scholarly journals Myocardial Injury in Post Mortem Biopsies of Patients with COVID-19

2020 ◽  
Author(s):  
Camila Hartmann ◽  
Anna Flavia dos Santos Miggiolaro ◽  
Jarbas da Silva Motta Junior ◽  
Lucas Baena Carstens ◽  
Caroline Busatta Vaz De Paula ◽  
...  
Keyword(s):  
Myocardial Injury ◽  
Histopathological Analysis ◽  
Interstitial Edema ◽  
Th2 Response ◽  
Caspase 1 ◽  
Tnf Α ◽  
Pathogenesis Related ◽  
Type 3

Abstract Background: Myocardial injury is significantly and independently associated with mortality in COVID-19 patients. However, the pathogenesis of myocardial injury in COVID-19 is still not clear, and cardiac involvement by SARS-CoV-2 remains a major challenge worldwide.Aim: This histopathological and immunohistochemical study seeks to clarify the pathogenesis of myocardial injury in COVID-19.Methods: Postmortem minimally invasive autopsies were performed in two patients who died from COVID-19, and the myocardium samples were compared to a control patient. Immunohistochemistry (IHC) staining was performed using monoclonal antibodies against the following targets: caspase-1, ICAM-1, TNF-α, IL-4, IL-6, CD163, TGF-β, MMP-9, type 1 and type 3 collagen.Results: The histopathological analysis showed severe pericellular interstitial edema surrounding each of the cardiomyocytes. The IHC analysis showed increased expression of caspase-1, ICAM-1, IL-4, IL-6, CD163, MMP-9 and type 3 collagen in the COVID-19 patients compared to the control. On the other hand, no difference from the control was observed in expression of TNF-α, TGF-β and type 1 collagen. Conclusion: Our findings point to a pathogenesis related with pyroptosis leading to endothelial disfunction. The subsequent inflammation with associated interstitial edema could explain the myocardial disfunction and arrythmias in COVID-19 patients. The presence of Th2 response, MMP-9 and type-3 collagen suggests progression to myocardial fibrosis in the long term.

scholarly journals The Pathogenisis of COVID-19 Myocardial Injury: an Immunohistochemical Study of Postmortem Biopsies 

2020 ◽  
Author(s):  
Camila Hartmann ◽  
Anna Flavia dos Santos Miggiolaro ◽  
Jarbas da Silva Motta Junior ◽  
Lucas Baena Carstens ◽  
Caroline Busatta Vaz De Paula ◽  
...  
Keyword(s):  
Myocardial Injury ◽  
Immunohistochemical Study ◽  
Tunel Assay ◽  
Blue Staining ◽  
Histopathological Analysis ◽  
Interstitial Edema ◽  
Caspase 1 ◽  
Tnf Α ◽  
Type 3

Abstract Rationale: Myocardial injury is significantly and independently associated with mortality in COVID-19 patients. However, the pathogenesis of myocardial injury in COVID-19 is still not clear, and cardiac involvement by SARS-CoV-2 remains a major challenge worldwide. Objective: This histopathological and immunohistochemical study seeks to clarify the pathogenesis and propose a mechanism with pathways involved in COVID-19 myocardial injury. Methods and Results: Postmortem minimally invasive autopsies were performed in six patients who died from COVID-19, and the myocardium samples were compared to a control patient. Histopathological analysis was performed using hematoxylin-eosin and toluidine blue staining. Immunohistochemical (IHC) staining was performed using monoclonal antibodies against the following targets: caspase-1, ICAM-1, TNF-α, IL-4, IL-6, CD163, TGF-β, MMP-9, type 1 and type 3 collagen. The samples were also subjected to a TUNEL assay to detect potential apoptosis. The histopathological analysis showed severe pericellular interstitial edema surrounding each of the cardiomyocytes and higher mast cells count by high-power field in all COVID-19 myocardium samples. The IHC analysis showed increased expression of caspase-1, ICAM-1, IL-4, IL-6, CD163, MMP-9 and type 3 collagen in the COVID-19 patients compared to the control. No difference from the control was observed in expression of TNF-α, TGF-β and type 1 collagen. The TUNEL assay was positive in all the COVID-19 samples confirming the presence of endothelial apoptosis. Conclusions: The pathogenesis of COVID-19 myocardial injury seems to be related with pyroptosis leading to endothelial cell injury and disfunction. The subsequent inflammation with associated interstitial edema could explain the myocardial disfunction and arrythmias in these patients. Our findings also show that COVID-19 myocardial injury may cause myocardial fibrosis in the long term. These patients should be monitored for myocardial dysfunction and arrythmias after the acute phase of COVID-19.

scholarly journals The Pathogenesis of COVID-19 Myocardial Injury: An Immunohistochemical Study of Postmortem Biopsies

2021 ◽  
Vol 12 ◽  
Author(s):  
Camila Hartmann ◽  
Anna Flavia Ribeiro dos Santos Miggiolaro ◽  
Jarbas da Silva Motta ◽  
Lucas Baena Carstens ◽  
Caroline Busatta Vaz De Paula ◽  
...  
Keyword(s):  
Myocardial Injury ◽  
Histological Analysis ◽  
Immunohistochemical Study ◽  
Myocardial Dysfunction ◽  
Blue Staining ◽  
Control Group ◽  
Caspase 9 ◽  
Interstitial Edema ◽  
Caspase 1 ◽  
Tnf Α

RationaleMyocardial injury associates significantly and independently with mortality in COVID-19 patients. However, the pathogenesis of myocardial injury in COVID-19 remains unclear, and cardiac involvement by SARS-CoV-2 presents a major challenge worldwide.ObjectiveThis histological and immunohistochemical study sought to clarify the pathogenesis and propose a mechanism with pathways involved in COVID-19 myocardial injury.Methods and ResultsPostmortem minimally invasive autopsies were performed in six patients who died from COVID-19, and the myocardium samples were compared to a control group (n=11). Histological analysis was performed using hematoxylin-eosin and toluidine blue staining. Immunohistochemical (IHC) staining was performed using monoclonal antibodies against targets: caspase-1, caspase-9, gasdermin-d, ICAM-1, IL-1β, IL-4, IL-6, CD163, TNF-α, TGF-β, MMP-9, type 1 and type 3 collagen. The samples were also assessed for apoptotic cells by TUNEL. Histological analysis showed severe pericardiocyte interstitial edema and higher mast cells counts per high-power field in all COVID-19 myocardium samples. The IHC analysis showed increased expression of caspase-1, ICAM-1, IL-1β, IL-6, MMP-9, TNF-α, and other markers in the hearts of COVID-19 patients. Expression of caspase-9 did not differ from the controls, while gasdermin-d expression was less. The TUNEL assay was positive in all the COVID-19 samples supporting endothelial apoptosis.ConclusionsThe pathogenesis of COVID-19 myocardial injury does not seem to relate to primary myocardiocyte involvement but to local inflammation with associated interstitial edema. We found heightened TGF-β and interstitial collagen expression in COVID-affected hearts, a potential harbinger of chronic myocardial fibrosis. These results suggest a need for continued clinical surveillance of patients for myocardial dysfunction and arrythmias after recovery from the acute phase of COVID-19.

Maintenance Efficacy of Low Dose Imiglucerase for Gaucher Disease

2020 ◽  
Author(s):  
Zhengqing Qiu ◽  
Baohui Zhang ◽  
Yuhang Song ◽  
Hongbing Zhang ◽  
Yuting Wu
Keyword(s):  
Gaucher Disease ◽  
Low Dose ◽  
Standard Dose ◽  
Mineral Density ◽  
Recommended Treatment ◽  
Type 3 ◽  
Term Maintenance

Abstract Background Imiglucerase is the recommended treatment for Gaucher disease (GD), a hereditary metabolic disease. In high risk adults and all children, the minimum recommended dose for long-term maintenance is 30 U/kg/2 weeks. However, the extremely high cost of this enzyme largely hinders its clinical use. The minimal maintenance dose of imiglucerase has thus been a subject of debate. We aimed to analyze the long-term maintenance outcomes of imiglucerase at dosage < 20 U/kg/2 weeks after standard dose. Methods Seventeen patients with GD type 1 or GD type 3 were enrolled for analysis. We evaluated maintenance efficacy of imiglucerase on hemoglobin, platelet, visceral volumes and bone conditions during the 7-year follow-up. Results Parameters on hemoglobin, platelet, liver, and spleen volumes of all patients were stabilized or improved. Seven out of 14 patients showed bone mineral density improvement. Three out of 16 patients showed worse bone pain; 6 out of 15 patients showed worse Erlenmeyer flask; 6 out of 15 patients showed worse bone infarction; 1 out of 16 patients showed worse marrow infiltration and 3 out of 15 patients showed worse osteonecrosis. Conclusions Imiglucerase less than 20 U/kg/2 weeks is enough to maintain blood and visceral parameters, but is not sufficient to stabilize skeletal conditions.

scholarly journals Sustainable Development of the Steppe in the Region of El Bayadh, Approach to a New Fattening System

2020 ◽  
pp. 30-37
Author(s):  
Mekhloufi Moulay Brahim ◽  
Mohamed Khader ◽  
Tayeb Nouri ◽  
Mahari Latifa
Keyword(s):  
Sampling Method ◽  
Farming Systems ◽  
Breeding Systems ◽  
Short Term ◽  
Land Use Patterns ◽  
Use Patterns ◽  
Type 3

The objective of this research is to follow the evolution and sustainability of the natural resource management systems adopted by different breeders found in the Al Bayadh region in Algeria. Using a stratified sampling method, 52 farms were surveyed between 2010 and 2015 to capture the diversity of farming systems and identify changes in land use patterns. The findings of the research reveal a predominance of sedentary and semi-transhumant farming systems with a sharp decline in nomadism. This study enabled us to identify three types of breeding: sedentary breeding systems with short-term fattening (type 1), semi-sedentary systems with medium-term fattening (type 2), and transhumant/nomadic systems with long-term fattening (type 3) that therefore reflect a diversity of actions in the management of the risk that threaten livestock production.

Hereditary and acquired angioedema

2019 ◽  
Vol 40 (6) ◽  
pp. 441-445 ◽  
Author(s):  
Gayatri Patel ◽  
Jacqueline A. Pongracic
Keyword(s):  
Factor Xii ◽  
Autosomal Dominant Disorder ◽  
Acquired Angioedema ◽  
Enzyme Replacement ◽  
Life Threatening ◽  
Type 3 ◽  
Esterase Inhibitor

Hereditary angioedema (HAE) is an autosomal dominant disorder defined by a deficiency of functional C1 esterase inhibitor (C1-INH). Acquired angioedema is due to either consumption (type 1) or inactivation (type 2) of CI-INH. Both HAE and acquired angioedema can be life-threatening. Of the three types of HAE, type 1 is most common, occurring in approximately 85% of patients and characterized by decreased production of C1-INH, which results in reduced functional activity to 5‐40% of normal. Type 2 occurs in 15% of cases; C1-INH is detectable in normal or elevated quantities but is dysfunctional. Also, HAE with normal CI-INH (previously called type 3 HAE) is rare and characterized by normal complement studies. Specific genetic mutations have been linked to factor XII, angiopoietin-1, and plasminogen gene. Patients with unknown mutations are classified as unknown. The screening test for types 1 and 2 is complement component C4, which is low to absent at times of angioedema and during quiescent periods. A useful test to differentiate HAE from acquired angioedema is C1q protein, which is normal in HAE and low in acquired angioedema. The management of HAE has been transformed with the advent of disease-specific therapies. On-demand therapy options include plasma and recombinant C1-INH for intravenous infusion; ecallantide, an inhibitor of kallikrein; and icatibant, a bradykinin β2 receptor antagonist, both administered subcutaneously. For long-term prophylaxis, intravenous or subcutaneous C1-INH enzyme replacement and lanadelumab, a monoclonal antibody against kallikrein that is administered subcutaneously, are effective agents.

scholarly journals Management of acute intestinal failure

2011 ◽  
Vol 70 (3) ◽  
pp. 321-328 ◽  
Author(s):  
Keith R. Gardiner
Keyword(s):  
Intestinal Failure ◽  
Intestinal Resection ◽  
Nutrition Support ◽  
Metabolic Disturbances ◽  
Hospital Transfer ◽  
Type 3 ◽  
Intestinal Absorptive Function

Intestinal failure (IF) occurs when intestinal absorptive function is inadequate to maintain hydration and nutrition without enteral or parenteral supplements. It has been classified into three types depending on duration of nutrition support and reversibility. Type 1 IF is commonly seen in the peri-operative period as ileus and usually spontaneously resolves within 14 d. Type 2 IF is uncommon and is often associated with an intra-abdominal catastrophe, intestinal resection, sepsis, metabolic disturbances and undernutrition. Type 3 IF is a chronic condition in a metabolically stable patient, which usually requires long-term parenteral nutrition. This paper focuses on Types 1 and 2 IF (or acute IF) that are usually found in surgical wards. The objectives of this paper are to review the incidence, aetiology, prevention, management principles and outcome of acute IF. The paper discusses the resources necessary to manage acute IF, the indications for inter-hospital transfer and the practicalities of how to transfer and receive a patient with acute IF.

Association of TNF-α and PTPN22 SNPs with the risk and clinical outcome of type 1 diabetes

2013 ◽  
Vol 8 (6) ◽  
pp. 513-519
Author(s):  
Marijana Hadžija ◽  
Marina Korolija ◽  
Gabrijela Vukadinović ◽  
Mirko Hadžija
Keyword(s):  
Type 1 Diabetes ◽  
Clinical Outcome ◽  
Bosnia And Herzegovina ◽  
Gain Of Function ◽  
Tnf Α ◽  
Pcr Rflp ◽  
Diabetes Development ◽  
1858T Allele

AbstractType 1 Diabetes mellitus (T1DM) begins with aberrant inflammatory process followed by auto-destruction in genetically susceptible individuals. Therefore, we hypothesized that gain-of-function allelic variants TNF-α-238A, -308A and PTPN22 1858T could be associated not only with T1DM development but also with the clinical outcome in patients of Bosnia and Herzegovina. A total of 402 subjects were enrolled in the association study. SNPs were determined by PCR-RFLP. Data was analyzed by GraphPad Prism and Sigma Stat 3.5 software. Genotypes frequencies at TNF-α-238 and -308 loci were not statistically different between patients and controls. In contrast, distribution of genotypes at the 1858 position of PTPN22 was significantly different, due to higher frequency of gain-of-function gene variants in patients than controls. Moreover, long term glucose regulation (based on HbA1c level) was significantly worse in patients with the risk TNF-α-308A allele than in patients with non-risk (G) allele. However, patients with the risk allele of both genes (TNF-α-308A and PTPN22 1858T) had the worst glycemic control, suggesting that those two work synergistically. In conclusion, in a cohort from Bosnia and Herzegovina TNF-α-308A allele is significantly associated with the worse long-term glucose control, but PTPN22 1858T allele is significantly associated with diabetes development.

Long-Term Outlook Improving for Type 1 Patients

2008 ◽  
Vol 38 (21) ◽  
pp. 14
Author(s):  
MIRIAM E. TUCKER
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