for insulin and hunger score. GLP-1 and PYY were correlated with symptoms of DS. CONCLUSION: Patients with DS complaints had lower postprandial glucose values. GLP-1 and PYY values were elevated in the DS+ group early and late during the test. These hormones also correlated with DS. These findings support the hypothesis of a common etiology of DS and PBH and a role of GLP-1 and PYY in both complications.

Outcomes of the One Anastomosis Gastric Bypass with Various Biliopancreatic Limb Lengths: a Retrospective Single-Center Cohort Study.

INTRODUCTION: One anastomosis gastric bypass (OAGB) is an effective and safe treatment for morbidly obese patients. Longer biliopancreatic (BP) limb length is suggested to result in better weight loss outcomes, but to date, no data are available for the OAGB to substantiate this. We hypothesized that applying a longer BP-limb length in the higher BMI classes would result in more weight reduction so that the attained BMI would be comparable to patients with a lower BMI, thereby compensating for differences in baseline BMI. METHOD: A retrospective cohort study in patients who underwent a primary OAGB at a teaching hospital in the Netherlands between January 2015 and December 2016. BP-limb length was tailored based on preoperative BMI. Patients were divided into three different groups depending on the length of the BP-limb: 150, 180, and 200 cm. Weight loss outcomes after 1 and 3 years and resolution of comorbidities were compared between these groups. RESULTS: Of the 632 included patients, a BP-limb length of 150 cm was used in 172 (27.2%), 180 cm in 388 (61.4%), and 200 cm in 72 (11.4%) patients. Despite more BMI loss, %EWL was lower and attained BMI remained higher in the groups with longer BP-limb lengths. After adjustment for the confounder preoperative BMI, longer BP-limb lengths were not associated with higher BMI loss. There was no difference in remission rates of comorbidities. CONCLUSION: Attained BMI remained higher in spite of tailoring BP-limb length according to baseline BMI with no differences in remission rates of comorbidities.

Measuring Muscle Mass and Strength in Obesity: a Review of Various Methods.

Lower muscle mass in populations with obesity is associated obesity-related diseases like hypertension and type 2 diabetes mellitus. Bariatric surgery leads to sustained weight loss. During the weight reduction, loss of muscle should be minimized. Thus reliable quantification of muscle mass is much needed and therefore the also the need for validated methods. Imaging methods, magnetic resonance imaging and computed tomography scan, have been the gold standard for many years. However, these methods are costly and have limitations such as the maximum weight. Dual-energy X-ray absorptiometry is currently the most used alternative. Other, less expensive methods are very limited in their validation in populations with morbid obesity. This narrative review summarizes the current knowledge regarding measuring muscle mass and strength in obesity.

Diminished Counterregulatory Responses to Meal-Induced Hypoglycemia 4 Years After RYGB.

PURPOSE: Post-bariatric hypoglycemia is a complication of bariatric surgery, especially Roux-en-Y gastric bypass (RYGB). The counterregulatory hormonal and sympathetic neural responses were measured during a previously reported meal test in which 48% had an almost asymptomatic hypoglycemic event. MATERIALS AND METHODS: Forty-four randomly selected patients 4 years after RYGB. A liquid meal test (MMT) after overnight fasting. Based on the glucose nadir during the MMT, patients were divided in a hypo group (glucose < 3.3 mmol/L) and a non-hypo group (glucose ≥ 3.3 mmol/L). Cortisol, epinephrine, norepinephrine, blood pressure, and heart rate were measured up to 180 min after ingestion of the meal. Incremental areas under the curve (iAUC), peak, and delta hormone responses after the glucose nadir were calculated. Parameters were compared between the hypo and non-hypo groups. RESULTS: A total of 21/44 (48%) had an almost asymptomatic hypoglycemic event. Cortisol and epinephrine responses in the hypo group were not increased compared to the non-hypo group, and there were no signs of increased sympathetic nerve activity. Peak and delta cortisol were lower in the hypo compared to the non-hypo group. Norepinephrine was higher in the hypo group especially in the time frame 60-120 and 120-180 min after start of the meal. CONCLUSION: No increase in epinephrine and a lower cortisol response to hypoglycemia were observed compared to normoglycemia during a meal test in patients after RYGB. Norepinephrine levels were higher in the hypo group. These findings may suggest that possible recurrent hypoglycemia after RYGB results in blunting of counterregulatory responses indicative of hypoglycemia-induced autonomic failure. CLIN TRIAL REGISTER ID: ISRCTN 11738149.

Applying an Anti-reflux Suture in the One Anastomosis Gastric Bypass to Prevent Biliary Reflux: a Long-Term Observational Study.

INTRODUCTION: The one anastomosis gastric bypass (OAGB) is an effective treatment to induce sustained weight loss in morbidly obese patients. Concerns remain regarding the development of reflux. The aim of this study was to investigate the effect of an "anti-reflux suture" as anti-reflux modification to prevent reflux. METHOD: This is a single-center retrospective cohort study of patients who underwent a primary OAGB at the Center Obesity North-Netherlands (CON) between January 2015 and December 2016. Reflux was defined as symptoms of acid/bilious regurgitation or pyrosis. This was consequently asked and reported at each follow-up visit. Outcomes of patients with an anti-reflux suture were compared to those without. RESULTS: In 414 (59%) of the 703 included patients, an anti-reflux suture was applied. Follow-up at 3 years was 74%. The incidence of reflux did not differ between patients with or without an anti-reflux suture (57 versus 56%, respectively; P = 0.9). The presence of an anti-reflux suture was significantly associated with a lower incidence of conversion to Roux-en-Y gastric bypass (RYGB) for reflux (OR 0.56, 95%CI 0.34-0.91). Patients preoperatively diagnosed with gastroesophageal reflux disease (GERD) were 5.2 times more likely to need a conversion to RYGB for reflux (95%CI 2.7-10.1). CONCLUSION: The presence of preoperative GERD should be weighted heavily in the decision to perform an OAGB as this is a major risk factor for conversion surgery due to reflux. The anti-reflux suture might be a valuable addition to the procedure of the OAGB because it results in fewer conversion surgeries for reflux.

Cholecystectomy increases the risk of dumping syndrome and postbariatric hypoglycemia after bariatric surgery.

BACKGROUND: Dumping syndrome (DS) and postbariatric hypoglycemia (PBH) are frequent complications of bariatric surgery. Bile acids (BA) have been implicated in their pathogenesis because both bariatric surgery and cholecystectomy (CCx) are known to modulate human BA metabolism. OBJECTIVES: Our investigation aimed to compare the prevalence of self-reported complaints of DS and PBH in postbariatric patients with and without CCx. SETTING: A large peripheral hospital in the Netherlands. METHODS: All patients who underwent bariatric surgery in 2008-2011 received standardized questionnaires on DS/PBH complaints. The relative risk (RR) of CCx was calculated as the risk of perceived DS and PBH in patients with and without CCx. RESULTS: Of 590 participants, 146 (25%) had CCx before assessment of DS/PBH complaints. Participants were mostly female (82%) with median age of 46 years (interquartile range, 39-53). The RR for DS after CCx was higher in patients with body mass index <30 kg/m2 at the study (RR, 1.59; 95% CI, 1.04-2.42; P = .007) and in primary Roux-and-Y gastric bypass surgery patients (RR, 1.63; 95% CI, 1.10-2.42; P = .018). Detailed analysis of the latter group associated women, age younger than 50 years, without diabetes and (most prominently) with excess weight loss ≥70% (RR, 2.73; 95% CI, 1.57-4.77; P = .0004) with greater risk of DS. The RR for PBH was higher after CCx in sleeve gastrectomy patients (RR, 4.5; 95% CI, 1.00-20.3; P = .036). CONCLUSION: High suspicion of DS and PBH after CCx is increased after bariatric surgery in certain subgroups, suggesting involvement of altered BA metabolism in their pathophysiology.

Prevalence of hypoglycaemia in a random population after Roux-en-Y gastric bypass after a meal test.

OBJECTIVE: Roux-en-Y gastric bypass (RYGB) is an effective way to induce sustainable weight loss and can be complicated by postprandial hyperinsulinaemic hypoglycaemia (PHH). To study the prevalence and the mechanisms behind the occurrence of hypoglycaemia after a mixed meal tolerance test (MMTT) in patients with primary RYGB. DESIGN: This is a cross-sectional study of patients 4 years after primary RYGB. METHODS: From a total population of 550 patients, a random sample of 44 patients completed the total test procedures. A standardized mixed meal was used as stimulus. Venous blood samples were collected at baseline, every 10 min during the first half hour and every 30 min until 210 min after the start. Symptoms were assessed by questionnaires. Hypoglycaemia is defined as a blood glucose level below 3.3 mmol/L. RESULTS: The prevalence of postprandial hypoglycaemia was 48% and was asymptomatic in all patients. Development of hypoglycaemia was more frequent in patients with lower weight at surgery (P = 0.045), with higher weight loss after surgery (P = 0.011), and with higher insulin sensitivity calculated by the homeostasis model assessment indexes (HOMA2-IR, P = 0.014) and enhanced beta cell function (insulinogenic index at 20 min, P = 0.001). CONCLUSION: In a randomly selected population 4 years after primary RYGB surgery, 48% of patients developed a hypoglycaemic event during an MMTT without symptoms, suggesting the presence of hypoglycaemia unawareness in these patients. The findings in this study suggest that the pathophysiology of PHH is multifactorial.

Pharmacokinetics of Glucocorticoid Replacement Before and After Bariatric Surgery in Patients With Adrenal Insufficiency.

Adequate glucocorticoid replacement in patients with primary or secondary adrenal insufficiency is essential to maintain general well-being. Little is known about the effects of bariatric surgery on glucocorticoid absorption. This study evaluates glucocorticoid absorption before and after bariatric surgery, with assessment of plasma cortisol profiles in five patients receiving glucocorticoid replacement therapy for primary (n = 1) or secondary (n = 4) adrenal insufficiency. One patient underwent sleeve gastrectomy (SG), one a one-anastomosis gastric bypass (mini-GB), and three a Roux-en-Y gastric bypass (RYGB). Pharmacokinetic calculations were based on plasma cortisol measurements performed during the first 6 hours after ingestion of the morning dose. Plasma cortisol profiles were very similar before and after surgery; only minor differences were observed. After SG, plasma peak cortisol concentration and cortisol area under the curve (AUC) were higher by 23% and 24%, respectively, and time to peak cortisol was 10 minutes shorter. The mini-GB had no marked effect on pharmacokinetic parameters. In the three patients who underwent RYGB, AUC changes ranged from -12% to 20%. In conclusion, in this small number of patients with adrenal insufficiency, plasma cortisol profiles were similar before and after bariatric surgery. However, in view of individual differences in response to different types of surgery, we recommend postoperative cortisol profiling to guide appropriate glucocorticoid dose adjustment.

Satiety and gastrointestinal hormones during a Mixed Meal Tolerance Test after gastric bypass surgery: association with plasma amino acid concentrations.

BACKGROUND: Circulating amino acids have been associated with both appetite and the secretion of anorexigenic hormones in healthy and obese populations. This effect has not been investigated in subjects having undergone Roux-en-Y gastric bypass surgery (RYGB). OBJECTIVE: To investigate the association between postprandial plasma concentrations of amino acids and the anorexigenic hormones glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine (PYY), the orexigenic hormone ghrelin, and satiety and hunger in post-RYGB subjects. SETTING: A Dutch surgical department. METHODS: Participants after primary RYGB were studied during a Mixed Meal Tolerance Test (MMTT). Satiety and hunger were assessed every 30 minutes on visual analogue scales. Blood samples were collected at baseline, every 10 minutes during the first half hour and every 30 minutes until 210 minutes after the start. The samples were assessed for 24 amino acids and 3 gastrointestinal hormones. Incremental areas under the curve (iAUCs) were calculated. Exploratory analyses were performed in which subjects were divided into high and low responders depending on the median iAUC. RESULTS: 42 subjects, aged 48 ± 11 (mean ± SD) years, 31 to 76 months post-RYGB and with total weight loss of 30 ± 9% completed the MMTT. Subjects with high satiety scores had more than a 25% higher net iAUC of PYY and GLP-1 and at least a 10% higher net iAUC of 10 amino acids compared to subjects with low scores (P < 0.05). The net iAUC of five of these amino acids (i.e. arginine, asparagine, histidine, serine and threonine) was more than 10% higher in subjects with high responses on GLP-1 and/or PYY (P < 0.05). CONCLUSIONS: Certain postprandial amino acids were associated with satiety and anorexigenic hormones and could therefore play a role in appetite regulation after RYGB; either by a direct effect on satiety, indirectly through gastrointestinal hormones, or both.

An observational study on the effects of nadroparin-based and citrate-based continuous venovenous hemofiltration on calcium metabolism.

BACKGROUND: To study calcium homeostasis during citrate-based compared to nadroparin-based CVVH in critically-ill patients with acute renal failure. METHODS: 11 patients were observed during citrate anticoagulation, 9 with nadroparin and 10 controls. Citrate was chosen for patients with active or at risk for bleeding. RESULTS: The controls had, at 24 h, a median serum iCa of 1.1 mmol/l, the citrate group 0.87 mmol/l and the nadroparin group 1.1 mmol/l (citrate vs. control p = 0.001, citrate vs. nadroparin p = 0.002). At 48 h, iCa was not significantly different anymore. Ca balance was negative for the citrate group in contrast to the nadroparin group (p = 0.012). Median serum PTH was higher (30.0 pmol/l vs. 6.5 pmol/l, p = 0.003) in the citrate group. CONCLUSION: With a relative low target-serum-iCa (0.8-0.9 mmol/l) citrate CVVH-treated patients had a negative daily calcium balance and a temporarily lower iCa level resulting in an enhanced PTH response in comparison to nadroparin.

Pancreatic Uptake by 18F-FDOPA PET/CT in Patients With Hypoglycemia After Gastric Bypass Surgery Compared With Controls With or Without Carbidopa Pretreatment.

PURPOSE: The use of Fluorine-labeled dihydroxy-phenyl-alanine (F-FDOPA) PET/CT in patients with hypoglycemia suspected to be caused by pancreatic disease can be helpful to localize the source of excess insulin production. In this setting, carbidopa pretreatment is not recommended. However, quantitative comparisons of pancreatic tracer uptake in patients with or without carbidopa pretreatment and in diffuse pancreatic disease are lacking. Therefore, we aimed to describe and quantify pancreatic F-FDOPA uptake in patients without pancreatic disease with or without carbidopa pretreatment and in patients with hypoglycemia after gastric bypass surgery. PATIENTS AND METHODS: This is a retrospective data analysis of F-FDOPA PET/CT scans performed at a university medical center in the period from 2009 to 2015. All scans were reconstructed and calculated based on the European Association of Nuclear Medicine/EANM Research Ltd guidelines. Of 358 patients without evidence of pancreatic disease or hypoglycemic disorders, 344 received carbidopa and 14 did not. Another 9 patients had post-gastric bypass hypoglycemia. The main outcome measurement was F-FDOPA SUVmax for pancreatic head, body, and tail regions. RESULTS: Carbidopa pretreated patients had a lower median SUVmax (-1.15, -1.20, and -0.84 in pancreatic head, body, and tail [all P < 0.01]) than patients without carbidopa pretreatment. Patients with post-gastric bypass hypoglycemia scanned without carbidopa pretreatment had higher median SUVmax (+1.18, +1.39, and +1.63, all P < 0.03) compared with controls without pretreatment. CONCLUSIONS: Patients with post-gastric bypass hypoglycemia have increased uptake in all pancreatic regions. Carbidopa pretreatment lowers pancreatic F-FDOPA uptake in the nonaffected pancreas and may therefore mask disease activity in post-gastric bypass hypoglycemia.

Strategies for the characterization of disorders in cortisol sensitivity.

CONTEXT: The clinical presentation of abnormalities in glucocorticoid (GC) sensitivity is diverse, and therefore it is difficult to diagnose this condition. OBJECTIVE AND DESIGN: The objective of the study was to develop strategies for the characterization of GC sensitivity disorders. SETTING: The study was conducted in an outpatient clinic. PATIENTS: Nine patients with GC sensitivity disorders participated. INTERVENTIONS: Sequence analysis of the GC receptor (GR), determination of GR number per cell, GR ligand-binding affinity, and GR splice regulation were performed in freshly prepared peripheral blood mononuclear lymphocytes and Epstein-Barr virus-transformed lymphoblasts. Cellular GC sensitivity was determined ex vivo by measuring the effect of dexamethasone on GC-induced leucine-zipper and IL-2 mRNA levels and on cell proliferation. RESULTS: Differences in GR number per cell, GR affinity, GR splice variants, and effects on transactivation or transrepression of GC-sensitive genes were observed between patients and controls. Epstein-Barr virus transformation of lymphoblasts had no influence on GR affinity but increased the GR number 5-fold in healthy controls. In patients diagnosed as cortisol resistant, however, GR number after transformation was increased significantly less than 5-fold, whereas a higher GR number was observed in a patient suspected of cortisol hypersensitivity. CONCLUSION: This study illustrates several strategies to define abnormalities in GC sensitivity by describing nine patients with affected GC sensitivity, all with a unique clinical course and background.