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Daily monitoring of viral load measured as SARS-CoV-2 antigen and RNA in blood, IL-6, CRP and complement C3d predicts outcome in patients hospitalized with COVID-19

Clin Chem Lab Med. 2021 Aug 27. doi: 10.1515/cclm-2021-0694. Online ahead of print.

ABSTRACT

OBJECTIVES: We hypothesized that the amount of antigen produced in the body during a COVID-19 infection might differ between patients, and that maximum concentrations would predict the degree of both inflammation and outcome for patients.

METHODS: Eighty-four hospitalized and SARS-CoV-2 PCR swab-positive patients, were followed with blood sampling every day until discharge or death. A total of 444 serial EDTA plasma samples were analyzed for a range of biomarkers: SARS-CoV-2 nuclear antigen and RNA concentration, complement activation as well as several inflammatory markers, and KL-6 as a lung marker. The patients were divided into outcome groups depending on need of respiratory support and death/survival.

RESULTS: Circulating SARS-CoV-2 nuclear antigen levels were above the detection limit in blood in 65 out of 84 COVID-19 PCR swab-positive patients on day one of hospitalization, as was viral RNA in plasma in 30 out of 84. In all patients, complete antigen clearance was observed within 24 days. There were definite statistically significant differences between the groups depending on their biomarkers, showing that the concentrations of virus RNA and antigen were correlated to the inflammatory biomarker levels, respiratory treatment and death.

CONCLUSIONS: Viral antigen is cleared in parallel with the virus RNA levels. The levels of antigens and SARS-CoV-2 RNA in the blood correlates with the level of IL-6, inflammation, respiratory failure and death. We propose that the antigens levels together with RNA in blood can be used to predict the severity of disease, outcome, and the clearance of the virus from the body.

PMID:34455731 | DOI:10.1515/cclm-2021-0694

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Efficacy of lettuce seed syrup on insomnia in patients with breast cancer: a pilot double blind randomized placebo controlled clinical trial

J Complement Integr Med. 2021 Aug 30. doi: 10.1515/jcim-2021-0181. Online ahead of print.

ABSTRACT

OBJECTIVES: Insomnia and sleep disorders are common and can be severe amongst patients with cancer, especially during chemotherapy. The aim of this study was to evaluate the efficacy of lettuce seed syrup in breast cancer patients who suffer from insomnia or disordered sleep.

METHODS: This pilot study was a double-blinded randomized controlled clinical trial conducted in Shohae-Tajrish Hospital (Tehran, Iran) from September 2018 to June 2019. 50 adult patients with breast cancer with insomnia or sleep disorders were enrolled. Participants were randomly allocated to lettuce seed syrup (5 mL twice daily), or placebo syrup at the same dose for four weeks. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate sleep quality before and after the intervention.

RESULTS: Compared to placebo, the mean of the total PSQI score decreased significantly in participants who received lettuce seed syrup (p=0.014). In addition, there were statistically significant reductions in the mean scores of subject quality sleep (p=0.002), sleep duration (p=0.038), habitual sleep efficacy (p=0.029) and sleep disturbance (p=0.032) in patients who received lettuce seed syrup.

CONCLUSIONS: Lettuce seed syrup may improve self-reported sleep quality in participants with breast cancer. Larger trials are indicated in diverse samples of participants with caner to learn if these finds are generalizable.

PMID:34455726 | DOI:10.1515/jcim-2021-0181

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Risk factors for gastrointestinal bleeding in patients with gastrointestinal cancer using edoxaban

J Thromb Haemost. 2021 Aug 29. doi: 10.1111/jth.15516. Online ahead of print.

ABSTRACT

BACKGROUND: In the Hokusai VTE Cancer study, the risk of major bleeding was 2.9% higher in the edoxaban group compared with the dalteparin group, mainly due to more gastrointestinal bleedings in patients with gastrointestinal cancer. The identification of risk factors for gastrointestinal bleeding may help to guide the use of DOACs in these patients OBJECTIVES: To evaluate risk factors for gastrointestinal bleeding in patients with gastrointestinal cancer receiving edoxaban.

PATIENTS/METHODS: In this nested case-control study in patients with gastrointestinal cancer randomized to edoxaban in the Hokusai VTE Cancer study, cases (patients with clinically relevant gastrointestinal bleeding during treatment) were randomly matched to three controls (patients who had no gastrointestinal bleeding). Data for the 4-week period prior to bleeding were retrospectively collected. Odds ratios (ORs) were calculated in a crude conditional logistic regression model and a multivariable model adjusted for age, sex, and cancer type.

RESULTS: 24 cases and 64 matched controls were included. In the multivariable analysis, advanced cancer, defined as regionally advanced or metastatic cancer (OR 3.6, 95% CI 1.01-12.6) and low hemoglobin levels (OR 4.8, 95% CI 1.5-16.0) were significantly associated with bleeding. There was no significant difference in patients with resected tumors (OR 0.4, 95% CI 0.1-1.4), or in patients on chemotherapy (OR 1.3, 95% CI 0.5-3.5).

CONCLUSION: Advanced cancer and low hemoglobin levels were associated with an increased risk of gastrointestinal bleeding in patients with gastrointestinal cancer receiving edoxaban. We were unable to identify other risk factors, mainly due to limited statistical power.

PMID:34455706 | DOI:10.1111/jth.15516

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Determination of Predictive Risk Factors for Severe Bronchiolitis

Int J Clin Pract. 2021 Aug 29:e14760. doi: 10.1111/ijcp.14760. Online ahead of print.

ABSTRACT

BACKGROUND: The aim of this study was to determine the predictive risk factors for development of severe bronchiolitis in patients with acute bronchiolitis with no previous chronic disease.

METHODS: Four hundred forty children aged 1-24 months hospitalized with acute bronchiolitis, were examined between February 2018 and February 2019 in this prospective study.

RESULTS: Eighty-five cases were regarded as severe bronchiolitis and 355 as mild-moderate bronchiolitis. Statistically significant differences were observed between the severe and mild-moderate bronchiolitis groups in terms of weight-for-age z-scores, history of bronchiolitis, hemoglobin levels, and time elapsed between onset of symptoms and admission. Weight-for-age z-scores, the mean time interval between onset of symptoms and admission, and mean hemoglobin values were lower in the severe bronchiolitis group while the mean number of bronchiolitis attacks was higher than in the mild-moderate bronchiolitis group. Logistic regression analysis determined that a low weight-for-age z-score increased the risk of severe bronchiolitis development 0.56-fold (CI: 0.409 – 0.760), a short duration between the onset of symptoms and admission increased the risk 0.62-fold (CI: 0.519 – 0.735), a frequent history of bronchiolitis increased the risk 1.81-fold (CI: 1.135 – 2.968) and low hemoglobin levels increased the risk 0.72-fold (CI: 0.537 – 0.969).

CONCLUSION: Low weight-for-age z-scores, a short duration between the onset of symptoms and admission, a high number of previous attacks, and low hemoglobin levels were identified as independent parameters of severe bronchiolitis development.

PMID:34455690 | DOI:10.1111/ijcp.14760

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The Frequency of Emergence Delirium in Children Undergoing Outpatient Anaesthesia for Magnetic Resonance Imaging

Int J Clin Pract. 2021 Aug 29:e14763. doi: 10.1111/ijcp.14763. Online ahead of print.

ABSTRACT

AIM: The aim of this study was to investigate the effect on the occurrence of emergence delirium of propofol and ketofol with intranasal dexmedetomidine and midazolam applied as premedication to paediatric patients during magnetic resonance imaging (MRI).

METHODS: The study included children aged 2-10 years who received sedation for MRI, separated into four groups. Group MP (midazolam-propofol) received intranasal midazolam (0.2mg/kg) for premedication and intravenous (IV) propofol (1mg/kg) as the anaesthetic agent. Group MK (midazolam-ketofol) received intranasal midazolam (0.2mg/kg) for premedication and IV ketofol (1mg/kg) as the anaesthetic agent. Group DP (dexmedetomidine-propofol) received intranasal dexmedetomidine (1mcg/kg) for premedication and IV propofol (1mg/kg) as the anaesthetic agent. Group DK (dexmedetomidine-ketofol) received intranasal dexmedetomidine (1mcg/kg) for premedication and IV ketofol (1mg/kg) as the anaesthetic agent. The Paediatric Anaesthesia Emergence Delirium (PAED) scale was used to evaluate delirium. A PAED score ≥ 10 was accepted as delirium.

RESULTS: Statistical analysis was made of 140 paediatric patients. Delirium developed in 1.42% of all the patients, and in 5.7% of Group MP. The mean Aldrete and PAED scores were lower and the length of stay in the recovery room was shorter in Group DP than in the other groups. The need for additional anaesthetic was highest in Group DP at 94.3% and lowest in Group DK at 14.3%. The groups administered ketofol were observed to have a lower requirement for additional anaesthetic.

CONCLUSION: Delirium was seen at a very low rate only in the Group MP and it is difficult to say the best combination in terms of delirium frequency. However, intranasal dexmedetomidine and IV ketofol seem to be better and safer than the other groups in terms of the need for additional doses and the number of side effects. The addition of ketamine to propofol reduces the need for additional doses with a synergistic effect.

PMID:34455665 | DOI:10.1111/ijcp.14763

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Tumour-stroma ratio is a valuable prognostic factor for oral tongue squamous cell carcinoma

Oral Dis. 2021 Aug 29. doi: 10.1111/odi.14013. Online ahead of print.

ABSTRACT

OBJECTIVE: The objectives of this study were to estimate the prognostic value of the tumour-stroma ratio (TSR) and tumour budding (TB) in oral tongue squamous cell carcinoma (OTSCC) and to establish a reliable model to predict the outcome of OTSCC patients.

METHODS: A total of 103 patients surgically treated at our hospital were enrolled in this study. Chi-square tests, Kaplan-Meier analyses, and Cox proportional hazards regression models were performed for statistical analysis.

RESULTS: Fifty-six patients were categorized as stroma-rich, and forty-seven patients were categorized as stroma-poor. Only pathological grade was associated with the TSR (P=0.017). Kaplan-Meier analysis showed that stroma-rich, high-intensity budding and high risk groups were associated with worse prognosis. The Cox regression model showed that the TSR was an independent risk factor for OTSCC patients prognosis, and the high risk group was also related to poor prognosis (P<0.05). TB was significantly associated with poor prognosis but was not an independent risk factor.

CONCLUSIONS: We found that patients in the stroma-rich group had a worse long-term prognosis. The TSR is an independent risk factor for OTSCC patients outcome. In addition, a risk model that combined the TSR and TB proved to be valuable for predicting OTSCC patients outcome.

PMID:34455659 | DOI:10.1111/odi.14013

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C-reactive protein and procalcitonin after congenital heart surgery utilizing cardiopulmonary bypass: When should we be worried?

J Card Surg. 2021 Aug 29. doi: 10.1111/jocs.15952. Online ahead of print.

ABSTRACT

INTRODUCTION: To assess the efficacy of C-reactive protein (CRP) and procalcitonin (PCT) at identifying infection in children after congenital heart surgery (CHS) with cardiopulmonary bypass (CPB).

MATERIALS AND METHODS: Systematic review of the literature was conducted to identify studies with data regarding CRP and/or PCT after CHS with CPB. The primary variables identified to be characterized were CRP and PCT at different timepoints. The main inclusion criteria were children who underwent CHS with CPB. Subset analyses for those with and without documented infection were conducted in similar fashion. A p value of less than .05 was considered statistically significant.

RESULTS: A total of 21 studies were included for CRP with 1655 patients and a total of 9 studies were included for PCT with 882 patients. CRP peaked on postoperative Day 2. A significant difference was noted in those with infection only on postoperative Day 4 with a level of 53.60 mg/L in those with documented infection versus 29.68 mg/L in those without. PCT peaked on postoperative Day 2. A significant difference was noted in those with infection on postoperative Days 1, 2, and 3 with a level of 12.9 ng/ml in those with documented infection versus 5.6 ng/ml in those without.

CONCLUSIONS: Both CRP and PCT increase after CHS with CPB and peak on postoperative day 2. PCT has a greater statistically significant difference in those with documented infection when compared to CRP and a PCT of greater than 5.6 ng/ml should raise suspicion for infection.

PMID:34455653 | DOI:10.1111/jocs.15952

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Cane toad (Rhinella marina) vitamin A, vitamin E, and carotenoid kinetics

Zoo Biol. 2021 Aug 29. doi: 10.1002/zoo.21648. Online ahead of print.

ABSTRACT

Many amphibian species are threatened with extinction. Understanding their vitamin A (retinol), E (alpha-tocopherol), and carotenoid requirements is vital, as normal levels of these nutrients have a known connection to breeding success with abnormal levels leading to disease. This research examined vitamins A, E, and carotenoids (apocarotenoid, beta-carotene; beta-cryptoxanthin, lutein, zeaxanthin, and esters) concentration kinetics in the liver and plasma of 65 (57.8) cane toads (Rhinella marina) over 4 months supplemented with commercially available invertebrates in human care. Cane toads were opportunistically collected as part of a population control program for use as an amphibian model species. Toads were randomly assigned to one of two diets: treatment 1 was brown house crickets (Acheta domesticus) consuming Mazuri® Hi Calcium Gut Loading Diet without vitamin A or E supplement, plus fresh raw vegetables (carrot/sweet potato); Treatment 2 was the same diet except no vegetables. Ten toads were euthanized on Day 0 to analyze baseline free-ranging liver and plasma metabolites. Six toads consuming each treatment were euthanized on Days 22, 50, and 81, and n = 7 on Day 119 for analysis. Regardless of dietary treatment, most liver and blood metabolites were substantially higher at time 0 than all time points thereafter (p < .05); Ex: liver vitamin A at time 0 was 87.7 ± 16.12 µg/g while Day 119 for treatments 1 and 2 were 11.6 ± 1.19 and 8.2 ± 0.74, respectively. Few statistically significant differences between diets at the same time point were noted (p < .05). The results from this study indicate that additional or alternative diet supplementation may be needed for cane toads (and potentially other amphibians) to mimic their free-ranging diets.

PMID:34455629 | DOI:10.1002/zoo.21648

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Dorsomorphin attenuates Jagged1-induced mineralization in human dental pulp cells

Int Endod J. 2021 Aug 29. doi: 10.1111/iej.13620. Online ahead of print.

ABSTRACT

AIM: To investigate whether TGF-β/BMP signaling participates in Jagged1-induced osteogenic differentiation in human dental pulp cells (hDPs).

METHODOLOGY: Bioinformatic analysis of publicly available RNA sequencing data of Jagged1 treated hDPs was performed using NetworkAnalyst. The mRNA expression was validated using real-time polymerase chain reaction. hDPs were seeded on Jagged1 immobilized surface in the presence or absence of TGF-β or BMP inhibitor. Osteogenic differentiation was evaluated using alkaline phosphatase staining, osteogenic marker gene expression, and mineralization assay. Statistical analyses were performed using a Kruskal Wallis test, followed by a pairwise comparison for more than three group comparison. Mann Whitney U test was employed for two group comparison. The statistical significance was considered at p< 0.05.

RESULTS: Jagged1 treatment in growth medium significantly promoted TGFB1, TGFB2, and TGFB3 while significantly inhibited BMP2, BMP4, and BMP6 mRNA expression (p<0.05). In osteogenic induction medium, Jagged1 significantly upregulated TGFB1, TGFB2, and TGFB3 at day 1 and 3 (p<0.05). Pretreatment with TGF-β1, TGF-β2, or TGF-β3 prior to osteogenic induction resulted in the significant increase of osteogenic marker gene expression, collagen type 1 protein expression, alkaline phosphatase enzymatic activity, and mineral deposition (p<0.05). However, TGF-β signaling inhibition with SB431542 (4 μM) or SB505124 (47 and 129 nM) failed to attenuate the effect of Jagged1-induced osteogenic differentiation in hDPs. Dorsomorphin (4 and 8 μM) treatment significantly abolished the effect of Jagged1 on mineralization by hDPs (p<0.05).

CONCLUSION: Notch signaling activation by Jagged1 modulated TGF-β and BMP ligand expression. Dorsomorphin, but not TGF-β receptor inhibitor, attenuated Jagged1-induced osteogenic differentiation in hDPs.

PMID:34455605 | DOI:10.1111/iej.13620

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The efficacy of soy isoflavones combined with soy protein on serum concentration of interleukin-6 and tumor necrosis factor-α among postmenopausal women? A systematic review and meta-analysis of randomized controlled trials

Clin Exp Pharmacol Physiol. 2021 Aug 29. doi: 10.1111/1440-1681.13586. Online ahead of print.

ABSTRACT

The postmenopausal stage in women’s life is associated with the enhancement of inflammation that may be reduced using soy isoflavones or soy protein. The present study aimed to summarize the effect of soy isoflavones and soy protein on circulating interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in postmenopausal women. The English-language articles were identified from the databases such as Cochrane Library, clinicaltrials.gov, Web of Science, PubMed, and Scopus until December 2020. The mean change from baseline and its standard deviation (SD) for intervention and comparison groups were used to calculate the effect size. The statistical heterogeneity of the intervention effects was computing by Cochran’s Q test and I-squared statistic. Nine and seven studies were selected for systematic review and meta-analysis respectively. The results of our meta-analysis indicated a non-significant effect on the serum concentrations of IL-6 and TNF-α (weighted mean differences (WMD)=0.07 pg/mL; 95% confidence interval (CI): -0.03, 0.17 pg/mL; P=0.190; WMD=0.05 pg/mL; 95% CI: -0.01, 0.12 pg/mL; P=0.092; respectively). In subgroup analysis, soy isoflavones plus soy protein could increase the serum concentration of IL-6 in studies with soy isoflavones dose ≤87 mg/d, cross-over design, weak quality, and studies on participants who had health risk factors or diseases. The serum concentration of TNF-α increased in studies with cross-over design, intervention duration≤56 days, and body mass index (BMI)>27, and in studies which were conducted on at-risk or sick participants. In conclusion, our meta-analysis did not confirm any downward effect on serum concentration of IL-6 and TNF-α among postmenopausal women.

PMID:34455600 | DOI:10.1111/1440-1681.13586