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Κυριακή 7 Νοεμβρίου 2021

Functional laryngectomy for the dysfunctional larynx: indications and outcomes in setting of prior chemoradiotherapy

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imagePurpose of review To review the recent literature on indications for and functional outcomes following laryngectomy for severe laryngeal dysfunction. Recent findings The use of functional laryngectomy as a definitive treatment for severe laryngeal dysfunction is increasing as more patients with head and neck cancer are treated with definitive chemoradiotherapy. Data are emerging on the efficacy of this technique as measured by aspiration, recurrent pneumonias, enteral tube feeding dependence, and surgical complication rates. Though most patients have marked improvement in aspiration and oral intake, difficulties in swallowing and voicing functions may persist. Summary Functional laryngectomy is an effective treatment for end-stage laryngeal dysfunction. There is a clear benefit with regard to prevention of aspiration and alleviation of nothing by mouth status. However, qualitative speech and swallowing outcomes are less well studied, though available data suggest that many patients still suffer some degree of continued chronic impairment. More research is needed on these outcomes in order to appropriately counsel patients regarding long-term functional outcomes.
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Current approaches to reporting pharyngo-laryngeal secretions

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imagePurpose of review Accumulated secretions in the pharynx and larynx are associated with dysphagia, aspiration and pneumonia, as well as increased social, health and economic burden. This article reviews developments in the instrumental reporting of pharyngo-laryngeal secretions over the last 2 years. Recent findings Although the healthy pharynx and larynx is moist, accumulation of secretions is indicative of abnormality. Using standardized secretion scales allows early identification, quantification of risk in patients, and sensitive monitoring of patients over time. Nonstandardized and subjective secretion reporting is common in recently published research despite the validation of a number of publicly available tools. Research characterizing accumulated secretions has contributed to our understanding of pathophysiology associated with poor secretion management and may inform future treatment studies. Summary Routine and standardized reporting of secretions is critical for patient assessment and should be reported in the most standardized way possible. Further research investigating the clinical relevance and treatment of accumulated secretions relies on quantitative pharyngolaryngeal secretions reporting.
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How can we make better decisions about dystonic voice management?

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imagePurpose of review The optimal diagnosis and management of dystonic voice disorders are rooted in the nuanced understanding of their phenomenology. Distinguishing between subtypes of vocal dystonia is challenging, not only because the audible and physical presentations of these dystonia's can seem similar, but also because there is a lack of scientific consensus regarding the diagnostic criteria for these conditions. To help improve the clinician's acumen we focus on outlining the classification of the top three neurological voice disorders, notably: spasmodic dysphonia, (2) spasmodic dysphonia with tremor, and essential tremor of the voice. We also provide an algorithmic approach based on current evidence-based literature to guide practitioners through the clinical diagnosis and management of each possible etiology. Recent findings Much remains unknown about the subtypes of vocal dystonia, and this gap in our knowledge likely limits our ability to advance clinical management. Still, continued experience evaluating and treating these patients yields refined clinical evaluations and decision making. Summary Improvements in our clinical decision-making can be made by acknowledging that our limited understanding of vocal dystonia may hinder what therapeutic interventions we can offer, yet our ability to accurately diagnose the dystonia is central to providing optimal patient management.
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Higher incidences of neuropathic pain and altered sensation following radial forearm free flap: A systematic review

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J Plast Reconstr Aesthet Surg. 2021 Oct 8:S1748-6815(21)00466-6. doi: 10.1016/j.bjps.2021.09.028. Online ahead of print.

ABSTRACT

BACKGROUND: The radial forearm free flap (RFFF) has been used extensively for complex tissue defect reconstructions; however, the potential for significant donor-site morbidity remains a major drawback. Despite an abundance of literature on donor-site morbidities, no consensus has been reached on exact incidences of sensory morbidities that vary largely between 0% and 46%. Incidences of neuropathic pain in the donor site following RFFF still lack, even though clinical experience shows it often occurs. Therefore, the purpose of this systematic review was to identify the incidence of neuropathic pain and altered sensation in the hand following harvesting of a RFFF.

METHODS: A systematic search was performed in multiple databases (Embase, Medline, Cochrane, Web of Science, and Google Scholar). Studies fro m 1990 onwards that reported donor-site morbidities following harvest of the RFFF were included. Analyzed parameters included hand pain, hypoesthesia, cold intolerance, hyperesthesia, neuroma formation, paresthesia, sharp sensation loss, light sensation loss, and defect closure.

RESULTS: Of the 987 selected studies, 51 eligible articles were selected. The mean level of evidence was 3 (SD 0.6). Twenty articles reported pain as a donor-site morbidity, and the mean incidence of pain reported was 23% (SD 7.8). Hypoesthesia was reported by 37 articles and had a mean incidence of 34% (SD 25). Locations of pain and hypoesthesia included, amongst others, the area of the radial sensory nerve and the skin graft area. The mean incidences of cold intolerance and hyperesthesia were 13% (SD 13) and 16% (SD 15), respectively.

CONCLUSION: The results of this systematic review suggest that 23% of all patients are dealing with neuropathic pain in the donor-site following harvest of an RFF F. Future studies should therefore focus on the prognostic factors and preventive measures of neuropathic pain to further improve clinical outcomes of this widely used flap.

PMID:34736849 | DOI:10.1016/j.bjps.2021.09.028

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Patient-Reported Long-Term Outcomes After Free Vascularized Fibula Graft in Spinal Reconstruction: a 24-year Cohort

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J Plast Reconstr Aesthet Surg. 2021 Sep 20:S1748-6815(21)00425-3. doi: 10.1016/j.bjps.2021.08.036. Online ahead of print.

ABSTRACT

PURPOSE: The use of free vascularized fibula grafts (FVFG) in complex spinal deformity surgery intends to allow for life-long stability of the spine with good long-term clinical outcome. However, these long-term outcomes of this technique are still lacking. The objective of this study is to report the long-term postoperative outcomes and establish the long-term viability of this method for spinal reconstruction.

METHODS: A retrospective cohort study was conducted in all patients who underwent spinal reconstructive surgery utilizing a FVFG at a tertiary medical centre. Questionnaires taken from the participants were the Numeric Pain Rating Scale (NPRS), Oswestry Low Back Pain Disability (also known as Oswestry Disability Index (ODI)), Scoliosis Research Society 22r (SRS-22), the EQ-5D-5L and a self-ass embled questionnaire regarding donor site comorbidities and patient satisfaction.

RESULTS: Over a period of 24 years (1995-2019), we used FVFG for spinal reconstruction in 31 patients. A total of 25 patients were included in this study, 8 patients were deceased at the time of this study, and sixteen patients responded to the questionnaires. Patient satisfaction was rated 6.8 out of 10, the average SRS-22r score was 3.6, EQ-5D-5L score was 0.725, and the ODI score showed a minimal disability (0-20%) postoperatively. Overall complication-free survival was 8.9 years. Nine patients underwent a re-operation in the spinal area; five for the removal of the spinal instrumentation.

CONCLUSION: Patients reported satisfied and good long-term outcomes following FVFG surgical procedure for complex spinal deformities. Therefore, considering the alternatives, this procedure provides a good long-term solution for complex spinal deformity surgery.

PMID:34736853 | DOI:10.1016/j.bjps.2021.08.036

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5-Aminolevulinic acid combined with ferrous iron improves glucose tolerance in high-fat diet-fed mice via upregulation of glucose transporter 1

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Exp Ther Med. 2021 Dec;22(6):1454. doi: 10.3892/etm.2021.10889. Epub 2021 Oct 15.

ABSTRACT

Decreased mitochondrial metabolism suppresses glucose metabolism, resulting in obesity and diabetes. The present study aimed to investigate mechanisms underlying the 5-aminolevulinic acid (5-ALA) hydrochloride-mediated increase in glucose uptake in high-fat diet (HFD)-fed mice in vivo and C2C12 myotube cells in vitro. C57BL/6N male mice (20 weeks old) were fed either HFD or normal diet (ND) for 4 weeks. A total of five HFD-fed mice were orally administered with 300 mg/kg 5-ALA hydrochloride and 47.1 mg/kg sodium ferrous citrate (SFC; HFD + 5-ALA/SFC), whereas ND and other HFD-fed mice were orally administered with saline. After 4 weeks, these mice were intraperitoneally administered with 2 g/kg glucose and 3.2 mg/kg 2-deoxyglucose (2DG) for intraperitoneal glucose tolerance test (IPGTT) and glucose uptake test. Body weights, plasma glucose levels and the area under the curve of IPGTT were lower in mice treated with HFD + 5-ALA/SFC compared with in those treated with HFD alone. 2DG uptake in the gastrocnemius muscle and heart were more significantly improved in the HFD + 5-ALA/SFC mice compared with the HFD-fed mice. Furthermore, 5-ALA/SFC increased 2DG uptake in C2C12 cells to a similar level to the insulin-treated group. Moreover, it increased glucose transport (GLUT)1 translocation in the plasma membrane by 2.5-fold relative to the controls without affecting GLUT1 expression; however, it had no effect on GLUT4 translocation. Therefore, 5-ALA/SFC enhanced gastrocnemius and cardiac glucose uptake in HFD-fed mice, and upregulated GLUT1 translocation to the plasma membrane, but not GLUT4 in C2C12 myotube cells. Therefore, it could potentially be used as a novel drug for the treatment of diabetes.

PMID:34737794 | PMC:PMC8561763 | DOI:10.3892/etm.2021.10889

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Identification of potential novel biomarkers for abdominal aortic aneurysm based on comprehensive analysis of circRNA-miRNA-mRNA networks

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Exp Ther Med. 2021 Dec;22(6):1468. doi: 10.3892/etm.2021.10903. Epub 2021 Oct 21.

ABSTRACT

Abdominal aortic aneurysm (AAA) is a life-threatening disorder and, therefore, investigation into its underlying mechanisms in light of the competing endogenous RNAs (ceRNAs) hypothesis has gradually increased. However, there is still lacking systematic analysis on AAA-associated circular RNA (circRNA)-microRNA (miRNA/miR)-messenger RNA (mRNA) interaction networks based on bioinformatics methods. The present study attempted to identify novel molecular biomarkers for AAA by profiling circRNA-miRNA-mRNA networks using three public microarray datasets (GSE7084, GSE57691 and GSE144431). A total of 135 differentially expressed genes (DEGs) and 142 differentially expressed circRNAs were detected using the limma R package with the statistical threshold of P<0.05 and |log2fold change (FC)| >1.5. In addition, 12 circRNA-miRNA-mRNA axes we re identified to construct upregulated and downregulated ceRNA networks using Cytoscape. Based on molecular complex detection algorithm, (hsa_circ_0057691/0092108/0006845/0082182)- miR-330-5p-calponin 1 (CNN1) and (hsa_circ_0061482/0011450/0008351/0004121)-miR-326-CD8a molecule (CD8A) were recognized as the center axes in ceRNA networks. Reverse transcription-quantitative PCR results verified the significant downregulation of CNN1 and upregulation of CD8A in human AAA tissues (P<0.05). In addition, four upregulated circRNA/mRNA axes, and five downregulated circRNA/mRNA axes were revealed to have possible biological functions in the pathogenesis of AAA using the Cytoscape software. Receiver operating characteristic analysis demonstrated the accuracy of these nine DEGs involved in these axes for AAA diagnosis with area under the curves >0.80. The present study revealed novel circRNA-miRNA-mRNA networks associated with AAA, especially for CNN1 and CD8A axes with the potential fun ction of 'focal adhesion' and 'immune response', respectively. Overall, the present findings may provide evidence to explore the implicated ceRNAs in the molecular mechanisms and as novel biomarkers for AAA.

PMID:34737808 | PMC:PMC8561771 | DOI:10.3892/etm.2021.10903

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miR-199b-5p mediates adriamycin-induced podocyte apoptosis by inhibiting the expression of RGS10

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Exp Ther Med. 2021 Dec;22(6):1469. doi: 10.3892/etm.2021.10904. Epub 2021 Oct 21.

ABSTRACT

Podocyte apoptosis is a key risk factor for the progression of kidney diseases. MicroRNA (miR)-199b-5p has been shown to be involved in cell apoptosis. However, the molecular mechanisms of miR-199b-5p in podocyte apoptosis remain uncertain. Thus, the present study aimed to investigate whether miR-199b-5p participates in the regulation of podocyte apoptosis and to elucidate the involved mechanisms of this process. A podocyte apoptosis model was constructed using adriamycin (ADR) in vitro. miR-199b-5p mimic and inhibitor were transfected in podocytes to change the expression level of miR-199b-5p. RNA expression was examined by reverse transcription-quantitative PCR. Western blotting was used to measure protein expression. Apoptosis was monitored via flow cytometry and detection of apoptosis-associated proteins. The results from the present s tudy demonstrated that miR-199b-5p was upregulated and that regulator of G-protein signaling 10 (RGS10) was downregulated in ADR-stimulated podocytes. Overexpression of miR-199b-5p could inhibit RGS10 expression and stimulate podocyte apoptosis, whereas miR-199b-5p knockdown restored the levels of RGS10 and ameliorated podocyte apoptosis in ADR-induced podocytes. Furthermore, the effects of miR-199b-5p overexpression could be significantly reversed by RGS10 overexpression. In addition, podocyte transfection of miR-199b-5p activated the AKT/mechanistic target of rapamycin (mTOR) signaling, which was blocked following RGS10 overexpression. Taken together, the present study demonstrated that miR-199b-5p upregulation could promote podocyte apoptosis by inhibiting the expression of RGS10 through the activation of AKT/mTOR signaling.

PMID:34737809 | PMC:PMC8561778 | DOI:10.3892/etm.2021.10904

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Anagliptin alleviates lipopolysaccharide-induced inflammation, apoptosis and endothelial dysfunction of lung microvascular endothelial cells

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Exp Ther Med. 2021 Dec;22(6):1472. doi: 10.3892/etm.2021.10907. Epub 2021 Oct 22.

ABSTRACT

It has been reported that dipeptidyl peptidase-4 (DPP4) inhibition protects against acute lung injury (ALI). Anagliptin is a novel selective inhibitor of DPP4 but its role in ALI has not been studied. The present study aimed to investigate the effects of anagliptin on lipopolysaccharide (LPS)-induced human pulmonary microvascular endothelial cell (HPMVEC) injury, as well as its underlying mechanism. HPMVECs were exposed to LPS in the presence or absence of anagliptin co-treatment. MTT assay was used to evaluate cell viability and nitric oxide (NO) production was detected using a commercial kit. DPP4 and pro-inflammatory cytokine expression levels, apoptosis and migration were assessed via reverse transcription-quantitative PCR, western blotting, TUNEL staining and wound healing assay, respectively. Western blot analysis was performed to assess ex pression levels of proteins involved in NF-κB signaling, cell apoptosis and migration, as well as high mobility group box 1 (HMGB1)/receptor for advanced glycation end products (RAGE). LPS decreased cell viability and NO production, but elevated expression of DPP4 in HPMVECs. LPS promoted pro-inflammatory cytokine expression, NF-κB activation and cell apoptosis, but inhibited cell migration and phosphorylated-AKT/endothelial NO synthase expression. Anagliptin co-treatment significantly restored all of these effects. Mechanistically, the upregulation of HMGB1/RAGE expression induced by LPS was markedly blocked by anagliptin. In conclusion, anagliptin alleviated inflammation, apoptosis and endothelial dysfunction in LPS-induced HPMVECs via modulating HMGB1/RAGE expression. These data provide a basis for use of anagliptin in ALI treatment.

PMID:34737812 | PMC:PMC8561766 | DOI:10.3892/etm.2021.10907

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Relationship between inferior fascicle of anterior talofibular ligament and articular capsule in lateral ankle ligament complex

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Surg Radiol Anat. 2021 Nov 5. doi: 10.1007/s00276-021-02851-1. Online ahead of print.

ABSTRACT

PURPOSE: The lateral ankle ligament complex (LALC) is composed of anterior talofibular (ATFL), calcaneofibular (CFL), and posterior talofibular (PTFL) ligaments, all of which have a connection/continuous fiber. However, the structural link between the LALC and the articular capsule remains unknown. The goal of our study was to determine the connection between ATFL's inferior fascic le and the articular capsule.

METHODS: In this study, we utilized 84 formalin-fixed ankles to elucidate the structure of LALC. Between ATFL and CFL, the bundle number of ATFL and arciform fiber was investigated. The specimens were decalcified and sectioned coronally using a freezing microtome, in the case of double bundles of ATFL, to study the connection between the inferior fascicle of ATFL and the articular capsule.

RESULTS: ATFL had a single (25%), double (74%), and triple (1%) bundle number, respectively. The arciform fiber connecting the ATFL and the CFL was found in the superficial layer of all ankles (100%). There were two types of relationships between the inferior fascicle of ATFL and the articular capsule: 36 ankles (58%) were extracapsular, and 26 of 62 ankles (42%) were integrated with the inferior-lateral articular capsule. There are two kinds of relationships between the inferior fascicle of the ATFL and the articular capsule: extracapsular and integrated- capsular.

CONCLUSIONS: The inferior fascicle of ATFL has a variant and integrated-capsular type is reinforced inferior-lateral articular capsule and enters the joint to form continuous fibers with PTFL, making LALC. These anatomical findings are helpful in ultrasonography diagnosis and arthroscopic ankle surgery.

PMID:34738180 | DOI:10.1007/s00276-021-02851-1

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Impact of the COVID-19 pandemic on head and neck cancer diagnosis: data from a single referral center, South Tyrol, northern Italy

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Eur Arch Otorhinolaryngol. 2021 Nov 5. doi: 10.1007/s00405-021-07164-y. Online ahead of print.

ABSTRACT

OBJECTIVE: The aim of the study was to evaluate the impact of the COVID-19 pandemic on new diagnoses of head and neck cancer (HNC) in South Tyrol, northern Italy in terms of the number of new diagnoses and worsening disease stage due to diagnostic delay.

METHODS: Patients were divided into two groups: the control group with a first diagnosis of HNC in 10 months before the national lockdown (March 9th, 2020) and the study group with a first diagnosis of HNC in 10 months after lockdown.

RESULTS: A total of 124 patients were included in the study. Before the spread of COVID-19, 79 new diagnoses of HNCs were registered, while in the period after the lockdown, 45 new cancers cases were diagnosed and the difference was statistically significant (p = 0.01278). Early clinical T-stage results showed 52 cases in the control group a nd 21 in the study group, again with a significant difference (p = 0.03711). Advanced T-stage results showed 27 cases in the control group and 24 in the study group.

CONCLUSIONS: This study highlights the impact of the COVID-19 pandemic on HNCs, showing a statistically significant difference in the number of diagnoses before and after the lockdown which was related to the spread of the SARS-CoV-2 virus, and with a relevant decrease in early cT-staged HNCs.

PMID:34739577 | DOI:10.1007/s00405-021-07164-y

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