The Good Treatment, the Bad Virus, and the Ugly Inflammation: Pathophysiology of Kidney Involvement During COVID-19

Kidney involvement is a common complication during SARS-CoV-2 infection. Its association with poor outcomes, especially in critically ill patients, raises issues whether kidney involvement reflects multi-organ damage or if it is a specific feature of the infection. Based on observational studies, autopsy series, and on current understanding of the route of entry of the virus, this review will highlight the different types of kidney involvement during COVID-19 and put them in the perspective of the different pathophysiological hypotheses. Virus entry route through ACE2 ligation and TMPRSS2 coligation allows identifying potential viral targets in the kidney, including tubules, endothelial cells, and glomerulus. While reports have described damages of all these structures and virus kidney tropism has been identified in renal extracts in autopsy series, no direct viral infection has been found in the latter structures thus far on kidney biopsies. Notwithstanding the technical challenge of disclosing viral invasion within tissues and cells, viral direct cytopathogenic effect generally does not appear as the cause of the observed renal damage. Inflammation and altered hemodynamics, described as “viral sepsis,” might rather be responsible for organ dysfunction, including kidneys. We shall place these various mechanisms into an integrated vision where the synergy between direct viral pathogenicity and systemic inflammation enhances renal damage. As SARS-CoV-2 inexorably continues its rampant spread, understanding the sequence of events in the kidneys might thus help inform improved therapeutic strategies, including antiviral drugs and immunomodulators.

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Graft detachments in endothelial keratoplasty

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2020-318092 ◽

2021 ◽

pp. bjophthalmol-2020-318092

Author(s):

Rashmi Deshmukh ◽

Sridevi Nair ◽

Darren Shu Jeng Ting ◽

Tushar Agarwal ◽

Jacqueline Beltz ◽

...

Keyword(s):

Risk Factors ◽

Preventive Measures ◽

Endothelial Keratoplasty ◽

Common Complication ◽

Prevention Measures ◽

Descemet Stripping Endothelial Keratoplasty ◽

Secondary Interventions ◽

Different Types ◽

Incidence Risk ◽

Donor Graft

Graft detachment is the most common complication of endothelial keratoplasty. With the ongoing advancements in the field of endothelial keratoplasty, our understanding of risk factors of graft detachments and its management has been evolving. Various prevention measures have been described in literature including presoaking the donor graft, anterior chamber tamponade, venting incisions, sutures to prevent dislocation of graft. Management of a detached graft involves secondary interventions such as rebubbling, suturing and regrafts. In this review, we discuss graft detachment in different types of endothelial keratoplasty techniques including Descemet stripping endothelial keratoplasty, Descemet stripping automated endothelial keratoplasty and Descemet’s membrane endothelial keratoplasty; with emphasis on incidence, risk factors, preventive measures and their management.

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Electrocution Stigmas in Organ Damage: The Pathological Marks

Diagnostics ◽

10.3390/diagnostics11040682 ◽

2021 ◽

Vol 11 (4) ◽

pp. 682

Author(s):

Gelsomina Mansueto ◽

Mario Di Napoli ◽

Pasquale Mascolo ◽

Anna Carfora ◽

Pierluca Zangani ◽

...

Keyword(s):

Morphological Changes ◽

Organ Damage ◽

Pathological Findings ◽

Internal Organs ◽

Histological Changes ◽

Morphological Findings ◽

Starting Point ◽

Autopsy Series ◽

Golden Standard ◽

Wide Variability

Background: Diagnostic criteria for electrocution related death are still a challenge in forensic pathology and it seems that the electrical mark is the only reliable evidence. Methods: A comparison of histological and morphological findings of skin and internal organs from an autopsy series of electrocution deaths with those mostly reported in literature as representative for electrocution. Results: The morphological changes of heart, brain and other main internal organs are still unspecific. Organ’s damage observed in electrocution deaths shows a wide variability, not reliable for a certain diagnosis of electrocution. The electrical mark is still the golden standard for diagnosis of electrocution. Conclusions: In electrocution related deaths, pathological findings of the main internal organs are not enough evidence to support with certainty a post-mortem diagnosis that a victim suffered an electrical damage. Although the organ histological changes are undoubtedly the starting point for a better understanding of the fatal even, the diagnosis of death from electrical damage is still a dark and unsolved chapter. The electrical mark still represents a fundamental indicator above all in the medical-legal field, but the identification of pathognomonic elements and signs not limited to the skin alone could be a valid help in the future, especially in unclear cases.

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Preschoolers' Imaginativeness: Subtypes, Correlates, and Maladaptive Extremes

Imagination Cognition and Personality ◽

10.2190/59wg-p0j9-2n3x-e3ul ◽

1985 ◽

Vol 4 (4) ◽

pp. 349-364 ◽

Cited By ~ 2

Author(s):

Roni Beth Tower

Keyword(s):

Preschool Children ◽

Child Development ◽

Healthy Child ◽

Observational Studies ◽

Two Dimensions ◽

Different Types ◽

Research Questions ◽

Negative Implication

In a study of forty-three preschool children, ratings of four types of the children's imaginativeness were correlated with observational, behavioral, and interview measures. Research questions were: 1) Do correlates of imaginativeness found in observational studies replicate if trait rather than state measures are examined? 2) Do different types of imaginativeness have different correlates? and 3) What characteristics distinguish children at the maladaptive extremes of imaginativeness from those at more moderate levels? The conceptual and empirical utility of considering imaginativeness to have two dimensions, Expressive and Constructive, was demonstrated. While optimal levels of Constructive Imaginativeness correlated significantly with other indices of healthy child development, the correlations were fewer and tended to be weaker for Expressive Imaginativeness. The negative implication of extremes was documented.

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Sociodemographic, health and lifestyle characteristics reported by discrete groups of adult dietary supplement users in Alberta, Canada: findings from The Tomorrow Project

Public Health Nutrition ◽

10.1017/s136898000800219x ◽

2008 ◽

Vol 11 (12) ◽

pp. 1238-1247 ◽

Cited By ~ 20

Author(s):

Paula J Robson ◽

Geraldine Lo Siou ◽

Ruth Ullman ◽

Heather E Bryant

Keyword(s):

Dietary Supplement ◽

Observational Studies ◽

Multinomial Logistic Regression ◽

Discrete Groups ◽

Cross Sectional ◽

Supplement Use ◽

Random Digit ◽

Different Types ◽

Study Population ◽

Random Digit Dialling

AbstractObjectiveTo determine the extent to which differences in sociodemographic, dietary and lifestyle characteristics exist between users of different types of dietary supplements and supplement non-users.DesignWe analysed cross-sectional data obtained from self-administered questionnaires completed at baseline by participants in The Tomorrow Project; a prospective cohort study in Alberta, Canada. Participants who used at least one type of dietary supplement at least weekly in the year prior to questionnaire completion were defined as supplement users, while the remainder were classified as non-users. Seven discrete user categories were created: multivitamins (+/− minerals) only, specific nutritional supplements only, herbal/other supplements only, and all possible combinations. Differences in sociodemographic, dietary and lifestyle characteristics between different groups of supplement users and non-users were analysed using Rao–Scottχ2tests and multinomial logistic regression.Subjects and settingSubjects were 5067 men and 7439 women, aged 35–69 years, recruited by random digit dialling throughout Alberta.ResultsSupplement use was extensive in this study population (69·8 %). Users of herbal/other supplements only, and women who used multivitamins only, tended to report dietary and lifestyle characteristics that were not significantly different from non-users. In contrast, those who reported using a combination of multivitamins, specific nutritional and herbal/other supplements were more likely than non-users to report behaviours and characteristics consistent with current health guidelines.ConclusionsDichotomizing participants as supplement users or non-users is likely to mask further differences in sociodemographic, dietary and lifestyle characteristics among users of different types of supplements. This may have implications for analysis and interpretation of observational studies.

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AN UNUSUAL CASE OF NEW ONSET NEPHROPATHY IN A PATIENT OF PSORIASIS: CASE REPORT AND REVIEW OF LITERATURE

10.36106/ijsr/8400474 ◽

2021 ◽

pp. 13-14

Author(s):

VPS Punia ◽

Apoorva Shetty ◽

Prashant Prashant ◽

Akash Bharti ◽

Praveen Raman Mishra ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Case Report ◽

Male Patient ◽

Renal Damage ◽

Unusual Case ◽

Review Of Literature ◽

Immune Mediated ◽

Different Types ◽

Glomerular Lesions ◽

New Onset

Psoriasis is known to cause chronic inammatory disorder of the skin through an immune mediated mechanism, it may be complicated by different types of glomerular lesions. Three different mechanisms have been implicated by which psoriasis can cause renal damage: immune-mediated renal damage, drug-related renal damage and chronic renal damage. This report presents a case of 35 years old male patient with extensive psoriasis, who presented to our hospital with nephrotic syndrome

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Blood Pressure Response to Zofenopril or Irbesartan Each Combined with Hydrochlorothiazide in High-Risk Hypertensives Uncontrolled by Monotherapy: A Randomized, Double-Blind, Controlled, Parallel Group, Noninferiority Trial

International Journal of Hypertension ◽

10.1155/2015/139465 ◽

2015 ◽

Vol 2015 ◽

pp. 1-12 ◽

Cited By ~ 5

Author(s):

Ettore Malacco ◽

Stefano Omboni ◽

Gianfranco Parati

Keyword(s):

Blood Pressure ◽

Renal Damage ◽

Blood Pressure Response ◽

Target Organ Damage ◽

Organ Damage ◽

Target Organ ◽

Double Blind ◽

Treatment Groups ◽

Parallel Group ◽

Plaque Regression

In this randomized, double-blind, controlled, parallel group study (ZENITH), 434 essential hypertensives with additional cardiovascular risk factors, uncontrolled by a previous monotherapy, were treated for 18 weeks with zofenopril 30 or 60 mg plus hydrochlorothiazide (HCTZ) 12.5 mg or irbesartan 150 or 300 mg plus HCTZ. Rate of office blood pressure (BP) response (zofenopril: 68% versus irbesartan: 70%;p=0.778) and 24-hour BP response (zofenopril: 85% versus irbesartan: 84%;p=0.781) was similar between the two treatment groups. Cardiac and renal damage was equally reduced by both treatments, whereas the rate of carotid plaque regression was significantly larger with zofenopril. In conclusion, uncontrolled monotherapy treated hypertensives effectively respond to a combination of zofenopril or irbesartan plus a thiazide diuretic, in terms of either BP response or target organ damage progression.

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Correlations of Expression Levels of a Panel of Genes (IRF5, STAT4, TNFSF4, MECP2, and TLR7) and Cytokine Levels (IL-2, IL-6, IL-10, IL-12, IFN-γ, and TNF-α) with Systemic Lupus Erythematosus Outcomes in Jordanian Patients

BioMed Research International ◽

10.1155/2019/1703842 ◽

2019 ◽

Vol 2019 ◽

pp. 1-11 ◽

Cited By ~ 2

Author(s):

Amal H. Uzrail ◽

Areej M. Assaf ◽

Shtaywy S. Abdalla

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Renal Damage ◽

Organ Damage ◽

Systemic Lupus ◽

Expression Levels ◽

Cardiovascular Damage ◽

Tnf Α ◽

Cytokine Levels ◽

Ifn Γ

Systemic lupus erythematosus (SLE) is characterized by systemic end-organ damage. We investigated the involvement of IRF5, TLR-7, MECP2, STAT4, and TNFSF4 genes and TNF-α, IFN-γ, IL-2, IL-12, IL-6, and IL-10 cytokines in SLE pathogenesis and in organ damage in Jordanian patients. Blood was collected from 51 patients and 50 controls. Expression levels of SLE genes in PBMCs and cytokine levels were determined using RT-PCR and ELISA, respectively. Expression levels of all genes and levels of TNF-α, IL-12, IL-6, and IL-10 were higher in SLE patients than those in controls (p<0.05), whereas IL-2 level was lower. High STAT4 (α), TNFSF4, and IL-10 levels correlated with cardiovascular damage, and high MECP2 (α) and TNF-α correlated with renal damage. Pulmonary and musculoskeletal damages correlated with high levels of TNFSF4. We concluded that STAT4 and TNFSF4 genes with TNF-α and IL-10 cytokines could be used as biomarkers to assess SLE activity and manage treatment.

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Biomarkers and outcomes of COVID-19 hospitalisations: systematic review and meta-analysis

BMJ evidence-based medicine ◽

10.1136/bmjebm-2020-111536 ◽

2020 ◽

pp. bmjebm-2020-111536

Author(s):

Preeti Malik ◽

Urvish Patel ◽

Deep Mehta ◽

Nidhi Patel ◽

Raveena Kelkar ◽

...

Keyword(s):

Systematic Review ◽

Observational Studies ◽

Clinical Decision Making ◽

Meta Analysis ◽

Severe Disease ◽

Invasive Mechanical Ventilation ◽

Mesh Terms ◽

Hospitalised Patients ◽

Poor Outcomes ◽

D Dimer

ObjectiveTo evaluate association between biomarkers and outcomes in COVID-19 hospitalised patients. COVID-19 pandemic has been a challenge. Biomarkers have always played an important role in clinical decision making in various infectious diseases. It is crucial to assess the role of biomarkers in evaluating severity of disease and appropriate allocation of resources.Design and settingSystematic review and meta-analysis. English full text observational studies describing the laboratory findings and outcomes of COVID-19 hospitalised patients were identified searching PubMed, Web of Science, Scopus, medRxiv using Medical Subject Headings (MeSH) terms COVID-19 OR coronavirus OR SARS-CoV-2 OR 2019-nCoV from 1 December 2019 to 15 August 2020 following Meta-analyses Of Observational Studies in Epidemiology (MOOSE) guidelines.ParticipantsStudies having biomarkers, including lymphocyte, platelets, D-dimer, lactate dehydrogenase (LDH), C reactive protein (CRP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, procalcitonin (PCT) and creatine kinase (CK), and describing outcomes were selected with the consensus of three independent reviewers.Main outcome measuresComposite poor outcomes include intensive care unit admission, oxygen saturation <90%, invasive mechanical ventilation utilisation, severe disease, in-hospital admission and mortality. The OR and 95% CI were obtained and forest plots were created using random-effects models. Publication bias and heterogeneity were assessed by sensitivity analysis.Results32 studies with 10 491 confirmed COVID-19 patients were included. We found that lymphopenia (pooled-OR: 3.33 (95% CI: 2.51–4.41); p<0.00001), thrombocytopenia (2.36 (1.64–3.40); p<0.00001), elevated D-dimer (3.39 (2.66–4.33); p<0.00001), elevated CRP (4.37 (3.37–5.68); p<0.00001), elevated PCT (6.33 (4.24–9.45); p<0.00001), elevated CK (2.42 (1.35–4.32); p=0.003), elevated AST (2.75 (2.30–3.29); p<0.00001), elevated ALT (1.71 (1.32–2.20); p<0.00001), elevated creatinine (2.84 (1.80–4.46); p<0.00001) and LDH (5.48 (3.89–7.71); p<0.00001) were independently associated with higher risk of poor outcomes.ConclusionOur study found a significant association between lymphopenia, thrombocytopenia and elevated levels of CRP, PCT, LDH, D-dimer and COVID-19 severity. The results have the potential to be used as an early biomarker to improve the management of COVID-19 patients, by identification of high-risk patients and appropriate allocation of healthcare resources in the pandemic.

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Therapeutic Potential of Extracellular Vesicles in Hypertension-Associated Kidney Disease

Hypertension ◽

10.1161/hypertensionaha.120.16064 ◽

2021 ◽

Vol 77 (1) ◽

pp. 28-38

Author(s):

Olga Martinez-Arroyo ◽

Ana Ortega ◽

Josep Redon ◽

Raquel Cortes

Keyword(s):

Kidney Disease ◽

Extracellular Vesicles ◽

Renal Damage ◽

Therapeutic Potential ◽

Cell Communication ◽

Cell Types ◽

Organ Damage ◽

Renal Diseases ◽

Biological Processes ◽

Potential Use

Hypertension-mediated organ damage frequently includes renal function decline in which several mechanisms are involved. The present review outlines the state of the art on extracellular vesicles in hypertension and hypertension-related renal damage. Emerging evidence indicates that extracellular vesicles, small vesicles secreted by most cell types and body fluids, are involved in cell-to-cell communication and are key players mediating biological processes such as inflammation, endothelial dysfunction or fibrosis, mechanisms present the onset and progression of hypertension-associated kidney disease. We address the potential use of extracellular vesicles as markers of hypertension-mediated kidney damage severity and their application as therapeutic agents in hypertension-associated renal damage. The capacity of exosomes to deliver a wide variety of cargos to the target cell efficiently makes them a potential drug delivery system for treatment of renal diseases.

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Hydroxyurea for β-Thalassemia Major: A Meta-Analysis

Blood ◽

10.1182/blood.v124.21.4894.4894 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4894-4894 ◽

Cited By ~ 1

Author(s):

Ali H. Algiraigri ◽

Nicola A. Wright ◽

Aliya Kassam

Keyword(s):

Sample Size ◽

Clinical Efficacy ◽

Observational Studies ◽

Response Rate ◽

Meta Analysis ◽

Thalassemia Major ◽

Organ Damage ◽

Controlled Trials ◽

Cochrane Central Register

Abstract Background β-thalassemia major (β-TM) is one of the most common inherited diseases worldwide, characterized by a reduced ability to produce hemoglobin resulting in life-long transfusion-dependent anemia. Chronic transfusions carry significant risks such as infection, and result in iron overload that can cause significant multisystem organ damage. Hydroxyurea, an oral chemotherapeutic drug, is anticipated to decrease the need for transfusions, either completely or partially by raising hemoglobin levels and thus decreasing the short and long term complications of chronic transfusions. Objectives To evaluate the clinical efficacy and safety of hydroxyurea in β-thalassemia major (β-TM) patients of any age. Search strategy We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), ongoing trials registers, and major preceding conferences. Hand searches were also conducted using reference lists from primary studies. All searches were updated to June 5, 2014. Selection criteria Randomized controlled trials (RCTs) and observational studies (sample size ≥ 5) assessing the clinical efficacy of hydroxyurea alone for three months or longer, for the treatment of patients with β-TM were included. Data collection and analysis Two authors acted as reviewers and independently assessed study quality and extracted data from the included studies. Authors of included studies were contacted if further information was required. β-TM includes the classical β-TM as well as severe hemoglobin E/β thalassemia, both of which are characterized by lifelong transfusion needs. The effect size was estimated as a proportion (those showing response to treatment over the total number treated) and reported as overall response rate (ORR) or complete response rate (CRR). ORR was defined as ≥ 50% reduction in transfusion need and CRR was defined as complete cessation of regular transfusion. All data was analyzed using Stata, Version 13.0. Results A total of 10 observational studies involving 620 patients were included. Hydroxyurea was associated with a statistically significant decrease in transfusion need with CRR of 36% (95% CI, 23-50%) and ORR of 66% (95% CI, 52-79%). All of the studies had several limitations, such as small sample size, lack of comparison group, under-reporting of data and methods, and being observational studies. Adverse events (AEs) were transient and improved with temporary cessation of the drug and/or adjustment of the dose. No long-term AEs, including cancer or end organ damage were reported. Authors’ conclusion Hydroxyurea appears to be effective in the management of β-TM by decreasing the need for chronic blood transfusions completely or partially in a significant number of patients. It appears to be well tolerated and associated with mild and transient AEs. Patients with β-TM may benefit from a trial of hydroxyurea, though large RCTs assessing efficacy should be done to confirm the findings of this meta-analysis. Disclosures Off Label Use: Hydroxyurea for β-Thalassemia.

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