Thursday, November 10, 2022

The participation of fibroblast growth factor‐1 and interleukin‐10 in connective tissue repair following subcutaneous implantation of bioceramic materials in rats

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Abstract

Aim

To evaluate whether the bioceramic materials Bio-C Pulpo (Bio-C, Angelus, Londrina, Brazil) and MTA Repair HP (MTA-HP, Angelus, Londrina, Brazil) induce fibroblast proliferation and release of interleukin-10 (IL-10), an anti-inflammatory cytokine, stimulating connective tissue remodelling. The tissue response of Bio-C and MTA-HP was compared with the White MTA (WMTA; Angelus, Londrina, Brazil) since studies have demonstrated that WMTA induces tissue repair.

Methodology

Bio-C, MTA-HP, and WMTA were inserted into polyethylene tubes and implanted in the subcutaneous tissue of Holtzman rats for 7, 15, 30 and 60 days. As a control group (CG), empty tubes were implanted subcutaneously. The number of fibroblasts (FB), Ki-67-, fibroblast growth factor-1- (FGF-1) and IL-10-immunolabelled cells, and collagen content in the capsules was obtained. The data were subjected to two-way ANOVA followed by Tukey's test (P ≤ 0.05).

Results

At 7 days, significant differences in the number of FB were not detected among Bio-C, MTA-HP and WMTA groups (P ˃ 0.05). The capsules of all groups exhibited a significant increase in the number of FB and content of collagen over time. From 7 to 60 days, a significant reduction in the number of FGF-1- and Ki-67-immunolabelled cells was seen in the capsules of all specimens. In all periods, no significant difference in the number of FGF-1-immunolabelled cells was detected between Bio-C and CG specimens. At 60 days, significant differences in the immunoexpression of FGF-1 were not observed among the groups. At 7 and 15 days, the highest immunoexpression for Ki-67 was present in Bio-C specimens while, after 30 and 60 days, no significant difference was observed among the bioceramic materials. At 7 days, few IL-10 immunolabelled cells were present in the capsules of all specimens whereas, at 60 days, a significant increase in the IL-10-immunostaining was present in all groups. At 60 days, the Bio-C, MTA-HP and WMTA groups showed a greater number of IL-10-immunolabelled cells than in the CG specimens (P < 0.0001).

Conclusions

Bio-C, MTA-HP and WMTA stimulate fibroblast proliferation, leading to formation of collagen-rich capsules. FGF-1 and IL-10 may mediate the remodelling of capsules around Bio-C, MTA-HP and WMTA bioceramic materials.

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A GntR Family Transcription Factor in Porphyromonas gingivalis Regulates Bacterial Growth, Acylpeptidyl Oligopeptidase and Gingipains Activity

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SUMMARY

Porphyromonas gingivalis (P. gingivalis) is a keystone pathogen for periodontitis. The function of the GntR family transcription factor is poorly studied in P. gingivalis. Numerous processes govern bacterial growth. The survival and pathogenicity of P. gingivalis depend heavily on its capacity to acquire amino acids as nutritional sources. In this investigation, a GntR transcription factor, pg1007, was identified in P. gingivalis, the deletion of which significantly inhibited bacterial growth. The mutant strain also exhibited increased extracellular activity of gingipains and acylpeptidyl oligopeptidase (AOP). Global gene expression profiling revealed that the expression levels of 59 genes were significantly altered in the Δpg1007 mutant, with an up-regulation in gene expression for AOP, ABC transporters, and some membrane proteins. In addition, His-PG1007 protein was purified as a recombinant protein from Escherichia coli, and the conserved DNA sequence bound by it was determined using electrophoretic mobility shift assays (EMSA) and DNase I footprinting assays. Consequently, this study demonstrated that pg1007 is a crucial transcription factor in P. gingivalis and regulates the bacterial growth and activity of gingipains and AOP. These findings may enhance our understanding of the regulation of bacterial proliferation and protease activity in P. gingivalis.

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Endoscopic Versus Microscopic Type‐1 Tympanoplasty: A Meta‐Analysis of Randomized Trials

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Endoscopic Versus Microscopic Type-1 Tympanoplasty: A Meta-Analysis of Randomized Trials

Although microscope-assisted tympanoplasty remains the gold standard, the merits of endoscopic approaches have been well-documented. This meta-analysis compares the outcomes of endoscopic to microscopic tympanoplasty incorporating only randomized trials. The result from this meta-analysis provides level 1 evidence demonstrating that endoscopic and microscopic-assisted type-1 tympanoplasty have similar outcomes in both graft success and hearing improvement, with endoscopic approaches yielding a shorter operative time.


Objectives

Totally endoscopic ear surgery is becoming increasingly utilized in otologic practice. Although the well-established microscope-assisted tympanoplasty remains the most common technique to repair a tympanic membrane defect, the merits of endoscopic approaches have been well-documented. This systematic review and meta-analysis compares the outcomes of endoscopic to microscopic tympanoplasty incorporating only randomized trials.

Study Design

Systematic review and meta-analysis.

Methods

A comprehensive search of PubMed/MEDLINE, Scopus, Cochrane Library, and EMBASE was conducted. All randomized studies comparing endoscopic to microscopic tympanoplasty were collected according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Quality assessment was carried out utilizing the Risk of Bias 2.

Results

The initial search identified 1711 studies, of which 9 met the inclusion criteria comprising of 540 patients (microscopic tympanoplasty 51.5%; endoscopic tympanoplasty 49.5%). The mean age was 32.5 years with a similar number of males (50.1%) and females (49.9%). Both endoscopic and microscopic groups had comparable outcomes with regards to graft success rate (RD 0.00; 95% confidence interval [CI], −0.04 to. 0.05; p = 0.87) and hearing improvement (MD 0.57 dB; 95% CI, −1.23 to 2.36; p = 0.54). A significantly shorter operative time was noted in the endoscopic group (MD, −24.73 min; 95% CI, −38.56 to −10.89; p = 0.0005).

Conclusion

Our results, assimilating level 1 evidence, demonstrates that endoscopic and microscopic-assisted type-1 tympanoplasty have similar outcomes in both graft success and hearing improvement, with endoscopic approaches yielding a shorter operative time.

Level of Evidence

1 Laryngoscope, 2022

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CytoSorb haemoadsorption for removal of apixaban—A proof‐of‐concept pilot case for a randomized controlled trial

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CytoSorb haemoadsorption for removal of apixaban—A proof-of-concept pilot case for a randomized controlled trial

Timely discontinuation of NOAC's therapy before surgery is not always achievable, especially in an emergency setting. This case report proves, with direct blood concentration measurements, the efficacy of CytoSorb hemofilter in apixaban removal during cardiopulmonary bypass for emergency aortic valve replacement.


Abstract

What is known and objective

Emergent cardiac surgery in patients under anticoagulant therapy is still a major point of concern. Recently approved reversal agents are often not available or not suitable in the cardiac surgery setting, and timely discontinuation of the drug is not always feasible. CytoSorb® haemoadsorption therapy has been approved in Europe for intraoperative ticagrelor and rivaroxaban removal during cardiopulmonary bypass (CPB), but thus far the efficacy of CytoSorb® haemoadsorber on other anticoagulants (apixaban, dabigatran, edoxaban) has only been tested in vitro, and some signals of clinical benefits have reported in a few case reports.

Case summary

We describe a case of CPB implementation with CytoSorb® in a haemodynamic unstable patient with prosthetic aortic valve endocarditis on apixaban therapy.

What is new and conclusion

CytoSorb® proved to be effective for removal of apixaban in emergency surgery setting by direct measurements of drug levels before and during CPB circulation.

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Clinical outcomes of pediatric patients receiving multimodality treatment of second central nervous system relapse of neuroblastoma

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Abstract

Background

In high-risk neuroblastoma, multimodality therapy including craniospinal irradiation (CSI) is effective for central nervous system (CNS) relapse. Management of post-CSI CNS relapse is not clearly defined.

Procedure

Pediatric patients with neuroblastoma treated with CSI between 2000 and 2019 were identified. Treatment of initial CNS disease (e.g., CSI, intraventricular compartmental radioimmunotherapy [cRIT] with 131I-monoclonal antibodies targeting GD2 or B7H3) and management of post-CSI CNS relapse ("second CNS relapse") were characterized. Cox proportional hazards models to evaluate factors associated with third CNS relapse and overall survival (OS) were used.

Results

Of 128 patients (65% male, median age 4 years), 19 (15%) received CSI with protons and 115 (90%) had a boost. Most (103, 81%) received cRIT, associated with improved OS (hazard ratio [HR] 0.3, 95% confidence interval [CI]: 0.1–0.5, p < .001). Forty (31%) developed a second CNS relapse, associated with worse OS (1-year OS 32.5%, 95% CI: 19-47; HR 3.8; 95% CI: 2.4–6.0, p < .001), and more likely if the leptomeninges were initially involved (HR 2.5, 95% CI: 1.3–4.9, p = .006). Median time to second CNS relapse was 6.8 months and 51% occurred outside the CSI boost field. Twenty-five (63%) patients underwent reirradiation, most peri-operatively (18, 45%) with focal hypofractionation. Eight (20%) patients with second CNS relapse received cRIT, associated with improved OS (HR 0.1; 95% CI: 0.1–0.4, p < .001).

Conclusions

CNS relapse after CSI for neuroblastoma portends a poor prognosis. Surgery with hypofractionated radiotherapy was the most common treatment. Acknowledging the potential for selection bias, receipt of cRIT both at first and second CNS relapse was associated with improved survival. This finding necessitates further investigation.

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Similarities and controversies in imaging of pediatric renal tumors: A SIOP‐RTSG and COG collaboration

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Abstract

Malignant renal tumors are rare in children, and Wilms tumors (WTs) are the most common subtype. Imaging plays an essential role in the diagnosis, staging, and follow-up of these patients. Initial workup for staging is mainly performed by cross-sectional imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI). Imaging approach within the two core international groups, the Children's Oncology Group (COG, North America) and the International Society of Pediatric Oncology - Renal Tumor Study Group (SIOP-RTSG, Europe), differs. Whereas abdominal ultrasound (US) is used for the initial diagnosis of a suspected pediatric renal tumor globally, COG protocols support the use of CT or MRI for locoregional staging, contrary to the preference for MRI over CT for abdominopelvic evaluation within the SIOP-RTSG. The purpose of this manuscript is to summarize current imaging approaches, highlighting differences and similarities within these core international grou ps, while focusing on future innovative efforts and collaboration within the HARMONICA initiative.

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Surveillance for Survivors of Locoregionally Advanced Head and Neck Cancer

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The evaluation and management of head and neck cancers is an area of intense research and data-driven recommendations. However, once a patient completes definitive treatment for a head and neck cancer, there is surprisingly little evidence to guide the surveillance and long-term management of these patients. Most guidelines, such as those of the National Comprehensive Cancer Network, are based primarily on expert opinion and take a one-size-fits-all approach to head and neck cancers. However, the long-term prognoses of head and neck cancers vary widely, depending on numerous factors, such as subsite, staging, human papillomavirus (HPV) status for oropharyngeal cancers, and other tumor and patient characteristics. Furthermore, surveillance visits represent a substantial use of clinical resources, time, and patient expense for many years after cancer treatment. Clearly, this is an area in need of evidence-based approaches to ensure optimal patient care.
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BMI and Venous VTE Rates in Patients on Standard Chemoprophylaxis Regimens After H&N Surgery

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This cohort study assesses whether there is an association between body mass index and postoperative venous thromboembolism and hematoma rates in patients treated with prophylactic enoxaparin 30 mg twice daily.
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Cetuximab-Based vs Carboplatin-Based Chemoradiotherapy for Patients With Head and Neck Cancer

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This cohort study compares survival with cetuximab-based and carboplatin-based chemoradiotherapy in locally advanced head and neck squamous cell carcinoma.
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Assessment of Fat Fractions in the Tongue, Soft Palate, Pharyngeal Wall, and Parapharyngeal Fat Pad by the GOOSE and DIXON Methods

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imageObjective The 2-point DIXON method is widely used to assess fat fractions (FFs) in magnetic resonance images (MRIs) of the tongue, pharyngeal wall, and surrounding tissues in patients with obstructive sleep apnea (OSA). However, the method is semiquantitative and is susceptible to B0 field inhomogeneities and R2* confounding factors. Using the method, although several studies have shown that patients with OSA have increased fat deposition around the pharyngeal cavity, conflicting findings was also reported in 1 study. This discrepancy necessitates that we examine the FF estimation method used in the earlier studies and seek a more accurate method to measure FFs. Materials and Methods We examined the advantages of using the GOOSE (globally optimal surface estimation) method to replace the 2-point DIXON method for quantifying fat in the tongue and surrounding tissues on MRIs. We first used phantoms with known FFs (true FFs) to validate the GOOSE method and examine the errors in the DIXON method. Then, we compared the 2 methods in the tongue, soft palate, pharyngeal wall, and parapharyngeal fat pad of 63 healthy participants to further assess the errors caused by the DIXON method. Six participants were excluded from the comparison of the tongue FFs because of technical failures. Paired Student t tests were performed on FFs to detect significant differences between the 2 methods. All measures were obtained using 3 T Siemens MRI scanners. Results In the phantoms, the FFs measured by GOOSE agreed with the true FF, with only a 1.2% mean absolute error. However, the same measure by DIXON had a 10.5% mean absolute error. The FFs obtained by DIXON were significantly lower than those obtained by GOOSE (P
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