Distal Tract Research Articles

The effect of Campylobacter jejuni and Campylobacter coli colonization on the gut morphology, functional integrity, and microbiota composition of female turkeys

BackgroundCampylobacter (C.) species are the most common bacterial cause of foodborne diarrhea in humans. Despite colonization, most animals do not show clinical signs, making recognition of affected flocks and disruption of the infection chain before slaughter challenging. Turkeys are often cocolonized with C. jejuni and C. coli. To understand the pathogen-host-interaction in the context of two different Campylobacter species, we compared the colonization patterns and quantities in mono- and co-colonized female commercial turkeys. In three repeated experiments we investigated the impact on gut morphology, functional integrity, and microbiota composition as parameters of gut health at seven, 14, and 28 days post-inoculation.ResultsDespite successful Campylobacter colonization, clinical signs or pathological lesions were not observed. C. coli persistently colonized the distal intestinal tract and at a higher load compared to C. jejuni. Both strains were isolated from livers and spleens, occurring more frequently in C. jejuni- and co-inoculated turkeys. Especially in C. jejuni-positive animals, translocation was accompanied by local heterophil infiltration, villus blunting, and shallower crypts. Increased permeability and lower electrogenic ion transport of the cecal mucosa were also observed. A lower relative abundance of Clostridia UCG-014, Lachnospiraceae, and Lactobacillaceae was noted in all inoculated groups compared to controls.ConclusionsIn sum, C. jejuni affects gut health and may interfere with productivity in turkeys. Despite a higher cecal load, the impact of C. coli on investigated parameters was less pronounced. Interestingly, gut morphology and functional integrity were also less affected in co-inoculated animals while the C. jejuni load decreased over time, suggesting C. coli may outcompete C. jejuni. Since a microbiota shift was observed in all inoculated groups, future Campylobacter intervention strategies may involve stabilization of the gut microbiota, making it more resilient to Campylobacter colonization in the first place.

Irinotecan decreases intestinal UDP-glucuronosyltransferase (UGT) 1A1 via TLR4/MyD88 pathway prior to the onset of diarrhea.

Irinotecan is a first-line treatment for colorectal cancer and the prodrug of 7-ethyl-10-hydroxy-camptothecin (SN-38). However, its fatal gastrointestinal (GI) toxicity raises serious concern. In liver, irinotecan generates its inactive metabolite, SN-38G via UDP-glucuronosyltransferase (UGT)1A1. Subsequently, SN-38G is excreted into GI tract where it is reactivated by microbiome to yield the toxic metabolite, SN-38. Activation of toll-like receptor (TLR)/myeloid differentiation primary response 88 (MyD88) by bacterial endotoxin decreases drug-metabolizing enzymes. In this study, we treated C57BL6/J mice with 50 mg/kg irinotecan once daily until observing grade 4 diarrhea. Mice were sacrificed on day0, day2 and day8. Based on the finding in C57BL6/J mice, we repeated the treatment in Tlr2-/-, Tlr4-/- and Myd88-/- mice to determine the impact of inflammation on UGT metabolism. Our toxicity study in C57BL6/J mice showed that mice started bloody diarrhea after 6 days' injection of irinotecan. Ugt1a1 expression in GI tract started decreasing after 24h since first dose, before the onset of diarrhea. In Tlr4-/- and Myd88-/- mice, no Ugt1a1 reduction was observed in distal GI tract after irinotecan injection. In Tlr2-/- mice, intestinal Ugt1a1 expression was down-regulated. Our results indicate that after two doses of irinotecan, mice started losing capability of detoxifying SN-38. TLR4 plays more important role in Ugt1a1 reduction than TLR2, despite that TLR2 and TLR4 share MyD88 as common adaptor protein. We concluded that irinotecan reduced intestinal Ugt1a1 via TLR4/MyD88 pathway, which eventually triggers the onset of diarrhea. Our finding unveils a novel mechanism underlying irinotecan-induced diarrhea and provides a new direction to prevent chemotherapy side effect.

Inadvertent intra-arterial catheterisation using ultrasound guidance and endocavitary electrocardiography in a paediatric patient.

Venous access in small infants is difficult and central venous catheter placed into the brachiocephalic vein is often the preferred approach. Ultrasound guided vein cannulation is standard practice and endocavitary electrocardiography is a reliable catheter tip location method. We report a not immediately recognised 2 month old case of inadvertent intra-arterial catheterisation with a 3 Fr - 8 cm catheter during right innominate vein cannulation under ultrasound guidance. Endocavitary electrocardiography showed an increased amplitude P wave with a low P/R wave ratio but further insertion of the catheter resulted in a reduction of the P wave amplitude. At ultrasound re-evaluation of the innominate vein, the catheter seemed to be inside the vessel into the proximal part of the vein, but distally appeared to surpass the vein to get into the brachiocephalic artery at the level of the bifurcation of the right common carotid artery and the right subclavian artery. Cardiac ultrasound from the suprasternal notch view identified the catheter into the aortic arch. Contrast-enhanced CT scan with 3D reconstruction confirmed the intra-arterial catheterisation and showed that the innominate vein was shifted and partially compressed but not transfixed by the catheter. The catheter was non-surgically removed uneventfully. During innominate vein cannulation the catheter cannot always be visualised into the distal tract of the vein and the maximal P wave may have a low P/R ratio; a chest X-ray can identify intra-arterial but false negative results are possible. We recommend always using a real time ultrasound tip navigation and location protocol, like the Neo-ECHOTIP protocol, to confirm the correct position of the guidewire and the catheter. If the catheter cannot be identified inside the venous system, we suggest systematically visualising the aortic arch from the suprasternal notch view and the aortic root from the parasternal view to identify arterial malposition.

Experience in using the combined method "Rendezvous" in interventions on the distal biliary tract

The article presents our own experience of observation during interventions on the distal biliary tract using a combined method – "Rendezvous" in patients with pathology of the pancreatobiliary zone, complicated by obstruction of the bile ducts. In one case, with a pronounced adhesive process of the abdominal cavity with a surgical aid, the endoscope was carried out to the descending branch of the duodenum. Towards the endoscope through the stump of the cystic duct, a conductor string was brought down, which made it possible to visualize the major duodenal papilla (MDP), to perform retrograde papillosphincterotomy with choledocholithotomy. In the second case, if it was impossible to pass the guidewire retrogradely beyond the area of the tumor narrowing, an alternative method was used – bringing it down by percutaneous transhepatic access towards the endoscope to install a retrograde stent delivery system.

An Outdoor Access Period Improves Chicken Cecal Microbiota and Potentially Increases Micronutrient Biosynthesis.

Characterizing the gut microbiota of free-range and alternative poultry production systems provides information, which can be used to improve poultry welfare, performance, and environmental sustainability. Gut microbiota influence not only the health and metabolism of the host but also the presence of zoonotic agents contaminating food of animal origin. In this study, the composition and diversity of the cecal microbiota community of free-range grown chickens were characterized by 16S rDNA high-throughput Illumina sequencing. Significant differences were observed in the composition of chicken cecal microbiota at the time points of 28 days of age (Indoor group) and 56 days of age (Outdoor group), i.e., before and after the outdoor access period of chicken groups. The Outdoor group showed a richer and more complex microbial community, characterized by the onset of new phyla such as Deferribacterota and Synergistota, while the Indoor group showed an increase in Campylobacterota. At the species level, it is noteworthy that the occurrence of Mucispirillum schaedleri in Outdoor group is known to potentially stimulate mucus layer formation in the distal intestinal tract, thus being associated with a healthy gut. We also report a significant decrease in the Outdoor group of Helicobacter pullorum, highlighting that the lower abundance at the age of slaughter reduced the possibility to contaminate chickens' carcasses and, consequently, its zoonotic potential. As revealed by a mutual exclusion study in network analysis, H. pullorum was present only if Bacteroides barnesiae, an uncultured organism of the genus Synergistes, and Bacteroides gallinaceum were absent. Finally, microbiome predictive analysis revealed an increase of vitamins and micronutrient biosyntheses such as queuosine (Q) and its precursor pre Q0, in the Outdoor group, suggesting that the outdoor evolved microbiota of chickens do contribute to the vitamin pool of the gut and the biosynthesis of micronutrients involved in vital cell processes.

Abstract 3529: T-cell trafficking and extravasation is suppressed in distal tumors during gastrointestinal tract dysbiosis

Abstract The crosstalk between the microbiota and the host is crucial to maintaining immune homeostasis. A growing body of evidence shows that microbial imbalance affects cancer susceptibility and progression. A common significant influence on the microbiota in the gastrointestinal (GI) tract is the use of antibiotics. Oral antibiotics severely alter the bacteria in the GI tract by destroying beneficial bacteria alongside pathogenic ones — producing a state of microbial imbalance called dysbiosis. The overall use of antibiotics has increased by more than 30% in recent years, and moreover, many cancer patients are prescribed antibiotics during treatment, as infection is frequently a complication. We hypothesized that antibiotic-induced dysbiosis of the gut microbiota would suppress cytokine profiles in the host, thereby causing stromal immune surveillance suppression. We found that antibiotics as well as tumorigenesis caused changes in the bacterial abundance, composition, or diversity in the GI tract. On the host side, we found that antibiotic-induced dysbiosis caused the small intestine and cecum to enlarge and elongate, yet the colon was not affected. Moreover, B16-F10 melanoma and Lewis Lung carcinoma progressed more quickly during dysbiosis. Mechanistically, tumor progression was mediated by suppressed TNF-α levels, both locally and systemically. In contrast, IFN-γ and VEGF did not change significantly during dysbiosis. The suppressed levels of TNF-α, a pleiotropic regulator of intercellular adhesion molecule-1 (ICAM-1), resulted in reduced expression of tumor endothelial cell associated ICAM-1, and a subsequent decrease in the number of activated and effector CD8+ T-cells in the tumor. However, suppression of ICAM-1 or its binding site, the alpha subunit of lymphocyte function-associated antigen-1 (LFA-1), was not seen in established vasculature during dysbiosis as assessed in the spleen or the thymus. While dysbiosis enhanced tumor growth in ICAM-1+/+ and immunocompetent mice, it did not affect tumor growth in ICAM-1-/- or T-cell deficient mice, highlighting the influence and impact of dysbiosis on T-cell trafficking and extravasation. TNF-α supplementation in dysbiotic mice was able to overcome the dysbiosis-induced suppression as evident by increased ICAM-1 expression, leukocyte trafficking and tumor growth inhibition. Overall, these results demonstrate the importance of commensal bacteria in supporting immune surveillance and expand our understanding of the crosstalk between the gut microbiome and the stroma in distal non-GI tract tumors. Moreover, this knowledge has the potential to influence clinical decision-making when treating patients for solid cancers with dysbiosis-inducing antibiotics and may further inform concurrent and (neo-)adjuvant treatments to overcome the adverse effects of the antibiotics. Citation Format: Samir V. Jenkins, Michael S. Robeson, Eric R. Siegel, Charles M. Quick, Robert J. Griffin, Martin J. Cannon, Kieng B. Vang, Ruud P. Dings. T-cell trafficking and extravasation is suppressed in distal tumors during gastrointestinal tract dysbiosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3529.

Retrospective analysis of risk factors, clinical features, and prognostic indicators for urolithiasis in guinea pigs: 158 cases (2009-2019).

To investigate risk factors, clinical features, and prognostic indicators in guinea pigs with urolithiasis. 158 guinea pigs with urolithiasis. Medical records of an exotics animal specialty service were searched, identifying guinea pigs with urolithiasis. Signalment, clinical data, and outcomes were recorded. Variables of interest were analyzed for statistical associations with outcome. Overall, 54.4% (86/158) of animals survived to discharge. Median survival time was 177 days. Females (53.2%; 84/158) were more common than males (46.8%; 74/158). Males were presented younger (mean age, 3.64 years) than females (4.41 years). In 81 of 154 (52.5%) cases, animals were presented with primary urinary concerns, while 73 (47.5%) presented for nonurinary primary concerns. Females more commonly presented with distal urinary tract urolithiasis (63/84; 75%) but fared better overall with a longer median survival time (1,149 days) than males (59 days). Surgical intervention was not a risk factor for nonsurvival; however, increased age (> 4.1 years), male sex, anorexia, weight loss, and lower rectal temperature (< 37.2 °C) on presentation were associated with nonsurvival. Reoccurrence was noted in 13.9% (22/158) of cases, at an average of 284 days. Urolithiasis should always be considered a differential diagnosis for any unwell guinea pig. In particular, distal urinary tract urolithiasis should be considered in females. A poorer prognosis was associated with older, male guinea pigs, and those displaying anorexia, weight loss, and hypothermia. The need for surgical intervention should not confer a poorer outcome. Further studies are needed to determine specific risk factors and identify possible preventative measures.

P335 AORTIC VALVE INFECTIVE ENDOCARDITIS COMPLICATED BY SUPERIOR MESENTERIC ARTERY ACUTE TROMBOSIS

Abstract The infective endocarditis (IE) has a significant impact on mortality rate in the first year after diagnosis, despite the improvements in early diagnosis and therapy. Embolic complications cause worsening of patient’s prognosis and they occur in the 20–50% of cases, with a risk of new embolic events after the initiation of antibiotic therapy rated between 6 and 12%. Echocardiographic characterization of vegetation has an important role in the definition of the embolization risk, it is documented that vegetation with dimension more than 10 mm are at higher risk. Several characteristic of the patient (diabetes, previous embolization, atrial fibrillation) determine the increase of the embolization risk, as well as the initiation of antibiotic therapy. We describe the case of a 64 y.o. man with chronic coronary syndrome (previous PCI) and previous Bentall–De Bono intervention for ascending aorta aneurysm. Patient was under anticoagulant therapy with DOAC due to atrial fibrillation. He was admitted to the emergency department for intermittent fever during the last three months, dyspnea and fatigue. Blood test showed neutrophilic leukocytosis and increased value of inflammatory markers. Transthoracic echography revealed an hyperechoic image on the ventricular side of the aortic prosthesis. The diagnosis of infective endocarditis was confirmed with transesophageal echocardiography, and empiric antibiotic therapy was initiated. Cardiac surgeon suggested follow up and new evaluation after three weeks of therapy. Clinical course was complicated by acute abdomen. The CT exam revealed dilation of a distal tract of superior mesenteric artery (maximum axial diameter was 10 mm) associated with distal thrombosis extended for 6 mm. The transthoracic echocardiogram showed absence of the vegetation on aortic prosthesis previous documented. Therapy with intravenous infusion of unfractionated heparin was administrated for three weeks, but the control TC showed persistence of the thrombotic occlusion of superior mesenteric artery so the case was discussed with Vascular Surgery team. They decided to treat patient with embolization and aneurysmectomy surgery (cultures were negative). This clinical case demonstrates that embolic complication of infective endocarditis, even on proper antbiotic therapy and close monitorization, are unpredictable and can cause the worsening of patient’s clinical course.

P61 CORONARY ARTERY ECTASIA: AN ENEMY NOT TO BE UNDERESTIMATED IN ACUTE CORONARY SYNDROME

Abstract Coronary artery ectasia is an abnormal dilatation of coronary arterial segment of at least 1.5 times that of a narrow normal coronary artery. Even if the overall incidence ranges between 4–9% of total angiography, it is correlated with poor outcome due to lower percutaneous procedural success, an higher incidence of no–reflow, distal embolization and stent thrombosis. We present two cases of high risk acute coronary syndrome patients with right coronary artery ectasia and different management in which intravascular ultrasound played a key role in determining interventional strategy. Case #1 : 55–year–old man presented with STEMI after VT–induced cardiac arrest treated with CPR and DC–shock with subsequent ROSC. Coronary angiography showed thrombotic occlusion in the middle tract of the right coronary artery treated with thrombus aspiration and subsequent PTCA + DES from the proximal to the distal tract of the severely ectatic artery with apparent good final angiographic result. However, at the IVUS control performed to verify the possible need for an additional stent in the context of flow turbulence, malapposition of the stent to the proximal–middle tract was highlighted with an important amount of probably thrombotic material between the stent and the vessel wall. Post dilation was therefore performed with NC balloons with IVUS documentation of resolution of the malapposition. Case #2: 59–year–old man hospitalized for NSTEMI. Coronary angiography showed severe left coronary ectasia in the absence of significant stenosis and subocclusive thrombus in the posterolateral branch of the right coronary artery with TIMI 2 flow in the context of diffuse CAE . A conservative strategy was undertaken with DAPT + LMWH due to the absence of symptoms and hemodynamic stability, as well as the associated high embolic risk. A follow–up coronary angiography was performed after one week of therapy with evidence of good recanalization of the branch (TIMI 3). IVUS control showed only minimal thrombotic component adhering to atherosclerotic plaque in the posterolateral branch with a MLA of 11.47 mm2 and a low percentage of stenosis (34.5%). A conservative strategy was therefore undertaken (DAPT 12 months). ACS management in patients with CAE is still challenging and a standardized approach is difficult to please. Strategies should be individualized based on clinical presentation and anatomic characteristics but coronary imaging should be routinely performed in this context.

P57 SPONTANEOUS DISSECTION OF THE DISTAL MARGINAL BRANCH IN A YOUNG WOMAN IN THE PERIPARTUM WITH NO FLOW LIMITATION AT THE PRESENTATION EVOLVED INTO SEVERE DISSECTION OF THE ANTERIOR CIRCUMFLEX AND DESCENDING ARTERY COMPLICATED BY CARDIOGENIC SHOCK

Abstract We describe the case of a 39–year–old woman with a history of recent natural birth, who came to our observation for an episode of oppressive chest pain while breastfeeding her baby at night. At the entrance, the electrocardiographic and echocardiographic findings and myocardiocitonecrosis enzymes were normal; after three hours the second enzymatic determination was clearly increased, so the patient was admitted to our ICU with a diagnosis of SCA / NSTEMI. She was therefore subjected to coronary angiography with a small hematoma in the distal tract of the marginal branch without flow limitation; it was therefore decided, in accordance with the AHA and ESC guidelines, for a conservative medical therapy. On the third day of hospitalization, the patient presented recurrence of chest pain with electrocardiographic evidence of ST segment elevation in the anterolateral site. A new angiographic evaluation was therefore performed urgently, showing a complete retrograde dissection from the marginal branch to the circumflex branch and to the anterior descending branch with TIMI 0–1 flow. During the procedure the patient underwent a prolonged hypotensive episode associated with frequent polymorphic ventricular ectopic beats, with rapid evolution towards a picture of overt cardiogenic shock. Therefore we proceeded quickly to perform PTCA with placement of medicated stents on all branches involved in the dissection, with rapid improvement of the haemodynamic picture. Spontaneous coronary dissections represent for a hemodynamist a condition of great technical difficulty where the margins of error are very high. Thanks to the technological evolution of materials, an experienced hemodynamist is able, more and more easily, to be successful in the revascularization procedure and to resolve extremely serious clinical pictures. This case report describes a spontaneous coronary dissection that most often occurs in young women in good health and without risk factors for coronary heart disease, particularly in the peripartum period. The presentation was similar to an acute coronary syndrome. According to AHA and ESC guidelines, therapy was conservative if dissection / hematoma is not a flow restriction with coronary angiography after a few days to demonstrate vessel restoration.

Individual differences in digesta retention and their relation to chewing in cattle-A pilot investigation.

While information on individual differences in digesta mean retention time (MRT) might be interesting when selecting phenotypes for digestive efficiency, MRT measurements are prohibitively labour-intensive for large-scale application. Therefore, more easily measured proxies of MRT might be helpful. We used the opportunity of an experiment applying saliva stimulant in cattle to investigate the effect of different individual chewing behaviour on fluid and particle MRT with a consistent diet. Four non-lactating cattle (670-850 kg body mass [BM]) were used in a 4 × 4 Latin square design, treated with the saliva stimulant pilocarpine in dosages of 0, 1, 2.5and 5 mg/kg BM per day. The cattle were fed hay with dry matter intake (DMI) assigned according to their metabolic body weight. MRT in the whole gastrointestinal tract (GIT), the reticulorumen (RR) and the distal tract were measured using Co-EDTA, Cr-mordanted fibre and La-mordanted fibre as markers representing fluid, small particles (2 mm) and large particles (1 cm), respectively. The chewing behaviour was measured via noseband pressure sensor and expressed as chewing frequency (chews per time) and chewing intensity (chews per DMI), both for total chewing (ingestion plus rumination) and rumination chewing alone. The animals differed considerably in chewing behaviour and MRT measures. BM did not show a significant effect on chewing behaviour and MRT measures, though it tended to negatively correlated to total chewing intensity. Chewing intensity exerted a significant negative influence on MRT of fluid and particles in the RR, which was not the case for chewing frequency. Chewing frequency showed a significant relationship with MRT of large particles in the GIT. We suggest that chewing behaviour could influence MRT in two ways: (i) by affecting saliva production via the masticatory-salivary reflex and subsequently, the fluid inflow to the RR; (ii) by contributing to particle size reduction. Should the link between chewing behaviour and MRT be corroborated in larger studies, chewing measures, with their large interindividual variation, could emerge as an easy-to-measure proxy for MRT characteristics.

Activation by Cleavage of the Epithelial Na+ Channel α and γ Subunits Independently Coevolved with the Vertebrate Terrestrial Migration

Vertebrates evolved mechanisms for sodium conservation and gas exchange in conjunction with migration from aquatic to terrestrial habitats. Epithelial Na+ channel (ENaC) function is critical to systems responsible for extracellular fluid homeostasis and gas exchange. ENaC is activated by cleavage at multiple specific extracellular polybasic sites, releasing inhibitory tracts from the channel’s α and γ subunits. Here we investigated the evolution of ENaC regulatory mechanisms to determine which features coevolved with the marine‐terrestrial transition. We consistently found both activating cleavage sites in the ENaC α and γ subunits of terrestrial vertebrates, while they appeared only sporadically in fishes. We confirmed that cleavage occurred at sites found in the γ subunit from Australian lungfish, leading to channel activation. Phylogenetic analysis and likelihood ratio tests showed that proximal and distal polybasic tracts in ENaC subunits coevolved, consistent with the dual cleavage requirement for activation. They also showed a coevolutionary dependence of tandem polybasic tracts with terrestrial status and with lungs, coincident with the ENaC activator aldosterone. Amplification of transcripts by RT‐PCR in ray‐finned Polypteriformes and previously in lobe‐finned lungfish suggest that transcripts for ENaC subunits with cleavage sites are readily detected at important sites of ion exchange (gills and kidney), but are difficult to detect in lungs. Analysis of ancestral reconstructions strongly suggests that the polybasic tracts appeared independently in the α and γ subunits of ENaC. Similar analyses of the PY motif, required for Nedd4‐2 dependent regulation, showed no coevolutionary pattern and that the PY motif first arose in an ancient ancestral ENaC subunit. Our data suggest that changes associated with adaptation to terrestrial life provided selective pressure for the development of ENaC activation by proteolytic cleavage.

B-37 | Flower-Blossom Stenting Technique for Distal Right Ventricular Outflow Tract Stenosis in Pediatric Patients: A Case Series

The treatment of distal right ventricular outflow tract (RVOT) stenosis can be challenging given the proximity of the pulmonary arterial (PA) bifurcation. The flower-blossom stenting (FBS) technique involves deploying a single stent mounted on two balloons and has been described in older patients. We describe the use of this technique in a younger, pediatric cohort.

Cutaneous Manifestations of Inflammatory Bowel Disease: A Basic Overview.

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal (GI) tract that is subdivided into Crohn's disease (CD) and ulcerative colitis (UC). CD is characterized by involvement of the entire GI tract, while UC mainly affects the distal GI tract. Moreover, both CD and UC can present with extraintestinal manifestations (EIMs) of the disease affecting multiple organ systems including the hepatobiliary tract, kidney, bones, eyes, joints, and skin. These complications can cause significant morbidity and negatively impact the quality of life for IBD patients. Although the pathogenesis of EIMs is not clearly elucidated, it is postulated that the diseased GI mucosa similarly stimulates excess immune responses at the extraintestinal sites. Cutaneous EIMs occur in up to 15% of patients with IBD, often predating their IBD diagnosis. They are categorized into (1) specific, (2) reactive, (3) associated, and (4) treatment-induced. Here, we review the epidemiological, clinical, diagnostic, and histologic features of the most commonly described cutaneous EIMs of IBD along with their respective treatment options.

Celiac disease: Definition, classification, historical and epistemological profiles, anatomopathological aspects, clinical signs, differential diagnosis, treatments and prognosis. Proposed diagnostic scheme for celiac disease (DSCNC)

Celiac disease is an immune-mediated enteropathy, caused (in genetically predisposed or susceptible individuals) by the ingestion of gluten, the complex of water-insoluble proteins found in cereal grains such as wheat, rye and barley. In terms of terminology, it is the complex natural history and extremely polymorphous clinical presentation that has created some confusion. In fact, to date, at least three different forms of celiac disease are known, in addition to the simple non-celiac gluten sensitivity, since in common clinical practice most patients do not present the classic symptoms such as malabsorptive syndrome with diarrhoea, steatorrhoea, weight loss and nutritional deficiency, but rather an anaemia, asthenia, meteorism, abdominal tension, osteoporosis and infertility, thus painting an extremely varied and complex symptomatic picture that is linked to enteric microbiota and microbiome issues. Celiac disease affects the mucosa of the small intestine, while it generally spares the submucosa, muscolaris propria and serosa; if the disease does not involve the whole of the small intestine but only part of it, it is usually more serious in the proximal than the distal tract. The simultaneous presence of shortened villi, crypt hyperplasia, the abnormal cytological appearance of the absorbent surface and increased lamina propria cells is required for the diagnosis of celiac disease. Based on these findings, several forms of celiac disease have been identified in the clinic: typical, atypical (and in turn silent, latent, and potential), and sensitive non-celiac. Based on these considerations a specific diagnostic scheme is suggested to frame the celiac universe more functionally and structurally (so-called Diagnostic Scheme for Celiac Disease and Nonceliac Gluten Sensitivity, DSCNC), identifying at least eight clinical hypotheses based on the serological, genetic, bioptic and allergological tests suggested). From a pharmacological and integrative point of view, the protocols shared by the scientific community remain in place: gluten-free diet, vitamin and salt supplementation if appropriate, pharmacological therapy (antibiotics, antihistamines, corticosteroids and immunosuppressants) if necessary, also in the future with the majority orientation oriented towards oral glutenase able to counteract the effects of gliadin in sensitive subjects, the use of larazotide acetate to remedy the increase in intestinal permeability and tTG inhibitors to reduce the toxic effects of gluten intake. The state of the art on celiac disease is not yet able to explain the precise aetiology and atypical forms of the disease, as well as the real impact of genetic predisposition on clinical manifestations. Research continues and seems to point the way to a complete resolution of this enteropathy that has been so prevalent over the last two decades.

Application of In Vivo MRI Imaging to Track a Coated Capsule and Its Disintegration in the Gastrointestinal Tract in Human Volunteers.

Oral specially coated formulations have the potential to improve treatment outcomes of a range of diseases in distal intestinal tract whilst limiting systemic drug absorption and adverse effects. Their development is challenging, partly because of limited knowledge of the physiological and pathological distal gastrointestinal factors, including colonic chyme fluid distribution and motor function. Recently, non-invasive techniques such as magnetic resonance imaging (MRI) have started to provide novel important insights. In this feasibility study, we formulated a coated capsule consisting of a hydroxypropyl methylcellulose (HPMC) shell, coated with a synthetic polymer based on polymethacrylate-based copolymer (Eudragit®) that can withstand the upper gastrointestinal tract conditions. The capsule was filled with olive oil as MRI-visible marker fluid. This allowed us to test the ability of MRI to track such a coated capsule in the gastrointestinal tract and to assess whether it is possible to image its loss of integrity by exploiting the ability of MRI to image fat and water separately and in combination. Ten healthy participants were administered capsules with varying amounts of coating and underwent MRI imaging of the gastrointestinal tract at 45 min intervals. The results indicate that it is feasible to track the capsules present in the gastrointestinal tract at different locations, as they were detected in all 10 participants. By the 360 min endpoint of the study, in nine participants the capsules were imaged in the small bowel, in eight participants in the terminal ileum, and in four in the colon. Loss of capsule integrity was observed in eight participants, occurring predominantly in distal intestinal regions. The data indicate that the described approach could be applied to assess performance of oral formulations in undisturbed distal gastrointestinal regions, without the need for ionizing radiation or contrast agents.

Compressive ultrasound can predict early pulmonary embolism onset in COVID patients

PurposeTo evaluate the usefulness of compressive ultrasound (CUS) for the diagnosis of deep vein thrombosis (DVT) in patients with SARS-CoV-2-related infection.Methods112 hospitalized patients with confirmed SARS-CoV-2 infection were retrospectively enrolled. CUS was performed within 2 days of admission and consisted in the assessment of the proximal and distal deep venous systems. Lack of compressibility, or direct identification of an endoluminal thrombus, were the criteria used for the diagnosis of DVT. Pulmonary embolism (PE) events were investigated at computed tomography pulmonary angiography (CTPA) within 5 days of follow-up. Logistic binary regression was computed to determine which clinical and radiological parameters were independently associated with PE onset.ResultsOverall, the incidence of DVT in our cohort was about 43%. The most common district involved was the left lower limb (68.7%) in comparison with the right one (58.3%) while the upper limbs were less frequently involved (4.2% the right one and 2.1% the left one, respectively). On both sides, the distal tract of the popliteal vein was the most common involved (50% right side and 45.8% left side). The presence of DVT in the distal tract of the right popliteal vein (OR = 2.444 95%CIs 1.084–16.624, p = 0.038), in the distal tract of the left popliteal vein (OR = 4.201 95%CIs 1.484–11.885, p = 0.007), and D-dimer values (OR = 2.122 95%CIs 1.030–5.495, p = 0.003) were independently associated with the onset on PE within 5 days.ConclusionsCUS should be considered a useful tool to discriminate which category of patients can develop PE within 5 days from admission.

Activation by cleavage of the epithelial Na+ channel α and γ subunits independently coevolved with the vertebrate terrestrial migration.

Vertebrates evolved mechanisms for sodium conservation and gas exchange in conjunction with migration from aquatic to terrestrial habitats. Epithelial Na+ channel (ENaC) function is critical to systems responsible for extracellular fluid homeostasis and gas exchange. ENaC is activated by cleavage at multiple specific extracellular polybasic sites, releasing inhibitory tracts from the channel's α and γ subunits. We found that proximal and distal polybasic tracts in ENaC subunits coevolved, consistent with the dual cleavage requirement for activation observed in mammals. Polybasic tract pairs evolved with the terrestrial migration and the appearance of lungs, coincident with the ENaC activator aldosterone, and appeared independently in the α and γ subunits. In summary, sites within ENaC for protease activation developed in vertebrates when renal Na+ conservation and alveolar gas exchange were required for terrestrial survival.

Can we promote neural regeneration through microbiota-targeted strategies? Introducing the new concept of neurobiotics.

Can we promote neural regeneration through microbiota-targeted strategies? Introducing the new concept of neurobiotics.

The cutback revisited — The posterior rectal advancement anoplasty for certain anorectal malformations with rectoperineal fistula

BackgroundThe repair of rectoperineal fistulae can pose a significant challenge to the pediatric surgeon given the proximity of the fistula to the urethra in males and vagina in females. In these children, a simple cutback procedure may leave the neoanus in a position anterior to the center of the sphincter, which theoretically could impair future continence. We devised an adaptation of the cutback anoplasty which we call the posterior rectal advancement anoplasty (PRAA) to treat patients with a rectoperineal fistula that is both narrow in lumen and located within, but at the anterior-most limit of the sphincter complex. Material and MethodsPatient selection, operative steps, and perioperative care of patients undergoing PRAA are detailed. Results10 children (6 males, 4 females) underwent PRAA. There were no vaginal wall or urethral injuries. At 6 months postoperatively, all patients were passing stool spontaneously. No patients required dilation of the anoplasty in the postoperative period and there were no anal strictures identified. ConclusionsA modification of the cutback anoplasty can be performed in patients with a perineal fistula and the distal fistula tract within the sphincter complex. We have demonstrated that this can be performed safely and obviates the need for an anterior rectal wall dissection, thus eliminating the risk of injury to urethra or vagina.Level of evidence: IV