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Τρίτη 15 Μαρτίου 2022

Biodegradation of poly(L-lactic acid) and poly(epsilon-caprolactone) patches by human amniotic fluid in an in-vitro simulated fetal environment

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Sci Rep. 2022 Mar 10;12(1):3950. doi: 10.1038/s41598-022-07681-8.

ABSTRACT

Open spina bifida or myelomeningocele (MMC) is a devastating neurologic congenital defect characterized by primary failure of neural tube closure of the spinal column during the embryologic period. Cerebrospinal fluid leak caused by the MMC spinal defect in the developing fetus can result in a constellation of encephalic anomalies that include hindbrain herniation and hydrocephalus. The exposure of extruded spinal cord to amniotic fluid also poses a significant risk for inducing partial or complete paralysis of the body parts beneath the spinal aperture by progressive spinal cord damage in-utero. A randomized trial demonstrated that prenatal repair by fetal surgery, sometimes using patches, to cover the exposed spinal cord with a watertight barrier is effective in reducing the postnatal neurologic morbidity as evidenced by decreased incidence and severity of postnatal hydrocephalus and the reduced need for ventricular-peritoneal shunting. Currently, the use of inert or collagen-based patches are associated with high costs and inadequate structural properties. Specifically, the inert patches do not degrade after implantation, causing the need for a post-natal removal surgery associated with trauma for the newborn. Our present study is aimed towards in-vitro degradation studies of a newly designed patch, which potentially can serve as a superior alternative to existing patches for MMC repair. This novel patch was fabricated by blending poly(L-lactic acid) and poly(ε-caprolactone). The 16-week degradation study in amniotic fluid was focused on tracking changes in crystallinity and mechanical properties. An additional set of designed patches was exposed to phosphate-buffered saline (PBS), as a time-paired control. Crystallinity studies indicate the progress of hydrolytic degradation of the patch in both media, with a preference to bulk erosion in ph osphate buffered saline and surface erosion in amniotic fluid. Mechanical testing results establish that patch integrity is not compromised up to 16 weeks of exposure either to body fluids analog (PBS) or to amniotic fluid.

PMID:35273223 | PMC:PMC8913814 | DOI:10.1038/s41598-022-07681-8

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Posterior fossa chronic subdural hematoma associated with supratentorial chronic subdural hematoma

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World Neurosurg. 2022 Mar 11:S1878-8750(22)00298-4. doi: 10.1016/j.wneu.2022.03.017. Online ahead of print.

ABSTRACT

OBJECTIVE: Chronic subdural hematoma (CSDH) in the posterior fossa has until now been reported in only 16 patients. This study clarified the frequency and characteristics of the posterior fossa CSDH through the use of magnetic resonance imaging (MRI) in patients with supratentorial CSDH.

METHODS: We retrospectively examined presurgical MRI findings in patients with supratentorial CSDH who underwent surgery between 2006 and 2020.

RESULTS: MRI revealed posterior fossa CSDH in 24 (7.3%) of 329 patients. Multivariable analyses demonstrated that anticoagulant treatment (p = 0.033, odds ratio [OR] 3.53), cerebrospinal fluid leak (p = 0.001, OR 18.5), and lack of prior trauma 3 weeks or more before admission (p = 0.027, OR 3.03) were risk factors of posterior fossa CSDH. Computed tomography could not show the hematomas in 20 patients (83.3%). All the posterior fossa CSDHs improved after supratentorial CSDH drainage.

CONCLUSIONS: Posterior fossa CSDH was observed on MRI in a minority of patients with supratentorial CSDH. Although most patients with posterior fossa CSDH had good outcomes, large posterior fossa CSDH sometimes must be treated surgically, according to previous reports.

PMID:35288358 | DOI:10.1016/j.wneu.2022.03.017

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Management of Graves' hyperthyroidism: present and future

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Expert Rev Endocrinol Metab. 2022 Mar 14:1-14. doi: 10.1080/17446651.2022.2052044. Online ahead of print.

ABSTRACT

INTRODUCTION: Graves' disease (GD) is an autoimmune disorder due to loss of tolerance to the thyrotropin receptor (TSHR) and ultimately caused by stimulatory TSHR antibodies (TSHR-Ab). GD may be associated with extrathyroidal manifestations, mainly Graves' orbitopathy. Treatment of GD relies on antithyroid drugs (ATDs), radioactive iodine (RAI), thyroidectomy. The major ATD limitation is the high recurrence rate after treatment. The major drawback of RAI and thyroidectomy is the inevitable development of permanent hypothyroidism.

AREAS COVERED: Original articles, clinical trials, systematic reviews, meta-analyses from 1980 to 2021 were searched using the following terms: Graves' disease, management of Graves' disease, antithyroid drugs, radioactive iodine, thyroidectomy, Graves' orbitopathy, thyroid-eye disease.

EXPERT OPINION: ATDs are the first-line treatment worldwide, are overall safe and usually given for 18-24 months, long-term treatment may decrease relapses. RAI is safe, although associated with a low risk of GO progression, particularly in smokers. Thyroidectomy requires skilled and high-volume surgeons. Patients play a central role in the choice of treatment within a shared decision-making process. Results from targeted therapies acting on different steps of the autoimmune process, including iscalimab, ATX-GD-59, rituximab, b locking TSHR-Ab, small molecules acting as antagonists of the TSHR, are preliminary or preclinical, but promising in medium-to-long perspective.

PMID:35287535 | DOI:10.1080/17446651.2022.2052044

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Trends in the Management of Localized Papillary Thyroid Carcinoma

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Thyroid, Ahead of Print.
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Detection of Vocal Fold Image Obstructions in High-Speed Videoendoscopy During Connected Speech in Adductor Spasmodic Dysphonia: A Convolutional Neural Networks Approach

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Adductor spasmodic dysphonia (AdSD) is a neurogenic voice disorder, affecting the intrinsic laryngeal muscle control. AdSD leads to involuntary laryngeal spasms and only reveals during connected speech. Laryngeal high-speed videoendoscopy (HSV) coupled with a flexible fiberoptic endoscope provides a unique opportunity to study voice production and visualize the vocal fold vibrations in AdSD during speech. The goal of this study is to automatically detect instances during which the image of the vocal folds is optically obstructed in HSV recordings obtained during connected speech.
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Δευτέρα 14 Μαρτίου 2022

Efficacy of systematic voice training combined with swallowing function exercises for the prevention of swallowing dysfunction in stroke patients: a retrospective study

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Ann Transl Med. 2022 Feb;10(4):195. doi: 10.21037/atm-22-101.

ABSTRACT

BACKGROUND: Stroke is a common clinical brain disease, and swallowing dysfunction is one of the most common complications in stroke patients. Despite multiple treatments for swallowing dysfunction, it often leads to a series of complications. Interventions such as systematic voice training and swallowing function exercises have emerged in recent years, but their effectiveness remains unclear. Therefore, this stu dy was conducted to investigate the effect of systematic voice training combined with swallowing function exercise for the prevention of swallowing dysfunction and improving the quality of life of stroke patients.

METHODS: We retrospectively analyzed 90 stroke patients admitted to Baotou Central Hospital from October 2018 to October 2021 as study subjects, and divided the patients into a combined voice training group (n=45) and a single swallowing exercise group (n=45) according to the interventions. The single swallowing exercise group received routine swallowing function exercise, and the combined voice training group used systematic voice training combined with swallowing function exercise. The incidence of swallowing dysfunction, malnutrition, aspiration pneumonia, and exercise compliance rate were compared between the two groups, and the quality of life of the two groups was evaluated by the Generic Quality of Life Inventory 74 (GQOLI-74) before and after the intervention s, respectively.

RESULTS: The incidence of swallowing dysfunction, aspiration pneumonia, and malnutrition were lower in the combined voice training group than in the single swallowing exercise group (P<0.05), and there was no statistically significant difference in the exercise compliance rate between the two groups. The combined voice training group had higher psychological dimensions, physical dimensions, social adaptation, and total quality of life scores than the single swallowing exercise group (all P<0.05). Compared with the conventional intervention group, the combined voice training group had higher patient satisfaction (P<0.05).

CONCLUSIONS: Systematic voice training combined with swallowing function exercise can effectively prevent the occurrence of swallowing dysfunction and improve the quality of life of patients with stroke.

PMID:35280372 | PMC:PMC8908138 | DOI:10.21037/atm-22-101

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Use of Polysomnography and CPAP in Children Who Received Adenotonsillectomy, US 2004 to 2018

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Objectives

1) To determine the prevalence polysomnogram (PSG) and continuous positive airway pressure (CPAP) therapy use in children who received adenotonsillectomy (AT) for sleep symptoms. 2) To identify health care disparities in these regards.

Study Design

Retrospective database analysis.

Methods

This study used data from Optum (Health Services Innovation Company) to identify 92,490 children who received AT for sleep symptoms between 2004 and 2018. Prevalence of preoperative PSG and postoperative PSG and CPAP were described. Clinical and demographic characteristics were compared between children who had preoperative PSG and those who did not. Characteristics of children with trisomy 21 (T21) were compared to assess PSG and CPAP use in a high-risk cohort. Predictive modeling was used to identify patient characteristics associated with postoperative PSG and CPAP use.

Results

Preoperative PSG was obtained in 5.5% of children overall and 33.2% of children with T21. Male sex, obesity, other medical comorbidities, non-White race/ethnicity, and higher parent education were associated with preoperative PSG. Fewer than 3% of children received postoperative PSGs and approximately 3% went on to receive CPAP therapy postoperatively. Multiple logistic regression showed that age at surgery, male sex, obesity, other medical comorbidities, non-White race/ethnicity, and higher parent education were associated with postoperative PSG and CPAP use.

Conclusions and Relevance

This study described the prevalence pre-AT PSG use and post-AT PSG and CPAP use for persistent symptoms and identified sleep health care disparities in these regards. These results show that increased, equitable access to PSG is needed in children, particularly in the workup and treatment persistent symptoms after AT.

Level of Evidence

4 Laryngoscope, 2022

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Omaveloxolone attenuates squamous cell carcinoma growth and disease severity in an Epidermolysis Bullosa mouse model

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Abstract

Patients with Epidermolysis Bullosa (EB) are susceptible to development of squamous cell carcinomas (SCC) at sites of chronic inflammation and fibrosis. While triterpenoids such as RTA 408 (Omaveloxolone) have been shown to reduce inflammation and inhibit tumor growth in various cancer models, the utility of this class of drugs in the treatment of SCC has not been investigated. Given the dual anti-inflammatory and anti-neoplastic properties of triterpenoids, we hypothesized RTA 408 would be an effective treatment for SCCs that arise in the chronic inflammatory setting in EB. We tested the effects of topical RTA 408 on a mouse model of non-Herlitz, junctional EB. RTA 408 significantly reduced phenotypic severity in the affected ears of Lamc2jeb mice. In cultures, RTA 408 reduced cell viability in EB-associated SCC cell lines and normal human epidermal keratinocytes. When administered in vivo, RTA 408 inhibited SCC tumor growth in mice without cutaneous or systemic tox icity. These results suggest that RTA 408 can be a promising new therapy to reduce inflammation and inhibit SCC growth in patients with EB.

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Efficacy of radiotherapy combined with immune checkpoint inhibitors in patients with melanoma: a systemic review and meta-analysis

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imageThe purpose of this study is to review the efficacy of radiotherapy combined with immune checkpoint inhibitors (ICIs) in the treatment of melanoma and systematically evaluate the efficacy and safety of this combined treatment compared with ICIs alone. We searched a number of online databases up to 1 July 2021. Comprehensive Meta-Analysis 2.0 and RevMan 5.0 were used for summary analysis. The overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and treatment adverse effects (AEs) were calculated. In total, 624 patients were included from 12 studies, including nine published studies and the r esults of three clinical trials. Radiotherapy combined with ICIs had a higher ORR compared with ICIs alone (35.00 vs. 20.39%). In terms of survival effect, radiotherapy combined with ICIs had no obvious advantage in OS. There was no statistically significant difference between 6-month and 12-month OS (P = 0.13; P = 0.69). There was no significant difference in PFS at 6 months (P = 0.08), but there was a significant difference in PFS at 12 months (P = 0.005). For patients with melanoma, radiotherapy combined with ICIs can improve the effective rate of treatment. Although there is no obvious OS advantage, it can improve PFS without serious adverse effects. Most of the studies included in this article are retrospective analyses, and there are few randomized controlled studies at present. Therefore, more prospective studies are still needed to explore the efficacy of radiotherapy combined with immunotherapy in melanoma.
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Documenting the histologic response of metastatic melanoma to combination therapy with BRAF and MEK inhibitors

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imageNo abstract available
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Chemosaturation with percutaneous hepatic perfusion of melphalan for metastatic uveal melanoma

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imageUveal melanoma, the most common primary ocular malignancy in adults, carries a poor prognosis: 50% of patients develop the metastatic disease with a 10–25% 1-year survival and no established standard of care treatment. Prior studies of melphalan percutaneous hepatic perfusion (M-PHP) have shown promise in metastatic uveal melanoma (mUM) patients with liver predominant disease but are limited by small sample sizes. We contribute our findings on the safety and efficacy of the procedure in the largest sample population to date. A retrospective analysis of outcome and safety data for all mUM patients receiving M-PHP was perfor med. Tumour response and treatment toxicity were evaluated using RECIST 1.1 and Common Terminology Criteria for Adverse Events v5.03, respectively. 250 M-PHP procedures were performed in 81 patients (median of three per patient). The analysis demonstrated a hepatic disease control rate of 88.9% (72/81), a hepatic response rate of 66.7% (54/81), and an overall response rate of 60.5% (49/81). After a median follow-up of 12.9 months, median overall progression-free (PFS) and median overall survival (OS) were 8.4 and 14.9 months, respectively. There were no fatal treatment-related adverse events (TRAE). Forty-three grade 3 (29) or 4 (14) TRAE occurred in 23 (27.7%) patients with a significant reduction in such events between procedures performed in 2016–2020 vs. 2012–2016 (0.17 vs. 0.90 per patient, P
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Real-world frequency of BRAF testing and utilization of therapies in patients with advanced melanoma

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imageBoth BRAF/MEK targeted agents and immunotherapy are approved for the treatment of advanced melanoma. BRAF testing is recommended at the time of advanced melanoma diagnosis. In addition, little is known regarding the treatment trends for patients with BRAF mutated tumors. This investigation aims to assess the real-world prevalence of molecular testing and treatment trends for patients with BRAF mutated tumors. Using a de-identified database, patients of age ≥18 years with advanced melanoma from 2013 to 2018 were examined. Molecular testing performed within 3 months of advanced diagnosis was considered to have the test pe rformed at the time of diagnosis. Test prevalence was calculated and compared in groups stratified by the patient, tumor and treatment factors. In total 4459 patients were included; 1936 (43.4%) stage III, 1191 (26.7%) stage IV and 1332 (29.9%) recurrent. Totally 50.4% of patients received systemic treatment; 76.4% stage IV, 71% recurrent patients and 26.7% stage III patients. However, 73.5% received first-line immunotherapy. In total 73.8% of patients had molecular testing, and 50.5% had tested at the time of advanced diagnosis. Of those tested 42% had a BRAF mutated tumor. In total 48% of these patients received first-line immunotherapy whereas 43% received a BRAF inhibitor, with increasing immunotherapy use seen over time. The majority of patients with advanced melanoma undergo molecular testing at the time of advanced diagnosis. Immunotherapy is the most commonly prescribed treatment regardless of BRAF mutational status. These results provide real-world data on the frequency of molecular testing and treatment trends for patients with advanced melanoma.
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