Vascular Obliteration Due To Endothelial And Myointimal Growth In COVID-19

Abstract Background: Severe coronavirus disease 2019 (Covid-19) is a systemic multi-organ viral invasion. Previous studies found that many patients had a procoagulant state and/or severe hypoxemia with relatively well-preserved lung mechanics. Mechanisms underlying the vascular and its surrounding tissue are not well known yet. Histological data in Covid-19 tissues´ patients are still limited and mainly focused on post-mortem analysis. Since SARS-CoV-2 largely affects cutaneous tissue, we aim to examine in depth skin lesions related to Covid-19 in order to understand better how the disease might affect living tissue.Methods: Five skin lesions from Covid-19 adult patients were selected for histological tissue examination. Vast amount of data of immunohistochemistry (IHC) and direct immunofluorescent (DIF) were part of the assessment. Results: A common strong vasculopathic reaction pattern based on prominent vascular endothelial and myointimal cellgrowth was identified. Endothelial cell distortion generated vascular lumen obliteration and a strike erythrocyte and serum extravasation. Extensive significant vascular C4d and C3 deposition throughout vascular cell wall was also identified. A regenerative epidermal hyperplasia with tissue structure preservation was found. Conclusions: Covid-19 could comprise an obliterative micro-angiopathy consisting on endothelial and myointimal intensive growth with complement activation. This mechanism, together with increased vascular permeability identified, could contribute to obliterative vascular lumen and hemorrhage in Covid-19. Activation of the complement and angiogenic pathways could have an important role in inducing and maintaining this vasculopathic reaction pattern. Thus, anticoagulation by itself could not completely reverse vascular lumen obliteration, with consequent hemorrhagic increased risk associated. Skin is the largest organ in the body, the most accessible one and can mirror other organs of the body. Findings of this study could contribute to a better understanding of physio-pathological mechanisms underlying SARS-CoV-2 infection on living tissue and could help further studies find potential targets for specific therapeutic interventions in Covid-19 severe patients.

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Vascular Obliteration Due To Endothelial And Myointimal Growth In COVID-19

10.21203/rs.3.rs-32241/v1 ◽

2020 ◽

Author(s):

Jara Valtueña ◽

Gerardo Martínez-García ◽

Daniel Ruiz-Sánchez ◽

María Garayar-Cantero ◽

Carlos Dueñas ◽

...

Keyword(s):

Skin Lesions ◽

The Body ◽

Therapeutic Interventions ◽

Lung Mechanics ◽

Surrounding Tissue ◽

Reaction Pattern ◽

Vascular Lumen ◽

Increased Risk ◽

Cutaneous Tissue ◽

Histological Data

Abstract Background: Severe coronavirus disease 2019 (Covid-19) is a systemic multi-organ viral invasion. Previous studies found that many patients had a procoagulant state and/or severe hypoxemia with relatively well-preserved lung mechanics. Mechanisms underlying the vascular and its surrounding tissue are not well known yet. Histological data in Covid-19 tissues´ patients are still limited and mainly focused on post-mortem analysis. Since SARS-CoV-2 largely affects cutaneous tissue, we aim to assess the pathophysiologic mechanisms in depth in living skin tissue related to Covid-19.Methods: Five skin lesions from caucasian Covid-19 adult patients were selected for cutaneous tissue histological examination including immunohistochemistry (IHC) and direct immunofluorescent (DIF) vast amount of data. Results: A common strong vasculopathic reaction pattern based on prominent vascular endothelial and myointimal cellgrowth was identified. Endothelial cell distortion generated vascular lumen obliteration and a strike erythrocyte and serum extravasation. Extensive significant vascular C4d and C3 deposition throughout vascular cell wall was also identified. A regenerative epidermal hyperplasia with tissue structure preservation was also found. Conclusions: Covid-19 could comprise an obliterative micro-angiopathy consisting on endothelial and myointimal intensive growth with complement activation. This mechanism, together with increased vascular permeability identified, could contribute to obliterative vascular lumen and hemorrhage in Covid-19 disease. Activation of the complement and angiogenic pathways could have an important role in inducing and maintaining this vasculopathic reaction pattern. Thus, anticoagulation by itself could not completely reverse vascular lumen obliteration, with consequent hemorrhagic increased risk associated. Skin is the largest organ in the body, the most accessible one and can mirror other organs of the body. Findings of this study could contribute to a better understanding of physio-pathological mechanisms underlying Covid-19 infection on living tissue and could help further studies find potential targets for specific therapeutic interventions in Covid-19 severe patients.

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CD30+ Lymphoproliferative Disorder/Lymphomatoid Papulosis - A Regression Caused by Mistletoe Therapy.

Blood ◽

10.1182/blood.v106.11.4779.4779 ◽

2005 ◽

Vol 106 (11) ◽

pp. 4779-4779

Author(s):

Georg Seifert ◽

Christoph Tautz ◽

Karl Seeger ◽

Guenter Henze ◽

Alfred Laengler

Keyword(s):

Clinical Signs ◽

Immunohistochemical Analysis ◽

Skin Lesions ◽

High Risk Group ◽

The Body ◽

Topical Steroids ◽

Malignant Lymphomas ◽

Lymphomatoid Papulosis ◽

Systemic Involvement ◽

Increased Risk

Abstract Lymphomatoid papulosis (LyP) is a CD30+ cutaneous lymphoma according to the WHO classifications and regarded as a condition of uncertain malignant potential. The incidence of LyP in children is relatively low compared to that in adults. It is correlated with malignant lymphomas in 5–20% of adult LyP-patients. In children, an increased risk for the development of a malignant lymphoma is observed. The clinical course is often chronic. Most common treatment for LyP is topical steroids, antibiotics, phototherapy and low-dose methotrexate. Prognosis is excellent with a survival of 100% even for patients with malignant lymphomas. Case-report: An 8-years old boy suffered from reddish nodules (maximum 7 cm in diameter) on his right forearm and his left leg. Immunohistochemical analysis identified a CD30+large-T-cell-type-NHL of the skin. Topic steroids were effective but six months later he showed axillar lymph-node swelling. Immunohistochemically it was classified as anaplastic large cell T-type-lymphoma (ALCL) without signs of systemic involvement. Combination chemotherapy according to the European ALCL-trial (high-risk-group) was given for six months. All nodules (cutaneous and lympoid/axilla) resolved within a few weeks. Two months after cessation of chemotherapy a new skin-nodule on the left forearm appeared. The immunohistochemical diagnosis was now LyP. No specific therapy was given. In the following two months he developed two further solid and painful skin-lesions. In this situation we decided to start a therapeutic approach with subcutaneous mistleote (MT), which was injected close to one of these lesions. The skin-nodules decreased after the first dose and MT injections into all nodules were continued. Within the following two weeks the skin-lesions resolved completely and subcutaneous MT therapy was continued. Two months later, he developed two new nodules responding within a few days to increased dose of MT. While continuation therapy with MT the boy was without clinical signs both of the LvP and ALCL for nearly two years. Subsequently MT therapy was terminated. Three weeks after cessation the cutaneus LyP generally reactivated all over the body with typical nodules (maximum 1 cm in diameter). Subcutaneus MT therapy was restarted and the cutnaneus LyP regressed within 2 weeks completely without additional therapy.

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The role of iron metabolism indicators in predicting gestational diabetes mellitus

Diabetes Mellitus ◽

10.14341/dm12502 ◽

2021 ◽

Vol 24 (4) ◽

pp. 365-370

Author(s):

A. O. Torosyan ◽

E. V. Loginova ◽

C. G. Gagaev

Keyword(s):

Diabetes Mellitus ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Pregnant Women ◽

The Body ◽

Therapeutic Interventions ◽

Diagnostic Measures ◽

Increased Risk ◽

Excess Fe

Iron (Fe) deficiency and hyperglycaemia are both widely found throughout the world among pregnant women. According to the latest data from the American Diabetes Association (ADA), the prevalence of gestational diabetes mellitus (GDM) has increased and reaches 15–20%. Nowadays, there is growing evidence that a link between Fe metabolism and glucose homeostasis exists. The study of changes in the indicators of Fe metabolism in the serum of pregnant women with glucose intolerance and GDM plays an important role in expanding the understanding of the pathogenesis of these conditions. The hypothesis that excess Fe increases the risk of developing GDM has prompted us to review and evaluate the potential relationship between elevated Fe levels and the risk of developing GDM. The aim is to integrate all available data on the correlation between GDM and Fe status in the body. It is increasingly being recognised that excess Fe accumulation in the body is associated with an increased risk of diabetes. There is no available data on the relationship between serum ferritin and GDM in the Russian population, while early identification of the risk of GDM development will be of great importance for its related health effects and prevention. The role of Fe status as a GDM biomarker in high-risk populations is of interest, both for prognostic and diagnostic measures, and for therapeutic interventions. For a better understanding of whether an excess of Fe increases the risk of developing GDM, studies are needed to reveal the role of Fe in the mechanisms of GDM development.

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The Association of Obesity and Liver Enzyme Activities in a Student Population at Increased Risk for Cardiovascular Disease / Veza Između Gojaznosti I Aktivnosti Jetrenih Enzima U Studentskoj Populaciji Sa Povećanim Rizikom Za Nastanak Kardiovaskularnih Bolesti

Journal of Medical Biochemistry ◽

10.2478/v10011-012-0024-z ◽

2013 ◽

Vol 32 (1) ◽

pp. 26-31 ◽

Cited By ~ 1

Author(s):

Emina Čolak ◽

Dragana Pap ◽

Nada Majkić-Singh ◽

Ivana Obradović

Keyword(s):

Body Mass Index ◽

Waist Circumference ◽

Liver Enzyme ◽

Body Mass ◽

Statistical Processing ◽

The Body ◽

Control Group ◽

Anthropometric Parameters ◽

Nonalcoholic Fatty Liver ◽

Increased Risk

Summary Background: It has been reported that obesity is associated with metabolic syndrome, insulin resistance, cardiovascular risk but also with nonalcoholic fatty liver disease (NAFLD). The prevalence of obesity in children and adolescents is increasing rapidly all over the world. The aim of this study was to analyze the value of liver enzymes: AST, ALT and γGT in a group of obese students in order to establish their correlation to anthropometric parameters such as: BMI (body mass index), WC (waist circumference), HC (hip circumference), and WHR (waist-to-hip ratio) compared to non-obese students who comprised the control group (CG). Methods: In this study, 238 students from the University of Novi Sad of both sexes (126 men and 112 women) with a mean age of 22.32 ± 1.85 years were included. According to the body mass index (BMI) lower and higher than 25 kg/m2 and waist circumference (WC) lower and higher than 94 cm (80 cm for females) the whole group of 238 students was divided into 2 subgroups: the obese group at increased risk for CVD (Group 1) and the group at lower risk for CVD (Group 2). AST, ALT and γGT activities were determined in fasting blood samples. Results: Statistical processing data revealed significantly higher values of AST, ALT and γGT in the group of students with BMI>25 kg/m2, WC>94 cm for males and WC>80 cm for females, HC>108 cm for males and HC>111 cm for females, and WHR>0.90 for males and WHR>0.80 for females (P<0.001). Significant association was established between anthropometric parameters and liver enzyme levels (P<0.0001). Conclusions: Obese students with higher BMI, WC, HC and WHR values have higher liver enzyme activites and a higher chance to develop NAFLD in the future.

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Life Course Predictors of Allostatic Load Among LGBTQ Older Adults

Innovation in Aging ◽

10.1093/geroni/igaa057.2615 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 735-735

Author(s):

Charles Hoy-Ellis ◽

Hyun Kim ◽

Karen Fredriksen Goldsen

Keyword(s):

Older Adults ◽

Life Course ◽

Interpersonal Violence ◽

Allostatic Load ◽

Identity Management ◽

The Body ◽

Linear Regression Models ◽

Psychophysiological Stress ◽

Increased Risk ◽

Wear And Tear

Abstract LGBTQ older adults are at significantly increased risk for poor mental and physical health, likely consequential to lifelong bias. Allostatic load (AL), the net effect of “wear and tear” on the body resulting from repeated, chronic over-activation of the psychophysiological stress response system. Utilizing the Health Equity Promotion Model, the aim of this study was to test potential life course predictors of AL, including interpersonal violence, legal marriage, and identity management in a sample of LGBTQ adults 50 to 97 years of age (n=317). Results from a series of hierarchical linear regression models showed that adult physical abuse and late identity disclosure for those who had been in an opposite-sex marriage predicted higher AL in this sample of LGBTQ older adults, indicating need for increased research on bias over the life course as contributory to AL and biopsychosocial dysfunction among LGBTQ older adults.

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The Need for Personalized Risk-Stratified Approaches to Treatment for Gestational Diabetes: A Narrative Review

Seminars in Reproductive Medicine ◽

10.1055/s-0041-1723778 ◽

2021 ◽

Author(s):

Shamil D. Cooray ◽

Jacqueline A. Boyle ◽

Georgia Soldatos ◽

Shakila Thangaratinam ◽

Helena J. Teede

Keyword(s):

Gestational Diabetes ◽

Pregnancy Outcomes ◽

Population Based ◽

Adverse Pregnancy Outcomes ◽

Therapeutic Interventions ◽

Clinical Prediction Model ◽

Increased Risk ◽

Adverse Pregnancy ◽

The Individual ◽

Personalized Risk

AbstractGestational diabetes mellitus (GDM) is common and is associated with an increased risk of adverse pregnancy outcomes. However, the prevailing one-size-fits-all approach that treats all women with GDM as having equivalent risk needs revision, given the clinical heterogeneity of GDM, the limitations of a population-based approach to risk, and the need to move beyond a glucocentric focus to address other intersecting risk factors. To address these challenges, we propose using a clinical prediction model for adverse pregnancy outcomes to guide risk-stratified approaches to treatment tailored to the individual needs of women with GDM. This will allow preventative and therapeutic interventions to be delivered to those who will maximally benefit, sparing expense, and harm for those at a lower risk.

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Timing of Bisphosphonate Initiation After Fracture: What Does the Data Really Say?

Geriatric Orthopaedic Surgery & Rehabilitation ◽

10.1177/2151459320980369 ◽

2020 ◽

Vol 11 ◽

pp. 215145932098036

Author(s):

David W. Barton ◽

C. Taylor Smith ◽

Amit S. Piple ◽

Sterling A. Moskal ◽

Jonathan J. Carmouche

Keyword(s):

Fracture Healing ◽

Clinical Studies ◽

Osteoporosis Treatment ◽

The Body ◽

Non Union ◽

Increased Risk ◽

Level I ◽

Timing Of Initiation ◽

The Impact ◽

Published Research

Introduction: Osteoporosis is often not clinically recognized until after a fracture occurs. Individuals who have 1 fracture are at increased risk of future fractures. Prompt initiation of osteoporosis treatment following fracture is critical to reducing the rate of future fractures. Antiresorptives are the most widely used class of medications for the prevention and treatment of osteoporosis. Many providers are hesitant to initiate antiresorptives in the acute post-fracture period. Concerns include interference with bone remodeling necessary for successful fracture healing, which would cause increased rates of non-union, malunion, and refracture. While such concerns should not extend to anabolic medications, physicians may also hesitate to initiate anabolic osteoporosis therapies due to high cost and/or lack of familiarity. This article aims to briefly review the available data and present a digestible narrative summary to familiarize practicing orthopaedic surgeons with the essential details of the published research on this topic. Results: The results of 20 clinical studies and key pre-clinical studies related to the effect of anti-resorptive medications for osteoporosis on fracture healing are summarized in the body of this narrative review. Discussion & Conclusions: While few level I studies have examined the impact of timing of initiation of osteoporosis medications in the acute post-fracture period, the few that have been published do not support these concerns. Specifically, data from level I clinical trials indicate that initiating bisphosphonates as early as 2 weeks post-fracture does not increase rates of non-union or malunion. By reviewing the available data, we hope to give clinicians the confidence to initiate osteoporosis treatment promptly post-fracture.

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Dynamic Imaging of IEL-IEC Co-Cultures Allows for Quantification of CD103-Dependent T Cell Migration

International Journal of Molecular Sciences ◽

10.3390/ijms22105148 ◽

2021 ◽

Vol 22 (10) ◽

pp. 5148

Author(s):

Karin Enderle ◽

Martin Dinkel ◽

Eva-Maria Spath ◽

Benjamin Schmid ◽

Sebastian Zundler ◽

...

Keyword(s):

T Cell ◽

Cross Talk ◽

Intestinal Inflammation ◽

Ex Vivo ◽

New Technology ◽

Surface Expression ◽

Intraepithelial Lymphocytes ◽

Dynamic Imaging ◽

The Body ◽

Therapeutic Interventions

Intraepithelial lymphocytes (IEL) are widely distributed within the small intestinal epithelial cell (IEC) layer and represent one of the largest T cell pools of the body. While implicated in the pathogenesis of intestinal inflammation, detailed insight especially into the cellular cross-talk between IELs and IECs is largely missing in part due to lacking methodologies to monitor this interaction. To overcome this shortcoming, we employed and validated a murine IEL-IEC (organoids) ex vivo co-culture model system. Using livecell imaging we established a protocol to visualize and quantify the spatio-temporal migratory behavior of IELs within organoids over time. Applying this methodology, we found that IELs lacking CD103 (i.e., integrin alpha E, ITGAE) surface expression usually functioning as a retention receptor for IELs through binding to E-cadherin (CD324) expressing IECs displayed aberrant mobility and migration patterns. Specifically, CD103 deficiency affected the ability of IELs to migrate and reduced their speed during crawling within organoids. In summary, we report a new technology to monitor and quantitatively assess especially migratory characteristics of IELs communicating with IEC ex vivo. This approach is hence readily applicable to study the effects of targeted therapeutic interventions on IEL-IEC cross-talk.

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Cutaneous anthrax outbreak associated with handling dead animals, Rhino Camp sub-county: Arua District, Uganda, January–May 2018

One Health Outlook ◽

10.1186/s42522-021-00040-z ◽

2021 ◽

Vol 3 (1) ◽

Author(s):

Vivian Ntono ◽

Daniel Eurien ◽

Lilian Bulage ◽

Daniel Kadobera ◽

Julie Harris ◽

...

Keyword(s):

Health Workers ◽

Clinical Sample ◽

Health Centre ◽

Skin Lesions ◽

Suspected Case ◽

Prevention Measures ◽

Multiple Exposures ◽

Increased Risk ◽

Control And Prevention ◽

Cutaneous Anthrax

Abstract Background On 18 January 2018 a 40 year old man presented with skin lesions at Rhino Camp Health Centre. A skin lesion swab was collected on 20 January 2018 and was confirmed by PCR at Uganda Virus Research Institute on 21 January 2018. Subsequently, about 9 persons were reported to have fallen ill after reporting contact with livestock that died suddenly. On 9 February 2018, Arua District notified Uganda Ministry of Health of a confirmed anthrax outbreak among humans in Rhino Camp sub-county. We investigated to determine the scope and mode of transmission and exposures associated with identified anthrax to guide control and prevention measures. Methods We defined a suspected cutaneous anthrax case as onset of skin lesions (e.g., papule, vesicle, or eschar) in a person residing in Rhino Camp sub-county, Arua District from 25 December 2017 to 31 May 2018. A confirmed case was a suspected case with PCR-positivity for Bacillus anthracis from a clinical sample. We identified cases by reviewing medical records at Rhino Camp Health Centre. We also conducted additional case searches in the affected community with support from Community Health Workers. In a retrospective cohort study, we interviewed all members of households in which at least one person had contact with the carcasses of or meat from animals suspected to have died of anthrax. We collected and tested hides of implicated animals using an anthrax rapid diagnostic test. Results We identified 14 case-patients (1 confirmed, 13 suspected); none died. Only males were affected (affected proportion: 12/10,000). Mean age of case-persons was 33 years (SD: 22). The outbreak lasted for 5 months, from January 2018–May 2018, peaking in February. Skinning (risk ratio = 2.7, 95% CI = 1.1–6.7), dissecting (RR = 3.0, 95% CI = 1.2–7.6), and carrying dead animals (RR = 2.7, 95% CI = 1.1–6.7) were associated with increased risk of illness, as were carrying dissected parts of animals (RR = 2.9, 95% CI 1.3–6.5) and preparing and cooking the meat (RR = 2.3, 95% CI 0.9–5.9). We found evidence of animal remains on pastureland. Conclusion Multiple exposures to the hides and meat of animals that died suddenly were associated with this cutaneous anthrax outbreak in Arua District. We recommended public education about safe disposal of carcasses of livestock that die suddenly.

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Fighting Oxidative Stress with Sulfur: Hydrogen Sulfide in the Renal and Cardiovascular Systems

Antioxidants ◽

10.3390/antiox10030373 ◽

2021 ◽

Vol 10 (3) ◽

pp. 373

Author(s):

Joshua J. Scammahorn ◽

Isabel T. N. Nguyen ◽

Eelke M. Bos ◽

Harry Van Goor ◽

Jaap A. Joles

Keyword(s):

Oxidative Stress ◽

Hydrogen Sulfide ◽

Redox Status ◽

The Body ◽

Therapeutic Interventions ◽

Oxygen Species ◽

Enzymatic Production ◽

Age Related ◽

Anti Oxidant ◽

Enzymatic Pathways

Hydrogen sulfide (H2S) is an essential gaseous signaling molecule. Research on its role in physiological and pathophysiological processes has greatly expanded. Endogenous enzymatic production through the transsulfuration and cysteine catabolism pathways can occur in the kidneys and blood vessels. Furthermore, non-enzymatic pathways are present throughout the body. In the renal and cardiovascular system, H2S plays an important role in maintaining the redox status at safe levels by promoting scavenging of reactive oxygen species (ROS). H2S also modifies cysteine residues on key signaling molecules such as keap1/Nrf2, NFκB, and HIF-1α, thereby promoting anti-oxidant mechanisms. Depletion of H2S is implicated in many age-related and cardiorenal diseases, all having oxidative stress as a major contributor. Current research suggests potential for H2S-based therapies, however, therapeutic interventions have been limited to studies in animal models. Beyond H2S use as direct treatment, it could improve procedures such as transplantation, stem cell therapy, and the safety and efficacy of drugs including NSAIDs and ACE inhibitors. All in all, H2S is a prime subject for further research with potential for clinical use.

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