Κυριακή 15 Ιανουαρίου 2023

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

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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.

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

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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.

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

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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.

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Automatic Dental Biofilm Detection Based on Deep Learning

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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.

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Hypothalamic-Pituitary-Gonadal Function, Pubertal Development and Fertility Outcomes in Male and Female Medulloblastoma Survivors: A Single Centre Experience

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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.
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Baricitinib or imatinib in hospitalized COVID‐19 patients: results from COVINIB, an exploratory randomized clinical trial.

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ABSTRACT

Background

Baricitinib and imatinib are considered therapies for COVID-19, but their ultimate clinical impact remains to be elucidated, so our objective is to determine whether these kinase inhibitors provide benefit when added to standard care in hospitalized COVID-19 patients.

Methods

Phase-2, open-label, randomized trial with a pick-the-winner design conducted from September 2020 to June 2021 in a single Spanish center. Hospitalized adults with COVID-19 pneumonia and a symptom duration ≤ 10 days were assigned to 3 arms: imatinib (400 mg qd, 7 days) plus standard-care, baricitinib (4 mg qd, 7 days) plus standard-care, or standard-care alone. Primary outcome was time to clinical improvement (discharge alive or a reduction of 2 points in an ordinal scale of clinical status) compared on a day-by-day basis in order to identify differences ≥ 15% between the most and least favorable groups. Secondary outcomes included oxygenation and ventilatory support requirements, additional therapies administered all-cause mortality and safety.

Results

165 patients analyzed. Predefined criteria for selection of the most advantageous arm were met for baricitinib, but not for imatinib. However, no statistically significant differences were observed in formal analysis, but a trend towards better results in patients receiving baricitinib was found compared to standard care alone (HR for clinical improvement 1.41, 95%CI 0.96-2.06; HR for discontinuing oxygen 1.46, 95%CI 0.94-2.28). No differences were found regarding additional therapies administered or safety.

Conclusions

Baricitinib plus standard care showed better results for hospitalized COVID-19 patients, being the most advantageous therapeutic strategy among those proposed in this exploratory clinical trial.

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Dentine thickness in maxillary fused molars depends on the fusion type: An ex vivo micro‐CT study

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Aim

The present study aimed to determine and compare the dentine thickness around the root canals of maxillary molars with fusion using micro-computed tomography (micro-CT).

Methodology

A total of 120 fused maxillary molars having more than a single canal with distinct canal orifices near the cementoenamel junction were selected from a pool of extracted maxillary molars, which were scanned on a micro-CT device (SkyScan 1172, Bruker-microCT, Kontich, Belgium). The minimum dentine thickness around the root canals in furcal direction was measured using CTAn software (v.1.18.8 Bruker-microCT) at each millimetre. The specimens were grouped according to their fusion type, and dentine thickness around the canals was compared. The data were statistically analysed using ANOVA and post hoc Tukey-Kramer tests following an assessment of the normality of their distribution with the Kolmogorov-Smirnov test (p .05).

Results

Dentine thickness showed a statistically significant decrease at 2 mm below the orifice irrespective of fusion type. The minimum dentine thickness values were detected around the second mesiobuccal canal as 0.30 mm at 6 mm below orifice. Dentine thickness around the mesiobuccal canal significantly greater in fusion type 1 than those of types 2 and 3 (p < .05), while those of distobuccal and palatal canals were significantly thinner in type 3 fusion compared to type 1 or 6 (p < .05).

Conclusion

Minimum dentine thickness values at the danger zone of distobuccal and palatal canals change according to the fusion type in fused maxillary second molars.

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