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Background: Opioids inhibit motility and secretion of the gut and have been used for antidiarrheal treatment for centuries. However, the underlying mechanisms of opium tincture are not evident. Aim: To investigate the effects of opium tincture on gastrointestinal motility, intestinal volumes, and water content of different gut segments assessed by magnetic resonance imaging (MRI). Methods: Twenty healthy volunteers were included in a randomized, placebo‐controlled, crossover study of 9 days of treatment with 30 drops of opium tincture per day. MRI was performed on day 1 (before treatment) and day 9 (during treatment). Measurements included assessments of gastric volume, gastric emptying, gastric motility, small bowel volume, small bowel water content, small bowel motility, colon volume, colon water content, and whole gut transit. Key Results: Opium tincture delayed gastric emptying by a mean difference of 5.6 min [95% CI: 1.8–9.4], p = 0.004, and increased postprandial gastric meal volume (17–21%, p = 0.02). Small bowel endpoints did not change. Opium tincture delayed whole gut transit time (p = 0.027) and increased ascending colon volume by 59 mL [95% CI: 15–103], p = 0.004, and transverse colon volume by 48 mL [95% CI: 4–92], p = 0.027. T1‐relaxation time of the descending colon chyme was decreased during opium treatment, indicating dryer feces (difference: −173 ms [95% CI: −336 ‐11], p = 0.03). Conclusion and Inferences: Opium tincture induced changes in the stomach and colon in healthy volunteers. An improved understanding of how opioids affect gut functions may lead to a better understanding and optimized management of diarrhea. [ABSTRACT FROM AUTHOR]

Tramadol is a weak opioid used to treat moderate pain. Stronger opioids inhibit gastrointestinal function, but little is known about the gastrointestinal effects of tramadol. Our aim was to investigate if tramadol causes opioid‐induced bowel dysfunction (OIBD). Twenty healthy male participants (mean age 24 [range 20–31] years) were included. Tramadol (extended‐release formulation, 200 mg/day) or placebo was administered for 10 days in two study periods separated by 3 weeks. Gastrointestinal transit times and segmental volume, motility and water content were investigated with the 3D‐transit system and magnetic resonance imaging. Bowel movements and gastrointestinal symptoms were recorded daily. Tramadol prolonged colonic transit time (34 h vs. 25 h, p < 0.001) and increased small bowel motility (p < 0.01) and water content (p = 0.002) compared to placebo. Across all days of treatment, tramadol reduced the number of mean daily bowel movements (p = 0.001) and increased mean stool consistency (p = 0.006). Gastrointestinal symptom scores increased with tramadol (indigestion: +358%, p = 0.01; constipation: +475%, p = 0.01). Additionally, more participants fulfilled the diagnostic criteria for constipation after tramadol treatment compared to placebo (40% vs. 0%, p < 0.001). This study showed that tramadol treatment is associated with OIBD, and management of constipation and other bowel symptoms should, therefore, be prioritised when treating pain patients with tramadol. [ABSTRACT FROM AUTHOR]

Background/Aims: During esophagectomy for malignancy, the anterior and posterior branches of the vagus nerve are transected in order to achieve surgical radicality. This leads to loss of central nervous system-control of the pylorus which may lead to delayed gastric emptying. We aimed to investigate the feasibility of the EndoFLIP technique for assessment of pyloric biomechanical properties in patients undergoing esophagectomy. Methods: A feasibility study in six patients undergoing surgery was conducted. EndoFLIP measurements were carried out preoperative (Pre-op), after surgical resection (Post-op) and following prophylactic balloon dilatation of the pylorus (Post-dil). By measuring the cross-sectional area and pressure of the pylorus the pyloric compliance and the incremental pressure-strain elastic modulus (Ep) were calculated. Results: Placing the catheter in the pyloric region was successfully achieved in all six patients. No complications were observed. Resection of the esophagus increased the incremental pyloric elastic modulus (Ep) from 0.59 ± 0.18 kPa to 0.99 ± 0.34 kPa (p = 0.03). After dilatation, the Ep was reduced to 0.53 ± 0.23 kPa (p = 0.04), which was close to Pre-op (p = 0.62). The pyloric compliance showed a similar pattern as that found for Ep. Conclusion: The EndoFLIP system holds promise for assessment of biomechanics of the pyloric region in patients undergoing esophagectomy for cancer. [ABSTRACT FROM AUTHOR]

Background: Spinal cord stimulation (SCS) has emerged as a treatment option for patients with chronic pancreatitis (CP) who experience pain that does not respond to standard interventions. However, there is a lack of sham‐controlled trials to support its efficacy. Methods: This randomized, double‐blinded, sham‐controlled, cross‐over trial enrolled 16 CP patients with insufficient pain relief from standard therapies. Patients underwent high‐frequency (1000 Hz) paraesthesia‐free SCS or sham for two 10‐day stimulation periods, separated by a 3‐day washout period. The primary outcome was daily pain intensity registered in a pain diary based on a numeric rating scale (NRS). Secondary outcomes included various questionnaires. Quantitative sensory testing was used to probe the pain system before and after interventions. Results: The average daily pain score on the NRS at baseline was 5.2 ± 1.9. After SCS, the pain score was 4.2 ± 2.1 compared to 4.3 ± 2.1 in the sham group (mean difference −0.1, 95% CI [−1.4 to 1.1]; P = 0.81). Similarly, no differences were observed between groups for the maximal daily pain score, secondary outcomes or quantitative sensory testing parameters. During an open‐label, non‐sham‐controlled and non‐blinded extension of the study, the average daily NRS was 5.2 ± 1.7 at baseline, 3.2 ± 1.8 at 3 months, 2.9 ± 1.9 at 6 months and 3.4 ± 2.2 at 12 months of follow‐up (P = 0.001). Conclusion: In this first sham‐controlled trial of SCS in painful CP, we did not find evidence of short‐term pain relief with paraesthesia‐free high‐frequency (1000 Hz) stimulation. However, evaluation of the long‐term effect by larger sham‐controlled trials with long‐term follow‐up is warranted. Significance Statement: In this first sham‐controlled trial to apply high‐frequency (1000 Hz) spinal cord stimulation in patients with visceral pain due to chronic pancreatitis, we did not find evidence for clinically relevant pain relief. Taken together with potential procedure‐related complications, adverse effects and costs associated with spinal cord stimulation, our findings question its use for management of visceral pain. [ABSTRACT FROM AUTHOR]

Objective: Chronic diarrhea affects approximately 5% of the population. Opioids inhibit gastrointestinal motility, and opium tincture has shown anti-propulsive effects in healthy, but no controlled studies of its clinical efficacy exist. We aimed to investigate the anti-propulsive and central nervous system (CNS) effects of opium tincture in patients with chronic diarrhea. Materials and methods: The study was a randomized, double-blinded, placebo-controlled, cross-over trial in subjects with chronic diarrhea refractory to standard treatment. Participants received opium tincture or placebo during two intervention periods, each lasting seven days. Bowel movements were recorded daily, and gastrointestinal transit time was investigated with the wireless motility capsule system. Gastrointestinal symptoms, health-related quality of life, and CNS effects (pupil size, reaction time, memory, and general cognition) were also investigated, along with signs of addiction. Results: Eleven subjects (mean age: 45 ± 17 years, 46% males) with a median of 4.7 daily bowel movements were included. The number of daily bowel movements was reduced during opium tincture treatment to 2.3 (p = 0.045), but not placebo (3.0, p = 0.09). Opium tincture prolonged the colonic transit time compared to placebo (17 h vs. 12 h, p < 0.001). In both treatment arms, there were no changes in self-reported gastrointestinal symptoms, health-related quality of life, or CNS effects, and no indication of addiction was present. Conclusion: Opium tincture induced anti-propulsive effects in patients with chronic diarrhea refractory to standard treatment. This indicates that opium tincture is a relevant treatment strategy for selected patients with chronic diarrhea. Moreover, no evidence of opioid-induced sedation or addiction was found. Trial Registration Number: NCT05690321 (registered 2023-01-10) [ABSTRACT FROM AUTHOR]

Aim To study social disparity in acute pancreatitis (AP) and chronic pancreatitis (CP).We also aimed at exploring whether an interaction exists between alcohol intake and socioeconomic factors. Methods Prospective cohort study based on data from 271 696 men and women participating in the Danish National Health Surveys 2010, and 2013. Information on alcohol and smoking parameters, body mass index (BMI), diet, and education, were self-reported and information on family income was obtained from administrative registers. Outcome variables (acute and chronic pancreatitis) were obtained from national health registers. Results The incidence rate ratio (IRR) of developing AP and CP increased with decreasing family income. Compared to participants in the highest income quintile, participants in the lowest income quintile had 43 (95% CI: 14–80%), 99 (95% CI: 26–214%), and 56% (95% CI: 26–94%) higher incidence rates of AP, CP, and all pancreatitis, respectively. The associations persisted after adjustment for alcohol intake, smoking, BMI, and diet. Likewise, participants with only primary school education had an IRR for an AP of 1.30 (95% CI: 1.06–1.59) compared to those with higher education after adjustment for baseline year, age, and sex. We found no interactions between alcohol intake and income or between alcohol intake and education in relation to neither AP, CP, nor all pancreatitis. Conclusion This large prospective population study showed a significant social disparity in incidence rates of pancreatitis by family income, with higher rates among those with the lowest income and education independent of risk factors such as alcohol intake, smoking, BMI, and diet. [ABSTRACT FROM AUTHOR]

Intra-pancreatic fat deposition (IPFD) is suspected to be associated with various medical conditions. This study aimed to assess pancreatic fat content in lean and obese individuals, characterize obese individuals with and without IPFD, and explore the underlying mechanisms. Sixty-two obese individuals without diabetes and 35 lean controls underwent magnetic resonance imaging (MRI) using proton density fat fraction (PDFF) maps to evaluate pancreatic and hepatic fat content, and visceral adipose tissue (VAT) content. Pancreatic fibrosis was explored by T1 relaxation time and MR elastography (MRE) measurements. Associations between pancreatic fat, measures of obesity and metabolic syndrome were examined using uni- and multivariate regression analyses. Pancreatic PDFF was higher in obese than in lean controls (median 8.0%, interquartile range (6.1;13.3) % vs 2.6(1.7;3.9)%, p < 0.001). Obese individuals with IPFD (PDFF ≥6.2%) had higher waist circumference (114.0 ± 12.5 cm vs 105.2 ± 8.7 cm, p = 0.007) and VAT (224.9(142.1; 316.1) cm2 vs 168.2(103.4; 195.3) cm2, p < 0.001) than those without. In univariate analysis, pancreatic PDFF in obese individuals correlated with BMI (r = 0.27, p = 0.03), waist circumference (r = 0.44, p < 0.001), VAT (r = 0.37, p = 0.004), hepatic PDFF (r = 0.25, p = 0.046) and diastolic blood pressure (r = 0.32, p = 0.01). However, in multivariate analysis, only VAT was associated to pancreatic fat content. MRI measures of pancreatic fibrosis indicated no evident fibrosis in relation to increased pancreatic fat content. Pancreatic fat content was increased in obese individuals compared with lean controls and predominantly correlated with the amount of visceral adipose tissue. Pancreatic fat content was not clearly linked to measures of pancreatic fibrosis. [ABSTRACT FROM AUTHOR]

Background: The functional lumen imaging probe (FLIP) is a test of anal sphincter distensibility under evaluation by specialist centers. Two measurement protocols termed "stepwise" and "ramp" are used, risking a lack of standardization. This study aims to compare the performance of these protocols to establish if there are differences between them. Methods: Patients with fecal incontinence were recruited and underwent measurement with both protocols at a tertiary pelvic floor referral unit. Differences in minimum diameter, FLIP bag pressure, and distensibility index (DI) at rest and during squeeze were calculated at various FLIP bag volumes. Key Results: Twenty patients (19 female, mean age 61 [range: 38–78]) were included. The resting minimum diameter at 30 and 40 mL bag volumes were less in the stepwise protocol (mean bias: −0.55 mm and −1.18 mm, p < 0.05) along with the DI at the same bag volumes (mean bias: −0.37 mm2/mmHg and −0.55 mm2/mmHg, p < 0.05). There was also a trend towards greater bag pressures at 30 mL (mean bias: +2.08 mmHg, p = 0.114) and 40 mL (mean bias: +2.81 mmHg, p = 0.129) volumes in the stepwise protocol. There were no differences between protocols in measurements of minimum diameter, maximum bag pressure, or DI during voluntary squeeze (p > 0.05). Conclusion and Inferences: There are differences between the two commonly described FLIP measurement protocols at rest, although there are no differences in the assessment of squeeze function. Consensus agreement is required to agree the most appropriate FLIP measurement protocol in assessing anal sphincter function. [ABSTRACT FROM AUTHOR]

Background and Objective: Pain is a major clinical challenge, and understanding the pathophysiology is critical for optimal management. The autonomic nervous system reacts to pain stimuli, and autonomic dysfunction may predict pain sensation. The most used assessment of autonomic function is based on electrocardiographic measures, and the ability of such measures to predict pain was investigated. Databases and Data Treatment: English articles indexed in PubMed and EMBASE were reviewed for eligibility and included when they reported electrocardiographic‐derived measures' ability to predict pain response. The quality in prognostic studies (QUIPS) tool was used to assess the quality of the included articles. Results: The search revealed 15 publications, five on experimental pain, five on postoperative pain, and five on longitudinal clinical pain changes, investigating a total of 1069 patients. All studies used electrocardiographically derived parameters to predict pain assessed with pain thresholds using quantitative sensory testing or different scales. Across all study modalities, electrocardiographic measures were able to predict pain. Higher parasympathetic activity predicted decreased experimental, postoperative, and long‐term pain in most cases while changes in sympathetic activity did not consistently predict pain. Conclusions: Most studies demonstrated that parasympathetic activity could predict acute and chronic pain intensity. In the clinic, this may be used to identify which patients need more intensive care to prevent, for example postoperative pain and develop personalized chronic pain management. Significance: Pain is a debilitating problem, and the ability to predict occurrence and severity would be a useful clinical tool. Basal autonomic tone has been suggested to influence pain perception. This systematic review investigated electrocardiographic‐derived autonomic tone and found that increased parasympathetic tone could predict pain reduction in different types of pain. [ABSTRACT FROM AUTHOR]

To investigate the co-existence of hepatic and pancreatic fibrosis using magnetic resonance elastography (MRE) in chronic pancreatitis (CP), including the association between hepatic and pancreatic MRE-derived stiffness and exploration of potential etiological risk factors. Fifty-four CP patients and 35 healthy controls underwent hepatic and pancreatic MRE with measurements of tissue stiffness. Clinical parameters including stage (probable or definite CP), etiology of CP, the presence of diabetes or exocrine insufficiency, and previous history of common bile duct stenosis were assessed. Uni- and multivariate regression models were used to investigate risk factors associated with hepatic fibrosis/stiffness in CP patients. Fifteen percent of CP patients and none of the controls had abnormal liver stiffness (>2.5 kPa), p = 0.02. 5.6% of CP patients had liver stiffness indicating F1 fibrosis (>2.93 kPa). However, hepatic stiffness was not higher in patients than in healthy controls (2.20 ± 0.41 vs 2.08 ± 0.21 kPa, p = 0.10). In patients, a positive association was seen between hepatic and pancreatic stiffness (r = 0.270, p = 0.048). In the multivariate analysis (adjusted for age, gender and BMI), liver stiffness was significantly associated with alcoholic etiology of CP (p = 0.029). In contrast, stage of CP, history of common bile duct stenosis, and the presence of diabetes or exocrine insufficiency were not associated with liver stiffness (all p > 0.14). Only a modest co-existence of hepatic and pancreatic fibrosis was observed in CP. However, the positive association between hepatic and pancreatic stiffness indicates some level of common pathophysiology. Especially, alcoholic etiology of CP was related to increased hepatic stiffness. [ABSTRACT FROM AUTHOR]

The article discusses the use of pan-alimentary magnetic resonance imaging (MRI) to diagnose and treat severe gastroparesis in a 51-year-old male patient with Type 1 diabetes. The MRI protocol provided detailed images of the stomach, small bowel, and colon, revealing delayed gastric emptying and constipation. Treatment adjustments were made based on the MRI findings, including an endoscopic pyloromyotomy to relieve symptoms. The study highlights the potential of MRI in improving diagnostic accuracy and treatment planning for gastrointestinal disorders. [Extracted from the article]

Methods: The review was conducted adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist., Results: 15 studies including 147 patients (adult n = 71/paediatric n = 76) reported on CGM use post-TP (n = 42) and TPIAT (n = 105). 4 were randomized controlled trials and 10 observational studies. 6 studies evaluated CGM use in the peri-operative and 6 in the immediate post-operative period (n = 8) with variable follow-up (14 hours -20 months). CGM was used as a stand-alone device (8 studies) which allowed assessment of dynamic islet function and detection of hypoglycemia (n = 1) resulting in lower glucose levels (n = 1). 6 studies evaluated insulin pump with CGM with reduction in post-operative mean glucose (n = 4), and hypoglycaemic episodes (n = 2). There were no patient reported outcome measures (PROMs) or quality of life (QoL) measures reported., Conclusions: CGM can be used following TP for glucose monitoring and/or linked with insulin pump device in the peri-operative period with improved glycaemic control. However, the data are limited by short follow-up and lack of PROMs and QoL measures., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Autonomic neuropathy is associated with dysglycemia that is difficult to control. We investigated if transcutaneous vagus nerve stimulation (tVNS) could improve glycemic levels. Methods: We randomized 145 individuals with type 1 diabetes (T1D) ( n = 70) or type 2 diabetes (T2D) ( n = 75) and diabetic autonomic neuropathy (DAN) to self-administered treatment with active cervical tVNS ( n = 68) or sham ( n = 77) for 1 week (4 daily stimulations) and 8 weeks (2 daily stimulations), separated by a wash-out period of at least 2 weeks. Continuous glucose monitoring (CGM) indices were measured for 104 participants starting 5 days prior to intervention periods, during the 1-week period, and at end of the 8-week period. Primary outcomes were between-group differences in changes in coefficient of variation (CV) and in time in range (TIR 3.9-10 mmol/L). Secondary outcomes were other metrics of CGM and HbA1c. Results: For the 1-week period, median [interquartile range] changes of CV from baseline to follow-up were -1.1 [-4.3;2.0] % in active and -1.5 [-4.4;2.5] % in sham, with no significance between groups ( P = 0.54). For TIR, the corresponding changes were 2.4 [-2.1;7.4] % in active and 5.1 [-2.6;8.8] in sham group ( P = 0.84). For the 8-week treatment period, changes in CV and TIR between groups were also nonsignificant. However, in the subgroup analysis, persons with T1D receiving active tVNS for 8 weeks had a significant reduction in CV compared with the T1D group receiving sham stimulation (estimated treatment effect: -11.6 [95% confidence interval -20.2;-2.0] %, P = 0.009). None of the changes in secondary outcomes between treatment groups were significantly different. Conclusions: Overall, no significant changes were observed in CGM metrics between treatment arms, while individuals with T1D and DAN decreased their CV after 8 weeks of tVNS treatment.

The basic principle for the treatment of idiopathic diarrhoea (functional diarrhoea K59.1) is to delay transit through the gut in order to promote the absorption of electrolytes and water. Under mild conditions, bulking agents may suffice. With increasing severity, antidiarrhoeal pharmaceuticals may be added in a stepwise manner. In diarrhoea of unknown aetiology, peripherally-acting opioid receptor agonists, such as loperamide, are first-line treatment and forms the pharmaceutical basis of antidiarrheal treatment. As second-line treatment opium drops have an approved indication for severe diarrhoea when other treatment options fail. Beyond this, various treatment options are built on experience with more advanced treatments using clonidine, octreotide, as well as GLP-1 and GLP-2 analogs which require specialist knowledge the field.

Introduction: Treatment for abdominal pain in patients with chronic pancreatitis (CP) remains challenging in the setting of central nervous system sensitisation, a phenomenon of remodelling and neuronal hyperexcitability resulting from persistent pain stimuli. This is suspected to render affected individuals less likely to respond to conventional therapies. Endotherapy or surgical decompression is offered to patients with pancreatic duct obstruction. However, the response to treatment is unpredictable. Pancreatic quantitative sensory testing (P-QST), an investigative technique of standardised stimulations to test the pain system in CP, has been used for phenotyping patients into three mutually exclusive groups: no central sensitisation, segmental sensitisation (pancreatic viscerotome) and widespread hyperalgesia suggestive of supraspinal central sensitisation. We will test the predictive capability of the pretreatment P-QST phenotype to predict the likelihood of pain improvement following invasive treatment for painful CP., Methods and Analysis: This observational clinical trial will enrol 150 patients from the University of Pittsburgh, Johns Hopkins and Indiana University. Participants will undergo pretreatment phenotyping with P-QST. Treatment will be pancreatic endotherapy or surgery for clearance of painful pancreatic duct obstruction., Primary Outcome: average pain score over the preceding 7 days measured by Numeric Rating Scale at 6 months postintervention. Secondary outcomes will include changes in opioid use during follow-up, and patient-reported outcomes in pain and quality of life at 3, 6 and 12 months after the intervention. Exploratory outcomes will include creation of a model for individualised prediction of response to invasive treatment., Ethics and Dissemination: The trial will evaluate the ability of P-QST to predict response to invasive treatment for painful CP and develop a predictive model for individualised prediction of treatment response for widespread use. This trial was approved by the University of Pittsburgh Institutional Review Board. Data and results will be reported and disseminated in conjunction with National Institutes of Health policies., Trial Registration Number: NCT04996628., Competing Interests: Competing interests: AEP: Board Member, National Pancreas Foundation. VKS: Consultant to Abbvie, Ariel Precision Medicine, Horizon Therapeutics and Panafina; Medical Advisory Board participant to Organon; Scientific advisory board participant for Kyttaro, Origin Endoscopy and Solv Endoscopy; Equity holder in Kyttaro, Origin Endoscopy, Solv Endoscopy. The other authors have no financial or personal competing interests to declare., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)