Assessment of cerebrovascular disease with computed tomography in COVID-19 patients: correlation of a novel specific visual score with increased mortality risk

Abstract Purpose Cerebrovascular disease (CVD) is considered a major risk factor for fatal outcome in COVID-19. We aimed to evaluate the possible association between computed tomography (CT) signs of chronic CVD and mortality in infected patients. Materials and methods We performed a double-blind retrospective evaluation of the cerebral CT scans of 83 COVID-19 patients looking for CT signs of chronic CVD. We developed a rapid visual score, named CVD-CT, which summarized the possible presence of parietal calcifications and dolichosis, with or without ectasia, of intracranial arteries, areas of chronic infarction and leukoaraiosis. Statistical analysis was carried out with weighted Cohen’s K test for inter-reader agreement and logistic regression to evaluate the association of in-hospital mortality with CVD-CT, chest X-ray (CXR) severity score (Radiographic Assessment of Lung Edema-RALE) for radiological assessment of pulmonary disease, sex and age. Results CVD-CT (odds ratio 1.6, 95% C.I. 1.2-2.1, p = 0.001) was associated with increased risk of mortality. RALE showed an almost significant association (odds ratio 1.05, 95% C.I. 1-1.1, p 0.06), whereas age and sex did not. Conclusion CVD-CT is associated with risk of mortality in COVID-19 patients. The presence of CT signs of chronic CVD may be correlated to a condition of fragility of the circulatory system, which constitutes a key risk factor for death in infected patients.

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Late-Life Vascular Risk Score in Association With Postmortem Cerebrovascular Disease Brain Pathologies

Stroke ◽

10.1161/strokeaha.120.030226 ◽

2021 ◽

Author(s):

Shahram Oveisgharan ◽

Lei Yu ◽

Ana Capuano ◽

Zoe Arvanitakis ◽

Lisa L. Barnes ◽

...

Keyword(s):

Cerebrovascular Disease ◽

Cerebral Amyloid Angiopathy ◽

Risk Score ◽

Odds Ratio ◽

Amyloid Angiopathy ◽

Individual Level ◽

Framingham Risk ◽

Increased Risk ◽

Cerebral Amyloid ◽

The Individual

Background and Purpose: The general cardiovascular Framingham risk score (FRS) identifies adults at increased risk for stroke. We tested the hypothesis that baseline FRS is associated with the presence of postmortem cerebrovascular disease (CVD) pathologies. Methods: We studied the brains of 1672 older decedents with baseline FRS and measured CVD pathologies including macroinfarcts, microinfarcts, atherosclerosis, arteriolosclerosis, and cerebral amyloid angiopathy. We employed a series of logistic regressions to examine the association of baseline FRS with each of the 5 CVD pathologies. Results: Average age at baseline was 80.5±7.0 years and average age at death was 89.2±6.7 years. A higher baseline FRS was associated with higher odds of macroinfarcts (odds ratio, 1.10 [95% CI, 1.07–1.13], P <0.001), microinfarcts (odds ratio, 1.04 [95% CI, 1.01–1.07], P =0.009), atherosclerosis (odds ratio, 1.07 [95% CI, 1.04–1.11], P <0.001), and arteriolosclerosis (odds ratio, 1.04 [95% CI, 1.01–1.07], P =0.005). C statistics for these models ranged from 0.537 to 0.595 indicating low accuracy for predicting CVD pathologies. FRS was not associated with the presence of cerebral amyloid angiopathy. Conclusions: A higher FRS score in older adults is associated with higher odds of some, but not all, CVD pathologies, with low discrimination at the individual level. Further work is needed to develop a more robust risk score to identify adults at risk for accumulating CVD pathologies.

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Is APC Resistance a Risk Factor for Venous Thromboembolism in Patients over 70 Years?

Thrombosis and Haemostasis ◽

10.1055/s-0037-1613260 ◽

2002 ◽

Vol 88 (10) ◽

pp. 587-591 ◽

Cited By ~ 8

Author(s):

Karine Lacut ◽

Grégoire Le Gal ◽

Patrick Van Dreden ◽

Luc Bressollette ◽

Pierre-Yves Scarabin ◽

...

Keyword(s):

Risk Factor ◽

Venous Thromboembolism ◽

Odds Ratio ◽

Dna Analysis ◽

Activated Protein C ◽

Factor V Leiden ◽

Factor V ◽

Apc Resistance ◽

Increased Risk ◽

History Of

SummaryActivated protein C (APC) resistance is the most common risk factor for venous thromboembolism (VTE). Previous studies mostly analysed patients under 70 years and reported a four-to sevenfold increased risk. This case-control study included consecutive patients referred for a clinical suspicion VTE to our medical unit: 621 patients with a well-documented diagnosis (cases) and 406 patients for which the diagnosis was ruled out and who had no personal history of VTE (controls). APC resistance related to factor V Leiden was defined by either a positive DNA analysis or a positive STA® Staclot APC-R assay. Under 70 years, APC resistance was associated with a threefold increased risk of VTE (odds ratio 3.2, 95% CI, 1.7 to 6.0), whereas in patients over 70 years, it appeared to be no longer a strong risk factor (odds ratio 0.8, 95% CI, 0.4 to 1.7). Age appeared as an effectmeasure modifier with a significant interaction (p = 0.005). Our data suggest that APC resistance is not a risk factor for VTE in elderly.

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MO039THE 24-WEEK INTERIM ANALYSIS RESULTS OF A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE II STUDY OF ATACICEPT IN PATIENTS WITH IGA NEPHROPATHY AND PERSISTENT PROTEINURIA

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa140.mo039 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Cited By ~ 1

Author(s):

Jonathan Barratt ◽

James A Tumlin ◽

Yusuke Suzuki ◽

Amy Kao ◽

Aida Aydemir ◽

...

Keyword(s):

Iga Nephropathy ◽

Phase Ii ◽

Interim Analysis ◽

Plasma Cells ◽

Enzyme Inhibitor ◽

Phase Ii Study ◽

Fatal Outcome ◽

Double Blind ◽

Persistent Proteinuria ◽

Increased Risk

Abstract Background and Aims IgA nephropathy (IgAN) is the most common primary glomerulonephritis in the world. Despite being described over 50 years ago, there remains no approved therapy for this common global cause of kidney failure. The central pathogenic feature in IgAN is the formation of circulating IgA containing immune complexes which have the propensity to deposit in the kidneys and trigger glomerular inflammation and tubulointerstitial scarring. The primary substrate for immune complex formation is an excess of poorly O-galactosylated polymeric IgA1 (Gd-IgA1) in the circulation. These IgA1 O-glycoforms are thought to trigger the formation of IgA and IgG autoantibodies. Atacicept is a human TACI-Ig fusion protein that inhibits B cell-stimulating factors, BLyS and APRIL, and has been associated with reductions in levels of serum IgA and IgG, as well as reductions in mature B cells and plasma cells. A number of studies have shown elevated levels of BLyS, APRIL and Gd-IgA1 in IgAN patients which have been linked to worse clinical outcomes. IgAN patients with persistent proteinuria >1 g/day are at increased risk of progression to end-stage renal disease. This Phase II study examines the safety and efficacy of atacicept in reducing pathogenic Gd-IgA1 levels and measures of renal activity in IgAN. Method This Phase II study (NCT02808429) enrolled patients with IgAN and proteinuria ≥1 g/day or 0.75 mg/mg on 24-hour urine protein-creatinine ratio (UPCR) despite maximal standard of care therapy (angiotensin converting enzyme inhibitor and/or angiotensin receptor blocker). Enrolled patients were randomized 1:1:1 to receive placebo or atacicept 25mg or 75mg once weekly by subcutaneous injection. The primary endpoint was a change in proteinuria by 24-hour UPCR at Week 48; key secondary endpoints included change in eGFR, serum immunoglobulin and Gd-IgA1 levels. Results Data from the 24-week interim analysis are reported here for enrolled patients (placebo=5; atacicept 25mg=6; atacicept 75mg=5). A consistent, dose-dependent reduction in serum immunoglobulins (IgA, IgG and IgM) and, in particular, Gd-IgA1 (Figure) were observed through Week 24. In parallel, proteinuria (24-hour UPCR) showed a higher median % reduction from baseline with atacicept at Week 24: -18.67% and -25.34% with atacicept 25 mg and 75 mg, respectively, vs +0.098% with placebo (Figure). eGFR remained stable over time. TEAEs were reported by 81% of the subjects. TEAEs were mild or moderate in severity, with no severe TEAEs reported. No serious related events, events with severe hypogammaglobulinemia or fatal outcome were reported. Conclusion These 24-week interim analysis results provide early proof of concept for the potential treatment of atacicept in patients with IgAN and persistent proteinuria.

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Increased fasting total homocysteine plasma levels as a risk factor for thromboembolism in children

Thrombosis and Haemostasis ◽

10.1160/th03-02-0038 ◽

2004 ◽

Vol 91 (02) ◽

pp. 308-314 ◽

Cited By ~ 24

Author(s):

Achim Heinecke ◽

Karin Kurnik ◽

Christine Heller ◽

Ulrike Nowak-Göttl ◽

Andrea Kosch ◽

...

Keyword(s):

Risk Factor ◽

Odds Ratio ◽

Thromboembolic Event ◽

Pediatric Patients ◽

Thromboembolic Disease ◽

Thromboembolic Events ◽

Thcy Level ◽

Increased Risk ◽

Total Homocysteine ◽

Mild Hyperhomocysteinemia

SummaryElevated total homocysteine (tHcy) concentrations are an inde- pendent risk factor for thromboembolic events in adults. In children with moderate hyperhomocysteinemia data are sparse. Therefore, between 1995 and 2002 we consecutively recruited 163 white pediatric patients with a first symptomatic thromboembolic event and 255 healthy controls (mean age: 6.4 years in patients vs. 6.6 years in controls, range: 3 months to 18 years) and measured fasting tHcy levels. Median tHcy levels in patients were significantly higher (6.6 µmol/l, range 2.9-20.4 µmol/l) than in controls (5.7 µmol/l, 2.0-14.0 µmol/l, p<0.0001). 48 of the 163 patients with thromboembolism (29.5%) versus 26 of the 255 controls (10.2%) had tHcy levels above the age- specific normal 90th percentile (OR 2.9, 95%CI: 1.7-4.8). The odds ratio for children in the highest quintile compared to chil- dren with levels in the lowest quintile was 4.3 (1.6-8.1; highest quintile: median tHcy level 9.6 µmol, range 8.0-20.4), showing a significantly increased risk for thromboembolic disease with even mild hyperhomocysteinemia. We conclude that hyperho- mocysteinemia above the age-specific cut-off values is a risk fac- tor for thromboembolic events in children. Therefore, screen- ing for elevated fasting tHcy levels of patients with thromboem- bolism is recommended to stratify the risk of thromboembo- lism.

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The Factor V Gene A4070G Mutation and the Risk of Venous Thrombosis

Thrombosis and Haemostasis ◽

10.1055/s-0037-1614441 ◽

1999 ◽

Vol 81 (02) ◽

pp. 193-197 ◽

Cited By ~ 44

Author(s):

Viviane Nicaud ◽

Sophie Gandrille ◽

Patrick van Dreden ◽

Jean Amiral ◽

Marie-Laurence Aubry ◽

...

Keyword(s):

Risk Factor ◽

Odds Ratio ◽

Activated Protein C ◽

Allelic Frequency ◽

Factor V ◽

Apc Resistance ◽

Increased Risk ◽

Venous Thromboembolic ◽

Factor V Gene ◽

The Impact

SummaryThe A4070G polymorphism in exon 13 of the factor V (FV) gene, which replaces His by Arg at position 1299 of the B domain, was recently shown to influence circulating FV levels and to contribute to the activated protein C (APC) resistance phenotype. We examined the impact of this polymorphism in a population of unselected patients with venous thromboembolic disease (VTE). The prevalence of the G4070 (R2) allele was determined in 205 patients and 394 healthy subjects of similar age and sex distribution. Thirty-seven patients (18%) were heterozygous for the R2 allele and 1 (0.5%) was homozygous. Forty-four controls (11.2%) were heterozygous for the R2 allele and 1 (0.2%) was homozygous. Thus, the allelic frequency was significantly higher in the patients with VTE than in the healthy controls, with respective values of 9.5% and 5.8%. The odds ratio was 1.8 (95% CI: 1.1-2.8, p = 0.02), pointing to an increased risk of VTE in carriers of the R2 allele. After excluding subjects with putative or confirmed gene defects (mainly the FV R506Q mutation), the R2 allele was still a risk factor for VTE in the remaining patients, with an odds ratio of 2.0 (95% CI: 1.2-3.5, p = 0.01), demonstrating that this polymorphism is itself a risk factor. This study also confirms that the R2 allele influences APC resistance (APCR) in the absence of the FV R506Q mutation.

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Hypertension as a prognostic factor in the prediction of mortality in patients with COVID-19: a systematic review and meta-analysis

European Heart Journal ◽

10.1093/eurheartj/ehab724.2393 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

C D P Pagdanganan ◽

J Juangco ◽

Keyword(s):

Prognostic Factor ◽

Odds Ratio ◽

Positive Association ◽

Hazard Ratio ◽

P Value ◽

Comorbid Condition ◽

Significant Positive Association ◽

Prediction Of Mortality ◽

Risk Of Mortality ◽

Increased Risk

Abstract Background The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) brought the majority of the world into a halt when it started to spread outside the virus epicenter in Wuhan, China. With the alarming increase in the number of cases and deaths worldwide, the possible risk factors should be determined in order to have a general idea on those who are more susceptible to have this disease. Hypertension, being one of the world's leading causes of noncommunicable diseases, was identified by the CDC to be one of underlying medical conditions that might pose an increased risk for severe illness from COVID-19. Objective The aim of this study is to determine the predictive value of hypertension as a comorbidity in COVID-19 mortality. Materials and methods Participants included all patients clinically diagnosed with COVID-19, and have hypertension as their pre-existing medical condition. Studies were selected based on study design, participants, exposure, outcome, timing, setting and language. The following databases were searched from June to August 2020 for case control and cohort studies on MEDLINE and CINAHL, ScienceDirect, Clinical Key, OVID database, Wiley Online library, and UpToDate. The criteria for evaluation of risk of bias were based on the selection bias, comparability bias and outcome bias. All information gathered were collated and evaluated using the Newcastle-Ottawa Quality Assessment Scale and CEBM. Results Individual studies all showed a significant relationship between hypertension and mortality in COVID-19 patients. Odds ratio ranging from 1.75 to 28.88, and hazard ratio ranging from 1.49 to 3.32 are present in the studies. For the data analysis, Mantel Haenszel method and random effects model was used for case control studies with odds ratio as effect measure; while Inverse variance method and fixed model was used for cohort studies with hazard ratio as effect measure. Both groups showed significant positive association between mortality and hypertension as a prognostic factor. Overall odds ratio is 5.25 (2.42–11.40) with a p value of <0.ehab724.23931, and the pooled hazard ratio is 2.21 (1.75–2.80) with a p value of <0.ehab724.23931. This shows that there is an increased risk of mortality among COVID-19 patients with hypertension as a comorbid condition. Conclusions Hypertension as a comorbid condition is a prognostic factor in the prediction of mortality in hospitalized COVID-19 patients. The ten included studies showed that there is a significant positive association suggesting an increased risk of mortality in COVID-19 patients with hypertension. FUNDunding Acknowledgement Type of funding sources: Other. Main funding source(s): University of the East Ramon Magsaysay Memorial Medical Center College of Medicine Forest Plot HR Hypertension COVID

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Urine Cadmium as a Risk Factor for Osteoporosis and Osteopenia: A Meta-Analysis

Frontiers in Medicine ◽

10.3389/fmed.2021.648902 ◽

2021 ◽

Vol 8 ◽

Author(s):

Dong Li ◽

HaoJie Lin ◽

Min Zhang ◽

Jing Meng ◽

LiYou Hu ◽

...

Keyword(s):

Risk Factor ◽

Subgroup Analysis ◽

Odds Ratio ◽

Meta Analysis ◽

Review Of The Literature ◽

High Quality ◽

Heterogeneity Test ◽

Increased Risk ◽

Urine Cadmium ◽

The Relationship

Background: As society ages, the incidence of osteoporosis increases. In several studies, cadmium (Cd) is thought to be related to osteoporosis. However, there are conflicting reports about the relationship between Cd and the risk of osteoporosis and osteopenia. Therefore, the purpose of this meta-analysis was to explore the relationship between Cd and osteoporosis and osteopenia.Methods: Through a review of the literature, articles published in PubMed as of December 2020 were identified and the references of related publications and reviews were reviewed. Ultimately, 17 eligible articles were selected to determine the relationship between blood and urine Cd concentrations for the risk of osteoporosis or osteopenia. In this study, we performed a classification analysis, heterogeneity test, subgroup analysis, and evaluated publication bias.Results: A total of 17 studies were included, including seven on blood Cd and 10 on urine Cd. By combining the odds ratio (OR) and 95% confidence interval (CI) for the lowest and highest categories, the odds ratio of blood Cd concentration that increased the risk of osteoporosis or osteopenia was OR 1.21 (95% CI: 0.84–1.58) and that of urine Cd concentration that increased the risk of osteoporosis or osteopenia was OR 1.80 (95% CI: 1.42–2.18), and the results of the subgroup analysis were also consistent.Conclusions: Our research indicates that while urine cadmium (Cd) concentration may be related to increased risk of osteoporosis and osteopenia, blood Cd concentration may not. Therefore, compared to blood Cd concentration, urine Cd concentration may be more reliable as a risk factor for osteoporosis and osteopenia. This result should be interpreted with caution. Currently. research on the relationship between Cd concentration and osteoporosis and osteopenia is limited, thus, further large, high-quality prospective studies are required to elucidate the relationship between Cd concentration and osteoporosis and osteopenia.

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Obstructive Sleep Apnea as a Risk Factor for Intracerebral Hemorrhage

Stroke ◽

10.1161/strokeaha.120.033342 ◽

2021 ◽

Author(s):

Jacqueline H. Geer ◽

Guido J. Falcone ◽

Kevin N. Vanent ◽

Audrey C. Leasure ◽

Daniel Woo ◽

...

Keyword(s):

Obstructive Sleep Apnea ◽

Logistic Regression ◽

Risk Factor ◽

Sleep Apnea ◽

Intracerebral Hemorrhage ◽

Odds Ratio ◽

Berlin Questionnaire ◽

Multivariable Logistic Regression Model ◽

Obstructive Sleep ◽

Increased Risk

Background and Purpose: To determine whether obstructive sleep apnea (OSA) is associated with intracerebral hemorrhage (ICH) risk, we assessed premorbid OSA exposure of patients with nontraumatic ICH and matched controls. Methods: Ethnic/Racial Variations of Intracerebral Hemorrhage is a multicenter, case-control study evaluating risk factors for ICH that recruited 3000 cases with ICH and 3000 controls. OSA status was ascertained using the Berlin Questionnaire as a surrogate for premorbid OSA. We performed logistic regression analyses to evaluate the association between OSA and ICH. Results: Two thousand and sixty-four (71%) cases and 1516 (52%) controls were classified as having OSA by the Berlin Questionnaire. Cases with OSA were significantly more likely to be male and have hypertension, heart disease, hyperlipidemia, and higher body mass index compared with those without OSA. OSA was more common among cases compared with controls (71% versus 52%, odds ratio, 2.28 [95% CI, 2.05–2.55]). In a multivariable logistic regression model, OSA was associated with increased risk for ICH (odds ratio, 1.47 [95% CI, 1.29–1.67]). Conclusions: OSA is a risk factor for ICH.

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Recurrent Cerebral Infarction during Anticoagulation Therapy in Patients with Mitral Valve Prolapse

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100031590 ◽

1991 ◽

Vol 18 (2) ◽

pp. 137-139

Author(s):

Ashfaq Shuaib ◽

William F. Murphy

Keyword(s):

Risk Factor ◽

Mitral Valve ◽

Cerebral Infarction ◽

Cerebrovascular Disease ◽

Anticoagulant Therapy ◽

Mitral Valve Prolapse ◽

Anticoagulation Therapy ◽

Major Risk Factor ◽

Increased Risk ◽

Ischemic Events

ABSTRACT:Mitral valve prolapse has been associated with an increased risk of transient or lasting ischemic events. Recurrence is uncommon after initiation of antiplatelet or anticoagulant therapy. In this communication we report two patients, both female, who had mitral valve prolapse as the major risk factor for cerebrovascular disease and who developed cerebral infarction despite anticoagulation. The cerebral infarctions were bilateral and extensive in one patient and led to the patient's death. In the second case, three infarctions resulted in moderate disability.

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Menopause is more than Hot Flashes: What is Missing in Homeopathic Research? A Narrative Review

Homeopathy ◽

10.1055/s-0041-1733971 ◽

2021 ◽

Author(s):

Emma Macías-Cortés

Keyword(s):

Health Outcomes ◽

Hot Flashes ◽

Daily Practice ◽

Vasomotor Symptoms ◽

Double Blind ◽

High Quality Research ◽

Risk Of Mortality ◽

Increased Risk ◽

Menopausal Women ◽

Important Health

Abstract Background Menopausal complaints are frequently treated with homeopathy in daily practice worldwide. Recently, vasomotor symptoms have been understood to have implications as predictors of other important and long-term outcomes, causing increased risk of mortality and/or disability. Methods A comprehensive search of the literature was conducted to investigate whether homeopathic treatments for menopausal women with vasomotor symptoms have a positive effect on other important health outcomes associated with menopause, such as cardiovascular disease, neurocognitive impairment, metabolic and mood disorders, or osteoporosis. Results Though observational studies have shown encouraging results in reducing the severity and frequency of hot flashes in women treated with homeopathy, few randomized controlled trials have shown positive results. In most of the studies using homeopathy, the primary outcome is reduction in the frequency and severity of hot flashes, and other menopausal complaints are assessed secondarily as a part of the symptoms evaluated in the menopausal scales. Quality of life improves with homeopathic treatments for hot flashes, but there is scarce evidence of the effect of homeopathy on other health outcomes associated with menopause. Limited evidence exists in the case of menopausal women treated with individualized homeopathy for depression and metabolic disorders. Conclusion A more comprehensive approach for treating menopause in routine homeopathic practice constitutes a valuable opportunity to increase knowledge and high-quality research in this field. Future homeopathic research for menopause should be focused on well-designed, double-blind, placebo-controlled, randomized trials as well as on pragmatic trials to show whether homeopathic treatments for vasomotor symptoms can also improve outcomes that are well-known to increase the risk of mortality and/or disability.

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