Severe Gastrointestinal Disease Research Articles

Effect of the switch status of Helicobacter pylori outer inflammatory protein A on gastric diseases

Helicobacter pylori OipA (Outer Inflammatory Protein A) is an outer membrane protein that takes role in the adherence and colonization to the stomach. oipA gene expression is regulated by the slipped-strand mispairing mechanism through a hypermutable CT dinucleotide repeat motif in the 5΄ region. Alterations in the CT number repeats cause frame-shift mutations to result in phase variation of oipA expression. While a functional “On” status has been recognized as a risk factor for peptic ulcer diseases and gastric cancer in many studies, some controversial findings still exist. To this end, this study compiled the sequence data of oipA from 10 different studies between 2000–2019 and 50 oipA DNA sequences from our own research that examined the relationship between the phase On/Off status of oipA and gastric diseases based on CT repeat number. Overall, we have reached 536 oipA DNA sequences from patients. This large collection of oipA sequences first clarified the absolute conservation of the peptide-pentamer of FWLHA for phase ‘’On’’ status, suggesting this pentamer as a superior marker for the determination of oipA status than counting the number of CT repeats. Combining the sequence and patient data, we have re-analyzed the association between the ‘‘On’’ status of oipA and gastric diseases. Our results showed a strong association between oipA ‘‘On’’ status and gastric cancer supporting previous findings. We also investigated the AlphaFold2 computed structure of OipA that adopts a beta-barrel fold closely resembling to the autotransporter family of H. pylori. Altogether, this study confirms a strong association between oipA ‘‘On’’ statuses and severe gastrointestinal diseases like cancer and provides useful insights into the FWLHA pentamer as an indicator of “On” status of oipA putative autotransporter function rather than CT repeats number.

MAb Targeting a Link Between ExoN and MTase of TGEV NSP14.

Porcine transmissible gastroenteritis virus (TGEV) infection results in severe gastrointestinal disease manifesting vomiting, diarrhea in neonatal porcine, with extremely high mortality. Monoclonal antibody (MAb) specific to TGEV nonstructural protein (NSP)14 that contains two functional domains, exonuclease (ExoN) and methyltransferase (MTase) domains, may help elucidate the role of NSP14 in the viral life-cycle. In this study, we developed a murine MAb, designated 12F1, against TGEV NSP14 using traditional cell-fusion technique. It was shown the MAb can exclusively bind to viral NSP14, as evidenced by the results of indirect fluorescent assay and western blotting. Intriguingly, epitope screening assay shown that 12F1 targets a hinge region connecting ExoN and N7-MTase of NSP14.

Reverse genetics of parrot bornavirus 4 reveals a unique splicing of the glycoprotein gene that affects viral propagation.

Viruses can utilize host splicing machinery to enable the expression of multiple genes from a limited-sized genome. Orthobornaviruses use alternative splicing to regulate the expression level of viral proteins and achieve efficient viral replication in the nucleus. Although more than 20 orthobornaviruses have been identified belonging to eight different viral species, virus-specific splicing has not been demonstrated. Here, we demonstrate that the glycoprotein (G) transcript of parrot bornavirus 4 (PaBV-4; species Orthobornavirus alphapsittaciforme), a highly virulent virus in psittacines, undergoes mRNA splicing and expresses a soluble isoform termed sGP. Interestingly, the splicing donor for sGP is not conserved in other orthobornaviruses, including those belonging to the same orthobornavirus species, suggesting that this splicing has evolved as a PaBV-4-specific event. We have also shown that exogenous expression of sGP does not affect PaBV-4 replication or de novo virion infectivity. In this study, to investigate the role of sGP in viral replication, we established a reverse genetics system for PaBV-4 by using avian cell lines and generated a recombinant virus lacking the spliced mRNA for sGP. Using the recombinant viruses, we show that the replication of the sGP-deficient virus is significantly slower than that of the wild-type virus and that the exogenous expression of sGP cannot restore its propagation efficiency. These results suggest that autologous or controlled expression of sGP by splicing may be important for PaBV-4 propagation. The reverse genetics system for avian bornaviruses developed here will be a powerful tool for understanding the replication strategies and pathogenesis of avian orthobornaviruses. IMPORTANCE Parrot bornavirus 4 (PaBV-4) is the dominant cause of proventricular dilatation disease, a severe gastrointestinal and central nervous system disease among avian bornaviruses. In this study, we discovered that PaBV-4 expresses a soluble isoform of glycoprotein (G), called sGP, through alternative splicing of the G mRNA, which is unique to this virus. To understand the role of sGP in viral replication, we generated recombinant PaBV-4 lacking the newly identified splicing donor site for sGP using a reverse genetics system and found that its propagation was significantly slower than that of the wild-type virus, suggesting that sGP plays an essential role in PaBV-4 infection. Our results provide important insights not only into the replication strategy but also into the pathogenesis of PaBV-4, which is the most prevalent bornavirus in captive psittacines worldwide.

Chronic Pain and Mood Disorders Are Not Barriers to Symptom Improvement Under Collaborative Co-managed Care (C3).

Patients with comorbid chronic pain and mood disorders have more severe gastrointestinal disease and higher healthcare expenses than their peers. We sought to determine whether management under our innovative Collaborative Co-Managed Care (C3) general gastroenterology care model improved outcomes. Patient questionnaires completed by outpatients at our GI Motility Center were analyzed alongside demographic information to determine predictors of response to treatment based on adequate relief of gastrointestinal symptoms and improvement in quality of life. These comorbidities did not significantly impair response and may be associated with improved response under our model. The C3 general gastroenterology care model anchors on setting expectations and team-based communication and improves outcomes of, and access to, care.

Safety and Efficacy of Liraglutide, 3.0 mg, Once Daily vs Placebo in Patients With Poor Weight Loss Following Metabolic Surgery

Metabolic surgery leads to weight loss and improved health, but these outcomes are highly variable. Poor weight loss is associated with lower circulating levels of glucagon-like peptide-1 (GLP-1). To assess the efficacy and safety of the GLP-1 receptor agonist, liraglutide, 3.0 mg, on percentage body weight reduction in patients with poor weight loss and suboptimal GLP-1 response after metabolic surgery. The Evaluation of Liraglutide 3.0 mg in Patients With Poor Weight Loss and a Suboptimal Glucagon-Like Peptide-1 Response (BARI-OPTIMISE) randomized placebo-controlled trial recruited adult patients at least 1 year after metabolic surgery who had experienced 20% or less body weight loss from the day of surgery and a suboptimal nutrient-stimulated GLP-1 response from 2 hospitals in London, United Kingdom, between October 2018 and November 2019. Key exclusion criteria were type 1 diabetes; severe concomitant psychiatric, gastrointestinal, cardiac, kidney or metabolic disease; and use of insulin, GLP-1 receptor analogues, and medication that can affect weight. The study period was 24 weeks followed by a 4-week follow-up period. Last participant follow-up was completed in June 2020. All participants and clinical study personnel were blinded to treatment allocation. Of 154 assessed for eligibility, 70 met trial criteria and were included in the study, and 57 completed follow-up. Liraglutide, 3.0 mg, once daily or placebo as an adjunct to lifestyle intervention with a 500-kcal daily energy deficit for 24 weeks, on a 1:1 allocation by computer-generated randomization sequence, stratified by surgery type (Roux-en-Y gastric bypass [RYGB] or sleeve gastrectomy [SG]) and type 2 diabetes status. The primary outcome was change in percentage body weight from baseline to the end of the 24-week study period based on an intention-to-treat analysis. Participant safety was assessed through monitoring of biochemical parameters, including kidney and liver function, physical examination, and assessment for adverse events. A total of 70 participants (mean [SD] age, 47.6 [10.7] years; 52 [74%] female) with a poor weight loss response following RYGB or SG were randomized to receive 3.0-mg liraglutide (n = 35) or placebo (n = 35). All participants received at least 1 dose of the trial drug. Eight participants discontinued treatment (4 per group), and 2 in the 3.0-mg liraglutide group and 1 in the placebo group were lost to follow-up. Due to COVID-19 restrictions, 3 participants in the 3.0-mg liraglutide group and 7 in the placebo group were unable to attend their final in-person assessment. Estimated change in mean (SD) percentage body weight from baseline to week 24 was -8.82 (4.94) with liraglutide, 3.0 mg (n = 31), vs -0.54 (3.32) with placebo (n = 26). The mean difference in percentage body weight change for liraglutide, 3.0 mg, vs placebo was -8.03 (95% CI, -10.39 to -5.66; P < .001). Adverse events, predominantly gastrointestinal, were more frequent with liraglutide, 3.0 mg (28 events [80%]), than placebo (20 events [57%]). There were no serious adverse events and no treatment-related deaths. These findings support the use of adjuvant liraglutide, 3.0 mg, for weight management in patients with poor weight loss and suboptimal GLP-1 response after metabolic surgery. ClinicalTrials.gov Identifier: NCT03341429.

Clinical data analysis of 86 patients with invasive infections caused by Malassezia furfur from a tertiary medical center and 37 studies.

Malassezia furfur (M. furfur) is a lipophilic, conditionally pathogenic yeast that mainly causes skin infections, but the reports of related invasive infections are increasing. The aim of this study is to provide clinical data to assist physicians in the management of patients with invasive infections caused by M. furfur. A case of pulmonary infection caused by M. furfur in a hematopoietic stem cell transplant patient for aplastic anemia was reported. In addition, the literature on invasive infection by M. furfur published in PubMed and Web of Science in English until 31 July 2022 was reviewed. Clinical data analysis of 86 patients (from 37 studies and our case) revealed that most of them were preterm (44.2%), followed by adults (31.4%). M. furfur fungemia occurred in 79.1% of the 86 patients, and 45 of them were clearly obtained from catheter blood. Other patients developed catheter-related infections, pneumonia, peripheral thromboembolism, endocarditis, meningitis, peritonitis and disseminated infections. Thirty-eight preterm infants had underlying diseases such as very low birth weight and/or multiple organ hypoplasia. The remaining patients had compromised immunity or severe gastrointestinal diseases. 97.7% of patients underwent invasive procedures and 80.2% received total parenteral nutrition (TPN). Fever, thrombocytopenia and leukocytosis accounted for 55.8%, 38.4% and 24.4% of patients with M. furfur invasive infections, respectively. 69.8% of the patients received antifungal therapy, mainly amphotericin B (AmB) or azoles. Of 84 patients with indwelling catheters, 58.3% underwent the removal of catheters. TPN were discontinued in 30 of 69 patients. The all-cause mortality of 86 patients was 27.9%. M. furfur can cause a variety of invasive infections. These patients mostly occur in premature infants, low immunity and severe gastrointestinal diseases. Indwelling catheters and TPN infusion are major risk factors. AmB, l-AmB and azoles are the most commonly used agents, and simultaneous removal of the catheter and termination of TPN infusion are important for the treatment of M. furfur invasive infections.

PLGA nanoparticles containing Intimin-Flagellin fusion protein for E. coli O157:H7 nano-vaccine

Escherichia coli O157:H7 is a foodborne pathogen that can lead to severe gastrointestinal diseases in humans. Vaccination is a promising strategy for preventing E. coli O157:H7 infections, which offers socio-economic benefits and provides the possibility of stimulating both humoral and cellular immune responses at systemic and mucosal sites. In this study, we developed a needle-free vaccine candidate against E. coli O157:H7 using poly(lactic-co-glycolic acid) (PLGA) nanoparticles entrapping a chimeric Intimin-Flagellin (IF) protein. The IF protein was expressed and verified using SDS-PAGE and western blot analysis, with a yield of 1/7 mg/L and a molecular weight of approximately 70 kDa. The prepared nanoparticles showed uniformly shaped spherical particles in the 200-nm range, as confirmed by SEM and DLS analysis. Three different routes of vaccine administration were used, including intranasal, oral, and subcutaneous, and the groups vaccinated with NPs protein had a higher antibody response compared to those receiving free protein. Subcutaneous administration of IF-NPs resulted in the highest level of IgG antibody titer, while oral administration of IF-NPs produced the highest amount of IgA antibody titer. Finally, all mice in the nanoparticle- intranasal and oral administered groups challenged with 100LD50 survived, while all control mice died before day 5. Based on these findings, we conclude that the PLGA-encapsulated IF protein has the potential to serve as a promising needle-free vaccine candidate against E. coli O157:H7.

Fecal Calprotectin Levels Dynamics in Newborns with High-Risk of Necrotizing Enterocolitis

Background. Necrotizing enterocolitis (NEC) is severe gastrointestinal disease in newborns, its early clinical symptoms are nonspecific. Fecal сalprotectin (Cp) is considered as one of the early biomarkers of NEC, thus, its use in newborns is poorly known.Objective. The aim of the study is to evaluate clinical significance of fecal Cp measuring as an early NEC marker in newborns. Methods. The prospective cohort observational study included high-risk newborns (gestational age (GA) ˂ 33 weeks and/or body weight ˂ 1500 g) and moderate risk newborns (GV≥ 33 weeks at suspicion on NEC) of NEC admitted to the neonatal intensive care unit on the 1st day of life. The Cp level was studied via immune colorimetric method on the 3rd and 7th days of life in high-risk children and in all children at NEC manifestation. All patients were divided into 2 main subgroups after the end of the follow-up period: newborns with developed NEC (a) and children without NEC (b). Obtained Cp values were compared between these subgroups.Results. There were no statistically significant differences in Cp levels at the 3rd and 7th days of life in the high-risk group of children with NEC and without NEC. However, it was noted that children without NEC showed a decrease in Cp levels on the 7th day, while children with NEC manifestation, indeed, had increased levels. Cp levels did not differ in the moderate risk group.Conclusion. Single measurement of Cp level in newborns of any GA is uninformative towards the NEC prognosis and diagnosis. However, evaluation of the Cp level dynamics at the 7th day of life compared to the 3rd day of life may be considered as a promising non-invasive method for prognosis of NEC manifestation in premature infants (GA&lt;33 weeks).

Effect of Glycosaminoglycans on Cryptosporidium Oocyst Attachment and Excystation.

Cryptosporidium causes severe gastrointestinal disease resulting from the ingestion of oocysts, followed by oocyst excystation in the small intestine and the release of infective sporozoites. An understudied strategy for Cryptosporidium inactivation is purposeful oocyst excystation, as sporozoites do not survive long in the environment. This study showed that C. parvum oocyst excystation was induced by direct contact with various glycosaminoglycans (GAGs), including heparin (Hep), chondroitin sulfate A (CSA), and hyaluronan (HA), assembled on polydopamine (PD)-functionalized surfaces. PD surfaces elicited 97.9 ± 3.6% oocyst attachment, with some of the attached oocysts partially (7.3 ± 1.3%) or fully (4.0 ± 0.6%) excysted after 4 days. The PD-GAG surfaces (GAG concentration = 2 mg/mL) elicited similarly high attachment (>97%) and higher oocyst excystation efficiencies after 4 days. The PD-Hep surfaces elicited the highest number of attached excysted oocysts (11.8 ± 0.63% partially excysted; 11.9 ± 0.49% fully excysted), and the PD-HA surfaces elicited the lowest (8.8 ± 2.1% partially excysted; 7.8 ± 1.2% fully excysted). Surface characterization revealed that the addition of GAGs to the PD surface changed both the surface roughness as well as the surface wettability. Treatment of oocysts with an enzyme that degraded the surface glycocalyx markedly reduced excystation (to <2%) of the oocysts attached to the PD and PD-GAG surfaces. These findings suggest that GAGs provide an important local signal for the excystation of C. parvum oocysts and that certain surface-expressed oocyst receptors are necessary for efficient excystation. These oocyst-receptor relationships may be useful in the design of functionalized surfaces for the purposeful inactivation of oocysts in the environment or in water treatment systems. IMPORTANCE Polydopamine surfaces functionalized with glycosaminoglycans were shown to facilitate the attachment and excystation of Cryptosporidium parvum oocysts. Our findings suggest that a surface-expressed receptor on the oocyst wall plays a key role in excystation, with glycosaminoglycans serving as ligands that trigger the initiation of the process. Future technologies and treatment strategies designed to promote premature excystation of oocysts will minimize the ingestion of sporozoites that initiate infection. Therefore, the results from this study have important implications for the protection of public health from waterborne cryptosporidiosis and may serve as a foundation for engineered surfaces designed to remove oocysts from surface waters or inactivate oocysts in water treatment systems.

A hierarchy of cell death pathways confers layered resistance to shigellosis in mice.

Bacteria of the genus Shigella cause shigellosis, a severe gastrointestinal disease driven by bacterial colonization of colonic intestinal epithelial cells. Vertebrates have evolved programmed cell death pathways that sense invasive enteric pathogens and eliminate their intracellular niche. Previously we reported that genetic removal of one such pathway, the NAIP-NLRC4 inflammasome, is sufficient to convert mice from resistant to susceptible to oral Shigella flexneri challenge (Mitchell et al., 2020). Here, we investigate the protective role of additional cell death pathways during oral mouse Shigella infection. We find that the Caspase-11 inflammasome, which senses Shigella LPS, restricts Shigella colonization of the intestinal epithelium in the absence of NAIP-NLRC4. However, this protection is limited when Shigella expresses OspC3, an effector that antagonizes Caspase-11 activity. TNFα, a cytokine that activates Caspase-8-dependent apoptosis, also provides potent protection from Shigella colonization of the intestinal epithelium when mice lack both NAIP-NLRC4 and Caspase-11. The combined genetic removal of Caspases-1, -11, and -8 renders mice hyper-susceptible to oral Shigella infection. Our findings uncover a layered hierarchy of cell death pathways that limit the ability of an invasive gastrointestinal pathogen to cause disease.

Parasympathetic control of gastrointestinal motility and cross-branch actions of parasympathetic neuromodulation.

Parasympathetic control of gastrointestinal motility and cross-branch actions of parasympathetic neuromodulation.

Фактор транскрипції T-bet - діагностичний маркер розвитку некротизуючого ентероколіту в недоношених новонароджених

Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease that mainly affects preterm infants. The non-specificity of the clinical picture and the high percentage of complications determine the need for early diagnosis and prevention of the disease. Purpose - to establish a relationship between the T-bet expression level in the cells of the buccal mucosa, the development of HEC and the method of feeding in premature newborn infants. Materials and methods. We examined 74 newborns, who were treated in neonatal departments. We selected three groups for comparison: the Group 1 consisted of 32 newborns up to 37 weeks of gestation on breastfeeding (BF); the Group 2 - 30 preterm newborns on artificial feeding (AF); the control group - 12 full-term newborns on BF. We determined the expression level of T-bet transcription gene factor in the cells of the buccal mucosa scrapings of the newborns. Thereafter, we have calculated the T-bet normalized expression levels in the cells of the mucous membranes of infants of the Group 1 and the Group 2 in relation to the control group, where the expression level of the specified factors was taken as 1 c.u. Results. The gestational age median of the Group 1 children was 33 (31; 34) weeks; the Group 2 - 32.5 (32; 35) weeks; and it was comparatively higher versus in the Group 1 (p&lt;0.001) - 40 (39; 41) weeks. NEC has significantly more often developed in premature children on AF than on BF (p&lt;0.05) - 30.0±8.4% versus 9.4±5.2%. The T-bet expression in the cells of the buccal mucosa scrapings was higher in preterm children, and the highest level was in the Group 2 - 2.4 (1.98; 3.84) c.u. versus 1.48 (1.13; 2.22) c.u. in the Group 1. We have proved a direct relationship between AF and T-bet level (r=0.370; p&lt;0.004). Pairwise comparison revealed a higher level of T-bet in children with NEC (p=0.002): 2.36 (1.94; 3.17) c.u versus 1.74 (1.01; 3.27) c.u. without signs of NEC. We found a direct correlation between the T-bet level and the development of HEC (r=0,271; p=0.021). Conclusions. The T-bet expression level in the cells of the buccal mucosa increases in newborns with the appearance of the clinical signs of NEC. The level of T-bet expression in the buccal mucosa cells can be a marker of the inflammatory process development in intestine of infants. The expression of T-bet in the buccal mucosa cells of newborns with clinical signs of NEC is higher than in full-term newborns that reflects the tendency to NEC development. We have demonstrated that the T-bet expression level is higher in preterm neonates on AF. Therefore, AF can be considered as a risk factor for the development of NEC in preterm infants. 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 institutions. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Impact of COVID-19 on the digestive system: A descriptive cross-sectional study

Background: Various digestive symptoms caused by COVID-19 are frequently reported. This study aims to describe the most frequent digestive signs in patients with COVID-19, the relationship between the severity of digestive symptoms and some serological markers associated with liver manifestation, the detection of SARS-CoV-2 in a stool sample, and the mortality rate of those patients. Materials and Methods: A descriptive cross-sectional study on 100 confirmed COVID-19 cases with digestive and hepatic manifestation in one center (Fallujah Teaching Hospital), Anbar governorate, Iraq, during a period of study. Questioner’s data were formed for all patients regarding age, sex, and comorbidities such as diabetes and hypertension. Liver function enzymes such as alanine aminotransferase (ALT), aspartate aminotransferase, alkaline phosphatase, total bilirubin (TBIL), and direct bilirubin and haematological parameters such as ferritin D-dimer, C-reactive protein (CRP), albumin, amylase, leukocyte count, and prothrombin time were used. SARS-CoV-2 prevalence in stool is determined using reverse transcription polymerase chain reaction according to manufacturer’s instructions. The mortality rate of patients with COVID-19 was also determined. Data were followed up until April 22, 2022. Results: Patients with digestive symptoms who had COVID-19 had an average age of 45.03 (SD 20.078), 52 (52%) were men, and 48 (48%) were women. No statistically significant variances were observed in the severity of digestive symptoms among age groups. The three digestive symptoms that patients with COVID-19 experienced most frequently were fatigue, fever, and abdominal colic. SARS-CoV-2 was detected in the stool of 11% of the patients with COVID-19 with digestive signs. The COVID-19 mortality rate was 9%. Statistically, significant variance was observed in ALT (P value 0.01) and TBIL (P value 0.0027) levels between mild, moderate, and severe gastrointestinal (GI) diseases. The levels of CRP varied considerably among those with mild, moderate, and severe GI conditions (P value 0.0182, according to the findings). In mild, moderate, and severe GI disorders, ferritin levels differed considerably (P value 0.05). Conclusions: The faecal sample with a nasopharyngeal swab is needed to confirm COVID-19 diagnosis; hepatic manifestations are connected with increased COVID-19 mortality in individuals with digestive symptoms.

Updates and recommendations on the surgical management of NEC

Necrotizing enterocolitis is a severe gastrointestinal disease of the infant. It most commonly targets those that are born prematurely. NEC has been associated with initiation of feeds and in most cases, it can be managed with antibiotics and bowel rest. However, in up to half of the cases, intestinal perforation, peritonitis, and failure of medical treatment will require surgical intervention. The following review will discuss the surgical approach to managing NEC, based on an updated review of practice patterns and recently published literature.

Intra-Amniotic Administration-An Emerging Method to Investigate Necrotizing Enterocolitis, In Vivo (Gallus gallus).

Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease in premature infants and a leading cause of death in neonates (1-7% in the US). NEC is caused by opportunistic bacteria, which cause gut dysbiosis and inflammation and ultimately result in intestinal necrosis. Previous studies have utilized the rodent and pig models to mimic NEC, whereas the current study uses the in vivo (Gallus gallus) intra-amniotic administration approach to investigate NEC. On incubation day 17, broiler chicken (Gallus gallus) viable embryos were injected intra-amniotically with 1 mL dextran sodium sulfate (DSS) in H2O. Four treatment groups (0.1%, 0.25%, 0.5%, and 0.75% DSS) and two controls (H2O/non-injected controls) were administered. We observed a significant increase in intestinal permeability and negative intestinal morphological changes, specifically, decreased villus surface area and goblet cell diameter in the 0.50% and 0.75% DSS groups. Furthermore, there was a significant increase in pathogenic bacterial (E. coli spp. and Klebsiella spp.) abundances in the 0.75% DSS group compared to the control groups, demonstrating cecal microbiota dysbiosis. These results demonstrate significant physiopathology of NEC and negative bacterial-host interactions within a premature gastrointestinal system. Our present study demonstrates a novel model of NEC through intra-amniotic administration to study the effects of NEC on intestinal functionality, morphology, and gut microbiota in vivo.

Vedolizumab for pediatric patients with gastrointestinal acute graft-versus-host-disease.

Vedolizumab, an anti-α4β7 integrin monoclonal antibody, impairs homing of T-cells to the gastrointestinal (GI) endothelium and acts as a gut-selective anti-inflammatory agent. Recent reports of the efficacy of vedolizumab in treating lower GI acute graft-versus-host disease (aGVHD) are promising, but experience in children is scarce. We present a cohort of 13 pediatric patients who were treated with vedolizumab for GI aGVHD. Ten of the patients were treated for steroid-refractory disease, out of which, six suffered from severe (stage 3 or 4) GI disease before the first dose of vedolizumab. In the other three patients, vedolizumab was introduced early in the disease course. Median time between GI GVHD onset to vedolizumab treatment was 23 days (range 7-59 days), with a median of 3 doses (range 1-5) per patient. GI GVHD staging was evaluated at various time points after the first vedolizumab dose, showing improvement in nine of the 13 patients. After a median follow-up time of 13 months (range 6-34 months), eight patients completely recovered, two had ongoing chronic colitis, and threepatients died. During the vedolizumab treatment period, 38 infectious episodes were noted, most of them GI related. The unique activity profile of vedolizumab makes it an appealing treatment option for lower GI aGVHD, but caution for concurrent infections is warranted.

Escherichia coli infection, a negative prognostic factor on the evolution of patients with surgical diseases

The bacterium Escherichia coli, one of the most studied bacteria in the world, with the greatest epidemiological impact, includes both commensal and pathogenic strains, with a genome that can be extremely varied both in size and genetic content, and it also can produce numerous diseases with specific symptoms. The vast majority of these strains can cause severe gastrointestinal diseases, hemolytic uremic syndrome, hemorrhagic colitis, renal failure and even death. Hemolytic uremic syndrome can be a consequence of the presence of Escherichia coli infection in gastrointestinal diseases. In this study, uremia in patients with and without the declared renal comorbidity, was negatively correlated with the response to antibiotic treatment. The increase of uremia above 92 mg/dl increases the risk of death. The highest risk categories include people with kidney disease like comorbidities starting with admission in surgical and intensive care wards in IRGH Cluj-Napoca, having as main diagnosis of hospitalization surgical digestive diseases. The occurrence of Coli pathogen infection was associated with increased morbidity and mortality rates in patients included in the study. In these patients, it was noticed the need to introduce therapy with increasingly complex antibiotic formulas, which lead to an increase in the duration and cost of hospitalization. In the studied group, due to E coli infection at admission, uremia had an average value of 23.99mg/dl +/-8.987(SD) in the case of patients without kidney disease, the number of patients with normal uremia values ​​was lower than that of those with increased values ​​of uremia. In the case of patients with confirmed kidney disease, uremia had mean values ​​of 65.76 mg/dl +/-52.41(SD). At discharge, both in the case of patients with renal disease and in the case of those without confirmed renal disease, the number of patients with normal values ​​of uremia was higher than those with pathological values, this proportion being reversed in the case of deceased patients where the number of patients with values pathological urea levels were significantly higher than those with normal values, proving kidney damage.

Cryptosporidium infection in young dogs from Germany

Cryptosporidium is an enteric protozoan parasite which is able to cause severe gastrointestinal disease and is distributed all over the world. Since information about the prevalence of cryptosporidiosis in German dogs is rare, the aim of this study was to examine the occurrence of Cryptosporidium spp. in dogs and the potential zoonotic risk emanating from these infected animals. In total, 349 fecal samples of 171 dogs were collected during the dogs’ first year of life. The samples were examined for Cryptosporidium spp. using PCR, targeting the small subunit ribosomal RNA gene (SSU rRNA). Further analysis of Cryptosporidium parvum and Cryptosporidium canis positive samples was accomplished using the 60 kDa glycoproteine gene (GP60). Overall, 10.0% (35/349) of the specimens were tested positive for Cryptosporidium. Cryptosporidium canis was found in 94.3% (33/35) of these samples and the zoonotic type C. pavum in 5.7% (2/35). Both C. parvum infections were subtyped as IIaA15G2R1. Sixteen of the C. canis positive samples were successfully amplified at the GP60 gene locus. These isolates were identified to belong to the subtype families XXd, XXe, or XXb; however, 2 samples could not be assigned to any of the described subtype families. Considering the close contact between pets and their owners, dogs may act as a potential source of infection for human cryptosporidiosis. The results of this study, in context with other studies from different countries, provide important further insights into the distribution of Cryptosporidium species in dogs and their zoonotic potential.

Gastrointestinal involvement in systemic sclerosis: pathogenesis, assessment and treatment.

The majority of patients with systemic sclerosis (SSc) will experience involvement of their gastrointestinal over the course of their disease. Despite the high prevalence of gastrointestinal involvement in SSc, the strategies pertaining to the assessment and treatment for this clinical dimension of SSc have historically been limited. However, the present review highlights recent research contributions that enhance our understanding of SSc-GI patient subsets and provides updates on pathogenic mechanisms of disease, assessment and symptom-directed management. In the past few years, several studies have identified risk factors for more severe gastrointestinal disease in SSc and have provided insight to optimize diagnosis and management of SSc-GI symptoms. This article also provides a review of currently available investigations and therapies for individual SSc-GI disease manifestations and reflects on actively evolving areas of research, including our understanding the role of the gut microbiome in SSc. Here, we provide important updates pertaining to the risk stratification, assessment, diagnosis and management of SSc patients with gastrointestinal symptoms. These findings provide opportunities to enhance patient care and highlight exciting opportunities for future research.

Antibiotics Sensitivity of Bacterial Strains Isolated From Cold Meat in Saudi Markets

The objective research works on cold and ready-to-eat meat products from local markets and how they are affected by external factors and the transmission of microorganisms to them and their reproduction despite their preservation, despite the preservation of these meats in consumers' refrigerators, and how some of these microbes are pathogenic or cause diseases by excreting toxins. The result of our research centers on displaying the total number of bacteria in all samples, identifying the strain contained in these ready-to-eat meats, and comparing them with the permissible limits imposed by most food and drug authorities in the world to preserve the safety of consumers. Also, we test the microbes' sensitivity to antibiotics. The types of bacteria were identified through approved protocols. The total count of bacteria was not in the range of the FDA limits rate, and we found some strains that should not be in the product as E. coli and Salmonella. spp. These strains can cause severe gastrointestinal tract diseases. The results of the Antibiotic test were positive. Only two of the 30 species we identified were resistant to all the antibiotics we used. They were S. aureus. The microbiological quality of cold meats in Jeddah, Saudi Arabia, is barely within the limits of the FDA. In terms of coliforms, Staphylococcus, and streptococci. So, all the food handlers should receive training to increase the level of hygiene in the supermarkets in Jeddah, Saudi Arabia.