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Whole blood viscosity is associated with reduced myocardial mechano-energetic efficiency in nondiabetic individuals

Eur J Clin Invest. 2023 Nov 10:e14127. doi: 10.1111/eci.14127. Online ahead of print.

ABSTRACT

INTRODUCTION: This cross-sectional study aimed to investigate the association between myocardial mechano-energetic efficiency (MEE) and whole blood viscosity (WBV) in nondiabetic adults participating in the CATAnzaro MEtabolic RIsk factors (CATAMERI) study.

METHODS: 1143 participants underwent an oral glucose tolerance test and an echocardiogram for myocardial MEE per gram of left ventricular mass (MEEi) measurement. WBV was measured as: [0.12 × h] + [0.17 × (p-2.07)], where h is haematocrit and p is plasma protein levels.

RESULTS: Study population includes 595 males and 548 females with a mean age of 46 ± 12 years and a mean BMI of 30.0 ± 6.2 kg/m2 . Individuals with normal glucose tolerance were 63%, while those with impaired fasting glucose, impaired glucose tolerance and or the combination of both were 14.3%, 13% and 9.7%, respectively. A univariate analysis showed that MEEi was significantly associated with sex, age, smoking, BMI, waist circumference, total cholesterol, HDL, triglycerides, fasting glucose, fasting insulin, HOMA-IR index, glucose tolerance, C-reactive protein, haematocrit, haemoglobin, plasma protein and WBV. In a multivariable regression model including variables that were significantly associated with MEEi in univariate analysis, MEEi was associated with HOMA-IR (β = -0.144, p < .001), age (β = -0.140, p < .001), WBV (β = -0.129, p < .001) and glucose tolerance (β = -0.064, p = .04). The independent association between WBV and MEEi remained statistically significant (β = -0.122, p < .001) when antihypertensive therapy and lipid-lowering therapy were included in the model.

CONCLUSION: WBV is associated with decreased myocardial MEE independently of other cardiovascular risk factors.

PMID:37950492 | DOI:10.1111/eci.14127

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Multidimensional Sleep Health Problems Across Middle and Older Adulthood Predict Early Mortality

J Gerontol A Biol Sci Med Sci. 2023 Nov 9:glad258. doi: 10.1093/gerona/glad258. Online ahead of print.

ABSTRACT

BACKGROUND: Having multiple sleep problems is common in adulthood. Yet, most studies have assessed single sleep variables at one timepoint, potentially misinterpreting health consequences of co-occurring sleep problems that may change over time. We investigated the relationship between multidimensional sleep health across adulthood and mortality.

METHOD: Participants from the Midlife in the United States Study reported sleep characteristics in 2004-2006 (MIDUS-2; M2) and in 2013-2016 (MIDUS-3; M3). We calculated a composite score of sleep health problems across five dimensions: Regularity, Satisfaction, Alertness, Efficiency, and Duration (higher=more problems). Two separate models for baseline sleep health (n=5,140; median follow-up time=15.3 years) and change in sleep health (n=2,991; median follow-up time=6.4 years) to mortality were conducted. Cox regression models controlled for sociodemographics and key health risk factors (body mass index, smoking, depressive symptoms, diabetes, hypertension).

RESULTS: On average, 88% of the sample reported having one or more sleep health problems at M2. Each additional sleep health problem at M2 was associated with 12% greater risk of all-cause mortality (hazard ratio [HR]=1.12, 95% confidence interval [CI]=1.04-1.21), but not heart disease related mortality (HR=1.14, 95% CI=0.99-1.31). An increase in sleep health problems from M2 to M3 was associated with 27% greater risk of all-cause mortality (HR=1.27, 95% CI=1.005-1.59), and 153% greater risk of heart disease mortality (HR=2.53, 95% CI=1.37-4.68).

CONCLUSIONS: More sleep health problems may increase the risk of early mortality. Sleep health in middle and older adulthood is a vital sign that can be assessed at medical check-ups to identify those at greater risk.

PMID:37950462 | DOI:10.1093/gerona/glad258

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Lewis a-b- histo-blood group antigen phenotype is predictive of severe COVID-19 in the black South African population group

Glycobiology. 2023 Nov 9:cwad090. doi: 10.1093/glycob/cwad090. Online ahead of print.

ABSTRACT

Several risk factors have been associated with SARS-CoV-2 infections and severity of COVID-19 disease it causes. This study investigated whether variations in histo-blood group antigen (HBGA) expression can predispose individuals to SARS-CoV-2 infections and severity of the disease. Nasopharyngeal swabs, randomly selected from SARS-CoV-2 positive and SARS-CoV-2 negative individuals, were tested for Lewis and H-type 1 HBGA phenotypes by ELISA using monoclonal antibodies specific to Lewis a, Lewis b and H type 1 antigens. The most common Lewis HBGA phenotype among all study participants was Lewis a-b+ (46%), followed by Lewis a-b- (24%), Lewis a+b- and Lewis a+b+ (15% each), while 55% of the study participants were H-type 1. Although SARS-CoV-2 negative individuals had a lower likelihood of having a Lewis a-b- phenotype compared to their SARS-CoV-2 positives counterparts (OR: 0.53, 95% C.I: 0.255-1.113), it did not reach statistical significance (P = 0.055). The frequency of Lewis a+b+, Lewis a+B-, Lewis a-b+, H type 1 positive and H type 1 negative were consistent between SARS-CoV-2 positive and SARS-CoV-2 negative individuals. When stratified according to severity of the disease, individuals with Lewis a+b- phenotype had a higher likelihood of developing mild COVID-19 symptoms (OR: 3.27, 95% CI; 0.9604-11.1), but was not statistically significant (P = 0.055), while Lewis a-b- phenotype was predictive of severe COVID-19 symptoms (OR: 4.3, 95% CI: 1.274-14.81), P = 0.016. In conclusion, individuals with Lewis a-b- phenotype were less likely to be infected by SARS-CoV-2, but when infected, they were at risk of severe COVID-19.

PMID:37950443 | DOI:10.1093/glycob/cwad090

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Comparative Analysis of Symptomatology in Hospitalized Children with RSV, COVID-19, and Influenza Infections

Med Sci Monit. 2023 Nov 11;29:e941229. doi: 10.12659/MSM.941229.

ABSTRACT

BACKGROUND The clinical course of respiratory syncytial virus (RSV), SARS-CoV-2, and influenza infections comprises many non-specific symptoms, which makes diagnosis difficult. The aim of this study was to retrospectively analyze the symptomatology of these infections in children and to search for correlations between them. MATERIAL AND METHODS A total of 121 children with a positive RSV (n=61), influenza (n=31), or SARS-CoV-2 (n=29) antigen test were enrolled in this retrospective analysis. Children were aged up to 71 months (median, 8 months). The collected data were collated by performing statistical analysis using the chi-square test and comparing the results using OR (odds ratio) and 95%CI (confidence interval). RESULTS There was a higher risk of fever in children with influenza than in those with RSV. Patients infected with RSV had a higher risk of nasal blockage than those with SARS-CoV-2. Dyspnea was more common in RSV infection than in influenza. Severe, sleep-awakening cough was more frequent in children with RSV than in those with COVID-19. Influenza was more prevalent in children aged >24 months than in those aged 7-24 months. RSV-infected children had a higher risk of numerous auscultatory changes compared to those with SARS-CoV-2. In the case of RSV infection, symptoms requiring hospitalization occurred later than in SARS-CoV-2 infection. CONCLUSIONS Children aged >24 months were at higher risk of contracting influenza. Numerous auscultatory changes, nasal blockage, and dyspnea were more common in children with RSV. There was a higher risk of dyspnea in children with RSV. Fever was more frequent in children with influenza. However, none of the symptoms clearly indicated the etiology of the infection.

PMID:37950434 | DOI:10.12659/MSM.941229

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Identification of Myocardial Scarring Using Contrast-Free Cardiac MRI in Patients With Autoimmune Rheumatic Diseases

J Magn Reson Imaging. 2023 Nov 10. doi: 10.1002/jmri.29130. Online ahead of print.

ABSTRACT

BACKGROUND: Late gadolinium enhancement (LGE) cardiac MRI is the method of choice in revealing the presence of myocardial scarring, but its availability remains limited in clinical practice.

PURPOSE: To assess myocardial scarring in patients with autoimmune rheumatic diseases (ARDs) using contrast-free cardiac MRI with a radiomics model.

STUDY TYPE: Retrospective.

POPULATION: One hundred ninety-two patients (mean age, 41 years ± 15, 62 men) with or without ARDs, grouped into a training set of 153 patients and a testing set of 39 patients.

FIELD STRENGTH/SEQUENCE: 3.0 T/ cine imaging with a balanced steady-state free precession sequence, T1 mapping with a modified Look-Locker inversion recovery sequence, and LGE imaging with a phase-sensitive inversion recovery gradient echo sequence.

ASSESSMENT: LGE assessment was the reference standard for identifying myocardial scarring. Based on motion features extracted from cine images and tissue characterization features extracted from native T1 maps, a fully automated radiomics model with T1, cine MRI, or combined inputs was developed.

STATISTICAL TESTS: Logistic regression model was used to detect myocardial scarring using contrast-free cardiac MRI parameters. Receiver operating characteristic curves were analyzed to assess the accuracy, sensitivity, and specificity in detecting myocardial scarring. Sensitivities of the models were further assessed in patients with various myocardial scarring proportions. Z-statistic and dice coefficient were assessed to compare the performance. P-values <0.05 were considered significant.

RESULTS: The multivariable regression model exhibited an accuracy of 85.3%, a sensitivity of 93.5%, and a specificity of 50.0%. The radiomics model with T1 and cine MRI input exhibited an accuracy of 75.7%, a sensitivity of 60.9%, and a specificity of 85.5%. Moreover, the radiomics model showed a sensitivity of 90.9% among patients with >25% myocardial scarring.

DATA CONCLUSIONS: The proposed radiomics model allowed for the identification of myocardial scarring similar to LGE, but on contrast-free cardiac MRI in patients with ARDs.

EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 1.

PMID:37950412 | DOI:10.1002/jmri.29130

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Dark Blood Contrast-Enhanced Brain MRI Using Echo-uT1 RESS

J Magn Reson Imaging. 2023 Nov 10. doi: 10.1002/jmri.29124. Online ahead of print.

ABSTRACT

BACKGROUND: The widely used magnetization-prepared rapid gradient-echo (MPRAGE) sequence makes enhancing lesions and blood vessels appear bright after gadolinium administration. However, dark blood imaging using T1-weighted Sampling Perfection with Application optimized Contrast using different flip angle Evolution (T1 SPACE) can be advantageous since it improves the conspicuity of small metastases and leptomeningeal disease. As a potential alternative to T1 SPACE, we evaluated a new dark blood sequence called echo-uT1 RESS (unbalanced T1 Relaxation-Enhanced Steady-State).

PURPOSE: We compared the performance of echo-uT1 RESS with Dixon fid-uT1 RESS, MPRAGE, and T1 SPACE.

STUDY TYPE: Retrospective, IRB approved.

SUBJECTS/PHANTOM: Phantom to assess flow properties of echo-uT1 RESS. Twenty-one patients (14 female, age range 35-82 years) with primary and secondary brain tumors.

FIELD STRENGTH/SEQUENCES: 3 Tesla/MPRAGE, T1 SPACE, Dixon fid-uT1 RESS, echo-uT1 RESS.

ASSESSMENT: Flow phantom signal vs. velocity as a function of flip angle and sequence. Qualitative image assessment on 4-point scale. Quantitative evaluation of tumor-to-brain contrast, apparent contrast-to-noise ratio (aCNR), and vessel-to-brain aCNR.

STATISTICAL TESTS: Friedman and Mann-Whitney U tests. A P value <0.05 was considered statistically significant.

RESULTS: In the phantom, echo-uT1 RESS showed greater flow-dependent signal loss than fid-uT1 RESS. In patients, blood vessels appeared bright with MPRAGE, gray with fid-uT1 RESS, and dark with T1 SPACE and echo-uT1 RESS. For MPRAGE, Dixon fid-uT1 RESS, echo-uT1 RESS, and T1 SPACE, respective tumor-to-brain contrast values were 0.6 ± 0.3, 1.3 ± 0.5, 1.0 ± 0.4, and 0.6 ± 0.4, while normalized aCNR values were 68.9 ± 50.9, 128.4 ± 59.2, 74.2 ± 42.1, and 99.4 ± 73.9.

DATA CONCLUSION: Volumetric dark blood contrast-enhanced brain MRI is feasible using echo-uT1 RESS. The dark blood effect was improved vs. fid-uT1 RESS, while both uT1 RESS versions provided better tumor-to-brain contrast than MPRAGE. Whereas T1 SPACE provided better tumor aSNR, echo-uT1 RESS provided better Weber contrast, lesion sharpness and a more consistent dark blood effect.

EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 1.

PMID:37950398 | DOI:10.1002/jmri.29124

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Evaluation of Vascular Endothelial Growth Factor Gene Expression in Recellularized Liver Tissue by Mouse Embryo Fibroblast

Iran Biomed J. 2023 Jun 22. doi: 10.52547/ibj.3862. Online ahead of print.

ABSTRACT

BACKGROUND: The aim of the present study was to evaluate alterations in the vegf gene expression as an angiogenic factor in mouse embryo fibroblasts seeded on the decellularized liver fragments.

METHODS: Liver tissue samples (n = 10) collected from adult male mice were randomly divided into decellularized and native control groups. Tissues were decellularized by treating with 1% Triton X-100 and 0.1% SDS for 24 hours and assessed by H&E staining and SEM. Then DNA content analysis and toxicity tests were performed. By centrifugation, DiI-labeled mouse embryo fibroblasts were seeded on each scaffold and cultured for one week. The recellularized scaffolds were studied by H&E staining, SEM, and LSCM. After RNA extraction and cDNA synthesis, the expression of the vegf gene in these samples was investigated using real-time RT-PCR.

RESULTS: Our observations showed that the decellularized tissues had morphology and porous structure similar to the control group, and their DNA content significantly reduced (p < 0.05) and reached to 4.12% of the control group. The MTT test indicated no significant cellular toxicity for the decellularized scaffolds. Light microscopy, SEM, and LSCM observations confirmed the attachment and penetration of embryonic fibroblast cells on the surface and into different depths of the scaffolds. There was no statistically significant difference in terms of vegf gene expression in the cultured cells in the presence and absence of a scaffold.

CONCLUSION: The reconstructed scaffold had no effect on vegf gene expression. Decellularized mouse liver tissue recellularized by embryonic fibroblasts could have an application in regenerative medicine.

PMID:37950395 | DOI:10.52547/ibj.3862

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Investigation of Simulated Adherence in Long-Term Buprenorphine/Naloxone Treatment Patients

Subst Use Misuse. 2023 Nov 10:1-5. doi: 10.1080/10826084.2023.2275559. Online ahead of print.

ABSTRACT

BACKGROUND: Buprenorphine is a medication that is used to treat opioid use disorder by reducing withdrawal symptoms and cravings for opioids. Patients with poor adherence are at higher risk of relapse and overdose. Providers often test adherence through urine testing but are not aware of simulated adherence, where patients may directly add buprenorphine to the urine samples. As of now, there exists no literature on the simulated adherence practices for patients who stayed in the treatment for more than three months.

METHODS: This study is a cross-sectional analysis of simulated adherence through urine toxicology results of 3950 patients undergoing buprenorphine/naloxone treatment. Simulated adherence was measured by the ratio of norbuprenorphine and buprenorphine <0.02 in the urine sample. Descriptive statistics as well as multivariate analysis was conducted to examine the relationship between patient information and outcomes.

RESULTS: Out of 3950 patients, 411 (10.4%) had a history of one or more simulated adherence. On average, patients with multiple simulated adherences had 48.1% of their tests simulated, while on the contrary, patients with a single occurrence of simulated adherence had 17.6% of their tests simulated. Weekly testing and visit number of over 15 were associated with a higher likelihood of simulated adherence.

CONCLUSION: The study demonstrates that simulated adherence is a recurring phenomenon among buprenorphine/naloxone treatment patients regardless of the duration in the treatment. Utilization of quantitative urine toxicology to identify simulated adherence will enable healthcare providers to formulate a more precise and effective treatment plan tailored to support individual patient needs.

PMID:37950394 | DOI:10.1080/10826084.2023.2275559

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Cerebral Microbleeds and Asundexian in Non-cardioembolic Ischemic Stroke: Secondary Analyses of the PACIFIC-STROKE Randomized Trial

Int J Stroke. 2023 Nov 10:17474930231216339. doi: 10.1177/17474930231216339. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Cerebral microbleeds are MRI markers of hemorrhage-prone cerebral small-vessel disease that predict future risk of ischemic stroke and intracranial hemorrhage (ICrH). There exists concerns about the net benefit of antithrombotic therapy in patients with microbleeds. We aimed to investigate the effects of an oral factor-XIa inhibitor (asundexian), that is hypothesized to inhibit thrombosis without compromising hemostasis, on the development of new microbleeds over time and interactions between microbleeds and asundexian treatment on clinical outcomes. We additionally assessed associations between baseline microbleeds and the risks of clinical and neuroimaging outcomes in patients with non-cardioembomic ischemic stroke.

METHODS: This is a subgroup analysis of the PACIFIC-STROKE, international, multi-center Phase 2b double-blind, randomized clinical trial. PACIFIC-STROKE enrolled patients aged ≥45 years with mild-to-moderate non-cardioembolic ischemic stroke who presented within 48 hours of symptom onset for whom antiplatelet therapy was intended. Microbleeds were centrally adjudicated, and participants with an interpretable T2*-weighted sequence at their baseline MRI were included in this analysis. Patients were randomized to asundexian (10/20/50mg daily) vs. placebo plus standard antiplatelet treatment. Regression models were used to estimate the effects of i) all pooled asundexian doses and ii) asundexian 50 mg daily on new microbleed formation on 26-week MRIs. Cox proportional hazards or regression models were additionally used to estimate interactions between treatment assignment and microbleeds for ischemic stroke/TIA (primary outcome), as well as ICrH, all-cause mortality, hemorrhagic transformation (HT), and new microbleeds (secondary outcomes).

RESULTS: Of 1746 participants (mean age, 67.0±10.0; 34% female) with baseline MRIs, 604 (35%) had microbleeds. During a median follow-up of 10.6 months, 7.0% (n=122) had ischemic stroke/TIA, 0.5% (n=8) ICrH, and 2.1% (n=37) died. New microbleeds developed in 10.3% (n=155) of participants with adequate up-MRIs and HT in 31.4% (n=345). In the total sample of patients with adequate baseline and 26-week follow-up MRIs (n=1507, ), new microbleeds occurred in 10.2% of patients assigned to any asundexian dose and 10.5% of patients assigned to placebo (OR 0.96, 95%CI 0.66-1.41). There were no interactions between microbleeds and treatment assignment for any of the outcomes (p for interaction>0.05). The rates of new microbleeds, HT and ICrH were numerically less in patients with microbleeds assigned to asundexian relative to placebo. The presence of microbleeds was associated with a higher risk of HT (aOR, 1.6; 95%CI, 1.2-2.1) and new microbleeds (aOR, 4.4; 95%CI, 3.0-6.3).

CONCLUSIONS: Factor XIa inhibition with asundexian appears safe in patients with non-cardioembolic ischemic stroke and hemorrhage-prone cerebral small-vessel disease marked by microbleeds on MRI. These preliminary findings will be confirmed in the ongoing OCEANIC-STROKE randomized trial.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04304508.

PMID:37950392 | DOI:10.1177/17474930231216339

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Long-term stroke risk in moyamoya disease

Int J Stroke. 2023 Nov 10:17474930231216037. doi: 10.1177/17474930231216037. Online ahead of print.

ABSTRACT

BACKGROUND: Moyamoya disease is considered a progressive disease with an ongoing risk of recurrent stroke. However, there is a lack of long-term observational data to quantify the extent of the stroke risk.

METHODS: This study aimed to provide insight into the long-term stroke risk in MMD and explore possible risk factors for stroke. Records from all patients diagnosed with MMD in 13 clinical departments from six different Danish hospitals between 1994 and 2017 were retrospectively reviewed until 2021.

RESULTS: The cohort comprised 50 patients (33 females and 17 males). Patients were followed up for a median of 9.4 years, with more than 10 years of follow-up for 24 patients. Ten patients had 11 new stroke events – 6 ischemic strokes and 5 brain hemorrhages. Events occurred at a median of 7 years and up to 25 years after diagnosis. The overall Kaplan-Meier 5-year stroke risk was 10%. Patients with bypass performed had significantly fewer events than conservatively treated patients (HR 0.25, 95% CI 0.07 – 0.91, p<0.05). All but one event occurred in females, a difference that reached statistical significance.

CONCLUSIONS: The study provides data on the extent of the risk of recurrent stroke in MMD. Bypass surgery patients had fewer stroke events than those treated conservatively. There was a trend toward a higher stroke risk in females.

DATA ACCESS STATEMENT: The data supporting this study’s findings are available from the corresponding author upon reasonable request.

PMID:37950387 | DOI:10.1177/17474930231216037