Clinicopathological findings in patients with COVID-19-associated ischaemic enterocolitis.

AIMS: Coronavirus disease 2019 (COVID-19) has been recognised as a predominantly respiratory tract infection, but some patients manifest severe systemic symptoms/coagulation abnormalities. The aim of this study was to evaluate the impact of severe COVID-19 infection on the gastrointestinal tract. METHODS AND RESULTS: We examined clinicopathological findings in 28 resected ischaemic bowels from 22 patients with severe COVID-19. Most patients required intubation preoperatively and presented with acute decompensation shortly before surgery. D-dimer levels were markedly elevated in all measured cases (mean, 5394 ng/ml). Histologically, 25 cases (19 patients) showed evidence of acute ischaemia with necrosis. In this group, the most characteristic finding was the presence of small vessel fibrin thrombi (24 of 25 cases, 96%), which were numerous in 64% of cases. Patients with COVID-19 were significantly more likely than a control cohort of 35 non-COVID-19-associated acute ischaemic bowels to show isolated small intestine involvement (32% versus 6%, P < 0.001), small vessel fibrin thrombi (100% versus 43%, P < 0.001), submucosal vessels with fibrinous degeneration and perivascular neutrophils (90% versus 54%, P < 0.001), fibrin strands within submucosal vessels (58% versus 20%, P = 0.007), and histological evidence of pneumatosis (74% versus 34%, P = 0.010). Three cases in this cohort had histopathological findings normally seen in the setting of chronic ischaemia, notably prominent fibroblastic proliferation affecting the outer layer of the muscularis propria. CONCLUSIONS: Herein, we describe the histopathological findings in COVID-19-associated ischaemic bowels and postulate a relationship with the hypercoagulable state seen in patients with severe COVID-19 infection. Additional experience with these cases may further elucidate specific features or mechanisms of COVID-19-associated ischaemic enterocolitis.

Multiple thrombosis associated with Cytomegalovirus enterocolitis in an immunocompetent patient: a case report.

BACKGROUND: Cytomegalovirus (CMV) is reported to have thrombogenic characteristics that activate factor X in vitro and stimulate the production of factor VIII and von Willebrand factor (vWF). Thrombosis associated with CMV infection is prevalent among immunocompromised patients and predominantly presents as a solitary large thrombus in the deep vein, pulmonary artery, splanchnic arteriovenous ducts, or other similar sites. Multiple thrombi, however, are rarely observed in such cases. Here, we report about an immunocompetent man with multiple microthrombi associated with CMV infection. CASE PRESENTATION: A 72-year-old Japanese man who complained of abdominal pain was hospitalized with multiple colonic stenosis. He was later diagnosed with CMV enterocolitis and treated with ganciclover from Day 27 post-admission. During hospitalization, the patient developed thrombi in his fingers. He was initially treated with anticoagulant therapy (rivaroxaban); however, the therapy was discontinued owing to a prolonged activated thromboplastin time and an elevated international normalized ratio of prothrombin time. Instead, vitamin K and fresh-frozen plasma were administered. Nevertheless, his coagulation profile remained abnormal. Eventually, he developed colonic perforation and had to undergo emergency surgery. An intraoperative specimen showed several microthrombi in the middle and small arteriovenous ducts of his small and large intestines. The patient's coagulopathy improved preoperatively, and his overall condition improved postoperatively. Since the activation of ADAMTS13 was reduced remarkably, the thrombotic tendency was determined to be a thrombotic microangiopathy-like condition owing to increased vWF. We could not attribute the coagulopathy to any other cause except CMV infection; therefore, we concluded that this was a case of multiple thrombosis associated with CMV. CONCLUSIONS: We present an extremely rare case of a patient with multiple thrombotic microangiopathy-like microthrombosis caused by CMV infection. Our findings suggest that CMV infection may be considered as a differential diagnosis for immunocompetent individuals who present with thrombosis of unspecified cause.

Cytomegalovirus Colitis Followed by Colonic Pseudolipomatosis and Gastric Emphysema in a Post-resuscitation Patient.

A 64-year-old Japanese man suffered cardiopulmonary arrest, which may have resulted from sepsis and/or hyperosmolar hyperglycemic non-ketonic coma, and was admitted after successful resuscitation. He had watery diarrhea on day 18 and was diagnosed with cytomegalovirus enterocolitis. In addition, computed tomography performed on day 27 and colonoscopy revealed gastric emphysema and intestinal pseudolipomatosis, respectively. This report is the first to describe a patient with cytomegalovirus enterocolitis and subsequent gastric emphysema and pseudolipomatosis. Gastrointestinal cytomegalovirus infection may underlie gastric emphysema and intestinal pseudolipomatosis, particularly in patients with relative or obvious immune dysfunction.

MODERN ETIOLOGICAL STRUCTURE OF ACUTE GASTROENTEROCOLITIS IN THE SOUTHERN UKRAINE.

The etiological structure of the acute diarrhoeal infections among the population of the Odessa region during 2015-2017 was analyzed. Based on the registered cases, an assessment of the frequency of hospitalization of sick persons from different age groups was undertaken. The most frequent pathogens from 18 detected bacterial causative agents were St. aureus, Kl. pneumoniae, Ps. aeruginosa, E. coli, Pr. vulgaris, Ent.cloacae. During 2016-2017 the mixed infection was detected in 54 fecal samples. Bacterial-virus associations were detected in 20 samples and were presented in St. aureus, Kl. pneumoniae, Ps. Aeruginosa and Rotavirus. During the summer period of 2016, the detection rate of rota-, noro-, adenovirus antigens in the examined fecal samples of adult patients was 13.60%. According to the results of genotyping of the circulating rotaviruses strains in 2016, strains G1P[8] (46.70%) and G3P[8] (26.70%) are most commonly detected.

Detection of cytomegalovirus DNA in fecal samples in the diagnosis of enterocolitis after allogeneic stem cell transplantation.

BACKGROUND: Cytomegalovirus enterocolitis is a rare but potentially life threatening complication after allogeneic stem cell transplantation. Its early diagnosis and treatment are essential for a successful outcome. OBJECTIVE: To determine the potential benefit of fecal CMV DNA detection in the diagnosis of CMV colitis among stem cell transplant recipients. STUDY DESIGN: Biopsies from the lower gastrointestinal tract, taken during 69 episodes of diarrhea, were compared with fecal samples previously examined for CMV DNA in 45 patients after allogeneic stem cell transplantation. RESULTS: Six confirmed cases of CMV colitis were observed, with 16 out of 69 (23%) fecal samples proving positive for CMV DNA. Only one positive sample correlated with histologically confirmed CMV colitis, and 15 samples were evaluated as false positive. These results provide a 16.7% sensitivity and 76.2% specificity in the diagnosis of CMV enterocolitis. CONCLUSION: The examination of fecal samples for the presence of CMV DNA has very low potential in the diagnosis of CMV enterocolitis after allogeneic stem cell transplantation; therefore, a biopsy of the gastrointestinal mucosa is still warranted for correct diagnosis.

Concurrent Acute Necrotizing Adenovirus Hepatitis and Enterocolitis in an Adult Patient After Double Cord Blood Stem Cell Transplant for Refractory Crohn's Disease.

It has been recently recognized that adenovirus is a pathogen with high morbidity and mortality among immunocompromised patients, particularly after solid organ or stem cell transplant. Confluent necrotizing hepatitis secondary to adenovirus infection alone or together with other organ involvement is extremely rare. There are only 32 cases of confluent necrotizing hepatitis reported in adults since 1960 and most occur after iatrogenic immunosuppression for bone marrow or solid organ transplantation or in other states of immunosuppression, including acquired immunodeficiency syndrome or chemotherapy treatment. We present the first case of concurrent adenovirus-induced necrotizing hepatitis and enterocolitis in an adult patient after double cord stem cell transplant for refractory Crohn's disease. Additionally, we report the imaging and morphologic findings and discuss the potential significance of morphology and immunohistochemistry as a practical approach for identifying adenovirus.

Infant death due to CMV enterocolitis.

An infant was admitted with symptoms of diarrhoea and vomiting. After initial improvement she unexpectedly died. Postmortem confirmed a diagnosis of cytomegalovirus (CMV) enterocolitis. The authors report this case and review other published cases of immunocompetent infants who presented with this infection. Clinicians should consider stool CMV PCR test or referral for endoscopy and biopsy in young babies who present with profuse and prolonged episodes of diarrhoea. The value of ganciclovir in immunocompetent infants who suffer with CMV gastrointestinal involvement is still not clear.

[Hemorrhagic colitis caused by dasatinib following cytomegalovirus enterocolitis in a patient with chronic myelogenous leukemia in the second chronic phase].

A 26-year-old female progressed to blastic crisis (BC) after three months administration of imatinib for chronic myelogenous leukemia (CML) chronic phase (CP) and was treated with a dasatinib containing chemotherapy regimen. After remission to second CP, she was hospitalized because of fever and hemorrhagic diarrhea during dasatinib maintenance therapy. She was diagnosed as having cytomegalovirus (CMV) colitis because CMV antigen in blood leukocytes was positive and CMV-positive cells were also detected on staining of an ileocecal mucosal biopsy specimen with an anti-CMV antibody. Although blood leukocyte CMV antigen and CMV staining in colonic mucosa became negative after ganciclovir treatment, hemorrhagic diarrhea did not improve. However, after discontinuance of dasatinib, hemorrhagic colitis drastically improved and did not recur after administration of nilotinib. It is possible that hemorrhagic diarrhea occurred due to dasatinib-related hemorrhagic colitis. Previous case reports have indicated that CD8-positive T-lymphocytes infiltrate the colonic mucosa in dasatinib-related hemorrhagic colitis, and the same pathological findings were seen in our case. Dasatinib may cause hemorrhagic colitis via immunological mechanisms in CML. Dasatinib-related gastrointestinal bleeding is less frequent in Japan compared to that in western countries, and Japanese cases diagnosed as having hemorrhagic colitis are extremely rare.

Cytomegalovirus enterocolitis in apparently immunocompetent hosts: evaluation of the radiologic findings and clinical features.

OBJECTIVE: To describe the clinical and radiologic features of cytomegalovirus (CMV) enterocolitis in apparently immunocompetent hosts. MATERIALS AND METHODS: Our institutional review board approved this retrospective study, and informed consent was waived. Twelve apparently immunocompetent patients (7 women and 5 men; mean age, 58 years) with pathologically proven CMV enterocolitis were included. Computed tomographic (CT) scans were retrospectively reviewed to determine the extent and the location of mural thickening, maximal mural thickness, enhancement pattern, that is, single-halo, double-halo, and homogeneous patterns, and ascites. RESULTS: Eight patients had comorbidities potentially affecting the host immune status, whereas 4 patients were apparently healthy before presentation. On CT, all patients showed mural thickening (range, 4-11 mm) involving the colon (n = 8), the small bowel (n = 1), or both (n = 3). Segmental involvement was most common (n = 9 for colon and n = 2 for small bowel), whereas focal involvement of the rectum (n = 1) and diffuse involvement of the entire ileum (n = 1) or the entire small bowel and colon (n = 1) were also noted. Colonic lesions showed variable enhancement patterns, including the single-halo (n = 6), homogeneous (n = 3), and double-halo patterns (n = 2), whereas all small-bowel lesions in 4 patients exhibited a single-ring pattern. Ascites was present in 7 patients. Complications requiring surgery occurred in 3 patients and included refractory bleeding (n = 2) and bowel perforation (n = 1). CONCLUSIONS: Cytomegalovirus enterocolitis in immunocompetent hosts typically develops in elderly subjects with comorbidities, although it may also affect relatively young and healthy subjects. On CT, it is characterized by mild mural thickening of the small bowel and the colon and frequently shows segmental involvement and a single-halo enhancement pattern.

Oral gancyclovir therapy for immunocompetent infants with cytomegalovirus-associated hemorrhagic or intractable enterocolitis.

Three infants, who had prenatal or immediately postnatal cytomegalovirus (CMV) infection associated with persistently severe enterocolitis requiring total parenteral or nasal gastric feeding, were treated with gancyclovir. The intestinal CMV involvement was shown by the detection of CMV-DNA in the stools of all 3 infants and in the enteral sample from 1 of 2 biopsied infants. Gancyclovir, when given intravenously to the infants, was not followed by CMV clearance or stable clinical improvement. On the contrary, oral gancyclovir that was given for 1- to 2-month courses at the dosage of 70 mg/kg, was associated with clinical improvement or recovery and reintroduction of oral feeding. Cytomegalovirus-DNA detection became persistently negative in the stools of the infants within 17 months after starting oral gancyclovir. Each child showed normal growth and sensorial, mental, and motor development at the age of 4.7 to 6 years. Oral gancyclovir may be suggested for treatment of CMV-associated chronic hemorrhagic or intractable enterocolitis.

[Case of cytomegalovirus colitis during standard chemotherapy for testicular cancer].

CMV infection is uncommon in our practice except kidney transplantation. We report a case of cytomegalovirus enterocolitis during standard chemotherapy for testicular cancer. A 31-year-old male presented to his local urologist in January, 2006 with left scrotal swelling. He was diagnosed as left testicular tumor and underwent radical orchiectomy. Pathological examination showed Mixed germ cell tumor (seminoma, yolk sac, embryonal). Four months later, follow-up CT scan revealed multiple metastasis in lung and para aortic lymph nodes. The patient was referred to our institution for further consultation. During 3rd cycle of standard BEP chemotherapy, laboratory data showed severe bone marrow suppression and he subsequently presented prolonged spike fever with watery diarrhea. Despite intensive diagnostic examination including colon fiberscopy, those symptoms remained undiagnosed. One month later, the patient recovered with conservative treatment and serological data showed slightly elevated anti-CMV Ig-M, Ig-G antibody. Immunohistological examination demonstrated CMV positive inclusion bodies in colorectal mucosa. Accordingly the patient's complication was finally diagnosed as CMV enterocolitis. Significant immunosuppression leading to severe colitis by CMV infection or reactivation can occur after standard chemotherapy. It is necessary to screen for CMV infection in patients with prolonged fever with diarrhea during chemotherapy.

A case of cytomegalovirus enterocolitis diagnosed by the double-balloon enteroscopy.

A 73-year-old woman presented with massive bloody stools while undergoing hospitalization for multiple myeloma. Colonoscopy and transrectal double-balloon enteroscopy revealed multiple punched-out ulcers throughout the entire colon and in the distal ileum. Cytomegalovirus was detected in the biopsy specimens of both the colonic and ileal mucosa and in the peripheral blood, which lead the diagnosis of CMV enterocolitis. The patient's gastrointestinal bleeding was temporarily improved by the administration of ganciclovir, though she died thereafter due to progression of the primary disease. We herein report the effectiveness of transrectal double-balloon enteroscopy for the diagnosis of cytomegalo-virus enterocolitis.

Gastrointestinal disease in simian immunodeficiency virus-infected rhesus macaques is characterized by proinflammatory dysregulation of the interleukin-6-Janus kinase/signal transducer and activator of transcription3 pathway.

Gastrointestinal disease and inflammation are common sequelae of human and simian immunodeficiency virus (SIV) infection. Nevertheless, the molecular mechanisms that lead to gastrointestinal dysfunction remain unclear. We investigated regulation of the interleukin (IL)-6-JAK-STAT3 pathway in jejunum and colon, collected at necropsy, from 10 SIV-infected macaques with diarrhea (group 1), 10 non-SIV-infected macaques with diarrhea (group 2), and 7 control uninfected macaques (group 3). All group 1 and 2 macaques had chronic diarrhea, wasting, and colitis, but group 1 animals had more frequent and severe lesions in the jejunum. A significant increase in IL-6 and SOCS-3 gene expression along with constitutive STAT3 activation was observed in the colon of all group 1 and 2 macaques and in the jejunum of only group 1 macaques compared to controls. Further, in colon, histopathology severity scores correlated significantly with IL-6 (groups 1 and 2) and SOCS-3 (group 2) gene expression. In jejunum, a similar correlation was observed only in group 1 animals. Phosphorylated STAT3 (p-STAT3) was localized to lymphocytes (CD3+) and macrophages (CD68+), with fewer CD3+ lymphocytes expressing p-STAT3 in group 1 macaques. Despite high SOCS-3 expression, STAT3 remained constitutively active, providing a possible explanation for persistent intestinal inflammation and immune activation that may favor viral replication and disease pro-gression.

Cytomegalovirus enterocolitis complicated by perforated appendicitis in a premature infant.

A 9-week-old, former 30-week estimated gestational age premature infant had recurrent episodes of abdominal distention. Laparotomy revealed partial small bowel obstruction caused by ileocecal inflammation with stenosis, and a perforated appendix with fistulization into the cecum. The resected appendix and ileocecal junction showed intranuclear and intracytoplasmic viral inclusions, and were cytomegalovirus positive by immunoperoxidase staining, which implicated cytomegalovirus as the etiology of the recurring bouts of enterocolitis with appendicitis. Cytomegalovirus is frequently overlooked in the differential diagnosis of enterocolitis and chronic gastrointestinal symptoms in infants, but should be included as in older immunocompromised patients.

Severe cytomegalovirus enterocolitis after standard chemotherapy for non-Hodgkin's lymphoma.

Reports of cytomegalovirus (CMV) colitis mainly concern patients with immunocompromisation resulting from, among others, HIV infection, allogeneic bone marrow transplantation and solid organ transplantation. CMV colitis rarely occurs during standard chemotherapy for non-Hodgkin's lymphoma (NHL). An unusual case of CMV enterocolitis in a 62-year-old patient is reported. After a first course of salvage chemotherapy for NHL, diffuse erosions and sloughing mucosa were seen throughout the large bowel. The final diagnosis was based on histological findings. Although ganciclovir and foscarnet are effective for CMV viremia, their use in the treatment of severe diarrhea in our patient did not result in improvement for one week, whereas concomitant use of octreotide led to rapid improvement. Octreotide may therefore be an effective agent for severe colitis.

Ileal ulcers and cytomegalovirus infection in a case of Churg-Strauss syndrome.

Churg-Strauss syndrome, or allergic granulomatous angiitis, is an uncommon vasculitic syndrome. We describe a 53-year-old man with Churg-Strauss syndrome and subsequent opportunistic cytomegalovirus enterocolitis. During intensive care, including steroid-pulse therapy, the patient developed rapidly progressive anemia caused by active bleeding from his small intestine, resulting in resection of 20 cm of ileum. Diagnosis of Churg-Strauss syndrome was confirmed both by characteristic clinical features and by histology. Histologic examination also revealed multiple shallow ulcers accompanied by cytomegalovirus infection. Characteristic angiitis was found in the ileum with normal-like mucosa, and it was not necessarily associated with ileal ulcers. This finding suggests that cytomegalovirus infection may be one of the causes or exacerbating factors for ileal ulcers in Churg-Strauss syndrome, although ulcers of the intestine have usually been considered to be caused by ischemia resulting from angiitis.

Clinical application of rapid assay of interleukin-6 in influenza-associated encephalopathy.

The characteristics of influenza-associated encephalopathy is the high mortality and nimble progress with coma which appears in general cases within 48 hours. Most of patients show no abnormalities in the standard blood checks on admission or in early stage. In this study we investigated if a rapid assay of interleukin (IL)-6 is useful in influenza-associated encephalopathy in early stages. The levels of IL-6 in patients with influenza-associated encephalopathy did not show any significant difference compared with those in patients with febrile convulsion and rotavirus-associated convulsion. However the levels of IL-6 in severe cases were significantly higher than those of mild cases with influenza-associated encephalopathy. Consequently the rapid assay of serum IL-6 is useful to evaluate and decide the therapies.