Acute Mesenteric Ischemia in COVID-19 Patients

Acute mesenteric ischemia is a rare but extremely severe complication of SARS-CoV-2 infection. The present review aims to document the clinical, laboratory, and imaging findings, management, and outcomes of acute intestinal ischemia in COVID-19 patients. A comprehensive search was performed on PubMed and Web of Science with the terms “COVID-19” and “bowel ischemia” OR “intestinal ischemia” OR “mesenteric ischemia” OR “mesenteric thrombosis”. After duplication removal, a total of 36 articles were included, reporting data on a total of 89 patients, 63 being hospitalized at the moment of onset. Elevated D-dimers, leukocytosis, and C reactive protein (CRP) were present in most reported cases, and a contrast-enhanced CT exam confirms the vascular thromboembolism and offers important information about the bowel viability. There are distinct features of bowel ischemia in non-hospitalized vs. hospitalized COVID-19 patients, suggesting different pathological pathways. In ICU patients, the most frequently affected was the large bowel alone (56%) or in association with the small bowel (24%), with microvascular thrombosis. Surgery was necessary in 95.4% of cases. In the non-hospitalized group, the small bowel was involved in 80%, with splanchnic veins or arteries thromboembolism, and a favorable response to conservative anticoagulant therapy was reported in 38.4%. Mortality was 54.4% in the hospitalized group and 21.7% in the non-hospitalized group (p < 0.0001). Age over 60 years (p = 0.043) and the need for surgery (p = 0.019) were associated with the worst outcome. Understanding the mechanisms involved and risk factors may help adjust the thromboprophylaxis and fluid management in COVID-19 patients.

TNF-α Induces Neutrophil Apoptosis Delay and Promotes Intestinal Ischemia-Reperfusion-Induced Lung Injury through Activating JNK/FoxO3a Pathway

Background. Intestinal ischemia is a common clinical critical illness. Intestinal ischemia-reperfusion (IIR) leads to acute lung injury (ALI), but the causative factors of ALI are unknown. The aim of this study was to reveal the causative factors and mechanisms of IIR-induced lung injury. Methods. A mouse model of IIR was developed using C57BL/6 mice, followed by detection of lung injury status and plasma levels of inflammatory factors in sham-operated mice and model mice. Some model mice were treated with a tumor necrosis factor-α (TNF-α) inhibitor lenalidomide (10 mg/kg), followed by observation of lung injury status through hematoxylin and eosin staining and detection of neutrophil infiltration levels through naphthol esterase and Ly6G immunohistochemical staining. Additionally, peripheral blood polymorphonuclear neutrophils (PMNs) were cultured in vitro and then stimulated by TNF-α to mimic in vivo inflammatory stimuli; this TNF-α stimulation was also performed on PMNs after knockdown of FoxO3a or treatment with the c-Jun N-terminal kinase (JNK) inhibitor SP600125. PMN apoptosis after stimulation was detected using flow cytometry. Finally, the role of PMN apoptosis in IIR-induced lung injury was evaluated in vivo by detecting the ALI status in the model mice administered with ABT-199, a Bcl-2 inhibitor. Results. IIR led to pulmonary histopathological injury and increased lung water content, which were accompanied by increased plasma levels of inflammatory factors, with the TNF-α plasma level showing the most pronounced increase. Inhibition of TNF-α led to effective reduction of lung tissue injury, especially that of the damaging infiltration of PMNs in the lung. In vitro knockdown of FoxO3a or inhibition of JNK activity could inhibit TNF-α-induced PMN apoptosis. Further in vivo experiments revealed that ABT-199 effectively alleviated lung injury and decreased inflammation levels by promoting PMN apoptosis during IIR-induced lung injury. Conclusion. TNF-α activates the JNK/FoxO3a pathway to induce a delay in PMN apoptosis, which promotes IIR-induced lung injury.

Intestinal ischemia in the COVID-19 era: case series from peripheral healthcare centre

Coronavirus disease-2019 (COVID-19) caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has caused global health crisis. Initially considered a respiratory tract pathogen, it can cause multiple organ dysfunction. It has also been described to predispose to venous and arterial thromboembolism; however, limited published data is available regarding mesenteric thrombosis COVID-19. We report 6 cases of COVID-19 positive patients with mesenteric/intestinal ischemia. These patients were examined with variables including demographics, laboratory blood tests including coagulation panels, medical and surgical history, comorbidities, and postoperative follow-up period.

Hyponatremia at the onset of necrotizing enterocolitis is associated with intestinal surgery and higher mortality

It has previously been shown that hyponatremia reflects the severity of inflammation in pediatric gastrointestinal diseases. Interpretation of electrolyte disorders is a common, but not well studied challenge in neonatology, especially in the context of early detection of necrotizing enterocolitis and bowel necrosis. The aim of this study was to assess if hyponatremia, or a decrease in plasma sodium level, at the onset of necrotizing enterocolitis (NEC) is associated with intestinal ischemia/necrosis requiring bowel resection and/or NEC-related deaths. This was a retrospective cohort study including patients with verified NEC (Bell’s stage ≥ 2) during the period 2009–2014. Data on plasma sodium 1–3 days before and at the onset of NEC were collected. The exposure was hyponatremia, defined as plasma sodium < 135 mmol/L and a decrease in plasma sodium. Primary outcome was severe NEC, defined as need for intestinal resection due to intestinal ischemia/necrosis and/or NEC-related death within 2 weeks of the onset of NEC. Generalized linear models were applied to analyze the primary outcome and presented as odds ratio. A total of 88 patients with verified NEC were included. Fifty-four (60%) of them had severe NEC. Hyponatremia and a decrease in plasma sodium at onset of NEC were associated with increased odds of severe NEC (OR crude 3.91, 95% CI (1.52–10.04) and 1.19, 95% CI (1.07–1.33), respectively). Also, a sub-analysis, excluding infants with pneumoperitoneum during the NEC episode, showed an increased odds ratio for severe NEC in infants with hyponatremia (OR 23.0, 95% CI (2.78–190.08)).Conclusions: The findings of hyponatremia and/or a sudden decrease in plasma sodium at the onset of NEC are associated with intestinal surgery or death within 2 weeks. What is Known:• Clinical deterioration, despite optimal medical treatment, is a relative indication for surgery in infants with necrotizing enterocolitis.• Hyponatremia is a common condition in preterm infants from the second week of life. What is New:• Hyponatremia and a decrease in plasma sodium level at the onset of necrotizing enterocolitis are positively associated with need of surgery or death within 2 weeks.• In infants with necrotizing enterocolitis, without pneumoperitoneum, where clinical deterioration despite optimal medical treatment is the only indication for surgery, hyponatremia, or a decrease in plasma sodium level can predict the severity of the disease.