Faculty Bibliography

AIMS/OBJECTIVE:To determine if a simple prewash step added to the processing workflow of tissue procurement by a core needle biopsy device will recover enough cells to expand the laboratory testing armamentarium. METHODS:Tissue was obtained from unfixed resection specimens using a core needle device and washed in a buffered solution before fixation. This creates a liquid aliquot from which dislodged cells can be kept and separated from the tissue specimen, the latter of which can then undergo traditional formalin-fixed, paraffin-embedded processing. RESULTS:Cells dislodged from the tissue during the biopsy procedure are recoverable, are representative of the tissue section and of sufficient quantities for additional laboratory testing. CONCLUSIONS:The core needle biopsy wash is an under-recognised and underutilised approach to extending the diagnostic capabilities of the limited amount of targeted material obtained during this common procedure. The ability to recover supplemental amounts of diagnostic material yields great potential as a substrate for a multitude of current and developing laboratory assays.

Maintenance of immune homeostasis involves a synergistic relationship between the host and the microbiome. Canonical interferon (IFN) signaling controls responses to acute microbial infection, through engagement of the STAT1 transcription factor. However, the contribution of tonic levels of IFN to immune homeostasis in the absence of acute infection remains largely unexplored. We report that STAT1 KO mice spontaneously developed an inflammatory disease marked by myeloid hyperplasia and splenic accumulation of hematopoietic stem cells. Moreover, these animals developed inflammatory bowel disease. Profiling gut bacteria revealed a profound dysbiosis in the absence of tonic IFN signaling, which triggered expansion of T_H17 cells and loss of splenic T_reg cells. Reduction of bacterial load by antibiotic treatment averted the T_H17 bias and blocking IL17 signaling prevented myeloid expansion and splenic stem cell accumulation. Thus, tonic IFNs regulate gut microbial ecology, which is crucial for maintaining physiologic immune homeostasis and preventing inflammation.

Background: In addition to respiratory distress, GI symptoms have been reported in COVID-19 patients at various stages of the disease. Among the GI symptoms that have been reported, diarrhea, nausea, vomiting, abdominal pain and GI bleeding were often seen. Age and comorbid conditions such as obesity, HTN, DM and/or CAD have been considered as risk factors for COVID-19 patients for severe disease. GI manifestations in COVID-19 patients appeared to act as a sign for a serious condition. The virus has been identified in the stool and in rectal swabs of some infected patients, even after a negative nasopharyngeal test. There is a lack of reports on pathological alterations of the GI tract in COVID-19 infected patients.
Design(s): 16 PCR confirmed COVID-19 patients (11 males and 5 females) were included in the study. Biopsy or resection specimens were taken from the esophagus (4), stomach (6), small intestine (5), appendix (3), colon (5) and gallbladder (3). Clinical information including demographics, comorbidities, GI symptoms, related laboratory tests were collected. Histopathologic evaluation was performed and correlated with clinical properties.
Result(s): The age of the patients ranged from 10 to 84 years old, with an average of 47 years. Eight (50%) patients had at least one comorbid condition, two patients (12.5%) had prior history of cancer, and six patients had no significant medical history. Abdominal pain and GI bleeding were the most common presenting symptoms. Histologically, acute and chronic inflammation was seen in 14 of 16, and 15 of 16 cases, respectively. Eight cases showed severe acute inflammation with ulceration. The mucosal changes included nonspecific reactive change, hypermucinous, atrophic/ischemic changes, and necrosis, were indiscriminately noticed in these cases. Four cases showed intraepithelial lymphocytosis. Viral like inclusions were found in four cases. Microthrombi were identified in 5 cases with an average patient age of 60 years. Notably, microthrombi were seen in about 5 out of 8 (62%) patients with comorbidities. The patients with microthrombi had a higher D dimer test value than those without thrombus. Three patients died shortly after operation, and two of them showed microthrombi in the tissue specimens.
Conclusion(s): Acute and chronic inflammation were indiscriminately seen in these cases. Microthrombi were dominantly found in aging patients with comorbidities, suggesting microthrombi in the GI tract may be a histologic indication for severe COVID-19 patients with GI symptoms

Background: Digestive symptoms are often seen in COVID-19 patients with poor outcomes. The Viral RNA is mostly positive in the stool of these patients, and has a longer delay before viral clearance. However, its diagnostic value and significance for guiding clinical treatment remain unknown. And the pathologic alterations in the GI tract in COVID-19 patients have not been well defined. We evaluated rectal swab SAS-CoV-2 test and histopathologic changes in the small intestine in autopsy patients.
Design(s): 18 autopsy cases with confirmed SAS-CoV2 infection were included. Nasal, bronchial, and rectal swab SARS-CoV-2 PCR were performed at the time of autopsy. Clinical information included demographics, comorbidities, presenting symptoms, related laboratory tests were collected. Histopathologic evaluation was performed and correlated with clinical properties.
Result(s): 83% (15/18) of patients were male. Median age is 50 years. 7/18 (38.9%) patients had diarrhea in addition to cough, fever and other symptoms. Except in one case, all patients had underlying comorbidities of diabetes, hypertension and /or obesity. In the small intestine, acute inflammation was not seen in any cases. 5/18 displayed mild and one showed moderate chronic inflammation. Hypermucinous change was found in six patients but not associated with diarrhea. 3 cases had microthrombi identified in the sections. Notably, obviously increased D dimer in lab tests were noticed in all patients. Postmortem 17/17 (100%) nasal, 18/18 (100%) bronchial and 7/16 (43.8%) rectal swabs showed SARS-CoV-2 PCR positivity. 3 of 7 (42.9%) patients with diarrhea are positive in rectal swab for SARS-CoV-2.
Conclusion(s): There are no specific COVID-19 changes in the small intestine. More investigations are needed, especially on tissues from different locations of the GI tract. Data from rectal swab testing suggests that it is not ideal for diagnosing COVID-19, guiding treatment, or predicting small intestinal pathology

Gastrointestinal (GI) symptoms of SARS-CoV-2/COVID-19 in the form of anorexia, nausea, vomiting, abdominal pain and diarrhea are usually preceded by respiratory manifestations and are associated with a poor prognosis. Hematochezia is an uncommon clinical presentation of COVID-19, and we hypothesize that older patients with significant comorbidities (obesity and cardiovascular) and prolonged hospitalization are susceptible to ischemic injury to the bowel. We reviewed the clinical course, key laboratory data including acute-phase reactants, and drug/medication history in 2 elderly male patients admitted for COVID-19 respiratory failure. Both patients had a complicated clinical course and suffered from hematochezia, acute blood loss, and anemia which led to hemodynamic instability requiring blood transfusion around day 40 of their hospitalization. Colonoscopic impressions were correlated with the histopathological findings in the colonic biopsies that included changes compatible with ischemia and nonspecific acute inflammation, edema, and increased eosinophils in the lamina propria. Both patients were hemodynamically stable, on prophylactic anticoagulants, multiple antibiotics, and antifungal agents due to respiratory infections at the time of lower GI bleeding. Hematochezia resolved spontaneously with supportive care. Both patients eventually recovered and were discharged. Elderly patients with significant comorbid conditions are uniquely at risk for ischemic injury to the bowel. This case report highlights hematochezia as an uncommon GI manifestation of spectrum of COVID-19 complications. The causes of bleeding in these COVID-19 associated cases are likely multifactorial and can be attributed to concomitant etiologies based on their age, multiple comorbid conditions, prolonged hospitalization compounded by lung injury, and hypoxia precipitated by the virus. We hypothesize that rather than a direct viral cytopathic effect, ischemia and hypoperfusion may be unleashed due to the cytokine storm orchestrated by the virus that leads to abnormal coagulation profile. Additional factors that may contribute to ischemic injury are prophylactic use of anticoagulants and polypharmacy. There were no other causes to explain the brisk lower GI bleeding. Presentation of hematochezia was followed by hemodynamic instability that may further increase the mortality and morbidity of COVID-19 patients, and prompt consultation and management by gastroenterology is therefore warranted.