Dengue NS1 antibodies are associated with clearance of viral NS1.

BACKGROUND: Dengue vascular permeability syndrome is the primary cause of death in severe dengue infections. The protective versus potentially pathogenic role of dengue NS1 antibodies are not well understood. The main goal of this analysis was to characterize the relationship between free NS1 concentration and NS1 antibody titers in primary and secondary dengue infection in order to better understand the presence and duration of NS1 antibody complexes in clinical dengue infections. METHODS: Hospitalized participants with acute dengue infection were recruited from Northern Colombia between 2018 to 2020. Symptom assessment including dengue signs and symptoms, chart review and blood collection was performed. Primary versus secondary Dengue was assessed serologically. NS1 titers and anti-NS1 antibodies were measured daily. RESULTS: Patients with secondary infection have higher antibody titers than those in primary infection, and we find a negative correlation between anti-NS1 antibody titer and NS1 protein. We demonstrate that in a subset of secondary infection, there are indeed NS1 antibody-antigen complexes at the admission day during the febrile phase that are not detectable by the recovery phase. Furthermore, dengue infection status is associated with higher circulating sialidases. DISCUSSION: The negative correlation between antibody and protein suggests that antibodies may play a role in clearing this viral protein.

Protection of the myocardium against ischemia/reperfusion injury by angiotensin-(1-9) through an AT2R and Akt-dependent mechanism.

Angiotensin-(19), a peptide of the non-classical renin angiotensin system, has been shown to prevent and revert hypertension and cardiac hypertrophy. We hypothetized that systemic delivery of angiotensin-(1-9) following myocardial infarction will also be protective and extend to provide protection during reperfusion of the ischemic heart. Adult Sprague Dawley rats were subjected to left anterior descending artery ligation and treated with angiotensin-(1-9) via osmotic mini-pump for 2 weeks in the presence or absence of Mas receptor or AT2R antagonists (A779 and PD123319, respectively). Myocardial death and left ventricular function were evaluated after infarction. Infarct size and functional parameters were determined in isolated rat hearts after global ischemia/reperfusion in the presence of angiotensin-(1-9) plus receptor antagonists or Akt inhibitor at reperfusion. in vitro, neonatal rat ventricular cardiomyocytes underwent simulated ischemia/reperfusion and angiotensin-(1-9) was co-incubated with A779, PD123319 or Akt inhibitor. Systemic delivery of angiotensin-(1-9) significantly decreased cell death and improved left ventricular recovery after in vivo myocardial infarction. Perfusion with the peptide reduced the infarct size and improved functional recovery after ex vivo ischemia/reperfusion. In vitro, angiotensin-(1-9) decreased cell death in isolated neonatal rat ventricular cardiomyocytes subjected to simulated ischemia/reperfusion. The cardioprotective effects of angiotensin-(1-9) were blocked by PD123319 and Akti VIII but not by A779. Angiotensin-(1-9) limits reperfusion-induced cell death by an AT2R- and Aktdependent mechanism. Angiotensin-(1-9) is a novel strategy to protect against cardiac ischemia/reperfusion injury.

Tracking and Therapeutic Value of Human Adipose Tissue-derived Mesenchymal Stem Cell Transplantation in Reducing Venous Neointimal Hyperplasia Associated with Arteriovenous Fistula.

PURPOSE: To determine if adventitial transplantation of human adipose tissue-derived mesenchymal stem cells (MSCs) to the outflow vein of B6.Cg-Foxn1(nu)/J mice with arteriovenous fistula (AVF) at the time of creation would reduce monocyte chemoattractant protein-1 (Mcp-1) gene expression and venous neointimal hyperplasia. The second aim was to track transplanted zirconium 89 ((89)Zr)-labeled MSCs serially with positron emission tomography (PET) for 21 days. MATERIALS AND METHODS: All animal experiments were performed according to protocols approved by the institutional animal care and use committee. Fifty B6.Cg-Foxn1(nu)/J mice were used to accomplish the study aims. Green fluorescent protein was used to stably label 2.5 × 10(5) MSCs, which were injected into the adventitia of the outflow vein at the time of AVF creation in the MSC group. Eleven mice died after AVF placement. Animals were sacrificed on day 7 after AVF placement for real-time polymerase chain reaction (n = 6 for MSC and control groups) and histomorphometric (n = 6 for MSC and control groups) analyses and on day 21 for histomorphometric analysis only (n = 6 for MSC and control groups). In a separate group of experiments (n = 3), animals with transplanted (89)Zr-labeled MSCs were serially imaged with PET for 3 weeks. Multiple comparisons were performed with two-way analysis of variance, followed by the Student t test with post hoc Bonferroni correction. RESULTS: In vessels with transplanted MSCs compared with control vessels, there was a significant decrease in Mcp-1 gene expression (day 7: mean reduction, 62%; P = .029), with a significant increase in the mean lumen vessel area (day 7: mean increase, 176% [P = .013]; day 21: mean increase, 415% [P = .011]). Moreover, this was accompanied by a significant decrease in Ki-67 index (proliferation on day 7: mean reduction, 81% [P = .0003]; proliferation on day 21: mean reduction, 60%, [P = .016]). Prolonged retention of MSCs at the adventitia was evidenced by serial PET images of (89)Zr-labeled cells. CONCLUSION: Adventitial transplantation of MSCs decreases Mcp-1 gene expression, accompanied by a reduction in venous neointimal hyperplasia.

Adventitial transduction of lentivirus-shRNA-VEGF-A in arteriovenous fistula reduces venous stenosis formation.

Venous neointimal hyperplasia (VNH) causes hemodialysis vascular access failure. Here we tested whether VNH formation occurs in part due to local vessel hypoxia caused by surgical trauma to the vasa vasorum of the outflow vein at the time of arteriovenous fistula placement. Selective targeting of the adventitia of the outflow vein at the time of fistula creation was performed using a lentivirus-delivered small-hairpin RNA that inhibits VEGF-A expression. This resulted in significant increase in mean lumen vessel area, decreased media/adventitia area, and decreased constrictive remodeling with a significant increase in apoptosis (increase in caspase 3 activity and TUNEL staining) accompanied with decreased cellular proliferation and hypoxia-inducible factor-1α at the outflow vein. There was significant decrease in cells staining positive for α-smooth muscle actin (a myofibroblast marker) and VEGFR-1 expression with a decrease in MMP-2 and MMP-9. These results were confirmed in animals that were treated with humanized monoclonal antibody to VEGF-A with similar results. Since hypoxia can cause fibroblast to differentiate into myofibroblasts, we silenced VEGF-A gene expression in fibroblasts and subjected them to hypoxia. This decreased myofibroblast production, cellular proliferation, cell invasion, MMP-2 activity, and increased caspase 3. Thus, VEGF-A reduction at the time of arteriovenous fistula placement results in increased positive vascular remodeling.

Blood outgrowth endothelial cells reduce hypoxia-mediated fibroblast to myofibroblast conversion by decreasing proangiogenic cytokines.

PURPOSE: Hypoxic conditions cause fibroblasts to differentiate into alpha smooth-muscle cell actin (α -SMA)-positive cells, i.e. myofibroblasts. This process is a hallmark of venous neointimal hyperplasia (VNH) associated with hemodialysis vascular access. The purpose of this study was to determine if blood outgrowth endothelial cells (BOEC) may reduce the conversion of fibroblasts into myofibroblasts under hypoxic conditions, and to determine the potential mechanisms involved. METHODS: An experimental model was used, in which fibroblasts and BOEC were subjected to hypoxia under contact and transwell conditions to determine if BOEC reduce the conversion of fibroblasts into myofibroblasts under hypoxic conditions. Gene expression under different conditions was performed. In addition, functional assays including cell proliferation and migration were determined. RESULTS: This study demonstrates that contact needs to occur between BOEC and fibroblasts for the reduction of the hypoxia-driven conversion of fibroblasts into α-SMA. This is associated with a decrease in several proangiogenic genes including vascular endothelial growth factor A, platelet-derived growth factor, fibroblast growth factor and matrix metalloproteinase 2 in fibroblasts in contact with BOEC when compared to fibroblasts alone. In addition, migration is significantly reduced while proliferation remains unchanged. CONCLUSION: This study helps provide rationale for using BOEC delivered to the adventitia of the outflow vein of hemodialysis vascular access to reduce VNH.

Vasopressor stewardship: a case report and lesson shared.

A case report, focused on vasopressor use and presented in this article, is likely to resonate with many critical care nurses. In this article the authors describe opportunities to enhance safety with vasopressor therapy. Specifically, the goal of improving communication among physicians, nurses, and pharmacists around desired endpoints for vasopressor therapy, triggers for reassessment of the therapeutic strategy and cause of the patient's shock was identified as an area for improvement. A form piloted within an organization for use during multidisciplinary rounds and key findings is shared. Vasopressors constitute the mainstay of therapy for nearly every hemodynamically unstable patient in critical care. It is hoped that the lessons and information shared help empower critical care nurses to facilitate vasopressor stewardship within their facilities and, ultimately, enhance patient safety.

Intraventricular dimethyl sulfoxide (DMSO) induces hydrocephalus in a dose-dependent pattern.

Introduction: Dimethyl sulfoxide (DMSO), a widely utilized solvent in the medical industry, has been associated with various adverse effects, even at low concentrations, including damage to mitochondrial integrity, altered membrane potentials, caspase activation, and apoptosis. Notably, therapeutic molecules for central nervous system treatments, such as embolic agents or some chemotherapy drugs that are dissolved in DMSO, have been associated with hydrocephalus as a secondary complication. Our study investigated the potential adverse effects of DMSO on the brain, specifically focusing on the development of hydrocephalus and the effect on astrocytes. Methods: Varied concentrations of DMSO were intraventricularly injected into 3-day-old mice, and astrocyte cultures were exposed to similar concentrations of DMSO. After 14 days of injection, magnetic resonance imaging (MRI) was employed to quantify the brain ventricular volumes in mice. Immunofluorescence analysis was conducted to delineate DMSO-dependent effects in the brain. Additionally, astrocyte cultures were utilized to assess astrocyte viability and the effects of cellular apoptosis. Results: Our findings revealed a dose-dependent induction of ventriculomegaly in mice with 2%, 10%, and 100% DMSO injections (p < 0.001). The ciliated cells of the ventricles were also proportionally affected by DMSO concentration (p < 0.0001). Furthermore, cultured astrocytes exhibited increased apoptosis after DMSO exposure (p < 0.001). Conclusion: Our study establishes that intraventricular administration of DMSO induces hydrocephalus in a dose-dependent manner. This observation sheds light on a potential explanation for the occurrence of hydrocephalus as a secondary complication in intracranial treatments utilizing DMSO as a solvent.

Novel Strategies to Improve the Cardioprotective Effects of Cardioplegia.

The use of cardioprotective strategies as adjuvants of cardioplegic solutions has become an ideal alternative for the improvement of post-surgery heart recovery. The choice of the optimal cardioplegia, as well as its distribution mechanism, remains controversial in the field of cardiovascular surgery. There is still a need to search for new and better cardioprotective methods during cardioplegic procedures. New techniques for the management of cardiovascular complications during cardioplegia have evolved with new alternatives and additives, and each new strategy provides a tool to neutralize the damage after ischemia/reperfusion events. Researchers and clinicians have committed themselves to studying the effect of new strategies and adjuvant components with the potential to improve the cardioprotective effect of cardioplegic solutions in preventing myocardial ischemia/reperfusion-induced injury during cardiac surgery. The aim of this review is to explore the different types of cardioplegia, their protection mechanisms, and which strategies have been proposed to enhance the function of these solutions in hearts exposed to cardiovascular pathologies that require surgical alternatives for their corrective progression.

Novel Insights into the Cardioprotective Effects of the Peptides of the Counter-Regulatory Renin-Angiotensin System.

Currently, cardiovascular diseases are a major contributor to morbidity and mortality worldwide, having a significant negative impact on both the economy and public health. The renin-angiotensin system contributes to a high spectrum of cardiovascular disorders and is essential for maintaining normal cardiovascular homeostasis. Overactivation of the classical renin-angiotensin system is one of the most important pathophysiological mechanisms in the progression of cardiovascular diseases. The counter-regulatory renin-angiotensin system is an alternate pathway which favors the synthesis of different peptides, including Angiotensin-(1-7), Angiotensin-(1-9), and Alamandine. These peptides, via the angiotensin type 2 receptor (AT2R), MasR, and MrgD, initiate multiple downstream signaling pathways that culminate in the activation of various cardioprotective mechanisms, such as decreased cardiac fibrosis, decreased myocardial hypertrophy, vasodilation, decreased blood pressure, natriuresis, and nitric oxide synthesis. These cardioprotective effects position them as therapeutic alternatives for reducing the progression of cardiovascular diseases. This review aims to show the latest findings on the cardioprotective effects of the main peptides of the counter-regulatory renin-angiotensin system.

The Natural History of Post-Chikungunya Viral Arthritis Disease Activity and T-cell Immunology: A Cohort Study.

Background: Chikungunya virus (CHIKV) is an alphavirus spread by mosquitos that causes arthralgias and arthritis that may last for years. The objective of this study was to describe the arthritis progression and T cell immunology over a two-year period. Methods: A cohort of 40 cases of serologically confirmed CHIKV from Magdalena and Atlántico, Colombia were followed in 2019 and again in 2021. Arthritis disease severity, disability, pain, stiffness, physical function, mobility, fatigue, anxiety, sleep disturbances and depression were assessed. Serum cytokines and T-cell subsets were measured and tested for change. Correlations within each of the 2 time periods for laboratory parameters were also examined. Results: Although, arthritis disease severity, as measured by the Disease Activity Score-28 (DAS-28) did not change significantly over a two-year period, a new metric- the Chikungunya Disease Activity Score (CHIK-DAS)- was more sensitive to detect changes in disease severity than the Disease Activity Score-28 (DAS-28) and showed some improvement in average disease severity from moderate to mild over two years. Cases were characterized by moderate disability, pain, and stiffness with mild alterations of physical function, mobility, fatigue, anxiety, sleep disturbances and depression that did not change significantly over time. Small joints including the fingers and wrists were most affected without significant change over time. The percentage of effector T cells (Teffs) and regulatory T cells (Tregs) of CD4+ T cells both decreased over time. Teff percentages decreased more significantly resulting in a halving of the Teff/Treg ratio two years later. Furthermore, markers of Treg immunosuppressive function such as CTLA4, Helios, CD28, CD45RA and 41bb decreased over time. Cytokines did not change significantly over time. Conclusions: The presented data suggest that arthritis persists almost seven years after chikungunya infection in some patients with waning Teff and Treg numbers and activation markers over time. Treg activation may be a promising therapeutic target for further investigation.

Cytokine and T cell responses in post-chikungunya viral arthritis: A cross-sectional study.

OBJECTIVE: To define the relationship between chronic chikungunya post-viral arthritis disease severity, cytokine response and T cell subsets in order to identify potential targets for therapy. METHODS: Participants with chikungunya arthritis were recruited from Colombia from 2019-2021. Arthritis disease severity was quantified using the Disease Activity Score-28 and an Arthritis-Flare Questionnaire adapted for chikungunya arthritis. Plasma cytokine concentrations (interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, interferon-γ and tumor necrosis factor (TNF)) were measured using a Meso Scale Diagnostics assay. Peripheral blood T cell subsets were measured using flow cytometry. RESULTS: Among participants with chikungunya arthritis (N = 158), IL-2 levels and frequency of regulatory T cells (Tregs) were low. Increased arthritis disease activity was associated with higher levels of inflammatory cytokines (IL-6, TNF and CRP) and immunoregulatory cytokine IL-10 (p<0.05). Increased arthritis flare activity was associated with higher Treg frequencies (p<0.05) without affecting T effector (Teff) frequencies, Treg/Teff ratios and Treg subsets. Finally, elevated levels of IL-2 were correlated with increased Treg frequency, percent Tregs out of CD4+ T cells, and Treg subsets expressing immunosuppressive markers, while also correlating with an increased percent Teff out of live lymphocytes (p<0.05). CONCLUSION: Chikungunya arthritis is characterized by increased inflammatory cytokines and deficient IL-2 and Treg responses. Greater levels of IL-2 were associated with improved Treg numbers and immunosuppressive markers. Future research may consider targeting these pathways for therapy.

The use of factorial design, image analysis, and an efficiency calculation for multiplex PCR optimization.

BACKGROUND: The quality of multiplex polymerase chain reaction (PCR) assays depends on several factors. Therefore, it is important to establish the optimal conditions to achieve efficient amplification. The objective of this study was to implement a 5 × 4 factorial design combined with image analysis using agarose gels and an efficiency calculation to optimize a multiplex PCR assays for the detection of Salmonella enterica serovar typhimurium. METHODS: We used 12 ng of Salmonella DNA obtained from pure cultures and applied different annealing temperatures (65°C, 64.5°C, 63.3°C, 61.4°C, or 59°C) and different MgCl2 concentrations (1 mM, 1.5 mM, 2 mM, or 2.5 mM) to amplify regions of the fliC, rfbJ, and fljB genes. The 5 × 4 factorial design was performed using Statgraphics Plus software version 5.1, and the images were analyzed using Image Lab(TM) software. RESULTS: Superior amplification was obtained using an annealing temperature of 65°C and 2 mM MgCl2 . This finding was confirmed by calculating the efficiency of multiplex PCR assays (6.1%) at these conditions. CONCLUSION: We propose the application of factorial design and image analysis to determine the most suitable conditions for multiplex PCR optimization.

The Role of METTL3 in the Progression of Cardiac Fibrosis.

Cardiac fibrosis is known as the expansion of the cardiac interstitium through excessive deposition of extracellular matrix proteins; this process is performed by a multifunctional cell known as the cardiac fibroblast. After the myocardial injury, these cells are activated as a repair program, increase, and switch to a contractile phenotype, which is evidenced by an increase in alpha- smooth muscle actin. Likewise, there is an increase in type I and III collagen, which are considered profibrotic biomarkers. It is believed that one of the proteins involved in cardiac remodeling is METTL3, which is the enzyme responsible for N6-methyladenosine (m6A) methylation, the most common and abundant epigenetic modification of eukaryotic mRNA. This review focuses on recent studies in which the possible role of METTL3 in the progression of fibrosis has been demonstrated, mainly in cardiac fibrogenesis.

Mechanisms of the Quorum Sensing Systems of Pseudomonas Aeruginosa: Host and Bacteria.

Quorum-sensing is a communication mechanism between bacteria with the ability to activate signaling pathways in the bacterium and in the host cells. Pseudomonas aeruginosa is a pathogen with high clinical relevance due to its vast virulence factors repertory and wide antibiotic resistance mechanisms. Due to this, it has become a pathogen of interest for developing new antimicrobial agents in recent years. P. aeruginosa has three major QS systems that regulate a wide gene range linked with virulence factors, metabolic regulation, and environment adaption. Consequently, inhibiting this communication mechanism would be a strategy to prevent the pathologic progression of the infections caused by this bacterium. In this review, we aim to overview the current studies about the signaling mechanisms of the QS system of P. aeruginosa and its effects on this bacterium and the host.

Potential of Angiotensin-(1-7) in COVID-19 Treatment.

The new coronavirus currently named SARS-CoV-2 was announced by the World Health Organization as the virus causing the COVID-19 pandemic. The pathogenesis of SARS-CoV-2 initiates upon contact of a structural spike protein with the angiotensin II-converting enzyme receptor, leading to the induction of inflammatory mechanisms and progression to severe disease in some cases. Currently, studies have emerged linking COVID-19 with angiotensin-(1-7), demonstrating the potential of angiotensin-(1-7)/Mas Receptor axis induction to control disease severity due to its antiinflammatory, vasodilator, antioxidant, antiproliferative, anticoagulant, antiangiogenic and fibrosis inhibitory effects. The renin angiotensin-system peptide Angiotensin-(1-7) shows a high therapeutic potential for COVID-19 mainly because of its ability to counteract the adverse effects caused in various organs due to angiotensin II-converting enzyme blockade. In light of these factors, the use of convalescent plasma conjugated therapy and Ang (1-7) agonists for the treatment of COVID-19 patients could be recommended. The differential expression of ACE2 and the varied response to SARSCoV- 2 are thought to be connected. According to several investigations, ACE2 antibodies and pharmacological inhibitors might be used to prevent viral entry. Given its capacity to eliminate the virus while ensuring lung and cardiovascular protection by regulating the inflammatory response, angiotensin-( 1-7) is expected to be a safe choice. However, more clinical evidence is required to clarify the therapeutic usage of this peptide. The aim of this review article is to present an update of scientific data and clinical trials on the therapeutic potential of angiotensin-(1-7) in patients with COVID-19.

Effects of Metformin on Ischemia/Reperfusion Injury: New Evidence and Mechanisms.

The search for new drugs with the potential to ensure therapeutic success in the treatment of cardiovascular diseases has become an essential pathway to follow for health organizations and committees around the world. In June 2021, the World Health Organization listed cardiovascular diseases as one of the main causes of death worldwide, representing 32% of them. The most common is coronary artery disease, which causes the death of cardiomyocytes, the cells responsible for cardiac contractility, through ischemia and subsequent reperfusion, which leads to heart failure in the medium and short term. Metformin is one of the most-used drugs for the control of diabetes, which has shown effects beyond the control of hyperglycemia. Some of these effects are mediated by the regulation of cellular energy metabolism, inhibiting apoptosis, reduction of cell death through regulation of autophagy and reduction of mitochondrial dysfunction with further reduction of oxidative stress. This suggests that metformin may attenuate left ventricular dysfunction induced by myocardial ischemia; preclinical and clinical trials have shown promising results, particularly in the setting of acute myocardial infarction. This is a review of the molecular and pharmacological mechanisms of the cardioprotective effects of metformin during myocardial ischemia-reperfusion injury.

Novel Effects of Statins on Cancer via Autophagy.

Cancer is one of the main causes of death globally. Most of the molecular mechanisms underlying cancer are marked by complex aberrations that activate the critical cell-signaling pathways that play a pivotal role in cell metabolism, tumor development, cytoskeletal reorganization, and metastasis. The phosphatidylinositol 3-kinase/protein kinase-B/mammalian target of the rapamycin (PI3K/AKT/mTOR) pathway is one of the main signaling pathways involved in carcinogenesis and metastasis. Autophagy, a cellular pathway that delivers cytoplasmic components to lysosomes for degradation, plays a dual role in cancer, as either a tumor promoter or a tumor suppressor, depending on the stage of the carcinogenesis. Statins are the group of drugs of choice to lower the level of low-density lipoprotein (LDL) cholesterol in the blood. Experimental and clinical data suggest the potential of statins in the treatment of cancer. In vitro and in vivo studies have demonstrated the molecular mechanisms through which statins inhibit the proliferation and metastasis of cancer cells in different types of cancer. The anticancer properties of statins have been shown to result in the suppression of tumor growth, the induction of apoptosis, and autophagy. This literature review shows the dual role of the autophagic process in cancer and the latest scientific evidence related to the inducing effect exerted by statins on autophagy, which could explain their anticancer potential.

Quorum Sensing Regulation as a Target for Antimicrobial Therapy.

Some bacterial species use a cell-to-cell communication mechanism called Quorum Sensing (QS). Bacteria release small diffusible molecules, usually termed signals which allow the activation of beneficial phenotypes that guarantee bacterial survival and the expression of a diversity of virulence genes in response to an increase in population density. The study of the molecular mechanisms that relate signal molecules with bacterial pathogenesis is an area of growing interest due to its use as a possible therapeutic alternative through the development of synthetic analogues of autoinducers as a strategy to regulate bacterial communication as well as the study of bacterial resistance phenomena, the study of these relationships is based on the structural diversity of natural or synthetic autoinducers and their ability to inhibit bacterial QS, which can be approached with a molecular perspective from the following topics: i) Molecular signals and their role in QS regulation; ii) Strategies in the modulation of Quorum Sensing; iii) Analysis of Bacterial QS circuit regulation strategies; iv) Structural evolution of natural and synthetic autoinducers as QS regulators. This mini-review allows a molecular view of the QS systems, showing a perspective on the importance of the molecular diversity of autoinducer analogs as a strategy for the design of new antimicrobial agents.

Chronic urticaria associated with lung adenocarcinoma - a paraneoplastic manifestation: A case report and literature review.

BACKGROUND: Urticaria is one of the most common causes of emergency room visits. It is defined as an acute inflammatory dermatosis, characterized by localized degranulation of mast cells, with consequent dermal microvascular and formation of edematous and pruritic plaques called hives. Urticaria affects the skin and tissues of the superficial mucosa. Sometimes it is accompanied by angioedema, which is characterized by deeper edema of the dermis and subcutaneous cellular tissue known as the urticarial-angioedema syndrome. About 15%-25% of the general population has suffered at least one type of urticaria at some point during their lifetime and hyperpermeability estimated at 7.6%-16% and has experienced acute urticaria that is usually self-limited and spontaneously resolves without requiring medical attention. CASE SUMMARY: We present the case of a young male patient who was referred to our department with a clinical picture of 4 mo of pruritus associated with hives of variable sizes, irregular borders, with interlesional confluence, that were non-painful, without involvement of the palms and soles of the feet but with a tendency to progression in a generalized manner. He had multiple emergency room visits and poor response to antihistamines and systemic corticosteroids. Imaging studies demonstrated nodules in the lower lingula segment, at the level of the greater fissure and in the anterior contour of the left anterior basal segment associated with parahiliar adenopathies in the absence of findings suggestive of infectious or autoimmune etiology. Segmental lobectomy was performed by thoracoscopy with resection of a lung nodule in the lingula and biopsy of the para-aortic mediastinal ganglion. The histopathological report showed the presence of poorly differentiated invasive adenocarcinoma with a solid morphological and acinar pattern with immunohistochemical description of lung tissue that expresses strong positive and diffuse reaction for thyroid transcription factor 1 (TTF-1) with negativity to P40 for a histopathological diagnosis of malignant epithelial neoplasia with expression of infiltrating adenocarcinoma. Spontaneous chronic urticaria is considered possibly secondary to lung adenocarcinoma. CONCLUSION: Chronic spontaneous urticaria is considered a paraneoplastic dermatosis with a controversial association in the literature. In the presented case, a young patient presented with chronic refractory urticaria and after an exhaustive clinical work-up was found to have a diagnosis of poorly differentiated lung adenocarcinoma with high expression of TTF-1. According to the Curth criteria, the urticaria presented by the patient is related to the oncological diagnosis. In addition, the high expression of TTF-1 documented in this case could be acting as an autoantigen that would cause chronic spontaneous urticaria. Further research evaluating a causal relationship between the TFF-1 protein and urticaria in lung cancer is needed.

Recent Insights into COVID-19 in Children and Clinical Recommendations.

Pediatric coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome in children (MIS-C) have been recognized in multiple countries globally. In this review, we provide recent insights into SARS-CoV-2 infection in children from epidemiological, clinical, and laboratory perspectives, including reports on the disease course and therapy. We highlight key features of SARS-CoV-2 infection in children, the relationship between MIS-C and Kawasaki disease, and summarize treatment guidelines for COVID-19 in children from institutional protocols from Colombia, case reports, recommendations based on expert consensus, and official statements from organizations such as the World Health Organization (WHO), United States Center for Disease Control (CDC), Colombian Association of Infectious Diseases, and the Colombian Society of Pediatrics. Finally, we discuss gaps in research with suggestions for future research on the pathogenesis underlying pediatric COVID-19.