Avoiding the use of long-term parenteral support in patients without intestinal failure: A position paper from the European Society of Clinical Nutrition & Metabolism, the European Society of Neurogastroenterology and Motility and the Rome Foundation for Disorders of Gut-Brain Interaction.

The role of long-term parenteral support in patients with underlying benign conditions who do not have intestinal failure (IF) is contentious, not least since there are clear benefits in utilising the oral or enteral route for nutritional support. Furthermore, the risks of long-term home parenteral nutrition (HPN) are significant, with significant impacts on morbidity and mortality. There has, however, been a recent upsurge of the use of HPN in patients with conditions such as gastro-intestinal neuromuscular disorders, opioid bowel dysfunction, disorders of gut-brain interaction and possibly eating disorders, who do not have IF. As a result, the European Society of Clinical Nutrition and Metabolism (ESPEN), the European Society of Neuro-gastroenterology and Motility (ESNM) and the Rome Foundation for Disorders of Gut Brain Interaction felt that a position statement is required to clarify - and hopefully reduce the potential for harm associated with - the use of long-term parenteral support in patients without IF. Consensus opinion is that HPN should not be prescribed for patients without IF, where the oral and/or enteral route can be utilised. On the rare occasions that PN commencement is required to treat life-threatening malnutrition in conditions such as those listed above, it should only be prescribed for a time-limited period to achieve nutritional safety, while the wider multi-disciplinary team focus on more appropriate biopsychosocial holistic and rehabilitative approaches to manage the patient's primary underlying condition.

Avoiding the use of long-term parenteral support in patients without intestinal failure: A position paper from the European Society of Clinical Nutrition & Metabolism, the European Society of Neurogastroenterology and Motility and the Rome Foundation for Disorders of Gut-Brain Interaction.

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Habitat selection of resident and non-resident gray wolves: implications for habitat connectivity.

Habitat selection studies facilitate assessing and predicting species distributions and habitat connectivity, but habitat selection can vary temporally and among individuals, which is often ignored. We used GPS telemetry data from 96 Gray wolves (Canis lupus) in the western Great Lakes region of the USA to assess differences in habitat selection while wolves exhibited resident (territorial) or non-resident (dispersing or floating) movements and discuss implications for habitat connectivity. We used a step-selection function (SSF) to assess habitat selection by wolves exhibiting resident or non-resident movements, and modeled circuit connectivity throughout the western Great Lakes region. Wolves selected for natural land cover and against areas with high road densities, with no differences in selection among wolves when resident, dispersing, or floating. Similar habitat selection between resident and non-resident wolves may be due to similarity in environmental conditions, when non-resident movements occur largely within established wolf range rather than near the periphery or beyond the species range. Alternatively, non-resident wolves may travel through occupied territories because higher food availability or lower human disturbance outweighs risks posed by conspecifics. Finally, an absence of differences in habitat selection between resident and non-resident wolf movements may be due to other unknown reasons. We recommend considering context-dependency when evaluating differences in movements and habitat use between resident and non-resident individuals. Our results also provide independent validation of a previous species distribution model and connectivity analysis suggesting most potential wolf habitat in the western Great Lakes region is occupied, with limited connectivity to unoccupied habitat.

Review article: Functional dyspepsia-a gastric disorder, a duodenal disorder or a combination of both?

BACKGROUND: Functional dyspepsia (FD) is one of the most frequent conditions in gastroenterological outpatient health care. Most recent research in FD has shifted its focus to duodenal pathophysiological mechanisms, although current treatments still focus mainly the stomach. AIM: The aim of the study was to provide a comprehensive overview of the pathophysiology of FD focusing on a paradigm shift from gastric towards duodenal mechanisms. METHODS: We conducted a literature search in PubMed for studies describing mechanisms that could possibly cause FD. RESULTS: The pathophysiology of FD remains incompletely understood. Recent studies show that duodenal factors such as acid, bile salt exposure and eosinophil and mast cell activation correlate with symptom pattern and burden and can be associated with gastric sensorimotor dysfunction. The evolving data identify the duodenum an interesting target for new therapeutic approaches. Furthermore, the current first-line treatment, that is proton pump inhibitors, reduces duodenal low-grade inflammation and FD symptoms. CONCLUSION: Future research for the treatment of FD should focus on the inhibition of duodenal mast cell activation, eosinophilia and loss of mucosal integrity.

Distribution model transferability for a wide-ranging species, the Gray Wolf.

Using existing data can be a reliable and cost-effective way to predict species distributions, and particularly useful for recovering or expanding species. We developed a current gray wolf (Canis lupus) distribution model for the western Great Lakes region, USA, and evaluated the spatial transferability of single-state models to the region. This study is the first assessment of transferability in a wide-ranging carnivore, as well as one of few developed for large spatial extents. We collected 3500 wolf locations from winter surveys in Minnesota (2017-2019), Wisconsin (2019-2020), and Michigan (2017-2020). We included 10 variables: proportion of natural cover, pastures, and crops; distance to natural cover, agriculture, developed land, and water; major and minor road density; and snowfall (1-km res.). We created a regional ensemble distribution by weight-averaging eight models based on their performance. We also developed single-state models, and estimated spatial transferability using two approaches: state cross-validation and extrapolation. We assessed performance by quantifying correlations, receiver operating characteristic curves (ROC), sensitivities, and two niche similarity indices. The regional area estimated to be most suitable for wolves during winter (threshold = maximum sensitivity/specificity) was 106,465 km2 (MN = 48,083 km2, WI = 27,757 km2, MI = 30,625 km2) and correctly predicted 88% of wolf locations analyzed. Increasing natural cover and distance to crops were consistently important for determining regional and single-state wolf distribution. Extrapolation (vs. cross-validation) produced results with the greatest performance metrics, and were most similar to the regional model, yet good internal performance was unrelated to greater extrapolation performance. Factors influencing species distributions are scale-dependent and can vary across areas due to behavioral plasticity. When extending inferences beyond the current occurrence of individuals, assessing variation in ecology such as habitat selection, as well as methodological factors including model performance, will be critical to avoid poor scientific interpretations and develop effective conservation applications. In particular, accurate distribution models for recovering or recovered carnivores can be used to develop plans for habitat management, quantify potential of unoccupied habitat, assess connectivity modeling, and mitigate conflict, facilitating long-term species persistence.

Belgian consensus on irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is characterised by recurrent abdominal pain related to defaecation or associated with altered stool frequency or consistency. Despite its prevalence, major uncertainties in the diagnostic and therapeutic management persist in clinical practice. METHODS: A Delphi consensus was conducted by 20 experts from Belgium, and consisted of literature review and voting process on 78 statements. Grading of recommendations, assessment, development and evaluation criteria were applied to evaluate the quality of evidence. Consensus was defined as > 80 % agreement. RESULTS: Consensus was reached for 50 statements. The Belgian consensus agreed as to the multifactorial aetiology of IBS. According to the consensus abdominal discomfort also represents a cardinal symptom, while bloating and abdominal distension often coexist. IBS needs subtyping based on stool pattern. The importance of a positive diagnosis, relying on history and clinical examination is underlined, while additional testing should remain limited, except when alarm features are present. Explanation of IBS represents a crucial part of patient management. Lifestyle modification, spasmolytics and water-solube fibres are considered first-line agents. The low FODMAP diet, selected probiotics, cognitive behavioural therapy and specific treatments targeting diarrhoea and constipation are considered appropriate. There is a consensus to restrict faecal microbiota transplantation and gluten-free diet, while other treatments are strongly discouraged. CONCLUSIONS: A panel of Belgian gastroenterologists summarised the current evidence on the aetiology, symptoms, diagnosis and treatment of IBS with attention for the specificities of the Belgian healthcare system.

Therapeutic efficacy of the root tubers of Aconitum heterophyllum and its substitute Cyperus rotundus in the amelioration of pylorus ligation induced ulcerogenic and oxidative damage in rats.

The phenomenal increase in the demand of herbal drugs, leads to over exploitation of medicinal plants which ultimately resulted in the scarcity and endangerment of many valuable plant species. On observing the difficulties in procuring genuine herbal drugs arose the concept of substitution which was documented in many classical Ayurvedic texts. The present study made a comparative evaluation of the gastroprotective potential of hydroalcoholic extracts of an original drug Aconitum heterophyllum (HAAH) and its substitute Cyperus rotundus (HACR) in the treatment of gastric ulcer under in vivo experimental conditions. The anti-ulcer property of the plant extracts was investigated against pylorus ligation induced ulcer in Wistar albino rats. The results confirmed that both A. heterophyllum and C. rotundus deliver comparable significant protection against gastric ulcer, indicated by a decrease in the free and total acidity, volume of gastric content, total proteins and increase in pH of gastric content, total carbohydrates and total carbohydrates to total proteins ratio. The observed anti-ulcer potential of both the drugs is attributed mainly to prevention of the generation of damaging free radical cascades and oxidant radical release.

Green synthesis and characterization of gold nanoparticles using endophytic fungi Fusarium solani and its in-vitro anticancer and biomedical applications.

The present study aimed to explore the anticancer potentials of the gold nanoparticles (NPs) obtained by green synthesis method using an endophytic strain Fusarium solani ATLOY - 8 has been isolated from the plant Chonemorpha fragrans. The formation of the NPs was analyzed by UV, FTIR, SEM and XRD. The synthesized NPs showed pink-ruby red colors and high peak plasmon band was observed between 510 and 560 nm. It is observed that intensity of absorption steadily increases the wavelength and band stabilizes at 551 nm. The XRD pattern revealed the angles at 19, 38.32, 46.16, 57.50, and 76.81° respectively. Interestingly, the FTIR band absorption noted at 1413 cm-1, 1041 cm-1 and 690 cm-1 ascribed the presence of amine II bands of protein, C-N and C-H stretching vibrations of the nanoparticles. SEM analysis indicated that the average diameter of the synthesized nanoparticles was between 40 and 45 nm. These NPs showed cytotoxicity on cervical cancer cells (He La) and against human breast cancer cells (MCF-7) and the NPs exhibited dose dependent cytotoxic effect. IC50 value was 0.8 ± 0.5 µg/mL on MCF-7 cell line and was found to be 1.3 ± 0.5 µg/mL on MCF-7 cell lines. The synthesized NPs induced apoptosis on these cancer cell lines. The accumulation of apoptotic cells decreased in sub G0 and G1 phase of cell cycle in the MCF-7 cancer cells were found to be 55.13%, 52.11% and 51.10% after 12 h exposure to different concentrations. The results altogether provide an apparent and versatile biomedical application for safer chemotherapeutic agent with little systemic toxicity.

Evaluation of antidiabetic activity of Pleurotus pulmonarius against streptozotocin-nicotinamide induced diabetic wistar albino rats.

The current research aims to evaluate the antidiabetic properties of Pleurotus pulmonarius, an edible basidiomycetes mushroom fungi in diabetic induced wistar albino rats. Mycelial Hot Water Extracts (HWE) and Acetone Extracts (AE) of Pleurotus pulmonarius was orally administrated to STZ-NA induced (55 mg/kilogram body weight) diabetic wistar albino rats at a concentration of 200 and 400 mg/kg for 4 weeks. The outcomes revealed that the HWE of Pleurotus pulmonarius resulted in a significant (p < 0.001) reduction in blood glucose level. A noteworthy (p < 0.001) reduction in serum lipid profile and elevation in High-Density Lipoprotein Cholesterol (HDL-C) after administration with HWE, also demonstrating the protective effects of HWE in diabetes-related complications. Besides all antidiabetic parameters, pathological morphology of the pancreas, liver and kidney are regularised. This observation indicated that HWE of Pleurotus pulmonarius possessed higher antidiabetic activity than AE. Besides, HWE also promoted a significant control of alpha amylase enzyme in a concentration-dependent manner with a maximum activity of 99.23% inhibition at 1000 µg/ml. The outcomes of the present study indicated that the HWE possesses a potential antidiabetic activity both in vitro and in vivo. Thus, it can be used as a nontoxic complementary drug in the controlling of diabetes and related complications, thus providing scientific authentication of its use as an antidiabetic agent.

Current and emerging therapeutic options for the management of functional dyspepsia.

Introduction: Functional Dyspepsia (FD), defined as chronic symptoms originating from the gastroduodenal region in absence of readily identifiable organic disease, is one of the most common gastrointestinal disorders. FD is divided into two subgroups: Post-Prandial Distress Syndrome (PDS) or meal-related FD, characterized by postprandial fullness and early satiation, and Epigastric Pain Syndrome (EPS) or meal-unrelated FD, characterized by epigastric pain and burning.Areas covered: This review summarizes the existing and off-label therapeutic options for FD.Expert opinion: The identification of mechanisms, the Rome IV classification, the reduction of PDS/EPS overlap and pictograms for symptom identification allow a better diagnosis and a more targeted treatment choice. Acotiamide, a first-in-class prokinetic agent available only in Japan and India, is the only agent of proven efficacy for FD, but clinicians use acid-suppressive therapy, prokinetics, neuromodulators and herbal therapies for treating FD symptoms. New emerging targets are duodenal low-grade inflammation with eosinophils and duodenal or other modified luminal microbiota.

Analysis of Postprandial Symptom Patterns in Subgroups of Patients With Rome III or Rome IV Functional Dyspepsia.

BACKGROUND & AIMS: Among patients with functional dyspepsia (FD), there is overlap in symptoms between those in the Rome III subgroups of postprandial distress syndrome (PDS) and those with epigastric pain syndrome (EPS). The Rome IV consensus proposed to incorporate all patients with postprandial symptoms into the PDS group. We aimed to evaluate the assessment of meal-related dyspepsia symptoms in patients with FD according to the Rome III vs Rome IV subdivisions. METHODS: Consecutive patients with FD referred for a gastric emptying test (n = 96) were asked to fill out the Rome III gastroduodenal questionnaire, with questions on meal-related occurrence. Study participants underwent a gastric emptying breath test, during which the intensity of dyspeptic symptoms (fullness, bloating, belching, nausea, epigastric pain, and burning) was scored before and up to 4 hours after a meal. We analyzed the association between the Rome subdivision and symptom severity and pattern during the breath test. RESULTS: According to Rome III, 10% had EPS alone, 29% PDS alone, and 61% overlapping EPS and PDS. The frequency of the symptoms reported in the Rome questionnaire associated with the intensity of the symptoms during the breath test in the PDS group and in the groups with PDS and EPS overlap, but not in the group with EPS. We adapted the definition of the PDS subgroup to include patients with meal-related non-PDS symptoms (Rome IV); this reduced the proportion of patients with overlap of EPS and PDS symptoms from 61% to 18% and in this group the association of symptoms with the meal was reduced. CONCLUSIONS: In an analysis of patients with FD, a meal induced or exacerbated symptoms in most patients. The Rome IV criteria for PDS reduce the proportions categorized as having both PDS and EPS and identify a patient group whose symptoms are associated with the meals. University hospital of Leuven study no: S55426.

Prevalence and impact of self-reported irritable bowel symptoms in the general population.

Background and aims: The symptom-based diagnostic criteria for irritable bowel syndrome (IBS) have recently been revised in the Rome IV consensus. On the other hand, with rising public awareness of IBS, self-diagnosis and self-management is also increasing. We compared the prevalence and impact of Rome IV-based IBS vs self-diagnosed IBS in the general population. Methods: An internet panel filled out an online survey on bowel symptoms and their impact on health care utilization and daily activities. Results: A representative internet panel of 1012 individuals completed the online survey. Bowel symptoms were present in 68.6% of the population. Of these, 21% consulted a physician for these symptoms in the last year and 42% earlier. Rome IV IBS criteria were fulfilled by 5.5%, and these were younger and more likely to be female. In this subset, 37% had consulted a physician for IBS symptoms in the preceding year and 29% had done so earlier. A colonoscopy had been performed in 22%. Based on a brief description, 17.6% of the population self-identified as suffering from IBS (p < 0.001 compared to Rome IV IBS prevalence), and these were more likely to be female. Concordance with the Rome IV criteria was only 25%, but except for a lower reporting of pain, the symptom pattern, severity, impact on daily life, inability to work and health care utilization were similar to the Rome IV group. A total of 134 days of absence from work were attributed to bowel symptoms in those self-reporting with IBS. Conclusion: In the general population, bowel symptoms are highly prevalent, and the self-reported "IBS" is three times more prevalent than according to Rome IV criteria. Self-reported IBS is associated with a similar impact on health care utilization and quality of life but a higher impact on absence from work.

The 2018 ISDE achalasia guidelines.

Achalasia is a relatively rare primary motor esophageal disorder, characterized by absence of relaxations of the lower esophageal sphincter and of peristalsis along the esophageal body. As a result, patients typically present with dysphagia, regurgitation and occasionally chest pain, pulmonary complication and malnutrition. New diagnostic methodologies and therapeutic techniques have been recently added to the armamentarium for treating achalasia. With the aim to offer clinicians and patients an up-to-date framework for making informed decisions on the management of this disease, the International Society for Diseases of the Esophagus Guidelines proposed and endorsed the Esophageal Achalasia Guidelines (I-GOAL). The guidelines were prepared according the Appraisal of Guidelines for Research and Evaluation (AGREE-REX) tool, accredited for guideline production by NICE UK. A systematic literature search was performed and the quality of evidence and the strength of recommendations were graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Given the relative rarity of this disease and the paucity of high-level evidence in the literature, this process was integrated with a three-step process of anonymous voting on each statement (DELPHI). Only statements with an approval rate >80% were accepted in the guidelines. Fifty-one experts from 11 countries and 3 representatives from patient support associations participated to the preparations of the guidelines. These guidelines deal specifically with the following achalasia issues: Diagnostic workup, Definition of the disease, Severity of presentation, Medical treatment, Botulinum Toxin injection, Pneumatic dilatation, POEM, Other endoscopic treatments, Laparoscopic myotomy, Definition of recurrence, Follow up and risk of cancer, Management of end stage achalasia, Treatment options for failure, Achalasia in children, Achalasia secondary to Chagas' disease.

The 2018 ISDE achalasia guidelines

Achalasia is a relatively rare primary motor esophageal disorder, characterized by absence of relaxations of the lower esophageal sphincter and of peristalsis along the esophageal body. As a result, patients typically present with dysphagia, regurgitation and occasionally chest pain, pulmonary complication and malnutrition. New diagnostic methodologies and therapeutic techniques have been recently added to the armamentarium for treating achalasia. With the aim to offer clinicians and patients an up-to-date framework for making informed decisions on the management of this disease, the International Society for Diseases of the Esophagus Guidelines proposed and endorsed the Esophageal Achalasia Guidelines (I-GOAL). The guidelines were prepared according the Appraisal of Guidelines for Research and Evaluation (AGREE-REX) tool, accredited for guideline production by NICE UK. A systematic literature search was performed and the quality of evidence and the strength of recommendations were graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Given the relative rarity of this disease and the paucity of high-level evidence in the literature, this process was integrated with a three-step process of anonymous voting on each statement (DELPHI). Only statements with an approval rate >80% were accepted in the guidelines. Fifty-one experts from 11 countries and 3 representatives from patient support associations participated to the preparations of the guidelines. These guidelines deal specifically with the following achalasia issues: Diagnostic workup, Definition of the disease, Severity of presentation, Medical treatment, Botulinum Toxin injection, Pneumatic dilatation, POEM, Other endoscopic treatments, Laparoscopic myotomy, Definition of recurrence, Follow up and risk of cancer, Management of end stage achalasia, Treatment options for failure, Achalasia in children, Achalasia secondary to Chagas' disease.

The effect of sildenafil on gastric motility and satiation in healthy controls.

Sildenafil induces relaxation of smooth muscle cells by blocking PDE5. Dyspepsia is one of sildenafil's most frequently reported adverse events, suggesting its effect on gastric motility. Our aim was to study the effect of sildenafil on gastric accommodation (GA) and gastric emptying (GE) in healthy volunteers (HVs). METHODS: Sildenafil (50 mg) or placebo was randomly administered to 16 blinded HVs. After a manometry probe and an infusion catheter were positioned in the proximal stomach, the intragastric pressure (IGP) was measured before and during nutrient drink infusion (ND, 60 ml/min). HVs were asked to score their hunger, satiation and six epigastric symptoms at five-minute intervals. The experiment ended when the HVs scored maximal satiation during ND infusion at one-minute intervals. To assess GE, breath samples were collected every 15 minutes for six hours after the meal (244 kcal). RESULTS: ND infusion induced a drop in proximal stomach IGP, which was suppressed by sildenafil (average area under the curve for sildenafil: -33.6 ± 8.8 mmHg; placebo: -60.8 ± 11.3 mmHg, p = 0.005). Sildenafil-treated volunteers reached earlier maximal satiation compared to placebo (678 ± 70 ml vs. 836 ± 82.6 ml, p = 0.019). Finally, GE was significantly slower after sildenafil (90.6 ± 5.9 min vs. 76.6 ± 7.1 min, p = 0.04). CONCLUSION: Sildenafil inhibits GA, leading to significantly decreased nutrient tolerance, and slightly delays the GE rate in humans.

A single-center audit of the indications and clinical impact of prolonged ambulatory small intestinal manometry.

BACKGROUND: Small bowel manometry is a diagnostic test available only in a few specialized referral centers. Its exact place in the management of refractory symptoms is controversial. METHODS: The records of all patients who underwent 24-hour ambulatory duodenojejunal manometry over a 6-year period were retrospectively reviewed. We studied the clinical indications for small bowel manometry, and reviewed the impact of manometric findings on the clinical outcome. One hundred and forty-six studies were performed in 137 patients (46M, 91F) with a mean age of 44.9 ± 15.7 years. Mean follow-up duration was 15.1 ± 22.6 months. Appropriate endoscopic, radiological and gastric scintigraphy studies were performed in all patients prior to small bowel manometry. Criteria for abnormal motor activity were based on Bharucha's classification. KEY RESULTS: The indications for small bowel manometry were chronic abdominal pain (n = 43), slow-transit constipation (n = 17), refractory gastroparesis (n = 16), chronic diarrhea (n = 7), recurrent episodes of subocclusion (n = 16), postsurgical evaluation (n = 36), suspicion of gut involvement in systemic disease (n = 9), and unexplained nausea (n = 2). The most common finding was a normal 24-hour ambulatory small bowel manometry (n = 113). Thirty-three studies yielded abnormal findings which included extrinsic neuropathy (n = 6), intrinsic neuropathy (n = 18), intestinal myopathy (n = 2), and subocclusion (n = 7). Ambulatory small bowel manometry excluded a generalized motility disorder in 77% and had a significant impact on the subsequent clinical course in 23%. CONCLUSIONS & INFERENCES: Ambulatory small bowel manometry is a useful and safe diagnostic tool to complement traditional investigative modalities in patients with severe unexplained abdominal symptoms.

Safety and efficacy of pasireotide in dumping syndrome-results from a phase 2, multicentre study.

BACKGROUND: Dumping syndrome is a prevalent complication of oesophageal and gastric surgery characterised by early (postprandial tachycardia) and late (hypoglycaemia) postprandial symptoms. AIM: To evaluate efficacy and safety of the somatostatin analogue, pasireotide in patients with dumping syndrome after bariatric or upper gastrointestinal cancer surgery. METHODS: A single-arm, open-label, multicentre, intrapatient dose-escalation, phase 2 study with 4 phases: screening, 3-month SC (subcutaneous), 3-month IM (intramuscular) and 6-month optional extension IM phase. Primary endpoint was the proportion of patients without hypoglycaemia (plasma glucose <3.3 mmol/L [60 mg/dL] during an oral glucose tolerance test, OGTT) at the end of 3-month SC phase. A ≥50% response rate was considered clinically relevant. RESULTS: Forty-three patients with late dumping were enrolled; 33 completed the 3-month SC phase and 23 completed the 12-month study. The proportion of patients without hypoglycaemia at month 3 (primary endpoint) was 60.5% (26 of 43; 95% confidence interval, 44.4%-75.0%). Improvement in quality of life was observed during SC phase, which was maintained in the IM phase. The proportion of patients with a rise in pulse rate of ≥10 beats/min during OGTT reduced from baseline (60.5%) to month 3 (18.6%) and month 12 (27.3%). Overall (month 0-12), the most frequent (>20% of patients) adverse events were headache (34.9%); diarrhoea, hypoglycaemia (27.9% each); fatigue, nausea (23.3% each); and abdominal pain (20.9%). CONCLUSION: These results suggest that pasireotide is a promising option in patients with dumping syndrome after bariatric or upper gastrointestinal cancer surgery.