Distal Tract Research Articles

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

Structural brain abnormalities in children and young adults with severe chronic kidney disease

BackgroundThe pathophysiology of neurological dysfunction in severe chronic kidney disease (CKD) in children and young adults is largely unknown. We aimed to investigate brain volumes and white matter integrity in this population and explore brain structure under different treatment modalities.MethodsThis cross-sectional study includes 24 patients with severe CKD (eGFR < 30) aged 8–30 years (median = 18.5, range = 9.1–30.5) on different therapy modalities (pre-dialysis, n = 7; dialysis, n = 7; transplanted, n = 10) and 21 healthy controls matched for age, sex, and parental educational level. Neuroimaging targeted brain volume using volumetric analysis on T1 scans and white matter integrity with tract-based spatial statistics and voxel-wise regression on diffusion tensor imaging (DTI) data.ResultsCKD patients had lower white matter integrity in a widespread cluster of primarily distal white matter tracts compared to healthy controls. Furthermore, CKD patients had smaller volume of the nucleus accumbens relative to healthy controls, while no evidence was found for abnormal volumes of gray and white matter or other subcortical structures. Longer time since successful transplantation was related to lower white matter integrity. Exploratory analyses comparing treatment subgroups suggest lower white matter integrity and smaller volume of the nucleus accumbens in dialysis and transplanted patients relative to healthy controls.ConclusionsYoung CKD patients seem at risk for widespread disruption of white matter integrity and to some extent smaller subcortical volume (i.e., nucleus accumbens). Especially patients on dialysis therapy and patients who received a kidney transplant may be at risk for disruption of white matter integrity and smaller volume of the nucleus accumbens.Graphical abstract

Distribution and daily oscillation of GABA in the circadian system of the cockroach Rhyparobia maderae.

Gamma-aminobutyric acid (GABA) is the prevalent inhibitory neurotransmitter in nervous systems promoting sleep in both mammals and insects. In the Madeira cockroach, sleep-wake cycles are controlled by a circadian clock network in the brain's optic lobes, centered in the accessory medulla (AME) with its innervating pigment-dispersing factor (PDF) expressing clock neurons at the anterior-ventral rim of the medulla. GABA is present in cell clusters that innervate different circuits of the cockroach's AME clock, without colocalizing in PDF clock neurons. Physiological, immunohistochemical, and behavioral assays provided evidence for a role of GABA in light entrainment, possibly via the distal tract that connects the AME's glomeruli to the medulla. Furthermore, GABA was implemented in clock outputs to multiple effector systems in optic lobe and midbrain. Here, GABAergic brain circuits were analyzed further, focusing on the circadian system in search for sleep/wake controlling brain circuits. All GABA-immunoreactive neurons of the cockroach brain were also stained with an antiserum against the GABA-synthesizing enzyme glutamic acid decarboxylase. We found strong overlap of the distribution of GABA-immunoreactive networks with PDF clock networks in optic lobes and midbrain. Neurons in five of the six soma groups that innervate the clock exhibited GABA immunoreactivity. The intensity of GABA immunoreactivity in the distal tract showed daily fluctuations with maximum staining intensity in the middle of the day and weakest staining at the end of the day. Quantification via enzyme-linked immunosorbent assay and quantitative liquid chromatography coupled to electrospray ionization tandem mass spectrometry, likewise, showed higher GABA levels in the optic lobe during the inactivity phase of the cockroach during the day and lower levels during its activity phase at dusk. Our data further support the hypothesis that light- and PDF-dependently the circadian clock network of the cockroach controls GABA levels and thereby promotes sleep during the day.

Value of Geriatric Assessment in Patients With Genitourinary Carcinoma.

Objectives: This work aims to evaluatecomprehensive geriatric assessment (CGA) tools to better guide patients with urogenital carcinomas perioperatively and, consequently, to intensify or reduce hospital resource use. Methods: After informed consent, 111patients were included, all aged more than 65 years, with oncological surgery (with proof of a malignancy), a Mini Mental State Examination (MMSE) score of at least 23 points, and a prospective life expectancy of more than 2 months. Patients were divided into 2 groups: prostate cancer (n = 88) and distal urinary tract cancer (n = 29). Further CGA tools were Instrumental Activities of Daily Living (iADL), Activities of Daily Living (ADL), and the Charlson Comorbidity Index (CCI). The relationships between CGA and complications, hospital duration, death rate, and baseline characteristics were analyzed. Results: In comparison with the patients with prostate cancer, those with kidney/distal urinary tract cancer had higher CCI scores (median, 3 vs 2; P <.001), MMSE scores (29 vs 28; P = .031), complication rates (55.2% vs 22.0%; P = .001), and hospital duration (16 vs 10 days; P <.001), as well as more deaths in the group (8 vs 0). Comorbidities (6 vs 2; P <.001), Physical Status Classification System (ASA state [3 vs 2; P <.001]), and median age (74 vs 71 years; P =.008) were all higher in the kidney/distal urinary tract group, and they had fewer problems with postoperative ADL items, which were significantly lower than those of the prostate group (P = .043). Intra- and intergroup comparisons of preoperative and 1-year ADL/iADL values did not differ significantly. Conclusion: These study results underscore the importance of CGA in patients with genitourinary carcinoma; most patients have high regenerative potential. Patients with kidney/distal urinary tract cancers are older, have more comorbidities, and have more postoperative impairments than patients with prostate cancer.

Власний досвід реконструктивно-пластичних операцій на сечовому міхурі в дітей

In our country, complex surgical reconstruction of the distal urinary tract in severe bladder dysfunction in children is performed infrequently, given the number of children who need these operations. These operations were carried out in our country by specialists invited from abroad. Therefore, we want to share our first experience of performing a complex surgical reconstruction of the distal urinary tract in children. Purpose – to іmprove the quality of life of children with severe bladder dysfunction. Materials and methods. The results of reconstructive and plastic operations on the bladder in 7 children with severe bladder dysfunction were analyzed. Four patients had a neurogenic bladder 3 of them had a spinal bladder), and two patients had a microcyst after surgical correction of bladder exstrophy and total epispadias. Augmentation ileocystoplasty was performed in 3 children, two of them also underwent appendicocystostomy, 3 patients underwent only appendicocystostomy. An assessment of the urinary tract condition, the degree of urinary retention, postoperative complications and quality of life of operated children. Results. All operated children recovered. The bladders in three patients after augmentation have sufficient volume and fully provide reservoir function. We did not observe metabolic acidosis or other serious metabolic disorders described by other authors in the children we operated on. Urolithiasis was also not observed after surgery. In 5 patients who underwent appendicocystostomy, the latter is well catheterized, has a good cosmetic effect. In 4 out of 5 patients there is no leakage of urine through the stoma. All operated children were recovered for vesicoureteral reflux and chronic pyelonephritis. According to the results of the survey, the improvement of most parameters of quality of life of operated patients (cessation of urinary tract infection, complete urinary retention with more infrequent and controlled urination, the ability to visit children’s groups and social adaptation of these children in society). Conclusions. Based on the first own experience of augmentation ileocystoplasty and appendicocystostomy according to Mitrofanoff, the good efficiency of these reconstructive-plastic operations is noted. In all operated patients the quality of life significantly improved – controlled urination was achieved, the progression of kidney damage was stopped. All postoperative complications are successfully corrected. Of great importance for achieving a good effect of treatment is the correct choice of the the urinary tract surgical reconstruction type in each case. The research was carried out in accordance with the principles of the Helsinki declaration. The study protocol was approved by the Local ethics committee of all participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Key words: augmentation ileocystoplasty, appendicocystostomy, children.