Haemorrhagic ulcerative duodenitis in a patient with COVID-19 infection: clinical improvement following treatment with budesonide

We present a case of a male patient in his mid-30s with COVID-19-induced lung failure requiring extracorporeal membrane oxygenation, who needed an emergency oesophagogastroduodenoscopy due to major upper gastrointestinal bleeding. Endoscopy exposed severe ulcerative duodenitis with diffuse mucosal bleeding. While CT angiography did not show any signs of ischaemia, histopathology revealed duodenitis with substantial inflammatory cell infiltrates consisting of neutrophils and CD3+ T lymphocytes with equal CD4+/CD8+ distribution. Since the composition of cell infiltrates coincides with changes in inflammatory patterns of the respiratory mucosa from patients with COVID-19 and in COVID-19-associated enterocolitis, and systemic dexamethasone treatment became standard of care in ventilated intensive care unit patients with COVID-19 infection, we initiated an individualised therapeutic attempt to treat the duodenitis with topical enteral budesonide. Follow-up oesophagogastroduodenoscopies within 4 weeks of enteral budesonide administration revealed a full clinical and histological healing of the duodenal mucosa with marked reduction of neutrophilic and lymphocytic infiltrates.To our knowledge, the current report is the first description of enteral budesonide treatment of duodenitis in a patient with COVID-19 infection and warrants further investigation, whether budesonide might constitute a novel therapeutic strategy for the management of COVID-19-related intestinal mucosal damage.

Carbon nanoparticles in Mongolian medicine alleviate acute gastric ulcer induced by ethanol through regulating Fas/FasL pathway

Introduction: The consumption of large amounts of ethanol can directly lead to acute gastric mucosal bleeding, edema, and erosion, while long-term drinking has been associated with gastric ulcers. Previous research has demonstrated that Har Gabur, a traditional Mongolian medicine, alleviates gastric ulcers through the physical adsorption of its carbon components. It is well known that the immune response has an important role in gastric ulceration. Methods: In the present study, we used ethanol-induced injury cell and mice model to investigate whether Har Gabur can inhibit the immune response stimulated by ethanol and identify the active constituents of Har Gabur involved in this process. Results: We found that Har Gabur significantly repressed the activated Fas/FasL signal pathway and endogenous Bax/Bcl-2 apoptosis pathway. The molecular mechanism of the protective effect most likely involved the transcription or mRNA stability, as Har Gabur remarkably reversed the change in mRNA level of apoptosis-related genes induced by ethanol. Conclusion: Har Gabur operated in a cell-state specific manner in vivo without inducing adverse effects in normal mice. Importantly, GO was identified as the main active ingredient of Har Gabur for gastric ulcers.

The Value of Cystoscopy in the Assessment of Interstitial Cystitis/Bladder Pain Syndrome

Background. There are significant differences in the diagnosis of interstitial cystitis/painful bladder syndrome (IC/ BPS), in particular, controversy regarding the diagnostic role of cystoscopy or hydrodistension cystoscopy.The aim of the study was to evaluate the results of cystoscopy with hydrodistension in women with IC/BPS.Materials and methods. The study involved 126 women with IC/BPS, mean age – 46.7 ± 14.0 years. The duration of the disease was 6.0 ± 2.8 years. Questionnaires PUF, VAS, USS, and potassium test were used. Cystoscopy and urinary bladder hydrodistension were performed.Results. The sum of points on the PUF scale was 8.14 ± 1.76, on the VAS scale – 5.45 ± 0.93, on the USS scale – 2.63 ± 0.91. A positive potassium test was detected in 91.3 % of cases, the sensitivity of the test was 86.5 %, the specificity – 84.6 %. The anatomical bladder capacity was 308.0 ± 77.5 ml. The average indicator of maximum bladder filling in women with mild pain was higher than in moderate and severe pain by 30.9 % (p < 0.05) and 53.0 % (p < 0.01), respectively. In 11.9 % of cases, polyps were detected at the external opening of the urethra. During cystoscopy, diffuse mucosal bleeding was detected in 39.8 % of cases, diffuse submucosal bleeding – in 21.4 %, rare glomerulations – in 14.3 %, Gunner’s lesions in 12.7 % of cases. After hydrodistension, the changes were more often diffuse (n = 57). There was a significant relationship (r = –0.57, p < 0.01) between the maximum filling of the bladder and the degree of severity of mucosal abnormalities. The severity of changes in the mucous membrane of the bladder positively correlated with the sum of points on the PUF questionnaire (r = +0.61, p = 0.003), on the VAS questionnaire (r = +0.59, p = 0.008) and according to the USS questionnaire (r = +0.66, p = 0.005).Conclusion. Cystoscopy can be used to examine IC/BPS in accordance with the recommendations of international societies. The obtained data can help to improve the effectiveness of IC/PBS diagnostics.

Long-term safety evaluation of Daxocox® tablets (enflicoxib) in dogs after weekly oral administrations for seven months

Background Daxocox® [Ecuphar/Animalcare Group] contains the selective COX-2 inhibitor enflicoxib, approved in the EU for the treatment of pain and inflammation associated with osteoarthritis in dogs. The safety of Daxocox® was evaluated in a target animal safety study: Groups of 4 dogs per sex each were treated once weekly with placebo or Daxocox tablets at 1-, 3- and 5-times (1X, 3X and 5X) the maximum recommended therapeutic dose of enflicoxib (0, 4, 12 or 20 mg/kg, respectively). After an initial loading dose, dogs in the placebo control, 1X and 3X groups were administered for 32 weeks, and those in the 5X group were administered for 13 weeks. Dogs were subjected to daily food consumption measurements and clinical and dose observations. Body weight measurements, physical examinations, clinical pathology, urinalysis, faecal occult blood (FOB) and electrocardiographic (ECG) and blood pressure measurements, buccal mucosal bleeding time (BMBT), ophthalmology and gastroduodenal endoscopy examinations were conducted throughout the study. At study completion, all dogs were subjected to gross necropsy. Histopathology was performed on selected tissues from all animals in all groups. Results No clinical signs were noted, and no toxicologically relevant dose-associated effects were observed. Conclusions Results show that Daxocox® is well-tolerated and has a broad safety margin when administered as directed in dogs.

Subacute Enteritis Two Months After COVID-19 Pneumonia With Mucosal Bleeding, Perforation, and Internal Fistulas

Chronic sequelae of COVID-19 remain undetermined. We report a case of postinfection sequelae in a patient presenting with subacute obstruction 2 months after COVID-19 infection. A 34-year-old man with a prior prolonged hospital stay due to COVID-19 complicated by upper gastrointestinal (GI) bleed presented with subacute obstruction and failure to thrive. Upper GI push enteroscopy revealed residual ulcers and multiple proximal jejuno-jejunal fistulae. Midline laparotomy revealed strictures with dense intra-abdominal adhesions, a large jejuno-jejunal fistula, and evidence of prior jejunal perforation following severe COVID-19 infection. The patient recovered after small bowel resection with anastomoses and was discharged home. Histopathological examination of resected specimen confirmed transmural infarction with evidence of prior hemorrhage, diffuse ulcers, and multifocal inflammation. This is the first report of a chronic GI sequelae resulting from COVID-19. As the pandemic evolves, medical professionals must be vigilant to consider alternative GI diagnoses in the COVID-19 survivors.

Oral mucosal lesions in patients with blood disorders

Signs of many diseases of body organs and systems are manifested in the oral cavity. Patients with blood disorders are characterized by prominent oral mucosal alterations. One of the most common symptoms includes increased mucosal bleeding, as well as vulnerability and impaired epithelialization of the oral mucosa. The clinical manifestations spectrum depends on the underlying disease severity. Secondary (fungal, herpes virus) infections complicate the diagnosis. Such patients require comprehensive physical and laboratory examination. Blood tests, as well as laboratory tests on other bodily fluids allow dentists to clarify the systemic disease diagnosis, and to provide proper topical treatment.

Immune Thrombocytopenic Purpura as Initial Presentation of Paediatric SLE: A Case Report

The systemic lupus erythematosus (SLE) is a connective tissue disorder with variable presentationsin children. The usual presentation includes arthritis, malar rash, nephritis, hemolytic anemia, andfever. Isolated hematologic abnormality as the only presentation of SLE is rare. Here is a case reportof a female child presented to us with superficial and mucosal bleeding with isolated low plateletcount and anemia in proportion to blood loss. When platelet count didn’t go up despite appropriatetreatment in lines of ITP, further investigations were done, diagnosis of SLE was established, andmanagement was done accordingly.

Association of ABO Blood Group with Bleeding Severity in Patients with Bleeding of Unknown Cause

Introduction: Antigens of the ABO blood group system have an impact on the hemostatic balance. The association of blood group non-O and thrombosis risk is well known. In patients with different bleeding manifestations, an overrepresentation of blood group O has been previously reported (Dentali et al, Semin.Thromb. Hemost, 2013). Nevertheless, the independent effect of the ABO blood group on bleeding severity, when considering VWF as a major contributing factor, has not yet been thoroughly investigated. Patients with bleeding of unknown cause (BUC) have a similar bleeding phenotype as patients with a diagnosis of an established bleeding disorder, but the causes underlying their bleeding tendency are currently unclear and might be multifactorial (Gebhart et al, Haemophilia, 2018). Thus, we investigated the prevalence of blood group O and its role as an independent risk factor for increased bleeding severity in a thoroughly characterized cohort of patients with BUC. Methods: For this analysis, we selected all patients with normal results in the assessments of plasmatic coagulation and platelet function consecutively recruited between October 2009 and April 2019 within the Vienna bleeding biobank study (Figure 1; Gebhart et al, Haemophilia, 2018). After informed consent, all patients underwent a structured interview on their previous medical and bleeding history including the assessment of the bleeding severity with the Vicenza bleeding assessment tool (BAT). Biomaterial was processed and stored according to standard operating procedures at the Biobank facility (http://www.biobank.at/). A thorough hemostatic laboratory assessment and measurements of thrombin generation, plasma clot properties, and rotational thromboelastometry (ROTEM), as well as platelet function tests (PFA-100, light transmission aggregometry) were performed. Data on the blood group distribution of 23,145 healthy first-time blood donors were provided by the Austrian Red Cross for comparison. Results: We observed an overrepresentation of blood group O in 199 out of 422 BUC patients (47.2%) compared to 8709 out of 23,145 healthy blood donors (37.6%), odds ratio for blood group O 1.48; 95% CI=1.22-1.79, p&lt;0.001 (Table 1). Blood group O in comparison to non-blood group O was independently associated with an increased bleeding severity (least square mean [95% CI]: 6.2 [5.8-6.6] vs. 5.3 [4.9-5.7], p=0.006) and a higher number of bleeding symptoms (least square (LS) mean [95% CI] 3.5 [3.2-3.7] vs. 3.0 [2.8-3.2], p=0.016), after adjustment for sex, VWF:Ag, VWF:RCo and FVIII activity (Table 2). The prevalence of oral mucosal bleeding was significantly higher in blood group O than in patients with a non-O blood group (26.1% vs. 14.3%), even after adjustment for sex, VWF and FVIII, and multiple testing (p=0.013). When analyzing the influence of blood group O on tests of global hemostatic capacity, results indicated increased clot firmness and reduced lysis in blood group O patients. In ROTEM, the maximum clot firmness was higher (LS mean [95% CI]: 57.4 [56.5-58.3] vs. 55.8 [55.0-56.6] mm, p&lt;0.05) and the maximal lysis lower (LS mean [95% CI]: 13.3 [12.5-14.1] vs. 15.1 [14.4-15.9] %, p&lt;0.05) in patients with blood group O compared to non-O patients, after adjustment for sex, VWF and FVIII, and correction for multiple testing. Also in the analysis of plasma clot properties, the maximum clot absorbance was increased in patients with blood group O after adjustment for sex, VWF and FVIII (LS mean [95% CI]: 0.77 [0.74-0.79] vs 0.71 [0.69-0.74] OD, p&lt;0.05), whereas there was no difference in plasma clot lysis. There was no difference in thrombin generation between BUC patients with blood group O and non-O. We could not identify any differences in platelet function, as assessed by the platelet function analyser-100 and light transmission aggregometry between patients with blood group O in comparison to non-O patients after adjustment for sex, VWF and FVIII, and correction for multiple testing. Conclusion : Blood group O is a risk factor for a more severe bleeding phenotype, especially oral mucosal bleeding, independent of VWF and FVIII levels in patients with BUC. Alterations in global hemostatic capacity in BUC patients with blood group O were identified, whereas platelet function was not different. Our data are important for a better understanding of underlying mechanisms of bleeding in BUC patients, which are most probably multifactorial. Disclosures Jilma: True North Therapeutics: Consultancy, Other: reimbursement for travel costs for scientific presentations; Bioverativ: Consultancy, Other: reimbursement for travel costs for scientific presentations.