Delineating phenotypes of Kawasaki disease and SARS-CoV-2-related inflammatory multisystem syndrome: a French study and literature review.

OBJECTIVE: To better define the clinical distinctions between the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related paediatric inflammatory multisystem syndrome (PIMS) and Kawasaki disease (KD). METHODS: We compared three groups of patients: group 1, cases from our national historic KD database (KD-HIS), before the SARS-CoV-2 pandemic; group 2, patients with KD admitted to an intensive care unit (KD-ICU) from both our original cohort and the literature, before the SARS-CoV-2 pandemic; and group 3, patients with PIMS from the literature. RESULTS: KD-HIS included 425 patients [male:female ratio 1.3, mean age 2.8 years (s.d. 2.4)], KD-ICU 176 patients [male:female ratio 1.3, mean age 3.5 years (s.d. 3.1)] and PIMS 404 patients [male:female ratio 1.4, mean age 8.8 years (s.d. 3.7)]. As compared with KD-HIS patients, KD-ICU and PIMS patients had a higher proportion of cardiac failure, digestive and neurological signs. KD-ICU and PIMS patients also had a lower frequency of typical KD-mucocutaneous signs, lower platelet count, higher CRP and lower sodium level. As compared with KD-HIS and KD-ICU patients, PIMS patients were older and more frequently had myocarditis; they also had fewer coronary abnormalities and lower sodium levels. Unresponsiveness to IVIG was more frequent in KD-ICU than KD-HIS and PIMS patients. CONCLUSION: On clinical grounds, KD-HIS, KD-ICU and PIMS might belong to a common spectrum of non-specific pathogen-triggered hyperinflammatory states. The causes of increasing inflammation severity within the three entities and the different effects on the heart remain to be determined.

The Way to Man's Heart Is through the Stomach.

Organ systems do not exist in a vacuum. However, in an era of increasingly specialized medicine, the focus is often on the organ system alone. Many symptoms are associated with differential diagnoses from upper gastrointestinal (GI) and cardiovascular medical and surgical specialties. Furthermore, a large number of rare but deadly conditions cross paths between the upper GI tract and cardiovascular system; a significant proportion of these are iatrogenic injuries from a parallel specialty. These include unusual fistulae, herniae, and embolisms that transcend specialties. This review highlights these conditions and the shared anatomy and embryology of the two organ systems.

Aerodigestive Clinics as Emerging Pediatric Care Model: The First 100 Patients in Israel.

BACKGROUND: Aerodigestive clinics are run by interdisciplinary medical and surgical teams, and provide complex care coordination and combined endoscopies. OBJECTIVES: To describe the design and patient population of the first pediatric aerodigestive center in Israel. METHODS: A retrospective single-center cohort study was conducted describing patients followed in the aerodigestive clinic of Schneider Children's Medical Center of Israel, a tertiary pediatric hospital, between its inception in January 2017 and June 2020. RESULTS: During the study period, 100 patients were seen at the combined respiratory and digestive (NoAM) clinic, with a total of 271 visits. Median age at first assessment was 29.5 months (range 3-216). Fifty-six patients (56%) had esophageal atresia and tracheoesophageal fistula. Thirty-nine patients had an identified genetic disorder, 28 had a primary airway abnormality, 28 were oxygen dependent, and 21 were born premature. Fifty-two patients underwent triple endoscopy, consisting of flexible bronchoscopy, rigid bronchoscopy, and gastroscopy. In 33 patients, esophageal dilatation was necessary. Six patients underwent posterior tracheopexy at a median of 6 months of age (range 5 days to 8 years) all with ensuing symptom improvement. The total mean parental satisfaction score on a Likert-type scale of 1-5 (5 = highest satisfaction) was 4.5. CONCLUSIONS: A coordinated approach is required to provide effective care to the growing population of children with aerodigestive disorders. The cross fertilization between multiple disciplines offers a unique opportunity to develop high quality and innovative care. Outcome measures must be defined to objectively measure clinical benefit.

Digestive Symptoms in COVID-19 Patients With Mild Disease Severity: Clinical Presentation, Stool Viral RNA Testing, and Outcomes.

OBJECTIVES: Coronavirus disease 2019 (COVID-19) most commonly presents with respiratory symptoms, including cough, shortness of breath, and sore throat. However, digestive symptoms also occur in patients with COVID-19 and are often described in outpatients with less severe disease. In this study, we sought to describe the clinical characteristics of COVID-19 patients with digestive symptoms and mild disease severity. METHODS: We identified COVID-19 patients with mild disease and one or more digestive symptoms (diarrhea, nausea, and vomiting), with or without respiratory symptoms, and compared them with a group presenting solely with respiratory symptoms. We followed up patients clinically until they tested negative for COVID-19 on at least 2 sequential respiratory tract specimens collected ≥24 hours apart. We then compared the clinical features between those with digestive symptoms and those with respiratory symptoms. RESULTS: There were 206 patients with low severity COVID-19, including 48 presenting with a digestive symptom alone, 69 with both digestive and respiratory symptoms, and 89 with respiratory symptoms alone. Between the 2 groups with digestive symptoms, 67 presented with diarrhea, of whom 19.4% experienced diarrhea as the first symptom in their illness course. The diarrhea lasted from 1 to 14 days, with an average duration of 5.4 ± 3.1 days and a frequency of 4.3 ± 2.2 bowel movements per day. Concurrent fever was found in 62.4% of patients with a digestive symptom. Patients with digestive symptoms presented for care later than those with respiratory symptoms (16.0 ± 7.7 vs 11.6 ± 5.1 days, P < 0.001). Nevertheless, patients with digestive symptoms had a longer duration between symptom onset and viral clearance (P < 0.001) and were more likely to be fecal virus positive (73.3% vs 14.3%, P = 0.033) than those with respiratory symptoms. DISCUSSION: We describe a unique subgroup of COVID-19 patients with mild disease severity marked by the presence of digestive symptoms. These patients are more likely to test positive for viral RNA in stool, to have a longer delay before viral clearance, and to experience delayed diagnosis compared with patients with only respiratory symptoms.

Roles of Adipokines in Digestive Diseases: Markers of Inflammation, Metabolic Alteration and Disease Progression.

Adipose tissue is a highly dynamic endocrine tissue and constitutes a central node in the interorgan crosstalk network through adipokines, which cause pleiotropic effects, including the modulation of angiogenesis, metabolism, and inflammation. Specifically, digestive cancers grow anatomically near adipose tissue. During their interaction with cancer cells, adipocytes are reprogrammed into cancer-associated adipocytes and secrete adipokines to affect tumor cells. Moreover, the liver is the central metabolic hub. Adipose tissue and the liver cooperatively regulate whole-body energy homeostasis via adipokines. Obesity, the excessive accumulation of adipose tissue due to hyperplasia and hypertrophy, is currently considered a global epidemic and is related to low-grade systemic inflammation characterized by altered adipokine regulation. Obesity-related digestive diseases, including gastroesophageal reflux disease, Barrett's esophagus, esophageal cancer, colon polyps and cancer, non-alcoholic fatty liver disease, viral hepatitis-related diseases, cholelithiasis, gallbladder cancer, cholangiocarcinoma, pancreatic cancer, and diabetes, might cause specific alterations in adipokine profiles. These patterns and associated bases potentially contribute to the identification of prognostic biomarkers and therapeutic approaches for the associated digestive diseases. This review highlights important findings about altered adipokine profiles relevant to digestive diseases, including hepatic, pancreatic, gastrointestinal, and biliary tract diseases, with a perspective on clinical implications and mechanistic explorations.

[Age-related specifics or diseases and disability caused by digestive disorders among adults in Saint-Petersburg in 2013-2017.]

The paper presents the retrospective analysis of the structure and dynamics of diseases and disability caused by digestive disorders in Saint Petersburg citizens. The paper presents the results of the comparative analysis of disability among people of active working and pension ages living in Saint Petersburg, versus Russia's average 2013-2018 data. As a result, regularities and differences in the structure and dynamics of digestive disorders in people 18 years old and older, which manifested themselves in after-surgery complications, death rate, and disability rate. The results may be used as reference for making federal or regional-level decisions on developing the system for preventing and early diagnosis of digestive disorders and integrated rehabilitation of disabled persons.

Digestive Surgery at the Cirrhotic Patient.

In chronic liver disease, the incidence of cirrhosis is increasing. About 1 million deaths from cirrhosis are reported annually by WHO, occupying the 11th position in the hierarchy of pathologies that cause death (1). The prevalence of cirrhosis is often underestimated based on the fact that one third of the patients are asymptomatic (2). Regardless of whether it is elective or urgent extra-hepatic surgery, operative interventions in this range of patients are burdened by an increased risk of perioperative morbidity and mortality (3,4). This reality requires the evaluation of the benefit-risk balance for each patient with the surgical firm indication. A journal of the medical literature, presented over the period 1995-2018 (PubMed), noted that the most frequent extrahepatic interventions in the cirrhotic patient were addressed to the cholecyst and CBD (23%), parietal defects (hernias, events) in 17 %, gastric pathology (19%) and rectum-colon (19%).v Liver cirrhosis is frequently associated with abnormalities of coagulation mechanisms: thrombopenia and platelet dysfunctions, decreased coagulation factors but also proteins involved in fibrinolysis. Cardio-circulatory changes are all the more important as the cirrhotic pathology is more evolved, being expressed by hyperkinetic syndrome and systemic vasodilation with hyper-flow, tachycardia and low peripheral resistance (5). The "trigger" element of these anomalies is the portal hypertension and the porto-systemic shunts that involve vasodilating mediators but also the compensatory activation of the renin-angiotensin system (6). The perioperative anaesthetic strategy in the patients is integrated in a multidisciplinary effort of specific management.

Best Practice Update: Incorporating Psychogastroenterology Into Management of Digestive Disorders.

Chronic digestive diseases, including irritable bowel syndrome, gastroesophageal reflux disease, and inflammatory bowel diseases, cannot be disentangled from their psychological context-the substantial burden of these diseases is co-determined by symptom and disease severity and the ability of patients to cope with their symptoms without significant interruption to daily life. The growing field of psychogastroenterology focuses on the application of scientifically based psychological principles and techniques to the alleviation of digestive symptoms. In this Clinical Practice Update, we describe the structure and efficacy of 2 major classes of psychotherapy-cognitive behavior therapy and gut-directed hypnotherapy. We focus on the impact of these brain-gut psychotherapies on gastrointestinal symptoms, as well as their ability to facilitate improved coping, resilience, and self-regulation. The importance of the gastroenterologist in the promotion of integrated psychological care cannot be overstated, and recommendations are provided on how to address psychological issues and make an effective referral for brain-gut psychotherapy in routine practice.

[Systemic membrane-destabilizing distress syndrome in surgery: concept, pathogenesis, diagnosis]. / Sistemnyi membranodestabiliziruiushchii distress-sindrom v khirurgii: poniatie, patogenez, diagnostika.

AIM: To justify the concept of systemic membrane-destabilizing distress syndrome in surgery via analysis of phospholipid bilayer of cell membranes of various organs in urgent surgical abdominal diseases. MATERIAL AND METHODS: Experimental research on dogs (n=90) included modeling of peritonitis, pancreatitis, intestinal obstruction, obstructive jaundice, and post-hemorrhagic anemia. Clinical and laboratory studies were performed in patients (n=119) with acute peritonitis, severe pancreatitis, intestinal obstruction, post-hemorrhagic anemia, acute cholecystitis, gastrointestinal bleeding, benign mechanical jaundice. Lipid profile in tissues and blood cells was determined by extraction, fractionation and densitometry. Moreover, we assessed intensity of lipid peroxidation and phospholipase activity, endogenous intoxication, functional state of organs and blood cells. RESULTS: It was revealed that all above-mentioned acute abdominal diseases are followed by significant changes of lipid bilayer and dysfunction of tissues in target organs, blood cells and other organs (liver, kidney, colon and small intestine, heart, lungs, spleen, brain). Changes of phospholipid bilayer are correlated with severity and course of the disease. These data were used to determine a new complex in surgery - systemic membrane-destabilizing distress syndrome. Its concept, pathogenesis, and diagnosis are presented. It was analyzed its role in development and progression of dysregulation pathology and thanatogenesis. Evidence of its importance in the pathogenesis of surgical aggression was obtained.

[Systemic coagulopathic distress syndrome in surgery: concept, pathogenesis, prophylaxis]. / Ponyatie sistemnogo koagulopaticheskogo distress-sindroma v khirurgii, ego patogenez i printsipy profilaktiki.

OBJECTIVE: The purpose of the study is to determine the correlation of changes in the humoral and tissue components of the hemostasis system with lipid metabolism in case of various urgent surgical diseases, on the basis of which the systemic coagulopathic distress syndrome can be used as the scientific basis for the definition of a new syndrome. MATERIAL AND METHODS: The work includes the results of experimental and clinical laboratory tests. Experiments on dogs: in the first group (n=18) destructive pancreatitis; in the second (n=18) - fecal peritonitis; in the third (n=15), acute obstructive intestinal obstruction; in the fourth (n=16) fecal peritonitis, in the postoperative period, Remaxol (15 ml/kg) was included in the therapy. The analysis of 55 patients with acute peritonitis, operated on for acute appendicitis, perforated gastric or duodenal ulcer, acute intestinal obstruction, acute destructive cholecystitis. In the study group (n=28), Remaxol is included in the postoperative therapy. The state of the humoral and tissue (in the experiment, the tissues of the liver, intestines, kidneys, heart, lungs, pancreas, in the clinic - tissues of the resected organs) components of the hemostasis system was evaluated, a number of lipid metabolism indicators were determined, etc. RESULTS: In the early periods of all investigated urgent diseases of the abdomen, pronounced changes in the system of both humoral and tissue components of the hemostasis system were revealed. The modification of the coagulation system is registered not only in the tissues of the lesion organs, but also in the target organs (system tissue hemocoagulation modifications). The research established one of the most important processes - the trigger of the hemostatic cascade reaction - is membrane-destabilizing (the source of tissue thromboplastin), which is determined by changes in the phospholipid composition of various organs tissues (involved in the pathological process or not in it). Changes in lipid metabolism are due to the activation of phospholipases and membrane lipid peroxidation in tissues. The factual material was the scientific basis for the establishment of a new syndrome. Systemic coagulopathic distress syndrome is a set of pathological processes of the body, the most important component of which is a violation of the phospholipid bilayer of blood cell membranes and organ cells due to oxidative and phospholipase induced phenomena, leading to a coagulopathic condition. It changes understanding of the prevention of thrombohemorrhagic complications, proving the effectiveness of complex therapy, including not only anticoagulants, but also drugs with membrane-stabilizing activity, in particular, Remaxol.

SP and KLF Transcription Factors in Digestive Physiology and Diseases.

Specificity proteins (SPs) and Krüppel-like factors (KLFs) belong to the family of transcription factors that contain conserved zinc finger domains involved in binding to target DNA sequences. Many of these proteins are expressed in different tissues and have distinct tissue-specific activities and functions. Studies have shown that SPs and KLFs regulate not only physiological processes such as growth, development, differentiation, proliferation, and embryogenesis, but pathogenesis of many diseases, including cancer and inflammatory disorders. Consistently, these proteins have been shown to regulate normal functions and pathobiology in the digestive system. We review recent findings on the tissue- and organ-specific functions of SPs and KLFs in the digestive system including the oral cavity, esophagus, stomach, small and large intestines, pancreas, and liver. We provide a list of agents under development to target these proteins.

Intermediate filament proteins of digestive organs: physiology and pathophysiology.

Intermediate filament proteins (IFs), such as cytoplasmic keratins in epithelial cells and vimentin in mesenchymal cells and the nuclear lamins, make up one of the three major cytoskeletal protein families. Whether in digestive organs or other tissues, IFs share several unique features including stress-inducible overexpression, abundance, cell-selective and differentiation state expression, and association with >80 human diseases when mutated. Whereas most IF mutations cause disease, mutations in simple epithelial keratins 8, 18, or 19 or in lamin A/C predispose to liver disease with or without other tissue manifestations. Keratins serve major functions including protection from apoptosis, providing cellular and subcellular mechanical integrity, protein targeting to subcellular compartments, and scaffolding and regulation of cell-signaling processes. Keratins are essential for Mallory-Denk body aggregate formation that occurs in association with several liver diseases, whereas an alternate type of keratin and lamin aggregation occurs upon liver involvement in porphyria. IF-associated diseases have no known directed therapy, but high-throughput drug screening to identify potential therapies is an appealing ongoing approach. Despite the extensive current knowledge base, much remains to be discovered regarding IF physiology and pathophysiology in digestive and nondigestive organs.

Whats 'App-ening': the help of new technologies in nutrition in digestive diseases.

PURPOSE OF REVIEW: The aim of this study is to review the basic concepts of electronic health (eHealth), with a focus on its nutritional applications and its usefulness for digestive diseases. RECENT FINDINGS: eHealth applications for the treatment and monitoring of digestive disease are growing in number. ehealth helps patients in coping with their disease by promoting self-management, which increases adherence to medical treatment and diets, and leads to an improved quality of life. For irritable bowel syndrome (IBS), there are multiple applications that provide dietary advice, for example, a low FODMAP (Fermentable Oligo, Mono, Disaccharides And Polyols) diet. However, many applications lack a symptom scoring function and do not include a module for assisting the essential reintroduction of high FODMAP foods. In general, there are very few applications that enable direct patient communication with healthcare professionals. A more holistic approach that educates patients and enables them to communicate directly with eCare provider through a web application is one of the functions most requested by patients. SUMMARY: eHealth solutions for digestive diseases have a supportive function and a positive impact on patients. However, there is a need to increase patient education and further develop the possibility for care team-patient communication within eHealth solutions.

Advances with Neonatal Aerodigestive Science in the Pursuit of Safe Swallowing in Infants: Invited Review.

Feeding, swallowing, and airway protection are three distinct entities. Feeding involves a process of sequential, neurosensory, and neuromotor interactions of reflexes and behaviors facilitating ingestion. Swallowing involves anterograde bolus movement during oral-, pharyngeal-, and esophageal phases of peristalsis into stomach. During these events, coordination with airway protection is vital for homeostasis in clearing any material away from airway vicinity. Neurological-airway-digestive inter-relationships are critical to the continuum of successful feeding patterns during infancy, either in health or disease. Neonatal feeding difficulties encompass a heterogeneous group of neurological, pulmonary, and aerodigestive disorders that present with multiple signs posing as clinical conundrums. Significant research breakthroughs permitted understanding of vagal neural pathways and functional aerodigestive connectivity involved in regulating swallowing and aerodigestive functions either directly or indirectly by influencing the supra-nuclear regulatory centers and peripheral effector organs. These neurosensory and neuromotor pathways are influenced by pathologies during perinatal events, prematurity, inflammatory states, and coexisting medical and surgical conditions. Approaches to clarify pathophysiologic mapping of aerodigestive interactions, as well as translating these discoveries into the development of personalized and simplified feeding strategies to advance child health are discussed in this review article.

The self-evaluation of upper-gastrointestinal symptoms in Chinese patients with digestive disease: A multicenter questionnaire survey.

AIM: To investigate the self-evaluation of upper gastrointestinal symptoms in Chinese patients. To observe the role of patients' characters, such as sex, age, education background, and clinic visits, which might affect the self-understanding of patients. METHODS: The nationwide cross-sectional questionnaire was administered to 3000 patients with upper gastrointestinal symptoms at 50 hospitals across 9 provinces in China. Questionnaire items covered four basic patients' characters and five major upper gastrointestinal symptoms. RESULTS: A total of 2799 questionnaires (response rate: 93.3%) were analyzed. Only 35.29% patients could precisely understand the definition of dyspepsia. The misunderstanding of lower-gastroenterology discomforts is the major reason leading to low accuracy rate of dyspepsia. The accuracy rate of early satiety and postprandial fullness is 37.7% and 52.27% separately; they are most interrelated and easily confused concepts to each other. The accuracy rate of heartburn is 30.02%, while the location of burning sensation is the key aspect for misunderstanding of heartburn. The self-understanding of symptoms in patients was decreased with increasing age, and enhanced with higher education background and time of clinic visits. Gender is not the independent factor. CONCLUSION: Based on the low accuracy rate of self-understanding of patients, this survey suggests that the gastroenterologists should re-evaluate the symptoms of patients during the clinical inquiry.

Matrix Metalloproteinases in Non-Neoplastic Disorders.

The matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases belonging to the metzincin superfamily. There are at least 23 members of MMPs ever reported in human, and they and their substrates are widely expressed in many tissues. Recent growing evidence has established that MMP not only can degrade a variety of components of extracellular matrix, but also can cleave and activate various non-matrix proteins, including cytokines, chemokines and growth factors, contributing to both physiological and pathological processes. In normal conditions, MMP expression and activity are tightly regulated via interactions between their activators and inhibitors. Imbalance among these factors, however, results in dysregulated MMP activity, which causes tissue destruction and functional alteration or local inflammation, leading to the development of diverse diseases, such as cardiovascular disease, arthritis, neurodegenerative disease, as well as cancer. This article focuses on the accumulated evidence supporting a wide range of roles of MMPs in various non-neoplastic diseases and provides an outlook on the therapeutic potential of inhibiting MMP action.

The heart and the gut.

The heart and the gut seem to be two organs that do not have much in common. However, there is an obvious and clinically relevant impact of gut functions on the absorption of drugs and oral therapies on the one hand. On the other hand, the gut determines the quantity of nutrient uptake and plays a central role in metabolic diseases. Patients with inflammatory bowel diseases appear to have a higher risk for coronary heart disease despite a lower prevalence of 'classical' risk factors, indicating additional links between the gut and the heart. However, they certainly have a 'leaky' intestinal barrier associated with increased permeability for bacterial wall products. An impaired intestinal barrier function will be followed by bacterial translocation and presence of bacterial products in the circulation, which can contribute to atherosclerosis and chronic heart failure (CHF) as recent data indicate. Impaired cardiac function in CHF vice versa impacts intestinal microcirculation leading to a barrier defect of the intestinal mucosa and increased bacterial translocation. These pathways and the most recent insights into the impact of the gut on acute and chronic heart disease will be discussed in this review.

The intestinal barrier function and its involvement in digestive disease.

The gastrointestinal mucosal surface is lined with epithelial cells representing an effective barrier made up with intercellular junctions that separate the inner and the outer environments, and block the passage of potentially harmful substances. However, epithelial cells are also responsible for the absorption of nutrients and electrolytes, hence a semipermeable barrier is required that selectively allows a number of substances in while keeping others out. To this end, the intestine developed the "intestinal barrier function", a defensive system involving various elements, both intra- and extracellular, that work in a coordinated way to impede the passage of antigens, toxins, and microbial byproducts, and simultaneously preserves the correct development of the epithelial barrier, the immune system, and the acquisition of tolerance against dietary antigens and the intestinal microbiota. Disturbances in the mechanisms of the barrier function favor the development of exaggerated immune responses; while exact implications remain unknown, changes in intestinal barrier function have been associated with the development of inflammatory conditions in the gastrointestinal tract. This review details de various elements of the intestinal barrier function, and the key molecular and cellular changes described for gastrointestinal diseases associated with dysfunction in this defensive mechanism.