Coffee, Alcohol, and Artificial Sweeteners Have Temporal Associations with Gastrointestinal Symptoms.

BACKGROUND: Various dietary strategies for managing irritable bowel syndrome (IBS) target mechanisms such as brain-gut interactions, osmotic actions, microbial gas production, and local immune activity. These pathophysiological mechanisms are diverse, making it unclear which foods trigger IBS symptoms for a substantial proportion of patients. AIM: To identify associations between foods and gastrointestinal symptoms. METHODS: From the mySymptoms smartphone app, we collected anonymized diaries of food intake and symptoms (abdominal pain, diarrhea, bloating, and gas). We selected diaries that were at least 3 weeks long. The diaries were analyzed for food-symptom associations using a proprietary algorithm. As the participants were anonymous, we conducted an app-wide user survey to identify IBS diagnoses according to Rome IV criteria. RESULTS: A total of 9,710 food symptom diaries that met the quality criteria were collected. Of the survey respondents, 70% had IBS according to Rome IV criteria. Generally, strong associations existed for caffeinated coffee (diarrhea, 1-2 h postprandial), alcoholic beverages (multiple symptoms, 4-72 h postprandial), and artificial sweeteners (multiple symptoms, 24-72 h postprandial). Histamine-rich food intake was associated with abdominal pain and diarrhea. Some associations are in line with existing literature, whilst the absence of an enriched FODMAP-symptom association contrasts with current knowledge. CONCLUSIONS: Coffee, alcohol, and artificial sweeteners were associated with GI symptoms in this large IBS-predominant sample. Symptom onset is often within 2 h postprandial, but some foods were associated with a delayed response, possibly an important consideration in implementing dietary recommendations. Clinical trials must test the causality of the demonstrated food-symptom associations.

Post-Coronavirus Disease 2019 Pandemic Antimicrobial Resistance.

BACKGROUND AND AIM: Antimicrobial resistance (AMR) is a chronic issue of our Westernized society, mainly because of the uncontrolled and improper use of antimicrobials. The coronavirus disease 2019 (COVID-19) pandemic has triggered and expanded AMR diffusion all over the world, and its clinical and therapeutic features have changed. Thus, we aimed to review evidence from the literature on the definition and causative agents of AMR in the frame of the COVID-19 post-pandemic era. METHODS: We conducted a search on PubMed and Medline for original articles, reviews, meta-analyses, and case series using the following keywords, their acronyms, and their associations: antibiotics, antimicrobial resistance, severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), COVID-19 pandemic, personal protective equipment. RESULTS: AMR had a significant rise in incidence both in in-hospital and outpatient populations (ranging from 5 up to 50%) worldwide, but with a variegated profile according to the germ and microorganism considered. Not only bacteria but also fungi have developed more frequent and diffuse AMR. These findings are explained by the increased use and misuse of antibiotics and preventive measures during the first waves of the SARS-CoV2 pandemic, especially in hospitalized patients. Subsequently, the reduction in and end of the lockdown and the use of personal protective equipment have allowed for the indiscriminate circulation of resistant microorganisms from low-income countries to the rest of the world with the emergence of new multi- and polyresistant organisms. However, there is not a clear association between COVID-19 and AMR changes in the post-pandemic period. CONCLUSIONS: AMR in some microorganisms has significantly increased and changed its characteristics during and after the end of the pandemic phase of COVID-19. An integrated supranational monitoring approach to this challenge is warranted in the years to come. In detail, a rational, personalized, and regulated use of antibiotics and antimicrobials is needed.

Epidemiology of functional dyspepsia and gastroparesis as diagnosed in Flemish-Belgian primary care: A registry-based study from the Intego database.

BACKGROUND: Dyspepsia is a prevalent condition in the general population. Besides organic causes, the differential diagnosis of dyspepsia includes functional dyspepsia (FD) and gastroparesis (GP) which share similar pathophysiological mechanisms and clinical presentation. So far, no study investigated the prevalence of FD and GP in a primary care in Belgium. METHODS: Data were obtained from Intego, a Flemish-Belgian general practice-based morbidity registration network. From 586,164 patients between 2000 and 2021, we selected patients with ICD-10 code for FD and GP. Patients with organic gastrointestinal diseases were excluded. We determined demographics and comorbidities of FD/GP. For prevalence and incidence calculation, we included those who consulted their general practitioners at least once in the given year. Pair-wise comparison was conducted to access the impact of comorbidities on risk of FD/GP. KEY RESULTS: Between 2011 and 2021, the prevalence of FD/GP ranged from 1.03% to 1.21%. The incidence of FD/GP ranged from 109 to 142 per 100,000 adults. In total 5242 cases of FD/GP were identified. These cases shared commonly coexisting diagnoses of gastroesophageal reflux disease (18.8%), irritable bowel syndrome (17.1%), and chronic constipation (18.7%). Patients with somatization/anxiety/depression had significantly higher risk of FD/GP, compared to the control (OR 1.38, 95% CI 1.19-1.61, p < 0.01). CONCLUSIONS AND INFERENCES: The prevalence (1.03%-1.21%) and incidence (109-142/100,000) of FD/GP in primary care over last decade appear to conflict with epidemiological research in the general population. The discrepancies suggest a potential lack of awareness of FD and GP among physicians and/or patients in Flemish-Belgium.

Added Value of 13C Analysis in Breath Tests in H2-Negative Subjects to Diagnose Lactose Malabsorption: A Proof of Concept Study.

INTRODUCTION: Diagnosing lactose malabsorption is usually based on hydrogen excretion in breath after a lactose challenge. However, a proportion of subjects with lactose malabsorption will not present a rise in hydrogen. Measuring excretion of methane or stable isotope labeled 13CO2 after ingestion of 13C-lactose has been proposed to mitigate this problem. OBJECTIVE: The aim of the study was to assess the performance of measuring methane and 13CO2 in individuals with normal hydrogen excretion compared to a genetic lactase non-persistence test. METHODS: Individuals referred for lactose breath testing and healthy controls were included. Participants received 13C-enriched lactose, performed breath testing, and underwent genotyping for a marker of lactase non-persistence (13910C*T). Using genotype as gold standard, the performance of measuring methane and 13CO2 excretion was assessed. RESULTS: 151 subjects participated in the study, 50 of which presented a lactase non-persistent genotype. Of these, 72% were correctly diagnosed through hydrogen excretion of ≥ 20 ppm above baseline. In subjects with normal hydrogen excretion, cumulative 13C excretion had an area under the curve (AUC) of the receiver operating characteristics (ROC) curve of 0.852. Sensitivity was 93% and specificity was 51% for the current cutoff of 14.5%. The optimal cutoff was 12.65% (sensitivity 93%, specificity 70%). The ROC curve of peak methane had an AUC of 0.542 (sensitivity of 14%, specificity of 91% for cutoff ≥ 10 ppm). CONCLUSIONS: In individuals with genetically demonstrated lactase non-persistence and negative hydrogen breath test, the use of 13C-lactose with measurement of 13CO2 excretion and hydrogen is a well-performing test to detect the lactose malabsorption and performs better than methane in our cohort.

Clinical validation of the VIPUN™ gastric monitoring system versus manometry for the evaluation of gastric motility.

BACKGROUND: Gastrointestinal dysmotility is frequently suspected in patients with gastroparesis, functional dyspepsia, and ileus, and in the intensive care unit. Monitoring of gastric motility in clinical practice remains challenging. A novel technology was developed to meet the medical need for a widely available bedside tool to monitor gastric motility continuously. The VIPUN™ Gastric Monitoring System (GMS) comprises a nasogastric feeding tube with intragastric balloon to allow for measuring gastric contractions. AIMS: To compare the performance of the VIPUN GMS versus a reference technique (manometry). METHODS: In this validation study in healthy subjects, the investigational catheter and a solid-state manometry catheter were placed in the stomach concomitantly. Motility was recorded for 2.5 h: 2 h in a fasting state, followed by a 400-kcal liquid meal, and monitoring of the fed state for the remaining half hour. The performance of both systems was compared by automated recognition and manual identification of the contractile activity. Data are presented as mean (standard deviation). KEY RESULTS: The analysis set comprised 13 healthy subjects (6 women, age: 27.5 (8.1) years, BMI: 22.2 (2.46) kg/m2 ). Automatically-recognized contractility was strongly correlated between the two techniques (endpoint: contraction duration; Spearman ρ = 0.96, p < 0.001). A correlation was also observed between the number of individual contractions identified by expert gastroenterologists on both technologies independently (ρ = 0.71, p = .007) and between the contractions identified by the experts and by the GMS software (ρ = 0.87, p = 0.001). No serious or unanticipated adverse events occurred. CONCLUSIONS & INFERENCES: The observed strong correlations with the gold standard, manometry, validate the performance of the VIPUN GMS as a gastric monitoring system.

Prokinetics-safety and efficacy: The European Society of Neurogastroenterology and Motility/The American Neurogastroenterology and Motility Society expert review.

BACKGROUND: Prokinetics are a class of pharmacological drugs designed to improve gastrointestinal (GI) motility, either regionally or across the whole gut. Each drug has its merits and drawbacks, and based on current evidence as high-quality studies are limited, we have no clear recommendation on one class or other. However, there remains a large unmet need for both regionally selective and/or globally acting prokinetic drugs that work primarily intraluminally and are safe and without systemic side effects. PURPOSE: Here, we describe the strengths and weaknesses of six classes of prokinetic drugs, including their pharmacokinetic properties, efficacy, safety and tolerability and potential indications.

Patient-Reported Outcomes in Disorders of Gut-Brain Interaction.

Disorders of gut-brain interaction are characterized by chronic gastrointestinal symptoms in the absence of abnormal endoscopic or radiologic findings or objective biomarkers that can be identified during routine clinical evaluation. The assessment of the symptom pattern and severity, therefore, is the key modality to evaluate the presence, impact, and evolution of these conditions, for both clinical and regulatory purposes. Patient-reported outcomes are structured symptom assessment questionnaires designed to evaluate symptom patterns, quantify severity of symptoms, and evaluate response to treatment at follow-up. This review provides an overview of currently available patient-reported outcomes for evaluating the main disorders of gut-brain interaction, specifically, functional dyspepsia; irritable bowel syndrome; and chronic constipation. It summarizes their content, level of validation for clinical practice and for research, and the regulatory approach to these conditions. Expected future developments and need for further research on patient-reported outcomes for these and other disorders of gut-brain interaction are highlighted.

Effects of corticotropin-releasing hormone on gastric electrical activity and sensorimotor function in healthy volunteers: a double-blinded crossover study.

Biopsychosocial factors are associated with disorders of gut-brain interaction (DGBI) and exacerbate gastrointestinal symptoms. The mechanisms underlying pathophysiological alterations of stress remain unclear. Corticotropin-releasing hormone (CRH) is a central regulator of the hormonal stress response and has diverse impact on different organ systems. The aim of the present study was to investigate the effects of peripheral CRH infusion on meal-related gastrointestinal symptoms, gastric electrical activity, and gastric sensorimotor function in healthy volunteers (HVs). In a randomized, double-blinded, placebo-controlled, crossover study, we evaluated the effects of CRH on gastric motility and sensitivity. HVs were randomized to receive either peripheral-administered CRH (100 µg bolus + 1 µg/kg/h) or placebo (saline), followed by at least a 7-day washout period and assignment to the opposite treatment. Tests encompassed saliva samples, gastric-emptying (GE) testing, body surface gastric mapping (BSGM, Gastric Alimetry; Alimetry) to assess gastric myoelectrical activity with real-time symptom profiling, and a gastric barostat study to assess gastric sensitivity to distention and accommodation. Twenty HVs [13 women, mean age 29.2 ± 5.3 yr, body mass index (BMI) 23.3 ± 3.8 kg/m2] completed GE tests, of which 18 also underwent BSGM measurements during the GE tests. The GE half-time decreased significantly after CRH exposure (65.2 ± 17.4 vs. 78.8 ± 24.5 min, P = 0.02) with significantly increased gastric amplitude [49.7 (34.7-55.6) vs. 31.7 (25.7-51.0) µV, P < 0.01], saliva cortisol levels, and postprandial symptom severity. Eleven HVs also underwent gastric barostat studies on a separate day. However, the thresholds for discomfort during isobaric distensions, gastric compliance, and accommodation did not differ between CRH and placebo.NEW & NOTEWORTHY In healthy volunteers, peripheral corticotropin-releasing hormone (CRH) infusion accelerates gastric-emptying rate and increases postprandial gastric response, accompanied by a rise in symptoms, but does not alter gastric sensitivity or meal-induced accommodation. These findings underscore a significant link between stress and dyspeptic symptoms, with CRH playing a pivotal role in mediating these effects.

Efficacy and Findings of a Blinded Randomized Reintroduction Phase for the Low FODMAP Diet in Irritable Bowel Syndrome.

BACKGROUND AND AIMS: The efficacy of a low fermentable oligo-, di-, monosaccharides and polyols (FODMAP) diet in irritable bowel syndrome (IBS) is well established. After the elimination period, a reintroduction phase aims to identify triggers. We studied the impact of a blinded reintroduction using FODMAP powders to objectively identify triggers and evaluated the effect on symptoms, quality of life, and psychosocial comorbidities. METHODS: Responders to a 6-week low FODMAP diet, defined by a drop in IBS symptom severity score (IBS-SSS) compared with baseline, entered a 9-week blinded randomized reintroduction phase with 6 FODMAP powders (fructans, fructose, galacto-oligosaccharides, lactose, mannitol, sorbitol) or control (glucose). A rise in IBS-SSS (≥50 points) defined a FODMAP trigger. Patients completed daily symptom diaries and questionnaires for quality of life and psychosocial comorbidities. RESULTS: In 117 recruited patients with IBS, IBS-SSS improved significantly after the elimination period compared with baseline (150 ± 116 vs 301 ± 97, P < .0001, 80% responders). Symptom recurrence was triggered in 85% of the FODMAP powders, by an average of 2.5 ± 2 FODMAPs/patient. The most prevalent triggers were fructans (56%) and mannitol (54%), followed by galacto-oligosaccharides, lactose, fructose, sorbitol, and glucose (respectively 35%, 28%, 27%, 23%, and 26%) with a significant increase in abdominal pain at day 1 for sorbitol/mannitol, day 2 for fructans/galacto-oligosaccharides, and day 3 for lactose. CONCLUSION: We confirmed the significant benefit of the low FODMAP diet in tertiary-care IBS. A blinded reintroduction revealed a personalized pattern of symptom recurrence, with fructans and mannitol as the most prevalent, and allows the most objective identification of individual FODMAP triggers. Ethical commission University hospital of Leuven reference number: s63629; Clinicaltrials.gov number: NCT04373304.

Worldwide population prevalence and impact of sub-diagnostic gastrointestinal symptoms.

BACKGROUND: The Rome Foundation Global Epidemiology Study (RFGES) found that 40.3% of adults in 26 internet-surveyed countries met Rome IV criteria for disorders of gut-brain interaction (DGBI). However, additional people not meeting DGBI criteria may also be burdened by frequent gastrointestinal symptoms. AIMS: To explore the prevalence and demographic distribution of sub-diagnostic gastrointestinal symptoms, and the hypothesised associated effects on quality of life (QoL), life functioning and healthcare needs. METHODS: We analysed data from the RFGES survey, which included the Rome IV diagnostic questionnaire and QoL, psychological, work productivity and healthcare questions. RESULTS: Of the 50,033 people without a history of organic gastrointestinal disorders, 25.3% classified in the sub-diagnostic group (no DGBI but one or more frequent gastrointestinal symptoms), 41.4% had DGBI and 33.4% had no frequent gastrointestinal symptoms (non-GI group). Sub-diagnostic prevalence in different world regions ranged from 22.2% (North America) to 30.5% (Middle East), was slightly higher among males than females and decreased with age. The sub-diagnostic group was intermediate between the non-GI and DGBI groups, and significantly different from both of them on QoL, anxiety, depression, somatisation, healthcare utilisation and life and work impairment. CONCLUSIONS: One in four adults without organic gastrointestinal disorders or DGBI report frequent gastrointestinal symptoms. This sub-diagnostic group has reduced QoL, greater psychological and non-GI bodily symptoms, impaired work productivity and life activities and greater healthcare use compared to non-GI individuals. This suggests that many in this sub-diagnostic group might benefit from healthcare services or symptom self-management advice.

Nutrition and Disorders of Gut-Brain Interaction.

BACKGROUND: Disorders of gut-brain interaction (DGBIs) have a complex pathophysiology that is often characterized by a relationship between food ingestion and triggering of symptoms. Understanding of the underlying mechanisms and the role of nutrients as a therapeutic target are rapidly evolving. AIMS AND METHODS: We performed a narrative review of the literature using the following keywords, their acronyms, and their associations: nutrients, disorders of gut-brain interaction; functional dyspepsia; malabsorption; irritable bowel syndrome; diarrhea; constipation. RESULTS: Functional dyspepsia displayed a significant correlation between volume, fat and/or wheat abundance, chemical composition of ingested food and symptoms of early satiety, fullness and weight loss. Carbohydrate malabsorption is related to enzyme deficiency throughout the GI tract. Food composition and richness in soluble vs. non-soluble fibers is related to constipation and diarrhea. The elimination of fermentable oligo-, di-, monosaccharides and polyols (FODMAPs) has a significant and non-unidirectional impact on irritable bowel syndrome (IBS) symptoms. CONCLUSIONS: Food volume, nutritive and chemical composition, and its malabsorption are associated with symptom generation in DGBIs. Further multicenter, randomized-controlled clinical trials are needed to clarify the underlying pathophysiology.

Gastric Alimetry Expands Patient Phenotyping in Gastroduodenal Disorders Compared with Gastric Emptying Scintigraphy.

INTRODUCTION: Gastric emptying testing (GET) assesses gastric motility, however, is nonspecific and insensitive for neuromuscular disorders. Gastric Alimetry (GA) is a new medical device combining noninvasive gastric electrophysiological mapping and validated symptom profiling. This study assessed patient-specific phenotyping using GA compared with GET. METHODS: Patients with chronic gastroduodenal symptoms underwent simultaneous GET and GA, comprising a 30-minute baseline, 99m TC-labelled egg meal, and 4-hour postprandial recording. Results were referenced to normative ranges. Symptoms were profiled in the validated GA App and phenotyped using rule-based criteria based on their relationships to the meal and gastric activity: (i) sensorimotor, (ii) continuous, and (iii) other. RESULTS: Seventy-five patients were assessed, 77% female. Motility abnormality detection rates were as follows: GET 22.7% (14 delayed, 3 rapid), GA spectral analysis 33.3% (14 low rhythm stability/low amplitude, 5 high amplitude, and 6 abnormal frequency), and combined yield 42.7%. In patients with normal spectral analysis, GA symptom phenotypes included sensorimotor 17% (where symptoms strongly paired with gastric amplitude, median r = 0.61), continuous 30%, and other 53%. GA phenotypes showed superior correlations with Gastroparesis Cardinal Symptom Index, Patient Assessment of Upper Gastrointestinal Symptom Severity Index, and anxiety scales, whereas Rome IV Criteria did not correlate with psychometric scores ( P > 0.05). Delayed emptying was not predictive of specific GA phenotypes. DISCUSSION: GA improves patient phenotyping in chronic gastroduodenal disorders in the presence and absence of motility abnormalities with increased correlation with symptoms and psychometrics compared with gastric emptying status and Rome IV criteria. These findings have implications for the diagnostic profiling and personalized management of gastroduodenal disorders.

Global Prevalence of Psychological Distress and Comorbidity With Disorders of Gut-Brain Interactions.

INTRODUCTION: This study focused on defining the global prevalence of clinically relevant levels of psychological distress and somatic symptoms and the prevalence of coexistence between these symptoms and disorders of gut-brain interaction (DGBI). We also analyzed how clinically relevant psychological distress and somatic symptoms and coexistent DGBI are associated with health-related outcomes. METHODS: We included a representative sample of 54,127 adult participants (49.1% women; mean age of 44.3 years) from 26 countries worldwide. Participants completed an Internet survey (the Rome Foundation Global Epidemiology Study) with validated self-report questionnaires. RESULTS: Clinically relevant psychological distress and/or somatic symptom severity was reported by 37.5% of the sample. These participants had 4.45 times higher odds to have at least one DGBI than individuals without psychological distress and/or somatic symptoms. Compared with participants with psychological distress and/or somatic symptoms with vs without DGBI, participants with a DGBI reported increased healthcare and medication utilization (with OR from 1.6 to 2.8). Coexistent DGBI in participants with psychological distress and/or somatic symptoms was the variable most strongly associated with reduced mental (ß = -0.77; confidence interval [-0.86 to -0.68]) and physical (ß = -1.17; confidence interval [-1.24 to -1.10]) quality of life. DISCUSSION: This global study shows that psychological distress, somatic symptoms, and DGBI are very common and frequently overlap. The coexistence between psychological distress/somatic symptoms and DGBI seems to be especially detrimental to quality of life and healthcare utilization. Individuals with psychological distress/somatic symptoms and DGBI coexistence seem to be a group vulnerable to psychosocial problems that should be studied further and would likely benefit from psychological/psychiatric interventions.

10-year follow-up results of the European Achalasia Trial: a multicentre randomised controlled trial comparing pneumatic dilation with laparoscopic Heller myotomy.

OBJECTIVE: As achalasia is a chronic disorder, long-term follow-up data comparing different treatments are essential to select optimal clinical management. Here, we report on the 10-year follow-up of the European Achalasia Trial comparing endoscopic pneumodilation (PD) with laparoscopic Heller myotomy (LHM). DESIGN: A total of 201 newly diagnosed patients with achalasia were randomised to either a series of PDs (n=96) or LHM (n=105). Patients completed symptom (Eckardt score) and quality-of-life questionnaires, underwent functional tests and upper endoscopy. Primary outcome was therapeutic success defined as Eckardt score <3 at yearly follow-up. Secondary outcomes were the need for retreatment, lower oesophageal sphincter pressure, oesophageal emptying, gastro-oesophageal reflux and the rate of complications. RESULTS: After 10 years of follow-up, LHM (n=40) and PD (n=36) were equally effective in both the full analysis set (74% vs 74%, p=0.84) and the per protocol set (74% vs 86%, respectively, p=0.07). Subgroup analysis revealed that PD was superior to LHM for type 2 achalasia (p=0.03) while there was a trend, although not significant (p=0.05), that LHM performed better for type 3 achalasia. Barium column height after 5 min at timed barium oesophagram was significantly higher for patients treated with PD compared with LHM, while other parameters, including gastro-oesophageal reflux, were not different. CONCLUSIONS: PD and LHM are equally effective even after 10 years of follow-up with limited risk to develop gastro-oesophageal reflux. Based on these data, we conclude that PD and LHM can both be proposed as initial treatment of achalasia.

Perceptions, Definitions, and Therapeutic Interventions for Occasional Constipation: A Rome Working Group Consensus Document.

BACKGROUND & AIMS: Functional constipation is the most common of the disorders of gut-brain interaction, affecting approximately 12% of the world population. Although classically considered a chronic condition, many individuals experience shorter yet repetitive bouts of constipation representing a different clinical entity. There has been increased interest in this latter disorder, which has recently been classified as occasional constipation. This Rome Foundation working group document reflects the consensus of an international team of specialists who summarized currently available research to provide a working definition of and treatment algorithm for occasional constipation. The recommendations herein are based on current evidence, accounting for gaps in the literature as well as international variance in definitions and health seeking behaviors for constipation. METHODS: The committee members reviewed the scientific literature, focusing specifically on occasional constipation, with the understanding that as a new entity, a paucity of data would be available. We used Rome IV research and clinical definitions to establish the framework for our definition of occasional constipation. Where possible, treatment recommendations were determined on the basis of the earliest extractable data from functional constipation studies, focusing on positive results within the first 2 weeks of treatment. We used the Delphi method to create consensus with 100% agreement between the authors. RESULTS: An evidence-based review of the literature resulted in the definition of occasional constipation as follows: "individuals who experience the presence of at least 1 functional constipation symptom, in the absence of alarm signs or symptoms, occurring at irregular and infrequent intervals, which is bothersome enough to induce a patient to seek medical management." Medical management whether seeking medical care or self-treatment was left to the individual's discretion, and we did not include time anchors because these thresholds require further investigation. Polyethylene glycol and stimulant laxatives are recommended as first-line interventions, whereas magnesium-containing compounds are suggested in individuals failing to respond to these therapies. There are insufficient data to make recommendations for using fiber or stool softeners. Prescription laxatives should be reserved for individuals with chronic constipation. CONCLUSIONS: Occasional constipation is a unique clinical entity characterized by infrequent but recurrent symptoms. Data are limited because consensus definitions have been lacking. Establishing a standardized definition and therapeutic recommendations provides a framework for future studies focusing on epidemiologic and symptoms-based outcomes. Further studies are needed to confirm and refine these recommendations.

Prolonged Gastrointestinal Manifestations After Recovery From COVID-19.

BACKGROUND & AIMS: Acute enteric infections are well known to result in long-term gastrointestinal (GI) disorders. Although COVID-19 is principally a respiratory illness, it demonstrates significant GI tropism, possibly predisposing to prolonged gut manifestations. We aimed to examine the long-term GI impact of hospitalization with COVID-19. METHODS: Nested within a large-scale observational cohort study of patients hospitalized with COVID-19 across North America, we performed a follow-up survey of 530 survivors 12-18 months later to assess for persistent GI symptoms and their severity, and for the development of disorders of gut-brain interaction (DGBIs). Eligible patients were identified at the study site level and surveyed electronically. The survey instrument included the Rome IV Diagnostic Questionnaire for DGBI, a rating scale of 24 COVID-related symptoms, the Gastrointestinal Symptoms Rating Scale, and the Impact of Events-Revised trauma symptom questionnaire (a measure of posttraumatic stress associated with the illness experience). A regression analysis was performed to explore the factors associated with GI symptom severity at follow-up. RESULTS: Of the 530 invited patients, 116 responded (52.6% females; mean age, 55.2 years), and 73 of those (60.3%) met criteria for 1 or more Rome IV DGBI at follow-up, higher than the prevalence in the US general population (P < .0001). Among patients who experienced COVID-related GI symptoms during the index hospitalization (abdominal pain, nausea, vomiting, or diarrhea), 42.1% retained at least 1 of these symptoms at follow-up; in comparison, 89.8% of respondents retained any (GI or non-GI) COVID-related symptom. The number of moderate or severe GI symptoms experienced during the initial COVID-19 illness by self-report correlated with the development of DGBI and severity of GI symptoms at follow-up. Posttraumatic stress disorder (Impact of Events-Revised score ≥33) related to the COVID-19 illness experience was identified in 41.4% of respondents and those individuals had higher DGBI prevalence and GI symptom severity. Regression analysis revealed that higher psychological trauma score (Impact of Events-Revised) was the strongest predictor of GI symptom severity at follow-up. CONCLUSIONS: In this follow-up survey of patients 12-18 months after hospitalization with COVID-19, there was a high prevalence of DGBIs and persistent GI symptoms. Prolonged GI manifestations were associated with the severity of GI symptoms during hospitalization and with the degree of psychological trauma related to the illness experience.

Impact of Immuno-Nutrition on the Nutritional Status, Inflammatory Response and Clinical Outcome of Clinic-Admitted Mild-Intensity-COVID-19 Patients: A Pilot, Perspective-Concluding Study.

The SARS-CoV-2 pandemic has impacted our lives since early 2020. Both malnutrition and an overweight status significantly correlate with worse patient outcomes and mortality. Immuno-nutrition (IN) has shown promising results in the inflammatory bowel disease (IBD) clinical course and the extubation time and mortality of patients admitted to intensive care units (ICUs). Thus, we wanted to assess the impact of a standardized IN oral formula on COVID-19 patients admitted to our mild-intensity clinic in late 2021. We prospectively enrolled patients admitted to the Internal Medicine COVID-19 Unit of San Benedetto General Hospital. All patients had biochemical, anthropometric, HRCT chest scan, and nutritional assessments at the time of admission and, after oral immuno-nutrition formula administration, at 15 days of the interval follow up. We enrolled 52 consecutive patients (mean age of 60.9 ± 5.4 years, 17 F, and BMI of 23.5 Kg/m2). The main comorbidities were diabetes (20%, type 2: 90%), hyperuricemia (15%), hypertension (38%), chronic ischemic heart disease (12%), COPD (13%), anxiety (10%), and depression (8%). Upon informed consent, 14 patients (mean age of 67.9 ± 5.4 years, 7 F, and BMI of 26.7 Kg/m2) were accepted to be administered IN. A moderate to severe overweight status was present in 59% of the patients; MNA test (4.4 ± 0.7) and phase angle (PA) values, suggestive of malnutrition, were present in 13% of the patients. After 15 days of admission, we recorded three deaths (mean age of 68.9 ± 4.1 years, 3 F, and BMI of 27.5 Kg/m2). An overweight status significantly correlated with the exitus occurrence (r = 0.65). One death was reported among the IN-treated patients. IN administration was followed by a significant decrease in inflammatory markers with a tendency to be higher than those of non-treated patients. IN prevented the worsening of BMI and PA vs. non-treated patients. In this overweight COVID-19 population, immuno-nutrition prevented malnutrition development with a significant decrease in inflammatory markers.

The Acute Effect of Hydroxychloroquine Sulfate on Hunger, the Plasma Concentration of Orexigenic Peptides and Hedonic Food Intake: A Pilot Study.

The direct infusion of bitter solutions in the gastrointestinal tract can reduce the secretion of orexigenic hormones and influence appetite and food intake. We aimed to explore whether oral ingestion of the bitter tastant hydroxychloroquine sulfate can exert similar effects. Ten lean adult women were included in this double-blind, randomized, two-visit, crossover study. After an overnight fast, each volunteer received film-coated tablets containing 400 mg of hydroxychloroquine sulfate (Plaquenil®) or placebo. Plasma-ghrelin, -motilin, -insulin and blood-glucose concentrations were determined every 10 min before and 30 min after feeding; appetite was scored every 10 min. Hunger scores were investigated with a special interest 50-60 min after the ingestion of hydroxychloroquine sulfate, right before a rewarding chocolate milkshake was offered to drink ad libitum. Compared with the placebo, hydroxychloroquine sulfate tended to reduce hunger at the time of interest (p = 0.10). No effect was found upon subsequent milkshake intake. Motilin plasma concentrations were unaltered, but acyl-ghrelin plasma concentrations decreased after the ingestion of hydroxychloroquine sulfate (t = 40-50; p < 0.05). These data suggest that the oral intake of hydroxychloroquine sulfate tablets reduces subjective hunger via a ghrelin-dependent mechanism but does not affect motilin release, hedonic food intake or insulin levels in healthy women.