Inpatient outcomes of inflammatory bowel disease in hospitalized patients with COVID-19: analysis of a nationally representative sample.

Purpose: To compare the risks of adverse outcomes, including mortality, gastrointestinal bleeding, and venous thromboembolism, between COVID-19 patients with inflammatory bowel disease (IBD) and those without IBD. Methods: We analyzed data from the National Inpatient Sample between January and December 2020. The study included adult patients with Crohn's disease (CD) and ulcerative colitis (UC) who contracted COVID-19. Inpatient outcomes were compared between the IBD and non-IBD COVID-19 cohorts. Results: Out of 1,050,045 COVID-19 hospitalizations, 0.28% had CD (2954 patients) and 0.26% had UC (2794 patients). After adjusting for confounding factors, UC patients had a significantly higher risk of deep vein thrombosis compared to non-IBD patients, with an adjusted odds ratio (aOR) of 2.55 (P < 0.001). However, CD patients did not show a significant association with deep vein thrombosis (aOR 1.29, P = 0.329). There were no significant associations between IBD patients (both UC and CD) and pulmonary embolism, nonvariceal gastrointestinal bleeding, or in-hospital mortality. UC patients had a longer average hospital stay (8.25 days) compared to non-IBD patients (adjusted mean difference 0.89, P = 0.007). Healthcare resource utilization was similar among the three groups. Conclusion: Our national study on COVID-19 hospitalizations indicates that patients with IBD have comparable rates of gastrointestinal bleeding, pulmonary embolism, and mortality as those without IBD. However, patients with UC hospitalized with COVID-19 have a higher risk of deep vein thrombosis than COVID-19 patients hospitalized without UC. Further research is needed to better understand the relationship between COVID-19 and IBD.

Iliac Artery-Inferior Vena Cava-Duodenal Fistula: An Unusual Cause of Massive Gastrointestinal Bleeding.

An arteriovenous-enteric fistula is a 3-way connection between the vascular and enteric system and associated with high mortality. We describe a case of iliac artery-inferior vena cava-duodenal fistula in a young female with a retroperitoneal mass presenting with sepsis and hemorrhagic shock with a catastrophic clinical course. These fistulas can be missed on endoscopy/colonoscopy and are usually diagnosed on computed tomography angiogram of the abdomen. Complex vasculoenteric fistula should be among differentials in patients presenting with gastrointestinal bleeding, especially with a history of malignancy, radiation, foreign bodies, and trauma. The management is complex and should involve a multidisciplinary approach involving vascular surgery, intervention radiology, and gastroenterologist.

Racial and Ethnic Disparities in Peripheral Vascular Disease Admissions Using a Nationally Representative Sample.

Our study aimed to identify clinical outcomes and resource utilization associated with race and ethnicity in patients admitted with peripheral vascular disease (PVD) across the United States. We queried the National Inpatient Sample database from 2015 to 2019 and identified 622,820 patients admitted with PVD. Patients across 3 major race and ethnic categories were compared in terms of baseline characteristics, inpatient outcomes, and resource utilization. Black and Hispanic patients were more likely to be younger and of the lowest median income but incur higher total hospital costs. Black race predicted higher rates of acute kidney injury, need for blood transfusion, and need for vasopressor but lower rates of circulatory shock, and mortality. Black and Hispanic patients were less likely to undergo limb-salvaging procedures and more likely to undergo amputation than White patients. In conclusion, our findings indicate that Black and Hispanic patients experience health disparities in resource utilization and inpatient outcomes for PVD admissions.

An Unusual Presentation of Segmental Arterial Mediolysis.

Segmental arterial mediolysis (SAM) is a rare nonatherosclerotic and noninflammatory disease that often affects medium to large-sized arteries. We report a case of SAM involving bilateral hepatic arteries in an elderly woman. Although her initial presentation mimicked vasculitis, the clinical course and imaging led to the diagnosis of SAM. She was treated with coil embolization and stenting of the involved hepatic vessel leading to dramatic clinical improvement. It should be differentiated from vasculitis because there is no role of steroids in the management of SAM.

Nectin-1 Is an Entry Mediator for Varicella-Zoster Virus Infection of Human Neurons.

Varicella-zoster virus (VZV) maintains lifelong latency in neurons following initial infection and can subsequently be reactivated to result in herpes zoster or severe neurological manifestations such as encephalitis. Mechanisms of VZV neuropathogenesis have been challenging to study due to the strict human tropism of the virus. Although neuronal entry mediators of other herpesviruses, including herpes simplex virus, have been identified, little is known regarding how VZV enters neurons. Here, we utilize a human stem cell-based neuronal model to characterize cellular factors that mediate entry. Through transcriptional profiling of infected cells, we identify the cell adhesion molecule nectin-1 as a candidate mediator of VZV entry. Nectin-1 is highly expressed in the cell bodies and axons of neurons. Either knockdown of endogenous nectin-1 or incubation with soluble forms of nectin-1 produced in mammalian cells results in a marked decrease in infectivity of neurons. Notably, while addition of soluble nectin-1 during viral infection inhibits infectivity, addition after infection has no effect on infectivity. Ectopic expression of human nectin-1 in a cell line resistant to productive VZV infection confers susceptibility to infection. In summary, we have identified nectin-1 as a neuronal entry mediator of VZV. IMPORTANCE Varicella-zoster virus (VZV) causes chickenpox, gains access to neurons during primary infection where it resides lifelong, and can later be reactivated. Reactivation is associated with shingles and postherpetic neuralgia, as well as with severe neurologic complications, including vasculitis and encephalitis. Although the varicella vaccine substantially decreases morbidity and mortality associated with primary infection, the vaccine cannot prevent the development of neuronal latency, and vaccinated populations are still at risk for reactivation. Furthermore, immunocompromised individuals are at higher risk for VZV reactivation and associated complications. Little is known regarding how VZV enters neurons. Here, we identify nectin-1 as an entry mediator of VZV in human neurons. Identification of nectin-1 as a neuronal VZV entry mediator could lead to improved treatments and preventative measures to reduce VZV related morbidity and mortality.

Imaging in Encephalitis.

Despite recent advances in diagnostic and therapeutic modalities for infectious and autoimmune encephalitis, the management of patients with suspected or confirmed encephalitis poses a great challenge to physicians. Neuroimaging, including magnetic resonance imaging (MRI) and positron emission tomography (PET) scanning, can play a crucial role in substantiating the diagnosis of encephalitis and eliminating clinical mimics of encephalitis from consideration. Moreover, characteristic neuroimaging patterns can aid in defining specific infectious and autoimmune etiologies. Volumetric and functional MRI, in particular, are being increasingly used to characterize outcomes following encephalitis and can shed light on brain reorganization and function after the acute phase of disease has resolved. Here, we discuss the uses of structural, functional, and PET neuroimaging in the clinical assessment of the acute and recovery phases of encephalitis.

Role of the JNK Pathway in Varicella-Zoster Virus Lytic Infection and Reactivation.

Mechanisms of neuronal infection by varicella-zoster virus (VZV) have been challenging to study due to the relatively strict human tropism of the virus and the paucity of tractable experimental models. Cellular mitogen-activated protein kinases (MAPKs) have been shown to play a role in VZV infection of nonneuronal cells, with distinct consequences for infectivity in different cell types. Here, we utilize several human neuronal culture systems to investigate the role of one such MAPK, the c-Jun N-terminal kinase (JNK), in VZV lytic infection and reactivation. We find that the JNK pathway is specifically activated following infection of human embryonic stem cell-derived neurons and that this activation of JNK is essential for efficient viral protein expression and replication. Inhibition of the JNK pathway blocked viral replication in a manner distinct from that of acyclovir, and an acyclovir-resistant VZV isolate was as sensitive to the effects of JNK inhibition as an acyclovir-sensitive VZV isolate in neurons. Moreover, in a microfluidic-based human neuronal model of viral latency and reactivation, we found that inhibition of the JNK pathway resulted in a marked reduction in reactivation of VZV. Finally, we utilized a novel technique to efficiently generate cells expressing markers of human sensory neurons from neural crest cells and established a critical role for the JNK pathway in infection of these cells. In summary, the JNK pathway plays an important role in lytic infection and reactivation of VZV in physiologically relevant cell types and may provide an alternative target for antiviral therapy.IMPORTANCE Varicella-zoster virus (VZV) has infected over 90% of people worldwide. While primary infection leads to the typically self-limiting condition of chickenpox, the virus can remain dormant in the nervous system and may reactivate later in life, leading to shingles or inflammatory diseases of the nervous system and eye with potentially severe consequences. Here, we take advantage of newer stem cell-based technologies to study the mechanisms by which VZV infects human neurons. We find that the c-Jun N-terminal kinase (JNK) pathway is activated by VZV infection and that blockade of this pathway limits lytic replication (as occurs during primary infection). In addition, JNK inhibition limits viral reactivation, exhibiting parallels with herpes simplex virus reactivation. The identification of the role of the JNK pathway in VZV infection of neurons reveals potential avenues for the development of alternate antiviral drugs.