Endovascular resolution of complete common iliac vein stenosis in a case of May-Thurner syndrome with underlying malignancy.

INTRODUCTION AND IMPORTANCE: May-Thurner Syndrome (MTS) is an uncommon etiology of left common iliac vein thrombosis due to arterial compression. In this report, we describe a case of MTS with severe occlusion of the left common iliac vein in the context of a previously undiagnosed pancreatic cancer. We detail the endovascular resolution of the iliac vein compression and show long-term patency. CASE PRESENTATION: A 33-year-old woman on oral contraceptive pills presented with extensive thrombosis of the left common iliac vein extending cephalad into the lower IVC and inferiorly to the femoral vein. The thrombus was refractory to therapeutic heparin. Mechanical thrombectomy removed the occluding thrombus. Intravenous ultrasound identified severe compression of the left common iliac vein by the right common iliac artery. Angioplasty and stenting provided complete resolution of the lesion. Imaging and hematologic workup revealed a pancreatic malignancy and concomitant hypercoagulable state that likely precipitated the patient's presentation. CLINICAL DISCUSSION: Endovascular intervention provided complete resolution of severe iliac vein compression. Patency was maintained at 6-month follow-up. Research suggests that the anatomical lesion predisposing individuals to MTS is relatively common despite infrequent occurrence of the syndrome. This case highlights the importance of a high clinical suspicion for associated hypercoagulable states when MTS is discovered. CONCLUSION: There is limited research exploring the relationship between severity of iliac vein compression and endovascular treatment outcome. This case documents endovascular resolution of a severe lesion with maintained patency.

Site-specific development and progressive maturation of human tissue-resident memory T cells over infancy and childhood.

Infancy and childhood are critical life stages for generating immune memory to protect against pathogens; however, the timing, location, and pathways for memory development in humans remain elusive. Here, we investigated T cells in mucosal sites, lymphoid tissues, and blood from 96 pediatric donors aged 0-10 years using phenotypic, functional, and transcriptomic profiling. Our results revealed that memory T cells preferentially localized in the intestines and lungs during infancy and accumulated more rapidly in mucosal sites compared with blood and lymphoid organs, consistent with site-specific antigen exposure. Early life mucosal memory T cells exhibit distinct functional capacities and stem-like transcriptional profiles. In later childhood, they progressively adopt proinflammatory functions and tissue-resident signatures, coincident with increased T cell receptor (TCR) clonal expansion in mucosal and lymphoid sites. Together, our findings identify staged development of memory T cells targeted to tissues during the formative years, informing how we might promote and monitor immunity in children.

Longitudinal profiling of respiratory and systemic immune responses reveals myeloid cell-driven lung inflammation in severe COVID-19.

Immune response dynamics in coronavirus disease 2019 (COVID-19) and their severe manifestations have largely been studied in circulation. Here, we examined the relationship between immune processes in the respiratory tract and circulation through longitudinal phenotypic, transcriptomic, and cytokine profiling of paired airway and blood samples from patients with severe COVID-19 relative to heathy controls. In COVID-19 airways, T cells exhibited activated, tissue-resident, and protective profiles; higher T cell frequencies correlated with survival and younger age. Myeloid cells in COVID-19 airways featured hyperinflammatory signatures, and higher frequencies of these cells correlated with mortality and older age. In COVID-19 blood, aberrant CD163+ monocytes predominated over conventional monocytes, and were found in corresponding airway samples and in damaged alveoli. High levels of myeloid chemoattractants in airways suggest recruitment of these cells through a CCL2-CCR2 chemokine axis. Our findings provide insights into immune processes driving COVID-19 lung pathology with therapeutic implications for targeting inflammation in the respiratory tract.

Distinct antibody responses to SARS-CoV-2 in children and adults across the COVID-19 clinical spectrum.

Clinical manifestations of COVID-19 caused by the new coronavirus SARS-CoV-2 are associated with age1,2. Adults develop respiratory symptoms, which can progress to acute respiratory distress syndrome (ARDS) in the most severe form, while children are largely spared from respiratory illness but can develop a life-threatening multisystem inflammatory syndrome (MIS-C)3-5. Here, we show distinct antibody responses in children and adults after SARS-CoV-2 infection. Adult COVID-19 cohorts had anti-spike (S) IgG, IgM and IgA antibodies, as well as anti-nucleocapsid (N) IgG antibody, while children with and without MIS-C had reduced breadth of anti-SARS-CoV-2-specific antibodies, predominantly generating IgG antibodies specific for the S protein but not the N protein. Moreover, children with and without MIS-C had reduced neutralizing activity as compared to both adult COVID-19 cohorts, indicating a reduced protective serological response. These results suggest a distinct infection course and immune response in children independent of whether they develop MIS-C, with implications for developing age-targeted strategies for testing and protecting the population.

Analysis of respiratory and systemic immune responses in COVID-19 reveals mechanisms of disease pathogenesis.

Immune responses to respiratory viruses like SARS-CoV-2 originate and function in the lung, yet assessments of human immunity are often limited to blood. Here, we conducted longitudinal, high-dimensional profiling of paired airway and blood samples from patients with severe COVID-19, revealing immune processes in the respiratory tract linked to disease pathogenesis. Survival from severe disease was associated with increased CD4 + T cells and decreased monocyte/macrophage frequencies in the airway, but not in blood. Airway T cells and macrophages exhibited tissue-resident phenotypes and activation signatures, including high level expression and secretion of monocyte chemoattractants CCL2 and CCL3 by airway macrophages. By contrast, monocytes in blood expressed the CCL2-receptor CCR2 and aberrant CD163 + and immature phenotypes. Extensive accumulation of CD163 + monocyte/macrophages within alveolar spaces in COVID-19 lung autopsies suggested recruitment from circulation. Our findings provide evidence that COVID-19 pathogenesis is driven by respiratory immunity, and rationale for site-specific treatment and prevention strategies.

Antibody responses to SARS-CoV2 are distinct in children with MIS-C compared to adults with COVID-19.

Clinical manifestations of COVID-19 caused by the novel coronavirus SARS-CoV-2 are associated with age. While children are largely spared from severe respiratory disease, they can present with a SARS-CoV-2-associated multisystem inflammatory syndrome (MIS-C) similar to Kawasaki's disease. Here, we show distinct antibody (Ab) responses in children with MIS-C compared to adults with severe COVID-19 causing acute respiratory distress syndrome (ARDS), and those who recovered from mild disease. There was a reduced breadth and specificity of anti-SARS-CoV-2-specific antibodies in MIS-C patients compared to the COVID patient groups; MIS-C predominantly generated IgG Abs specific for the Spike (S) protein but not for the nucleocapsid (N) protein, while both COVID-19 cohorts had anti-S IgG, IgM and IgA Abs, as well as anti-N IgG Abs. Moreover, MIS-C patients had reduced neutralizing activity compared to COVID-19 cohorts, indicating a reduced protective serological response. These results suggest a distinct infection course and immune response in children and adults who develop severe disease, with implications for optimizing treatments based on symptom and age.

Impact and Clinical Implications of Prematurity on Adaptive Immune Development.

PURPOSE OF REVIEW: Detail normal adaptive immune maturation during fetal and neonatal life and review the clinical implications of arrested immune development. RECENT FINDINGS: Advancements in the field of immunology have enabled investigations of the adaptive immunity starting during fetal life. New insights have drawn important distinctions between the neonatal and adult immune systems. The presence of diverse immunologic responses in the perinatal period suggests the importance of in utero immune development. Disruption of immune maturation due to premature birth may have significant implications for clinical pathology. SUMMARY: Establishing protective adaptive immunity during the perinatal period is critical for effective immune responses later in life. Preterm infants are susceptible to aberrant immune system maturation and inflammatory immune responses have been associated with the development of necrotizing enterocolitis (NEC) and bronchopulmonary dysplasia (BPD). Improving our understanding of how immune responses contribute to the pathogenesis of NEC and BPD may offer new opportunities for future treatment and prevention of these diseases.

Differences in neuroplasticity after spinal cord injury in varying animal models and humans.

Rats have been the primary model to study the process and underlying mechanisms of recovery after spinal cord injury. Two weeks after a severe spinal cord contusion, rats can regain weight-bearing abilities without therapeutic interventions, as assessed by the Basso, Beattie and Bresnahan locomotor scale. However, many human patients suffer from permanent loss of motor function following spinal cord injury. While rats are the most understood animal model, major differences in sensorimotor pathways between quadrupeds and bipeds need to be considered. Understanding the major differences between the sensorimotor pathways of rats, non-human primates, and humans is a start to improving targets for treatments of human spinal cord injury. This review will discuss the neuroplasticity of the brain and spinal cord after spinal cord injury in rats, non-human primates, and humans. A brief overview of emerging interventions to induce plasticity in humans with spinal cord injury will also be discussed.