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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Defining the Optimal Duration of Therapy for Hospitalized Patients with Complicated Urinary Tract Infections and Associated Bacteremia

alexandrossfakianakis shared this article with you from Inoreader Defining the Optimal Duration of Therapy for Hospitalized Patients with Complicated Urinary Tract Infections and Associated Bacteremia via Clinical Infectious Diseases Advance Access Abstract Objective Limited data are available to guide effective antibiotic durations for hospitalized patients with complicated urinary tract infections (cUTI). Methods We conducted an observational study of patients ≥18 years at 24 United States hospitals to identify the optimal treatment duration for patients with cUTI. To increase the likelihood patients experienced true infection, eligibility was limited to those with associated bacteremia. Propensity sco res were generated for an inverse probability of treatment weighted analysis. The primary outcome was recurrent infection with the same species within 30 days of completing therapy. Results 1,099 patients met eligibility criteria and received 7, 10, or 14 days of therapy. There was no difference in the odds of recurrent infection for 382 (46%) patients receiving 10 days and 452 (54%) patients receiving 14 days of therapy (aOR 0.99, 95% CI, 0.52-1.87). An increased odds of recurrence was observed in 265 (37%) patients receiving 7 days versus 452 (63%) patients receiving 14 days of treatment (aOR 2.54, 95% CI, 1.40-4.60). When limiting the 7-day versus 14-day analysis to the 627 patients who remained on intravenous beta-lactam therapy or were transitioned to highly bioavailable oral agents, differences in outcomes no longer persisted; aOR 0.76, 95% CI, 0.38-1.52. Of 76 patients with recurrent infections, 2 (11%), 2 (10%), and 10 (36%) in the 7, 10, and 14-day groups, respecti vely, had drug-resistant infections (p=0.10). Conclusion Seven days of antibiotics appears effective for hospitalized patients with cUTI when antibiotics with comparable IV and oral bioavailability are administered; 10 days may be needed for all other patients. 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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Hypothalamic-Pituitary-Gonadal Function, Pubertal Development and Fertility Outcomes in Male and Female Medulloblastoma Survivors: A Single Centre Experience

alexandrossfakianakis shared this article with you from Inoreader Hypothalamic-Pituitary-Gonadal Function, Pubertal Development and Fertility Outcomes in Male and Female Medulloblastoma Survivors: A Single Centre Experience via Neuro-Oncology Advance Access Abstract Background Endocrine deficiencies, including hypothalamic-pituitary-gonadal axis (HPGA) impairment, are common in survivors of childhood and adolescent medulloblastoma. Still, data regarding pubertal development and fecundity are limited, and few studies assessed HPGA function in males. We aimed to describe HPGA function in a large cohort of patients with medulloblastoma. Methods A retrospective study comprising all 62 medulloblastoma patients treated in our center between 1987-2021, who were at least two years from completion of therapy. HPGA function was assessed based on clinical data, biochemical markers, and questionnaires. Results Overall, 76% of female patients had clinical or biochemical evidence of HPGA dysfunction. Biochemical evidence of diminished ovarian reserve was seen in all prepubertal girls (n=4). Among the males, 34% had clinical or biochemical evidence of gonadal dysfunction, 34% had normal function , and 29% were age-appropriately clinically and biochemically pre-pubertal. The difference between males and females was significant (p=0.003). Cyclophosphamide-equivalent dose (CED) was significantly associated with HPGA function in females, but not in males. There was no association between HPGA dysfunction and other endocrine deficiencies, length of follow up, weight status, and radiation treatment protocol. Two female and two male patients achieved successful pregnancies, resulting in 6 live births. Conclusions HPGA dysfunction is common after treatment for childhood medulloblastoma. This is seen more in females, likely due to damage to the ovaries from spinal radiotherapy. Our findings may assist in counselling patients and their families regarding risk to future fertility and need for fertility preservation. View on Web

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