scholarly journals APOE ε4 associates with increased risk of severe COVID-19, cerebral microhaemorrhages and post-COVID mental fatigue: a Finnish biobank, autopsy and clinical study

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Samu N. Kurki ◽  
Jonas Kantonen ◽  
Karri Kaivola ◽  
Laura Hokkanen ◽  
Mikko I. Mäyränpää ◽  
...  
Keyword(s):  
Histopathological Examination ◽  
Clinical Manifestations ◽  
Disease Status ◽  
Mental Fatigue ◽  
Genetic Studies ◽  
Intensive Care Patients ◽  
Clinical Cohort ◽  
Increased Risk ◽  
Increased Susceptibility

AbstractApolipoprotein E ε4 allele (APOE4) has been shown to associate with increased susceptibility to SARS-CoV-2 infection and COVID-19 mortality in some previous genetic studies, but information on the role of APOE4 on the underlying pathology and parallel clinical manifestations is scarce. Here we studied the genetic association between APOE and COVID-19 in Finnish biobank, autopsy and prospective clinical cohort datasets. In line with previous work, our data on 2611 cases showed that APOE4 carriership associates with severe COVID-19 in intensive care patients compared with non-infected population controls after matching for age, sex and cardiovascular disease status. Histopathological examination of brain autopsy material of 21 COVID-19 cases provided evidence that perivascular microhaemorrhages are more prevalent in APOE4 carriers. Finally, our analysis of post-COVID fatigue in a prospective clinical cohort of 156 subjects revealed that APOE4 carriership independently associates with higher mental fatigue compared to non-carriers at six months after initial illness. In conclusion, the present data on Finns suggests that APOE4 is a risk factor for severe COVID-19 and post-COVID mental fatigue and provides the first indication that some of this effect could be mediated via increased cerebrovascular damage. Further studies in larger cohorts and animal models are warranted.

scholarly journals DDAH gene and cardiovascular risk

2005 ◽  
Vol 10 (1_suppl) ◽  
pp. S45-S48 ◽  
Author(s):  
Veli-Pekka Valkonen ◽  
Tomi-Pekka Tuomainen ◽  
Reijo Laaksonen
Keyword(s):  
Cardiovascular Risk ◽  
Cardiovascular Diseases ◽  
High Plasma ◽  
No Synthase ◽  
Clinical Role ◽  
Plasma Adma ◽  
Increased Risk ◽  
Major Route ◽  
Increased Susceptibility

The crucial role of nitric oxide (NO) for normal endothelial function is well known. In many conditions associated with increased risk of cardiovascular diseases such as hypercholesterolemia, hypertension, abdominal obesity, diabetes and smok ing, NO biosynthesis is dysregulated, leading to endothelial dysfunction. The grow ing evidence from animal and human studies indicates that endogenous inhibitors of endothelial NO synthase such as asymmetric dimethylarginine (ADMA) and NG-monomethyl-L-arginine (L-NMMA) are associated with the endothelial dysfunc tion and potentially regulate NO synthase. The major route of elimination of ADMA is metabolism by the enzymes dimethylarginine dimethylaminohydrolase-1 and -2 (DDAH). In our recent study 16 men with either low or high plasma ADMA concen trations were screened to identify DDAH polymorphisms that could potentially be associated with increased susceptibility to cardiovascular diseases. In that study a novel functional mutation of DDAH-1 was identified; the mutation carriers had a significantly elevated risk for cardiovascular disease and a tendency to develop hypertension. These results confirmed the clinical role of DDAH enzymes in ADMA metabolism. Furthermore, it is possible that more common variants of DDAH genes contribute more widely to increased cardiovascular risk.

scholarly journals Sarcoidosis: Causes, Diagnosis, Clinical Features, and Treatments

2020 ◽  
Vol 9 (4) ◽  
pp. 1081 ◽  
Author(s):  
Rashi Jain ◽  
Dhananjay Yadav ◽  
Nidhi Puranik ◽  
Randeep Guleria ◽  
Jun-O Jin
Keyword(s):  
Clinical Features ◽  
Histopathological Examination ◽  
Clinical Manifestations ◽  
Endobronchial Ultrasound ◽  
Unknown Etiology ◽  
High Resolution Computed Tomography ◽  
Positron Emission ◽  
Increased Risk ◽  
Night Sweats ◽  
Spleen And Lymph Nodes

Sarcoidosis is a multisystem granulomatous disease with nonspecific clinical manifestations that commonly affects the pulmonary system and other organs including the eyes, skin, liver, spleen, and lymph nodes. Sarcoidosis usually presents with persistent dry cough, eye and skin manifestations, weight loss, fatigue, night sweats, and erythema nodosum. Sarcoidosis is not influenced by sex or age, although it is more common in adults (< 50 years) of African-American or Scandinavians decent. Diagnosis can be difficult because of nonspecific symptoms and can only be verified following histopathological examination. Various factors, including infection, genetic predisposition, and environmental factors, are involved in the pathology of sarcoidosis. Exposures to insecticides, herbicides, bioaerosols, and agricultural employment are also associated with an increased risk for sarcoidosis. Due to its unknown etiology, early diagnosis and detection are difficult; however, the advent of advanced technologies, such as endobronchial ultrasound-guided biopsy, high-resolution computed tomography, magnetic resonance imaging, and 18F-fluorodeoxyglucose positron emission tomography has improved our ability to reliably diagnose this condition and accurately forecast its prognosis. This review discusses the causes and clinical features of sarcoidosis, and the improvements made in its prognosis, therapeutic management, and the recent discovery of potential biomarkers associated with the diagnostic assay used for sarcoidosis confirmation.

HHV6 Specific T-Cells Are Predictive Biomarker of Active HHV6 Infection after Allogeneic Hematopoietic Stem Cell Transplantation: Results of a Prospective Study in 213 Patients

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3399-3399
Author(s):  
Raffaella Greco ◽  
Maddalena Noviello ◽  
Lara Crucitti ◽  
Sara Racca ◽  
Veronica Valtolina ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Clinical Manifestations ◽  
Disease Status ◽  
Hematopoietic Stem ◽  
Cmv Reactivation ◽  
Active Disease

Abstract BACKGROUND: Although Human herpesvirus 6 (HHV6) reactivation in healthy individuals usually occurs without significant morbidity, in recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is associated with severe clinical manifestations and increased transplant-related mortality (TRM). The role of HHV6 in transplant-related complications remains in question, considering that both latent and active viral infection can occur. Moreover, only limited experiences are reported on HHV6-specific immune responses after HSCT, and their correlation with clinical outcome is largely unexplored. METHODS: From February 2013 to October 2015, we conducted a prospective observational study to investigate HHV6 reactivation in 213 consecutive adult patients (median age 52 years) who received allo-HSCT for high-risk hematological malignancies (57% acute leukemia) in our institute. Stem cell donors were family haploidentical (104), HLA identical sibling (39), unrelated (63), cord blood (7). Stem cell source was mainly T-cell replete PBSCs (87%). Viral load was weekly monitored by quantitative PCR in plasma within the first month after HSCT. Numbers of IFNγ-producing HHV6-T-cells were determined by enzyme-linked immunospot assay (ELISPOT). We challenged patients PBMC against a library of overlapping peptides covering the entire sequence of the immunodominant virus protein U54, expressed during the lytic cycle of virus replication. Patients were evaluated at a median of 34 days after HSCT (HHV6-; 57 patients) for controls or by the 4th day after the first HHV6 DNAemia (median 32 days) for reactivating patients (HHV-6+; 54 patients). RESULTS: HHV6-reactivation occurred in 56% of patients at 100 days, with a median time of 28 days after HSCT. HHV6 was detected in plasma for 86% of patients, while 33% resulted positive in other materials: 9 BM aspirates, 39 gut biopsies, 3 BAL, 5 CSF. All patients received acyclovir as prophylaxis. Only 41% of reactivating patients presented a clinically relevant HHV6 infection (HHV6 positivity in presence of HHV6-related clinical symptoms and/or HHV6-disease). Clinical manifestations were: fever (25), skin rash (37), hepatitis (19), diarrhoea (28), encephalitis (5), BM suppression (30). According to center guidelines, antiviral treatment was given in 23% of reactivating patients, for uncontrolled clinically relevant HHV6 infection. Overall survival (OS) was not different in HHV6 reactivating patients compared to controls (p=0,2). Relapse incidence and TRM were not affected by HHV6. All HSCT recipients showed a better OS with CD3+ cells≥200/mcl at 30 days (p <0.001), independently of HHV6. In univariate analysis, we identified the following risk factors for HHV6-reactivation: active disease status before HSCT (p=0,052), haploidentical HSCT (p=0,003), PT-Cy use (p <0.001), CMV reactivation (p=0,001), GvHD (p=0,003), CD3+ cells<200/mcl at 30 days (p=0,013). The number of IFNγ-producing HHV6-specific T-cells was significantly higher in HHV6 reactivating patients (p= 0.0149; mean number of specific T-cells 43.48 per 10^5 PBMC) than in non-reactivating patients (specific T-cells 12.57 per 10^5 PBMC), especially in the presence of active and clinically relevant HHV6 infection (p<0,0001; mean number of specific T-cells 81.46 per 10^5 PBMC). No influence of IFNγ-producing CMV specific T-cells, absolute counts of CD3+ T cells or GvHD was observed. CONCLUSIONS: In this study, we observed that active disease status before HSCT, haploidentical donors, especially using PT-Cy, CMV reactivation, GvHD and lower CD3+ counts at 30 days, are strong predictors of HHV6 reactivation. HHV6-specific T-cells, detectable by ELISPOT assay despite extremely low T-cell numbers and immunosuppressive therapy, are significantly associated with active and clinically relevant HHV6 infections, representing a new and promising tool to unravel the role of HHV6 positivity in allo-HSCT recipients. Disclosures Ciceri: MolMed SpA: Consultancy. Bonini:TxCell: Membership on an entity's Board of Directors or advisory committees; Molmed SpA: Consultancy.

Cardiovascular Disease

2018 ◽  
Author(s):  
Mara Caroline ◽  
Ryan Bradley ◽  
Mimi Guarneri
Keyword(s):  
Cardiovascular Disease ◽  
Elderly Population ◽  
Cardiovascular Health ◽  
The Elderly ◽  
Nutrient Deficiencies ◽  
Comorbid Conditions ◽  
Increased Risk ◽  
Increased Susceptibility

The older population is challenging to treat for numerous reasons, including comorbid conditions and increased susceptibility to adverse drug reactions, limiting medical therapy. They are at increased risk for loneliness and depression, which strongly impacts their cardiovascular outcomes, and they also have different values, usually prioritizing quality of life over mortality objectives. Finally, the elderly are underrepresented in cardiovascular clinical trials, thus limiting the applicability of guideline recommendations. This chapter emphasizes the importance of a comprehensive assessment of individual circumstances when assessing cardiovascular health in the elderly population. The chapter focuses on the role of nutrition, resiliency, and exercise for the prevention and treatment of cardiovascular disease. Nutrient deficiencies commonly seen with cardiovascular drugs are also discussed, as well as specific integrative strategies for optimizing dyslipidemia, atrial fibrillation, and heart failure in this population.

scholarly journals T300A GENETIC POLYMORPHISM: a susceptibility factor for Crohn’s disease?

2014 ◽  
Vol 51 (2) ◽  
pp. 97-101 ◽  
Author(s):  
Bruno Lorenzo SCOLARO ◽  
Emily dos SANTOS ◽  
Leslie Ecker FERREIRA ◽  
Paulo Henrique Condeixa de FRANÇA ◽  
Harry KLEINUBING ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Fragment Length Polymorphism ◽  
Control Group ◽  
Polymorphism Analysis ◽  
Inflammatory Disorder ◽  
Increased Risk ◽  
Polymerase Chain ◽  
Increased Susceptibility

ContextCrohn’s disease is characterized by a chronic and debilitating inflammatory disorder of the gastrointestinal tract. Several factors may contribute to its development. From extensive studies of the human genome, the polymorphism T300A of the gene ATG16L1 (autophagy-related 16-like 1) has been related to increased risk of developing this disease.ObjectivesAnalyze the role of polymorphism T300A (rs2241880) in patients with Crohn’s disease.Methods238 samples from (control group) and 106 samples from patients with Crohn’s disease recruited at five Southern Brazilian reference centers were evaluated. The genotyping consisted of the amplification via Polymerase Chain Reaction of the genomic segment encompassing T300A, followed by Restriction Fragment Length Polymorphism analysis. The amplicons and fragments were separated by agarose gel electrophoresis and confirmed under ultraviolet light.ResultsThe genotype AG was more prevalent among patients and controls (50% vs 44.8%), followed by genotypes AA (26.4% vs 35.1%) and GG (23.6% vs 20.1%). The frequency of the allele G of the polymorphism T300A was higher in the group of patients with Crohn’s disease (48.6%) than in controls (42.4%), although not reaching statistical significance.ConclusionsIt was not possible to confirm the increased susceptibility on development of Crohn’s disease conferred by polymorphism T300A.

scholarly journals Seborrheic keratosis evolution into squamous cell carcinoma: A truly modified sun-related tumor? A case report and review of the literature

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Ioana Cimpean ◽  
Ivan Theate ◽  
Olivier Vanhooteghem
Keyword(s):  
Squamous Cell Carcinoma ◽  
Case Report ◽  
Malignant Transformation ◽  
Histopathological Examination ◽  
Clinical Manifestations ◽  
Immunocompromised Patients ◽  
Review Of The Literature ◽  
Seborrheic Keratosis ◽  
Increased Risk

The incidence of seborrheic keratosis (SK) generally increases with age and are mostly localized on the trunk, face and neck, especially on sun-exposed areas. The association between SK and skin malignancies appears to be accidental, but in situ transformation occurs more frequently in sun-exposed areas. Histopathological examination of all SK cases should be considered, especially when SK lesions exhibit atypical clinical manifestations, such as ulceration and cresting, as they may herald malignant transformation. In addition, other features associated with malignant transformation include excoriations or hemorrhages identified on the lesion, modification and evolution of the macroscopic characteristics, and the presence of local erythema or pruritus. Immunocompromised patients exhibit an increased risk of malignant transformation, even when radiation is involved.

scholarly journals Severity of COVID-19 at elevated exposure to perfluorinated alkylates

2020 ◽  
Author(s):  
Philippe Grandjean ◽  
Clara Amalie Gade Timmermann ◽  
Marie Kruse ◽  
Flemming Nielsen ◽  
Pernille Just Vinholt ◽  
...  
Keyword(s):  
Sampling Site ◽  
Disease Status ◽  
Industrial Chemicals ◽  
Ordered Logistic Regression ◽  
Increased Risk ◽  
Background Exposure ◽  
Study Population ◽  
Exposure Levels ◽  
Elevated Exposure

Background The course of coronavirus disease 2019 (COVID-19) seems to be aggravated by air pollution, and some industrial chemicals, such as the perfluorinated alkylate substances (PFASs), are immunotoxic and may contribute as well. Methods From Danish biobanks, we obtained plasma samples from 323 subjects aged 30-70 years with known SARS-CoV-2 infection. The PFAS concentrations measured at the background exposures included five PFASs known to be immunotoxic. Register data was obtained to classify disease status, other health information, and demographic variables. We used ordinal and ordered logistic regression analyses to determine associations between PFAS concentrations and disease outcome. Results Plasma-PFAS concentrations were higher in males, in subjects with Western European background, and tended to increase with age, but were not associated with the presence of chronic disease. Of the study population, 108 (33%) had not been hospitalized, and of those hospitalized, 53 (16%) had been in intensive care or were deceased. Among the five PFASs considered, perfluorobutanoic acid (PFBA) showed an odds ratio (OR) of 2.19 (95% confidence interval, CI, 1.39-3.46) for increasing severities of the disease, although the OR decreased to 1.77 (95% CI, 1.09, 2.87) after adjustment for age, sex, sampling site and interval between blood sampling and diagnosis. Conclusions Measures of individual exposures to immunotoxic PFASs included PFBA that accumulates in the lungs. Elevated plasma-PFBA concentrations were associated with an increased risk of more severe course of CIVID-19. Given the low background exposure levels in this study, the role of PFAS exposure in COVID-19 needs to be ascertained in populations with elevated exposures.

Genetics and epigenetics of rheumatoid arthritis

2020 ◽  
pp. 45-54
Author(s):  
Anne Barton
Keyword(s):  
Rheumatoid Arthritis ◽  
Treatment Response ◽  
Genetic Study ◽  
Genetic Factors ◽  
Family Studies ◽  
Genetic Component ◽  
Genetic Studies ◽  
Factors Associated ◽  
Increased Risk

Rheumatoid arthritis (RA) is known to have a genetic component: the evidence comes from twin and family studies as well as genetic studies themselves. Family studies consistently confirm that first degree relatives of patients with RA are at increased risk of developing the condition, supporting a genetic component. The most robust data comes from the Icelandic genealogical database. This chapter covers the basics of genetic studies in RA, designing the genetic study, RA-specific results and insights that can be gained from these. Detailed analyses of selected genetic regions are discussed, alongside genes that may indicate severity. Genetic factors associated with treatment response are also considered. Finally, the role of epigenetics is covered.

scholarly journals Adenocarcinoma of the Right Colon in a Patient with Bloom Syndrome

2016 ◽  
Vol 2016 ◽  
pp. 1-5
Author(s):  
Carlos Augusto Real Martinez ◽  
Lilian Vital Pinheiro ◽  
Debora Helena Rossi ◽  
Michel Gardere Camargo ◽  
Maria de Lourdes Setsuko Ayrizono ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Histopathological Examination ◽  
Clinical Manifestations ◽  
Bloom Syndrome ◽  
Right Colectomy ◽  
Histopathological Analysis ◽  
Tubular Adenocarcinoma ◽  
Surgical Specimen ◽  
Increased Risk ◽  
Risk Of Cancer

Introduction. Bloom syndrome (BS) is an inherited disorder due to mutation inBLMgene. The diagnosis of BS should be considered in patients with growth retardation of prenatal onset, a photosensitive rash in a butterfly distribution over the cheeks, and an increased risk of cancer at an early age. Clinical manifestations also include short stature, dolichocephaly, prominent ears, micrognathia, malar hypoplasia and a high-pitched voice, immunodeficiency, type II diabetes, and hypogonadism associated with male infertility and female subfertility. The aim of this report is to describe case of patient with BS who developed adenocarcinoma of the cecum, successfully treated by right colectomy.Case Report. A 40-year-old man underwent colonoscopy to investigate the cause of his diarrhea, weight loss, and anemia. The patient knew that he was a carrier of BS diagnosed at young age. The colonoscopy showed an expansive and vegetating mass with 5.5 cm in diameter, located within the ascending colon. Histopathological analysis of tissue fragments collected during colonoscopy confirmed the presence of tubular adenocarcinoma, and he was referred for an oncological right colectomy. The procedure was performed without complications, and the patient was discharged on the fifth postoperative day. Histopathological examination of the surgical specimen confirmed the presence of a grade II tubular adenocarcinoma (stage IIA). The patient is currently well five years after surgery, without clinical or endoscopic signs of relapse in a multidisciplinary approach for the monitoring of comorbidities related to BS.Conclusion. Despite the development of colorectal cancer to be, a possibility rarely described the present case shows the need for early screening for colorectal cancer in all patients affected by BS.

scholarly journals Accelerated Atherosclerosis in Systemic Lupus Erythematosus: Role of Proinflammatory Cytokines and Therapeutic Approaches

2010 ◽  
Vol 2010 ◽  
pp. 1-13 ◽  
Author(s):  
Chary López-Pedrera ◽  
Maria Ángeles Aguirre ◽  
Nuria Barbarroja ◽  
Maria José Cuadrado
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Combined Therapy ◽  
Clinical Manifestations ◽  
New Drugs ◽  
Type I ◽  
Systemic Lupus ◽  
Accelerated Atherosclerosis ◽  
Increased Risk

Systemic lupus erythematosus (SLE), a chronic multisystem autoimmune disease with a broad range of clinical manifestations, is associated with accelerated atherosclerosis (AT) and increased risk of cardiovascular complications. Relevant factors directly influencing the development of AT comprise immune complex generation, complement activation, and changes in the production and activity of a complex network of cytokines, including type I and II interferons, B lymphocyte stimulator (BLyS), TNFα, IL-6, IL-17 and migration macrophage inhibitor (MIF). Autoantibodies, also responsible for cytokine expression and activation, play a supplementary key role in the development of AT. Genomic and proteomic studies have contributed to the discovery of genes and proteins involved in AT, including some that may be suitable to be used as biomarkers. All that data has allowed the development of new drugs, most of them evaluated in clinical trials: inhibitors of IFN and TNFα, B cell directed therapies, synthetic oligodeoxynucleotides, intravenous immunoglobulin, or statins. The focus of the present paper is to summarize recent evidence showing the role of cytokines in the development of AT in SLE and the rationale, and safety concerns, in the use of combined therapy to prevent AT and cardiovascular disease.

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