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Effects of Medium Cutoff Membranes on Pro-Inflammatory Cytokine and Oxidative Marker Levels in Patients with Sepsis Who Developed Acute Kidney Injury

Blood Purif. 2021 Nov 23:1-8. doi: 10.1159/000519881. Online ahead of print.

ABSTRACT

INTRODUCTION: There is insufficient data on the role of the medium cutoff (MCO) membranes in the clearance of pro-inflammatory cytokines and oxidant radicals in patients with sepsis requiring hemodialysis.

METHODS: The study consisted of 38 septic patients who developed acute kidney injury (AKI) and who were scheduled to undergo 2 sessions of hemodialysis. Nineteen patients underwent their first dialysis session with the MCO membrane and 19 patients with the high-flux (HF) membrane. In the second session, the membranes were switched. Pro-inflammatory cytokine and oxidative marker levels were measured in blood samples obtained before and after both dialysis sessions. Reduction ratios were compared for the 2 types of hemodialysis membranes.

RESULTS: After the first session, there was a greater reduction in tumor necrosis factor (TNF)-α with the MCO membrane (28.2 ± 21.1 vs. 8.0 ± 6.6, p = 0.001). After the second session, there was a greater reduction in interleukin (IL)-6 (27.8 ± 26.5 vs. 5.9 ± 13.3, p = 0.003) and IL-1β (20.5 ± 21.1 vs. 4.0 ± 6.5, p = 0.004) with the MCO membrane. When the first and second sessions of all 38 patients were compared, the reductions in TNF-α, IL-6, and IL-1β were consistently greater for MCO than HF (p = 0.001, p = 0.006, p < 0.001, respectively). The reductions in total antioxidant status, total oxidant status, and myeloperoxidase were not statistically different for the 2 types of dialysis membranes.

CONCLUSIONS: MCO membrane was superior to HF membrane in the removal of cytokines in septic patients with AKI. However, a similar effect was not observed for oxidative stress markers.

PMID:34814149 | DOI:10.1159/000519881

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Inverse Association of Serum Adipsin with the Remission of Nonalcoholic Fatty-Liver Disease: A 3-Year Community-Based Cohort Study

Ann Nutr Metab. 2021 Nov 23:1-12. doi: 10.1159/000520368. Online ahead of print.

ABSTRACT

PURPOSES: Adipokine alterations contribute to the development and remission of nonalcoholic fatty-liver disease (NAFLD). Adipsin is one of the most abundant adipokines and is almost exclusively produced by adipocytes. However, data on adipsin in human NAFLD are limited and controversial. We performed this study to investigate the association between adipsin and the remission of NAFLD in middle-aged and elderly Chinese adults.

METHODS: Whether adipsin is associated with the remission of NAFLD in a 3-year community-based prospective cohort study was investigated. Baseline levels of adipsin were measured in serum samples collected from 908 NAFLD participants. NAFLD was diagnosed using abdominal ultrasonography. Logistic regression analysis and a multiple stepwise logistic regression model including different variables were conducted to evaluate the association between serum adipsin levels and the remission of NAFLD.

RESULTS: During a mean follow-up of 3.14 ± 0.36 years, 247 (27.20%) participants with NAFLD at baseline were in remission. At baseline, serum adipsin concentration was positively correlated with body mass index (r: 0.39, p < 0.001), insulin (r: 0.31, p < 0.001), and homeostasis model assessment of insulin resistance (r: 0.31, p < 0.001) and was inversely associated with NAFLD remission with a fully adjusted odds ratio (OR) of 0.28 (0.16-0.48) (p trend < 0.001). In a multiple stepwise logistic regression model, circulating adipsin independently predicted NAFLD remission (OR: 0.284, 95% confidence interval [CI]: 0.172-0.471, p for trend <0.001). The area under the receiver operating characteristic curve was 0.751 (95% CI: 0.717-0.785) (p < 0.001) for the prediction model of NAFLD remission.

CONCLUSIONS: We provide evidence for an association between serum adipsin levels and the remission of NAFLD in a community-based prospective cohort study. Serum adipsin can be a potential biomarker for predicting NAFLD remission.

PMID:34814152 | DOI:10.1159/000520368

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Soluble fluoride in Na2FPO3/CaCO3-based toothpaste as an indicator of systemically bioavailable fluoride

Caries Res. 2021 Nov 23. doi: 10.1159/000521068. Online ahead of print.

ABSTRACT

Fluoride chemically soluble in toothpaste is an indicator of fluoride bioavailability when the teeth are brushed and the same should be expected systemically when toothpaste is ingested. A four-phases study was conducted, in which eight participants were subjected in each phase to one of the assigned treatment groups: Group I: fresh sample of a Na2FPO3/CaCO3 toothpaste with 1,334 μg F/g of total soluble fluoride (TSF); groups II-IV: aged samples of toothpaste presenting TSF concentrations of 1,128, 808, and 687 μg F/g, respectively. In all phases, the participants ingested an amount of toothpaste equivalent to 70.0 µg F/kg body weight, as total fluoride (TF). Blood was collected before (baseline) and up to 180 min after toothpaste ingestion as indicator of fluoride bioavailability. Total urine (24 h before and 24 h after ingestion) was collected as indicator of absorbed fluoride that was excreted. F concentration in blood plasma and urine was determined with a fluoride ion-specific electrode. The areas under the curve of F concentration vs. time (AUC=ng F/ml x min) and the peaks of fluoride concentration in blood plasma (Cmax) were calculated. The net amount of fluoride excreted (mg/day) was calculated by subtraction. A significant correlation of the amount (mg) of TSF ingested was found between the AUC (r= 0.76; p<0.01) and Cmax (r= 0.86; p<0.01) in plasma, and the fluoride excreted (r= 0.65; p<0.01). For TF no statistical correlations were found (p>0.05). Data suggest that the concentration of TSF found in Na2FPO3/CaCO3-based toothpastes is a useful predictor of how much fluoride will be systemically bioavailable when this type of formulation is ingested.

PMID:34814135 | DOI:10.1159/000521068

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Kawasaki Disease and Atopic Diseases: A Systematic Review and Meta-Analysis of Observational Studies

Int Arch Allergy Immunol. 2021 Nov 23:1-9. doi: 10.1159/000520045. Online ahead of print.

ABSTRACT

INTRODUCTION: The etiology of Kawasaki disease (KD), an inflammatory and cardiovascular disorder, remains largely unexplained after more than 50 years of intensive research. In recent years, the association between KD and atopic diseases had been explored by some observational studies. We systematically reviewed and summarized the literature on the relationship between KD and atopic diseases.

METHODS: MEDLINE and EMBASE were searched to identify observational studies on the association between KD and atopic diseases from inception to May 2021. Odds ratio (OR) was pooled using random-effects models. Heterogeneity was assessed using the I2 and Cochran Q statistics. Primary outcomes were to compare the prevalence of KD among individuals with atopic diseases to nonatopic disease controls and the prevalence of atopic diseases among individuals with KD to non-KD controls.

RESULTS: Thirteen studies, including 12,651 cases and 170,708 controls, were included in this meta-analysis. In cross-sectional studies, KD was associated with allergic rhinitis (n = 6; OR, 1.69; 95% CI, 1.52-1.87), asthma (n = 3; OR, 1.72; 95% CI, 1.38-2.14), allergic conjunctivitis (n = 2; OR, 1.95; 95% CI, 1.68-2.27), and atopic dermatitis (n = 3; OR, 1.35; 95% CI, 1.22-1.49). In case-control and cohort studies, KD was associated with allergic rhinitis (n = 3; OR, 1.35; 95% CI, 1.28-1.43), asthma (n = 8; OR, 1.40; 95% CI, 1.19-1.65), allergic conjunctivitis (n = 1; OR, 1.74; 95% CI, 1.45-2.09), and atopic dermatitis (n = 3; OR, 1.39; 95% CI, 1.26-1.53).

CONCLUSION: KD diagnosed was associated with four common atopic diseases. Among the four allergic diseases, allergic conjunctivitis and asthma have the highest correlation with KD, which may provide a direction for exploring the etiology of KD.

PMID:34814144 | DOI:10.1159/000520045

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Correlation between radiographic and pathologic lymph node involvement and extranodal extension via CT and PET in HPV-associated oropharyngeal cancer

Oral Oncol. 2021 Nov 20;123:105625. doi: 10.1016/j.oraloncology.2021.105625. Online ahead of print.

ABSTRACT

PURPOSE/OBJECTIVES: Extranodal extension (ENE) and more than 4 pathologically involved lymph nodes (pN2) are critical prognostic factors in HPV-associated oropharyngeal cancer (HPV(+) OPSCC). We analyze a patient cohort with HPV(+) OPSCC to determine the sensitivity and specificity of CT and PET/CT in identifying involvement of more than 4 lymph nodes (rN2) compared to pN2 and radiographic ENE (rENE) compared to pathologic ENE (pENE).

MATERIALS/METHODS: The dataset consisted of 261 patients enrolled in two prospective clinical trials. All imaging studies were independently reviewed by a blinded neuroradiologist, classifying the presence or absence of rENE and rN2. Secondary analyses included correlations of imaging accuracy and pathologic size of the primary tumor.

RESULTS: CT demonstrated sensitivity of 59%, specificity of 92%, positive predictive value (PPV) of 53%, negative predictive value (NPV) of 94%, and accuracy of 88% for pN2. PET/CT showed similar results. Patients with up to 4 involved lymph nodes (rN0-1) had a 93-94% chance of remaining pN0-1. CT and PET/CT identified an equal number of involved nodes in 81% of patients. CT demonstrated sensitivity of 54%, specificity of 71%, PPV of 72%, NPV of 53%, and accuracy of 62% for pENE. PET/CT showed similar outcomes. Notably, when multiple radiographic criteria were used to identify rENE, PPV increased for both CT (84%) and PET/CT (79%).

CONCLUSION: Patients with rN0-1 had a 93-94% chance of remaining pN0-1, suggesting rN0-1 could effectively stratify patients for clinical trials and treatment de-escalation. While CT and PET/CT were highly correlated, both showed low sensitivity for identifying pENE.

PMID:34814068 | DOI:10.1016/j.oraloncology.2021.105625

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Risk of venous and arterial thromboembolic events in women with advanced breast cancer treated with CDK 4/6 inhibitors: A systematic review and meta-analysis

Thromb Res. 2021 Nov 17;208:190-197. doi: 10.1016/j.thromres.2021.11.009. Online ahead of print.

ABSTRACT

BACKGROUND: Cyclin-dependent kinase inhibitors (CDKIs) may increase the risk of thrombotic events of endocrine therapy (ET) in women with hormone-sensitive, HER2-negative advanced breast cancer (BC). Aim of our systematic review is the estimate of the risk of venous and arterial thromboembolism in women with advanced BC treated with CDKIs in phase III randomized controlled trials (RCTs).

METHODS: Studies were identified by electronic search of MEDLINE, EMBASE and CENTRAL database until October 2021. Risk of bias was assessed according to Cochrane criteria. Differences in thrombotic outcomes among groups were expressed as pooled odds ratio (OR) and corresponding 95% confidence interval (CI), which were calculated using both a fixed-effects and a random-effects model. Statistical heterogeneity was evaluated using the I2 statistic.

RESULTS: We included 7 phase III RCTs (4415 patients) for a total of 15 papers (7 were the first published paper and 8 the follow-up papers). Reporting of thrombotic events was at high risk of bias. Women with advanced BC treated with CDKIs and ET had a two to threefold increased risk of venous thromboembolic event (VTE) compared to ET plus placebo arm [OR 2.90 (95% CI 1.32, 6.37; I2 = 0%) in the main papers and OR 2.20 (95% CI 0.93, 5.20; I2 = 49%) in the follow-up papers]. Women with advanced BC treated with CDKIs and ET had a non-significant mild increased risk of arterial thromboembolic event compared to ET plus placebo arm [OR 1.22 (95% CI 0.47, 3.18 I2 = 0%)].

CONCLUSIONS: CDKIs in combination with endocrine therapy are associated with a two to threefold higher risk of VTE in comparison to endocrine therapy alone in women with advanced breast cancer, while the risk of arterial events is still to be defined.

PMID:34814055 | DOI:10.1016/j.thromres.2021.11.009

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The efficacy of bloodletting therapy in patients with acute gouty arthritis: A systematic review and meta-analysis

Complement Ther Clin Pract. 2021 Nov 11;46:101503. doi: 10.1016/j.ctcp.2021.101503. Online ahead of print.

ABSTRACT

BACKGROUND: Bloodletting therapy (BLT) is widely used to relieve acute gouty arthritis (AGA). However, limited evidence-based reports exist on the effectiveness and safety of BLT. This systematic review aims to evaluate the feasibility and safety of BLT in treating AGA.

METHODS: Seven databases were exhaustively screened from the date of establishment to July 31, 2020, irrespective of the publication source and language. The included articles were evaluated for bias risk by using the Cochrane risk of bias assessment tool. All statistical analyses were done with Review Manager 5.3.

RESULTS: Twelve studies involving 894 participants were included for the final analysis. Our meta-analysis revealed that BLT was highly effective in relieving pain (MD = -1.13, 95% CI [-1.60, -0.66], P < 0.00001), with marked alterations in the total effective (RR = 1.09, 95% [1.05, 1.14], P < 0.0001) and curative rates (RR = 1.37, 95%CI [1.17, 1.59], P < 0.0001). In addition, BLT could dramatically reduce serum C-reactive protein (CRP) level (MD = -3.64, 95%CI [-6.72, -0.55], P = 0.02). Both BLT and Western medicine (WM) produced comparable decreases in uric acid (MD = -18.72, 95%CI [-38.24, 0.81], P = 0.06) and erythrocyte sedimentation rate (ESR) levels (MD = -3.01, 95%CI [-6.89, 0.86], P = 0.13). Lastly, we demonstrated that BLT was safer than WM in treating AGA (RR = 0.36, 95%CI [0.13, 0.97], P = 0.04).

CONCLUSION: BLT is effective in alleviating pain and decreasing CRP level in AGA patients with a lower risk of evoking adverse reactions.

PMID:34814062 | DOI:10.1016/j.ctcp.2021.101503

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TMS-induced brain connectivity modulation in Genetic Generalized Epilepsy

Clin Neurophysiol. 2021 Nov 15;133:83-93. doi: 10.1016/j.clinph.2021.10.011. Online ahead of print.

ABSTRACT

OBJECTIVE: In epilepsy patients, Transcranial Magnetic Stimulation (TMS) may result in the induction and modulation of epileptiform discharges (EDs). We hereby investigate the modulatory effects of TMS on brain connectivity in Genetic Generalized Epilepsy (GGE) and explore their potential as a diagnostic biomarker in GGE.

METHODS: Patients with GGE (n=18) and healthy controls (n=11) were investigated with a paired-pulse TMS-EEG protocol. The brain network was studied at local and at global levels using Coherence as an EEG connectivity measure. Comparison of patients vs controls was performed in a time-resolved manner by analyzing comparatively pre- vs post-TMS brain networks.

RESULTS: There was statistically significant TMS-induced modulation of connectivity at specific frequency bands within groups and difference in TMS-induced modulation between the two groups. The most significant difference between patients and controls related to connectivity modulation in the γ band at 1-3 sec post-TMS (p=0.004).

CONCLUSIONS: TMS modulates the healthy and epileptic brain connectivity in different ways. Our results indicate that TMS-EEG connectivity analysis can be a basis for a diagnostic biomarker of GGE.

SIGNIFICANCE: The analysis identifies specific time periods and frequency bands of interest of TMS-induced connectivity modulation and elucidates the effect of TMS on the healthy and epileptic brain connectivity.

PMID:34814019 | DOI:10.1016/j.clinph.2021.10.011

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Primary stability of cement augmentation in locking plate fixation for proximal humeral fractures: A comparison of absorbable versus non-absorbable cement

Clin Biomech (Bristol, Avon). 2021 Nov 5;91:105516. doi: 10.1016/j.clinbiomech.2021.105516. Online ahead of print.

ABSTRACT

BACKGROUND: Cement augmentation has been suggested to increase the stability of screw anchoring in osteoporotic humeral fractures. Initial results are promising but may be jeopardized by cement leakage into the joint and difficult implant removal. Absorbable cement might have advantages in this regard, but it is unclear if the primary stability of both techniques is equivalent to each other. Therefore, this study aimed to compare its primary stability with that of non-absorbable cement augmentation.

METHODS: Nineteen cadaveric humeri with two-part fracture models were treated with locking plate osteosynthesis and cement augmentation using either absorbable calcium phosphate cement (group 1) or polymethylmethacrylate (group 2). Fracture movement, stiffness, failure mode, and ultimate load under cyclic compressive loading were examined and compared between the groups.

FINDINGS: The absolute and relative stiffness values in group 1 were significantly smaller than those in group 2 after 50 cycles (group 1: 114 ± 38 N/mm and 94 ± 8% vs. group 2: 188 ± 71 N/mm and 106 ± 9%; p50 = 0.022), 2000 cycles (group 1: 97 ± 34 N/mm and 81 ± 15% vs. group 2: 153 ± 47 N/mm and 88 ± 15%; p2000 = 0.028), and 5000 cycles (group 1: 98 ± 40 N/mm and 81 ± 22% vs. group 2: 158 ± 40 N/mm and 92 ± 16%; p5000 = 0.028). The failure load was not statistically significantly different between the groups.

INTERPRETATION: Although the PMAA group showed higher values for absolute and relative stiffness, no statistically significant difference was found in the primary stability between absorbable and non-absorbable cement augmentation supporting plate osteosynthesis in proximal humeral fractures. In view of the potential advantages of bio-absorbable cement during the healing process, its use should be considered for the augmentation and stabilization of osteoporotic fractures.

PMID:34814041 | DOI:10.1016/j.clinbiomech.2021.105516

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Tag Variants of LGALS-3 Containing Haplotype Block in Advanced Carotid Atherosclerosis

J Stroke Cerebrovasc Dis. 2021 Nov 20;31(1):106212. doi: 10.1016/j.jstrokecerebrovasdis.2021.106212. Online ahead of print.

ABSTRACT

OBJECTIVES: Galectin-3 affects a variety of biological processes. It is encoded by LGALS-3, located in unique haplotype block in Caucasians. Most of the studies regarding the gal-3 role in atherosclerosis are focused exclusively on protein/mRNA levels. Genetic analyses of LGALS-3 are scarce. We sought to thoroughly examine the genetic background of gal-3 and to analyze tag variants that cover more than 80% variability of the LGALS-3 containing hap-block in association with carotid plaque presence (CPP). According to Tagger server, rs4040064 G/T, rs11628437 G/A and rs7159490 C/T cover 82% (r2 > 0.8) of the genetic variance of this hap-block. Our aims were to investigate possible association of rs4040064, rs11628437 and rs7159490 haplotypes with CPP in patients with advanced carotid atherosclerosis (CA) and to analyze their possible effect on LGALS-3 mRNA expression in carotid plaques.

MATERIALS AND METHODS: Study group consisted of 468 patients and 296 controls. Rs4040064, rs11628437, rs7159490 and LGALS-3 mRNA expression were detected by TaqMan® technology.

RESULTS: We have found that haplotype TAC was associated with the cerebrovascular insult (CVI) occurrence (OR = 1.68, 95% CI = 1.09-2.58, p = 0.02), compared to the referent haplotype. OR was adjusted for hypertension, age and BMI. TAC also showed higher, but not statistically significant, LGALS-3 expression in carotid plaques.

CONCLUSIONS: Our results suggest that rs4040064, rs11628437 and rs7159490 bear no association with CPP, neither they affect LGALS-3 mRNA in carotid plaques. However, we showed a significant association of haplotype TAC with the CVI occurrence in CA patients from Serbia. Replication and validation of our results are required.

PMID:34814004 | DOI:10.1016/j.jstrokecerebrovasdis.2021.106212