Placenta in SARS-CoV-2 infection: a new target for inflammatory and thrombotic events

Abstract Infection by SARS-CoV-2 has been shown to involve a wide range of organs and tissues, leading to a kaleidoscope of clinical conditions. Within this spectrum, an increased rate of preterm deliveries has been reported in women with COVID-19. High expression of proteins (ACE2/TMPRSS2) required for SARS- CoV-2 cell entry has been observed in the maternal-fetal tissues, supporting the possibility of placental viral involvement. A consecutive series of 6 placentas, delivered by 5 women with COVID-19 have been investigated. Three out of six placentas showed changes consistent with chronic villitis, while in one case chronic histiocytic intervillositis was diagnosed. Vascular abnormalities consisting of thrombo- hemorrhagic alterations were identified in the three cases with chronic villitis. These pathological findings: i) provide a basis to explain the higher rate of obstetric complications in these patients; 2) suggest the need to investigate heparin use in COVID-19 affected pregnant patients to prevent adverse outcomes.

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Placenta histopathology in SARS-CoV-2 infection: analysis of a consecutive series and comparison with control cohorts

Virchows Archiv ◽

10.1007/s00428-021-03097-3 ◽

2021 ◽

Author(s):

Luca Bertero ◽

Fulvio Borella ◽

Giovanni Botta ◽

Andrea Carosso ◽

Stefano Cosma ◽

...

Keyword(s):

Cesarean Section ◽

Careful Consideration ◽

Unknown Etiology ◽

Consecutive Series ◽

Control Cohort ◽

Previous Cesarean Section ◽

Wide Range ◽

Chronic Villitis ◽

Clinical Conditions ◽

Previous Cesarean

AbstractInfection by SARS-CoV-2 has been shown to involve a wide range of organs and tissues, leading to a kaleidoscope of clinical conditions. Within this spectrum, an involvement of the fetal-maternal unit could be expected, but, so far, the histopathological evaluation of placentas delivered by women with SARS-CoV-2 infection did not show distinct hallmarks. A consecutive series of 11 placentas, delivered by 10 women with COVID-19 admitted to our Obstetrics and Gynecology clinic have been investigated and compared to a control cohort of 58 pre-COVID-19 placentas and 28 placentas delivered by women who had a previous cesarean section. Four out of eleven placentas showed changes consistent with chronic villitis/villitis of unknown etiology (VUE), while in one case, chronic histiocytic intervillositis was diagnosed. Thrombo-hemorrhagic alterations were observed in a subset of cases. Compared to the control cohort, chronic villitis/VUE (p < 0.001), chronic deciduitis (p = 0.023), microvascular thrombosis (p = 0.003), presence of infarction areas (p = 0.047) and of accelerated villous maturation (p = 0.005) showed higher frequencies in placentas delivered by women with COVID-19. Chronic villitis/VUE (p = 0.003) and accelerated villous maturation (p = 0.019) remained statistically significant by restricting the analysis to placentas delivered after a previous cesarean section. The observed differences in terms of pathological findings could be consistent with SARS-CoV-2 pathogenesis, but just a subset of alterations remained statistically significant after adjusting for a previous cesarean section. A careful consideration of potential confounders is warranted in future studies exploring the relationship between COVID-19 and pregnancy.

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COVID-19 in People Living with HIV: A Systematic Review and Meta-Analysis

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18073554 ◽

2021 ◽

Vol 18 (7) ◽

pp. 3554

Author(s):

Kai Wei Lee ◽

Sook Fan Yap ◽

Yun Fong Ngeow ◽

Munn Sann Lye

Keyword(s):

Systematic Review ◽

Laboratory Testing ◽

Meta Analysis ◽

Clinical Signs ◽

Adverse Outcomes ◽

People Living With Hiv ◽

Common Symptom ◽

Chest Imaging ◽

Wide Range ◽

Epidemiological Characteristics

COVID-19 is a global health emergency. People living with human immunodeficiency virus (PLHIV) have concerns about whether they have a higher risk of getting the infection and suffer worse COVID-19 outcomes. Findings from studies on these questions have largely been inconsistent. We aimed to determine the epidemiological characteristics, clinical signs and symptoms, blood parameters, and clinical outcomes among PLHIV who contracted COVID-19. Relevant studies were identified through Medline, Cinahl, and PubMed databases. A random-effects model was used in meta-analyses with a 95% confidence interval. Eighty-two studies were included in the systematic review and sixty-seven studies for the meta-analysis. The pooled incidence proportion of COVID-19 among PLHIV was 0.9% (95% CI 0.6%, 1.1%) based on the data from seven cohort studies. Overall, 28.4% were hospitalised, of whom, 2.5% was severe-critical cases and 3.5% needed intensive care. The overall mortality rate was 5.3%. Hypertension was the most commonly reported comorbidity (24.0%). Fever (71.1%) was the most common symptom. Chest imaging demonstrated a wide range of abnormal findings encompassing common changes such as ground glass opacities and consolidation as well as a spectrum of less common abnormalities. Laboratory testing of inflammation markers showed that C-reactive protein, ferritin, and interleukin-6 were frequently elevated, albeit to different extents. Clinical features as well as the results of chest imaging and laboratory testing were similar in highly active antiretroviral therapy (HAART)-treated and non-treated patients. PLHIV were not found to be at higher risk for adverse outcomes of COVID-19. Hence, in COVID-19 management, it appears that they can be treated the same way as HIV negative individuals. Nevertheless, as the pandemic situation is rapidly evolving, more evidence may be needed to arrive at definitive recommendations.

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High HSPA8 expression predicts adverse outcomes of acute myeloid leukemia

BMC Cancer ◽

10.1186/s12885-021-08193-w ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Jun Li ◽

Zheng Ge

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

Prognostic Factor ◽

Myeloid Leukemia ◽

Cell Function ◽

Adverse Outcomes ◽

High Expression ◽

Micro Rnas ◽

Acute Myeloid

Abstract Background Acute myeloid leukemia (AML) remains one of the most common hematological malignancies, posing a serious challenge to human health. HSPA8 is a chaperone protein that facilitates proper protein folding. It contributes to various activities of cell function and also is associated with various types of cancers. To date, the role of HSPA8 in AML is still undetermined. Methods In this study, public datasets available from the TCGA (Cancer Genome Atlas) and GEO (Gene Expression Omnibus) were mined to discover the association between the expression of HSPA8 and clinical phenotypes of CN-AML. A series of bioinformatics analysis methods, including functional annotation and miRNA-mRNA regulation network analysis, were employed to investigate the role of HSPA8 in CN-AML. Results HSPA8 was highly expressed in the AML patients compared to the healthy controls. The high HSPA8 expression had lower overall survival (OS) rate than those with low HSPA8 expression. High expression of HSPA8 was also an independent prognostic factor for overall survival (OS) of CN-AML patients by multivariate analysis. The differential expressed genes (DEGs) associated with HSPA8 high expression were identified, and they were enriched PI3k-Akt signaling, cAMP signaling, calcium signaling pathway. HSPA8 high expression was also positively associated with micro-RNAs (hsa-mir-1269a, hsa-mir-508-3p, hsa-mir-203a), the micro-RNAs targeted genes (VSTM4, RHOB, HOBX7) and key known oncogenes (KLF5, RAN, and IDH1), and negatively associated with tumor suppressors (KLF12, PRKG1, TRPS1, NOTCH1, RORA). Conclusions Our research revealed HSPA8 as a novel potential prognostic factor to predict the survival of CN-AML patients. Our data also revealed the possible carcinogenic mechanism and the complicated microRNA-mRNA network associated with the HSPA8 high expression in AML.

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Virtual Body Ownership Illusions for Mental Health: A Narrative Review

Journal of Clinical Medicine ◽

10.3390/jcm10010139 ◽

2021 ◽

Vol 10 (1) ◽

pp. 139

Author(s):

Marta Matamala-Gomez ◽

Antonella Maselli ◽

Clelia Malighetti ◽

Olivia Realdon ◽

Fabrizia Mantovani ◽

...

Keyword(s):

Mental Health ◽

Clinical Care ◽

Well Being ◽

Narrative Review ◽

Future Research ◽

Body Ownership ◽

Surrounding Environment ◽

Wide Range ◽

Clinical Conditions ◽

Virtual Body

Over the last 20 years, virtual reality (VR) has been widely used to promote mental health in populations presenting different clinical conditions. Mental health does not refer only to the absence of psychiatric disorders but to the absence of a wide range of clinical conditions that influence people’s general and social well-being such as chronic pain, neurological disorders that lead to motor o perceptual impairments, psychological disorders that alter behaviour and social cognition, or physical conditions like eating disorders or present in amputees. It is known that an accurate perception of oneself and of the surrounding environment are both key elements to enjoy mental health and well-being, and that both can be distorted in patients suffering from the clinical conditions mentioned above. In the past few years, multiple studies have shown the effectiveness of VR to modulate such perceptual distortions of oneself and of the surrounding environment through virtual body ownership illusions. This narrative review aims to review clinical studies that have explored the manipulation of embodied virtual bodies in VR for improving mental health, and to discuss the current state of the art and the challenges for future research in the context of clinical care.

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Combating escalating harms associated with pharmaceutical opioid use in Australia: the POPPY II study protocol

BMJ Open ◽

10.1136/bmjopen-2018-025840 ◽

2018 ◽

Vol 8 (12) ◽

pp. e025840 ◽

Cited By ~ 5

Author(s):

Natasa Gisev ◽

Sallie-Anne Pearson ◽

Timothy Dobbins ◽

David C Currow ◽

Fiona Blyth ◽

...

Keyword(s):

Risk Factors ◽

Opioid Dependence ◽

Service Use ◽

Population Level ◽

Ethics Committee ◽

Adverse Outcomes ◽

Opioid Use ◽

Research Committee ◽

Services Research ◽

Wide Range

IntroductionOpioid prescribing has increased 15-fold in Australia in the past two decades, alongside increases in a range of opioid-related harms such as opioid dependence and overdose. However, despite concerns about increasing opioid use, extramedical use and harms, there is a lack of population-level evidence about the drivers of long-term prescribed opioid use, dependence, overdose and other harms.Methods and analysisWe will form a cohort of all adult residents in New South Wales (NSW), Australia, who initiated prescribed opioids from 2002 using Pharmaceutical Benefits Scheme dispensing records. This cohort will be linked to a wide range of other datasets containing information on sociodemographic and clinical characteristics, health service use and adverse outcomes (eg, opioid dependence and non-fatal and fatal overdose). Analyses will initially examine patterns and predictors of prescribed opioid use and then apply regression and survival analysis to quantify the risks and risk factors of adverse outcomes associated with prescribed opioid use.Ethics and disseminationThis study has received full ethical approval from the Australian Institute of Health and Welfare Ethics Committee, the NSW Population and Health Services Research Committee and the ACT Health Human Research Ethics Committee. This will be the largest postmarketing surveillance study of prescribed opioids undertaken in Australia, linking exposure and outcomes and examining risk factors for adverse outcomes of prescribed opioids. As such, this work has important translational promise, with direct relevance to regulatory authorities and agencies worldwide. Project findings will be disseminated at scientific conferences and in peer-reviewed journals. We will also conduct targeted dissemination with policy makers, professional bodies and peak bodies in the pain, medicine and addiction fields through stakeholder workshops and advisory groups. Results will be reported in accordance with the REporting of studies Conducted using Observational Routinely collected Data (RECORD) Statement.

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The 3-O-sulfation of heparan sulfate modulates protein binding and lyase degradation

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2012935118 ◽

2021 ◽

Vol 118 (3) ◽

pp. e2012935118

Author(s):

Pradeep Chopra ◽

Apoorva Joshi ◽

Jiandong Wu ◽

Weigang Lu ◽

Tejabhiram Yadavalli ◽

...

Keyword(s):

Heparan Sulfate ◽

Binding Proteins ◽

Factor Xa ◽

Tissue Expression ◽

Cell Entry ◽

Synthetic Approach ◽

Array Technology ◽

Wide Range ◽

Simplex Virus

Humans express seven heparan sulfate (HS) 3-O-sulfotransferases that differ in substrate specificity and tissue expression. Although genetic studies have indicated that 3-O-sulfated HS modulates many biological processes, ligand requirements for proteins engaging with HS modified by 3-O-sulfate (3-OS) have been difficult to determine. In particular, the context in which the 3-OS group needs to be presented for binding is largely unknown. We describe herein a modular synthetic approach that can provide structurally diverse HS oligosaccharides with and without 3-OS. The methodology was employed to prepare 27 hexasaccharides that were printed as a glycan microarray to examine ligand requirements of a wide range of HS-binding proteins. The binding selectivity of antithrombin-III (AT-III) compared well with anti-Factor Xa activity supporting robustness of the array technology. Many of the other examined HS-binding proteins required an IdoA2S-GlcNS3S6S sequon for binding but exhibited variable dependence for the 2-OS and 6-OS moieties, and a GlcA or IdoA2S residue neighboring the central GlcNS3S. The HS oligosaccharides were also examined as inhibitors of cell entry by herpes simplex virus type 1, which, surprisingly, showed a lack of dependence of 3-OS, indicating that, instead of glycoprotein D (gD), they competitively bind to gB and gC. The compounds were also used to examine substrate specificities of heparin lyases, which are enzymes used for depolymerization of HS/heparin for sequence determination and production of therapeutic heparins. It was found that cleavage by lyase II is influenced by 3-OS, while digestion by lyase I is only affected by 2-OS. Lyase III exhibited sensitivity to both 3-OS and 2-OS.

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Impairment of coronary flow reserve in aortic stenosis

Journal of Applied Physiology ◽

10.1152/japplphysiol.00049.2008 ◽

2009 ◽

Vol 106 (1) ◽

pp. 113-121 ◽

Cited By ~ 69

Author(s):

Damien Garcia ◽

Paolo G. Camici ◽

Louis-Gilles Durand ◽

Kim Rajappan ◽

Emmanuel Gaillard ◽

...

Keyword(s):

Coronary Flow Reserve ◽

Coronary Flow ◽

Left Ventricular ◽

Adverse Outcomes ◽

Lumped Parameter Model ◽

Effective Orifice Area ◽

Sensitivity Index ◽

Coronary Perfusion ◽

Flow Reserve ◽

Wide Range

Coronary flow reserve (CFR) is markedly reduced in patients with severe aortic valve stenosis (AS), but the exact mechanisms underlying this impairment of CFR in AS remain unclear. Reduced CFR is the key mechanism leading to myocardial ischemia symptoms and adverse outcomes in AS patients. The objective of this study was to develop an explicit mathematical model formulated with a limited number of parameters that describes the effect of AS on left coronary inflow patterns and CFR. We combined the mathematical V3 (ventricular-valvular-vascular) model with a new lumped-parameter model of coronary inflow. One thousand Monte-Carlo computational simulations with AS graded from mild up to very severe were performed within a wide range of physiological conditions. There was a good agreement between the CFR values computed with this new model and those measured in 24 patients with isolated AS ( r = 0.77, P < 10−4). A global sensitivity analysis showed that the valve effective orifice area (EOA) was the major physiological determinant of CFR (total sensitivity index = 0.87). CFR was markedly reduced when AS became severe, i.e., when EOA was <1.0 cm2, and was generally exhausted when the EOA was <0.5–0.6 cm2. The reduction of CFR that is associated with AS can be explained by the concomitance of 1) reduced myocardial supply as a result of decreased coronary perfusion pressure, and 2) increased myocardial metabolic demand as a result of increased left ventricular workload.

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Specific diseases: chronic heart failure/hypertension

ESC CardioMed ◽

10.1093/med/9780198784906.003.0640 ◽

2018 ◽

pp. 2663-2665

Author(s):

Rodrigo Modolo ◽

Ana Paula de Faria

Keyword(s):

Heart Failure ◽

Cardiac Surgery ◽

Chronic Heart Failure ◽

Adverse Events ◽

Heart Function ◽

Adverse Outcomes ◽

Morbidity And Mortality ◽

Cardiac Markers ◽

Perioperative Morbidity ◽

Clinical Conditions

Hypertension and chronic heart failure are clinical conditions that greatly impact perioperative adverse outcomes of patients undergoing non-cardiac surgery. Although the first does not have a major impact on morbidity and mortality, it is the most frequent condition present in these patients. The second—chronic heart failure—is increasing in prevalence, with the ageing of the population and with the identification of incipient structural cardiac abnormalities, and has a major impact on the perioperative morbidity and mortality. For those reasons, the proper identification of these conditions in the perioperative setting is imperative in order to diminish perioperative adverse events. This chapter summarizes the current indications for identification, assessment of heart function and of cardiac markers, and the therapeutic management of these patients.

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Family Caregiving for Older Adults

Annual Review of Psychology ◽

10.1146/annurev-psych-010419-050754 ◽

2020 ◽

Vol 71 (1) ◽

pp. 635-659 ◽

Cited By ~ 18

Author(s):

Richard Schulz ◽

Scott R. Beach ◽

Sara J. Czaja ◽

Lynn M. Martire ◽

Joan K. Monin

Keyword(s):

Older Adults ◽

Family Caregiving ◽

Empirical Studies ◽

Primary Source ◽

Intervention Strategies ◽

Adverse Outcomes ◽

Care Recipient ◽

Wide Range ◽

Intensity Of Care ◽

The Impact

Family members are the primary source of support for older adults with chronic illness and disability. Thousands of published empirical studies and dozens of reviews have documented the psychological and physical health effects of caregiving, identified caregivers at risk for adverse outcomes, and evaluated a wide range of intervention strategies to support caregivers. Caregiving as chronic stress exposure is the conceptual driver for much of this research. We review and synthesize the literature on the impact of caregiving and intervention strategies for supporting caregivers. The impact of caregiving is highly variable, driven largely by the intensity of care provided and the suffering of the care recipient. The intervention literature is littered with many failures and some successes. Successful interventions address both the pragmatics of care and the emotional toll of caregiving. We conclude with both research and policy recommendations that address a national agenda for caregiving.

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Nutrition and malnutrition in elderly patients

Italian Journal of Medicine ◽

10.4081/itjm.2010.99 ◽

2013 ◽

pp. 99-104

Author(s):

Daniela Tozzuoli ◽

Emanuele Ceccherini ◽

Claudio Pedace

Keyword(s):

Elderly Patients ◽

Nutritional Support ◽

Adverse Outcomes ◽

Patient Specific ◽

Artificial Nutrition ◽

Oral Supplementation ◽

Protein Energy ◽

Age Related ◽

Clinical Conditions ◽

Underlying Diseases

Protein-energy undernutrition is a very common problem among elderly patients. It is promoted by age-related decreases in the basal metabolic rate, physiological change in body composition, progressive dysphagia, physical and/or cognitive impairments, depression, socioeconomic factors, effects of drugs on absorption and utilization of nutrients, and other factors. Several studies suggest that nutritional support can lower the risk of adverse outcomes among undernourished elderly patients. Monitoring food intake in patients with dysphagia may be useful in deciding between oral supplementation or artificial nutrition. The decision to provide nutritional support and the route to be used will depend on the clinical conditions of the patient, the severity of the dysphagia, the expected course of any underlying diseases, and several other patient-specific considerations. In geriatric patients, the main objectives of this type of therapy are usually the maintenance of function and improvement of the quality of life.

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