Addressing adherence to guidelines on prevention of acute chemotherapy‐induced nausea and vomiting in pediatric patients

alexandrossfakianakis shared this article with you from Inoreader Addressing adherence to guidelines on prevention of acute chemotherapy‐induced nausea and vomiting in pediatric patients via Pediatric Blood & Cancer Abstract Background Chemotherapy-induced nausea and vomiting (CINV) is a distressing adverse effect in children receiving cancer treatment. There are evidence-based pediatric clinical practice guidelines (CPG) on chemotherapy emetogenicity and acute CINV prevention, but adherence to these guidelines is low. Procedure A quality improvement-based study was conducted at McMaster Children's Hospital. The SMART aim was to increase adherence to guidelines on prevention of acute CINV in hospitalized patients receiving high (HEC) and moderately emetogenic chemotherapy (MEC) from baseline 25% to more than 70% by June 2021. Barriers were identified by process mapping, and a series of interventions were implemented. Results Guideline adherence was assessed in 270 inpatient chemotherapy administrations (HEC, MEC). Data were collected on 131 charts pre interventions and 139 charts post interventions. Interventions included education, addition of guideline-recommended anti-emetics to the inpatient formulary, and implementation of a standardized CPG tool. Initial rates of total CINV guideline adherence were 25%, which improved to 72% post intervention (p < .001). In subgroup analysis, guideline adherence in the MEC group improved from 13% to 34% (p = .015), and in the HEC group from 32% to 93% (p < .001). The most common reason for nonadherence in the HEC group was failure to use aprepitant as anti-emetic, and in MEC was option for ondansetron monotherapy prophylaxis. Conclusion Using quality improvement methodology, barriers to guideline adherence were identified and interventions implemented. Guideline adherence for prevention of CINV improved, particularly in the HEC group but less for the MEC group. Future steps will include sustainability of interventions and addressing adherence in the MEC group. View on Web

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Periodontitis and low cognitive performance: A population‐based study

alexandrossfakianakis shared this article with you from Inoreader Periodontitis and low cognitive performance: A population‐based study via Journal of Clinical Periodontology Abstract Aim To study the epidemiological association between periodontitis and low cognitive performance amongst older adults, within a representative sample of the US population. Materials and methods Data from 2086 older adults (≥60 years old), representative of 77.1 million people, were retrieved from the NHANES 2011–2014 database. Periodontitis cases were identified and classified according to the AAP/CDC criteria (mild, moderate, and severe). Cognitive function was assessed through the Consortium to Establish a Registry for Alzheimer's disease (CERAD), the Animal Fluency (AFT), the Digit Symbol Substitution (DSST) tests, and the global cognition score. The lowest non-survey weighted quartile for each cognitive test was defined as low cognitive performance. Simple and multiple regression analyses were performed. Results Moderate and severe periodontitis were significantly associated with a low DSST performance (OR = 1.66, and OR = 2.97, respectively). Each millimeter of increase in mean CAL was associated with a lower AFT (OR = 1.44), DSST (OR = 1.86), and global cognition (OR = 1.50) performance. Conclusions The findings of the present study suggest the presence of an independent association between periodontitis and low cognitive performance amongst older adults (≥60 years old). This article is protected by copyright. All rights reserved. View on Web

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Neuroinflammation related to the blood‐brain barrier and sphingosine‐1‐phosphate in a pre‐clinical model of periodontal diseases and depression in rats.

alexandrossfakianakis shared this article with you from Inoreader Neuroinflammation related to the blood‐brain barrier and sphingosine‐1‐phosphate in a pre‐clinical model of periodontal diseases and depression in rats. via Journal of Clinical Periodontology ABSTRACT Aim To explore the potential mechanisms of neuroinflammation (microglia, blood-brain barrier [BBB] permeability, and the sphingosine-1-phosphate [S1P] pathways) resulting from the association between periodontitis and depression in rats. Materials and methods This pre-clinical in vivo experimental study used Wistar rats, in which experimental periodontitis (P) was induced by using oral gavages with Porphyromonas gingivalis and Fusobacterium nucleatum. Then a chronic mild stress (CMS) model was implemented to induce depressive-like behavior, resulting in four groups: P with CMS (P+CMS+), P without CMS (P+CMS-), CMS without P (P-CMS+), and controls (P-CMS-). After harvesting brain samples, Protein/mRNA expression analyses and fluorescence immunohistochemistry were performed in the frontal cortex (FC). Results were analyzed by ANOVA tests. Results CMS exposure increased the number of microglia (an indicator of neuroinflammation) in the FC. In the combined model (P+CMS+), there was a decrease in the expression of tight junction proteins (zonula occludens-1 [ZO-1], occludin) and an increase in intercellular and vascular cell adhesion molecules (ICAM-1, VCAM-1) and matrix metalloproteinase 9 (MMP9), suggesting a more severe disruption of the BBB. The enzymes and receptors of S1P were also differentially regulated. Conclusions Microglia, BBB permeability, and S1P pathways could be relevant mechanisms explaining the association between periodontitis and depression. This article is protected by copyright. All rights reserved. View on Web

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Initial supplementary dose of dolutegravir in second-line antiretroviral therapy: a non-comparative, double-blind, randomised placebo-controlled trial

alexandrossfakianakis shared this article with you from Inoreader Initial supplementary dose of dolutegravir in second-line antiretroviral therapy: a non-comparative, double-blind, randomised placebo-controlled trial via Clinical Infectious Diseases Advance Access Abstract Background Dolutegravir concentrations are reduced by efavirenz induction effect necessitating twice daily dolutegravir dosing when co-administered. Efavirenz induction persists for several weeks after stopping, which could potentially select for dolutegravir resistance if switching occurred with unsuppressed HIV-1 RNA levels and standard dolutegravir dosing. We evaluated the need for a lead-in supplementary dolutegravir dose in adults failing first-line tenofov ir-emtricitabine-efavirenz (TEE). Methods We conducted a randomised, double-blind, placebo-controlled, phase 2 trial in Khayelitsha, South Africa. Eligible patients had virologic failure (two consecutive HIV-1 RNA≥1000 copies/mL) on first-line TEE. Participants were randomly assigned (1:1) to switch to tenofovir-lamivudine-dolutegravir (TLD) with a supplementary 50 mg dolutegravir dose or placebo taken 12 hours later for 14 days. Primary outcome was proportion with HIV-1 RNA<50 copies/mL at week 24. This study was not powered to compare arms. Results 130 participants were randomised (65 to each arm). Median baseline HIV-1 RNA was 4.0 log10 copies/mL and 76% had baseline resistance to both tenofovir and lamivudine. One participant died and two were lost to follow-up. At week 24, 55/64 (86%, 95% confidence interval [CI], 75–93%) in the supplementary dolutegravir arm and 53/65 (82%, 95% CI, 70–90%) in the placebo arm had HIV-1 RNA<50 copies/mL. Grade 3 or 4 adverse events were similar in frequency between arms. None of six participants (3 in each arm) eligible for resistance testing by 24 weeks developed dolutegravir resistance. Conclusions Our findings do not support the need for initial dolutegravir dose adjustment in patients switching to TLD who failed first-line TEE. View on Web

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Pharmacokinetic and pharmacodynamic study of 3 products of epoetin alfa as single subcutaneous dose in healthy volunteers

alexandrossfakianakis shared this article with you from Inoreader Pharmacokinetic and pharmacodynamic study of 3 products of epoetin alfa as single subcutaneous dose in healthy volunteers via Fundamental & Clinical Pharmacology Abstract Background Hemax® is an epoetin alfa product developed by Biosidus S.A. in Argentina at the end of the 1980's and has been present in that market since 1991. The initial presentation was a lyophilized powder containing albumin as stabilizer, to best adapt to environmental conditions in developing countries; more recently, a prefilled syringe, albumin-free presentation was developed, since this presentation has become the preferred standard in many markets. Objective The primary objective was to compare the pharmacokinetic profile of different formulations of epoetin alfa after a single subcutaneous administration to healthy volunteers of 40,000 IU of Eprex/Erypo® and Hemax® PFS. Methods This clinical trial was conceived following an open label, randomized, 3-way 3-period cross-over balanced, and sequential design. The study was conducted on 24 healthy volunteers. Results To analyze similarity between Hemax® PFS and the innovator product, Eprex®, AUC and Cmax of both products have been compared. The 90%CI lower limit for the geometric mean ratios was higher than 80% for any comparisons and the 90%CI upper limit for these geometric ratios was below 125% for all the comparisons made, thus demonstrating equivalence between both products. Conclusion The comparison between Hemax® PFS and Eprex® resulted in similar 90%CI for Cmax, AUC(0-120 h) and AUC(0-inf) ratios, all of them within the 80-125% interval, with a power above 95% for each ratio. These findings suggest biosimilar patterns for absorption velocity (with Tmax close to 15 h), absorption extent and elimination (with an elimination half-life close to 25-30 h for each formulation) View on Web

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Myeloid Phenotypes in Tracheostomy‐Associated Granulation Tissue

alexandrossfakianakis shared this article with you from Inoreader Myeloid Phenotypes in Tracheostomy‐Associated Granulation Tissue via The Laryngoscope In patients with indwelling tracheostomy, granulation tissue is a common, recurrent problem that may lead to multiple surgeries, difficulties with decannulation, and even wound contracture leading to stenosis at the site of prosthesis. This study demonstrates that alternatively activated M2 macrophages are increased in airway granulation tissue as determined by gene expression analysis of canonical biomarkers and cell surface antigens assessed by flow cytometry and immunohistochemistry. The monocyte cell populations associated with granulation tissue are predominantly classical subtype and the majority of macrophages were positive for pro-inflammatory marker S100A8/A9 with 36% of macrophages co-localizing the biomarker CD169+, highlighting these cell population as potential therapeutic targets for airway granulation tissue. Objective(s) Tracheostomy-associated granulation tissue is a common, recurrent problem occurring secondary to chronic mucosal irritation. Although granulation tissue is composed of predominantly innate immune cells, the phenotype of monocytes and macrophages in tracheostomy-associated granulation tissue is unknown. This study aims to define the myeloid cell population in granulation tissue secondary to tracheostomy. Methods Granulation tissue biopsies were obtained from 8 patients with tracheostomy secondary to laryngotracheal stenosis. Cell type analysis was performed by flow cytometry and gene expression was measured by quantitative real-time polymerase chain reaction. These methods and immunohistochemistry were used to define the monocyte/macrophage population in granulation tissue and were compared to tracheal autopsy control specimens. Results Flow cytometry demonstrated macrophages (CD45+CD11b+) and monocytes (CD45+FSClowSSClow) represent 23.2 ± 6% of the granulation tissue cell population. The M2 phenotype (CD206) is present in 77 ± 11% of the macrophage population and increased compared to the M1 phenotype (p = 0.012). Classical monocytes (CD45+CD14highCD16low) were increased in granulation tissue compared to controls (61.2 ± 7% and 30 ± 8.5%, p = 0.038). Eighty-five percent of macrophages expressed pro-inflammatory S100A8/A9 and 36 ± 4% of macrophages co-localized CD169, associated with tissue-resident macrophages. M2 gene expression (Arg1/CD206) was increased in granulation tissue (3.7 ± 0.4, p = 0.035 and 3.5 ± 0.5, p = 0.047) whereas M1 gene expression (CD80/CD86) was similar to controls (p = 0.64, p = 0.3). Immunohistochemistry of gra nulation tissue demonstrated increased cells co-localizing CD11b and CD206. Conclusions M2 macrophages are the dominant macrophage phenotype in tracheostomy-associated granulation tissue. The role of this cell type in promoting ongoing inflammation warrants future investigation to identify potential treatments for granulation tissue secondary to tracheostomy. Level of Evidence 3 Laryngoscope, 2023 View on Web

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Efficacy of Serum Apelin and Galectin‐3 as Potential Predictors of Mortality in Severe COVID‐19 Patients

alexandrossfakianakis shared this article with you from Inoreader Efficacy of Serum Apelin and Galectin‐3 as Potential Predictors of Mortality in Severe COVID‐19 Patients via Journal of Medical Virology Abstract Background Apelin is a cardioprotective biomarker while galectin-3 is a proinflammatory and profibrotic biomarker. Endothelial dysfunction, hyperinflammation, and pulmonary fibrosis are key mechanisms that contribute to the development of adverse outcomes in COVID-19 infection. This study aims to analyze the prognostic value of serum apelin and galectin-3 levels to early predict patients at high risk of mortality in patients hospitalized for severe COVID-19 pneumonia. Methods The study included 78 severe COVID-19 patients and 40 healthy controls. The COVID-19 patients were divided into 2 groups, survivors and non-survivors, according to their in-hospital mortality status. Basic demographic and clinical data of all patients were collected and blood samples were taken before treatment. Results In our study, serum apelin levels were determined to be significantly lower in both non-survivor and survivor COVID-19 patients compared to the control subjects (for both groups, p<0.001). However, serum apelin levels were similar in survivor and non-survivor COVID-19 patients (p>0.05). Serum galectin-3 levels were determined to be higher in a statistically significant way in non-survivors compared to survivors and controls (for both groups; p<0.001). Additionally, serum galectin-3 levels were significantly higher in the survivor patients compared to the control subjects (p<0.001). Positive correlations were observed between galectin-3 and age, ferritin, CK-MB and NT-proBNP variables (r=0.32, p=0.004; r=0.24, p=0.04; r=0.24, p=0.03 and r=0.33, p=0.003, respectively) while a negative correlation was observed between galectin-3 and albumin (r=-0.31, p=0.006). Multiple logistic regression analysis revealed that galectin-3 was an independent predictor of mortality in COVID -19 patients (OR=2.272, 95% CI, 1.106-4.667; p=0.025). When the threshold value for galectin-3 was regarded as 2.8 ng/mL, it was discovered to predict mortality with 80% sensitivity and 57% specificity (AUC: 0.738, 95% CI: 0.611-0.866, p=0.002). Conclusion Galectin-3 might be a simple, useful, and prognostic biomarker that can be utilized to predict patients who are at high risk of mortality in severe COVID-19 patients. This article is protected by copyright. All rights reserved. View on Web

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Wnt3a promotes odonto/osteogenic differentiation in vitro and tertiary dentin formation in a rat model

alexandrossfakianakis shared this article with you from Inoreader Wnt3a promotes odonto/osteogenic differentiation in vitro and tertiary dentin formation in a rat model via International Endodontic Journal Abstract Aim To investigate the effect of Wnt3a on odonto/osteogenic differentiation of stem cells isolated from human exfoliated deciduous teeth (SHEDs) and reparative dentine formation in a rat model. Methodology SHEDs were cultured in media with Wnt3a (50-200 ng/mL). Wnt activation was confirmed by β-catenin immunocytochemistry. Colony-forming unit assay (normalised percentage area), osteogenic gene expression analysis by real-time polymerase chain reaction and mineralisation assays measured by the absorption at 540 nm were performed. Tertiary dentine formation in vivo was evaluated using 8-week-old, male Wistar rats. Cavities with pinpoint pulp exposure by a sharp instrument were prepared at the mesial surface of the first molars. Teeth were divided into (n=6): 1) distilled water (negative control), 2) phosphate-buffered saline (PBS), 3) lithium chloride in DI (20 μM), and 4) Wnt3a in PBS (200 ng/mL). Collagen sponge was used as a scaffold. The cavity was sealed with glass ionomer restoration. Four weeks later, animals were euthanised by sodium pentobarbital (120 mg/kg body weight). Hard tissue formation was evaluated using micro-computerised tomography. Sixty consecutive slides from the initial plane were analysed and calculated as bone/dentine volume per total tissue volume. Paraffin sections (2 μm) were stained with haematoxylin and eosin and Masson's trichrome for morphological evaluation. Data are presented as the mean ± standard error. Mann-Whitney U test was used for two-group comparison. Kruskal Wallis followed by pairwise comparison was employed for three or more group comparisons. Statistical analysis was performed using GraphPad Prism 7. Differences were considered significant at p < 0.05. Results Wnt3a decreased SHEDs colony formation and increased OSX, BMP2, and DMP1 expression, corresponding to an increase in mineralisation. Additionally, a significant increase in dentine/bone volume per total tissue volume was observed in Wnt3a treated defects. Dentine bridge formation at the exposure sites treated with Wnt3a demonstrated, while fibrous tissues were observed in the control. Conclusions Wnt3a suppressed proliferation, increased osteogenic differentiation of SHEDs and promotes tertiary dentine formation. Wnt3a could be utilised as biological molecule for vital pulp therapy. View on Web

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Pediatric inflammatory myofibroblastic tumor of the bladder with ALK–FN1 fusion successfully treated by alectinib

alexandrossfakianakis shared this article with you from Inoreader Pediatric inflammatory myofibroblastic tumor of the bladder with ALK–FN1 fusion successfully treated by alectinib via Pediatric Blood & Cancer Abstract An inflammatory myofibroblastic tumor (IMT) is a mesenchymal neoplasm characterized by the proliferation of myofibroblasts and inflammatory cell infiltration. Although radical resection is the only established treatment strategy for IMT, it can cause functional disorders when vital organs are affected. We describe a case of pediatric IMT of the bladder with FN1–ALK (fibronectin 1–anaplastic lymphoma kinase) fusion. Radical resection might lead to urinary disturbance due to the large tumor size at diagnosis. However, the tumor was successfully treated with alectinib, a second-generation ALK inhibitor, followed by transurethral resection of the bladder tumor without any complications. View on Web

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Automatic Dental Biofilm Detection Based on Deep Learning

alexandrossfakianakis shared this article with you from Inoreader Automatic Dental Biofilm Detection Based on Deep Learning via Journal of Clinical Periodontology Abstract Aim To estimate the automated biofilm detection capacity of the U-Net neural network on tooth images. Material and methods Two datasets of intraoral photographs taken in the frontal and lateral views of permanent and deciduous dentitions were employed. The first dataset consisted of 96 photographs taken before and after applying a disclosing agent and was used to validate the domain's expert biofilm annotation (intraclass correlation coefficient = 0.93). The second dataset comprised 480 photos, with or without orthodontic appliances, without disclosing agents, and was used to train the neural network to segment the biofilm. Dental biofilm labeled by the dentist (without disclosing agents) was considered the ground-truth. Segmentation performance was measured using accuracy, F1 score, sensitivity, and specificity. Results The U-Net model achieved an accuracy of 91.8%, F1 score of 60.6%, specificity of 94.4%, and sensitivity of 67.2%. The accuracy was higher in the presence of orthodontic appliances (92.6%). Conclusion Visually segmenting dental biofilm employing a U-Net is feasible and can assist professionals and patients in identifying dental biofilm, thus improving oral hygiene and health. This article is protected by copyright. All rights reserved. View on Web

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