An Unusual Delayed Complication of Rib Graft Microtia Reconstruction After Two Decades: A Case Report

xlomafota13 shared this article with you from Inoreader An Unusual Delayed Complication of Rib Graft Microtia Reconstruction After Two Decades: A Case Report Via Otolaryngology Indian Abstract Microtia comprises a spectrum of congenital malformation characterized by partial deformities of the auricular components to complete absence of pinna. Surgical reconstructions of this anomaly are often complex and technically challenging. Infection, hematoma, and skin necrosis with resultant exposed cartilage graft tend to occur in the early phase of post-operative care. Herein, we report a case of a spontaneous auricular abscess with exposed cartilage framework 20 years following rib cartilage reconstruction. To our knowledge, this is the first case of such an occurrence. The treatment options are discussed, along with the review of the literature. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Using Interleaved Stimulation to Measure the Size and Selectivity of the Sustained Phase-Locked Neural Response to Cochlear Implant Stimulation

xlomafota13 shared this article with you from Inoreader Using Interleaved Stimulation to Measure the Size and Selectivity of the Sustained Phase-Locked Neural Response to Cochlear Implant Stimulation Via Journal of the Association for Research in Otolaryngology Abstract We measured the sustained neural response to electrical stimulation by a cochlear implant (CI). To do so, we interleaved two stimuli with frequencies F1 and F2 Hz and recorded a neural distortion response (NDR) at F2-F1 Hz. We show that, because any one time point contains only the F1 or F2 stimulus, the instantaneous nonlinearities typical of electrical artefact should not produce distortion at this frequency. However, if the stimulus is smoothed, such as by charge integration at the nerve membrane, subsequent (neural) nonlinearities can produce a component at F2-F1 Hz. We stimulated a single CI electrode with interleaved sinusoids or interleaved amplitude-modulated pulse trains such that F2 = 1.5F1, and found no evidence for an NDR when F2-F1 was between 90 and 120 Hz. However, interleaved amplitude-modulated pulse trains with F2-F1~40 Hz revealed a substantial NDR with a group delay of about 45 ms, consistent with a thalamic a nd/or cortical response. The NDR could be measured even from recording electrodes adjacent to the implant and at the highest pulse rates (> 4000 pps) used clinically. We then measured the selectivity of this sustained response by presenting F1 and F2 to different electrodes and at different between-electrode distances. This revealed a broad tuning that, we argue, reflects the overlap between the excitation elicited by the two electrodes. Our results also provide a glimpse of the neural nonlinearity in the auditory system, unaffected by the biomechanical cochlear nonlinearities that accompany acoustic stimulation. Several potential clinical applications of our findings are discussed. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Prolonged Use of n95 Mask a Boon or Bane to Healthcare Workers During Covid–19 Pandemic

xlomafota13 shared this article with you from Inoreader Prolonged Use of n95 Mask a Boon or Bane to Healthcare Workers During Covid–19 Pandemic Via Otolaryngology Indian Abstract The novel coronavirus, referred to as SARS-COV 2, originated in Wuhan, China in December 2019. Since many Health Care Workers (HCW) and general public lost their lives. The only thing which can prevent from being infected is social distancing and wearing of mask (N95) and wearing of mask has its own adverse effects. This is a retrospective study conducted in the Department of Otorhinolaryngology, Hind Institute of Medical Sciences, Sitapur from April 2020 to August 2020. The most common symptoms of wearing mask were headache, nasal dryness, eye dryness and acne for which extra precautions to be taken to deal with these conditions during COVID–19 pandemic. HCW should wear mask to prevent from exposing but while using the mask there are certain prerequisites which has to be followed to prevent from not only thr COVD – 19 but also the complications of prolonged use of N95 mask. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Immune-related Bell’s palsy in melanoma patients treated with immune checkpoint inhibitors

xlomafota13 shared this article with you from Inoreader Immune-related Bell's palsy in melanoma patients treated with immune checkpoint inhibitors Via Melanoma Research - Published Ahead-of-Print Immune-checkpoint inhibitors (ICIs) exposed the oncology community to novel immune-related adverse events (irAEs). Here, we report on a retrospective analysis of patients with melanoma who developed an ICI-related, unilateral, acute and peripheral facial nerve paralysis (Bell's palsy).We retrospectively reviewed a ll the cases of ICI-related Bell's palsy in patients with melanoma treated at our institution from January 2015 to January 2020. A total of five cases of ICI-related Bell's palsy were identified. Median age was 63 years. Median time-to-onset of Bell's palsy from ICIs initiation was 15 weeks. Four patients were treated with prednisone alone, whereas one patient was treated with prednisone plus valaciclovir. All the patients completely recovered from Bell's palsy without neurological sequelae. In melanoma patients treated with ICIs, Bell's palsy is a rare, neurologic irAE with a favorable outcome following administration of oral corticosteroids. Received 12 November 2020 Accepted 29 December 2020 Correspondence to Carolina Cimminiello, MD, Department of Medical Oncology and Hematology, Melanoma Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian, 1 – 20133, Milan, Italy, Tel: +39 02 2390 3823; e-mail: carolina.cimminiello@istitutotumori.mi.it Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Diagnostic and prognostic value of heat shock protein 90α in malignant melanoma

xlomafota13 shared this article with you from Inoreader Diagnostic and prognostic value of heat shock protein 90α in malignant melanoma Via Melanoma Research - Published Ahead-of-Print Malignant melanoma is one of the most common tumours of the skin. Heat shock protein 90α (HSP90α) has been applied in the auxiliary diagnosis of various malignancies, as a tumour marker. This study aims to evaluate diagnostic, therapeutic efficacy and prognostic value of plasma HSP90α levels in malignant melanoma. In this study, higher plasma HSP90α levels and abnormal rates were found in malignant melanoma patients than in healthy controls (92.63 vs. 51.84 ng/mL; P  4 mm, a high Clark level (IV + V), abnormal serum lactate dehydrogenase (LDH), distant metastases occurrence and Ki-67≥30% (P  View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Evaluation eines integrierten OP-Saals auf Basis offener Standards in der Cochlea-Implantat-Chirurgie

xlomafota13 shared this article with you from Inoreader Evaluation eines integrierten OP-Saals auf Basis offener Standards in der Cochlea-Implantat-Chirurgie Via Laryngo-Rhino-Otologie Laryngorhinootologie DOI: 10.1055/a-1346-9227 Hintergrund Die zunehmende Digitalisierung in der Chirurgie macht die Entwicklung moderner Operationskonzepte notwendig. Dabei werden neue Ansätze der Systemvernetzung und Integration auf Basis offener Standards der medizinischen Geräte verfolgt. Methodik Gemeinsam mit dem Innovationszentrum für Computerassistierte Chirurgie (ICCAS) konnte die Demonstration eines integrierten OP-Saals am Beispiel der Cochlea-Implantation durchgeführt werden. Evaluiert wurden das präoperative Management, die intraoperativen Prozeduren sowie die postoperative Dokumentation von insgesamt n = 30 Studienteilnehmern (2 Gruppen). Neben der Erhebung objektiver Parameter kamen qualitative Fragebögen und quantitative, intervallskalierte Fragen zur Anwendung. Ergebnisse Präoperativ wurde die digitale Präsentation klinischer Daten der Patienten von beiden Gruppen als hilfreich angesehen (Gruppe 1: Median = 5, Gruppe 2: Median = 4). Dies gilt auch für die personalisierten OP-Einstellungen, die intraoperativen Darstellungsmöglichkeiten sowie die dynamische, Operateur-zentrierte Visualisierung (Median = 4). Ähnlich positive Schlussfolgerungen wurden für die postoperative Dokumentation und die postoperative Nachsorge gezogen (Median = 4). Ein signifikanter Unterschied in der Gesamtbewertung des integrierten Operationskonzepts zwischen beiden Expertengruppen konnte nicht festgestellt werden (p > 0,05). Schlussfolgerungen Die positiven Studienergebnisse zeigen, dass die theoretische Idee der Systemvernetzung auf der Basis offener Standards am Beispiel einer Cochlea-Implantation erfolgreich in die Praxis umgesetzt werden kann. Damit scheint der intelligente „Operationssaal der Zukunft" keine fiktive Idee mehr zu sein, sondern ein realistisches Abbild der modernen chirurgischen Medizin. [...] Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany Article in Thieme eJournals: Table of contents  |  Abstract  |  Full text View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Circ_0008305‐mediated miR‐660/BAG5 axis contributes to hepatocellular carcinoma tumorigenesis

xloma.fota13 shared this article with you from Inoreader Circ_0008305‐mediated miR‐660/BAG5 axis contributes to hepatocellular carcinoma tumorigenesis Via Cancer Medicine circ_0008305 was greatly increased in HCC tissues and cells. circ_0008305 can act as a sponge of miR‐660. miR‐660 targeted Bcl‐2‐associated athanogene 5 (BAG5). Abstract Increasing circRNAs have attracted a lot of attention because of their significant biological effects in many diseases. It has been reported that circ_0008305 can modulate lung cancer progression. However, the association between circ_0008305 and hepatocellular carcinoma (HCC) needs to be well explored. In this current research, we studied the molecular function and potential mechanism of circ_0008305 in HCC progression. First, it was demonstrated that circ_0008305 was greatly increased in HCC tissues and cells. Moreover, we observed silencing circ_0008305 markedly repressed HCC cells in vitro growth and reduced tumor growth in vivo. Additionally, it was identified that circ_0008305 can act as a sponge of miR‐660 while miR‐660 targeted Bcl‐2‐associated athanogene 5 (BAG5). BAG5 belongs to a member of BAG family and it is involved in multiple diseases. We reported that circ_0008305 contributed to the inhibition of miR‐660, which resulted in an upregulated expression of BA G5 in HCC. Subsequently, rescue assays were conducted and it was indicated that loss of BAG5 reversed the effects of miR‐660 inhibitors on HCC partially. To sum up, it was illustrated by our study that circ_0008305‐mediated miR‐660‐5p/BAG5 axis triggered HCC progression, which could provide a novel insight on the underlying mechanism of HCC progression. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Real world outcomes of combination and timing of immunotherapy with radiotherapy for melanoma with brain metastases

xloma.fota13 shared this article with you from Inoreader Real world outcomes of combination and timing of immunotherapy with radiotherapy for melanoma with brain metastases Via Cancer Medicine In our study of the National Cancer Data Base (NCBD), addition of immunotherapy to radiation therapy improves survival in patients with melanoma with brain metastases when added to SBRT or WBRT, with the best survival observed for IT with SBRT. Concurrrent versus Noncurrent immunotherapy combined with radiation had no significantly different survival. Abstract Introduction Immunotherapy (IT) and radiotherapy (RT) have improved overall survival in patients with melanoma with brain metastasis (MBM). We examined the real‐world survival impact of IT and RT combination and timing strategies. Materials and Methods From the facility‐based National Cancer Database (NCDB) data set, 3008 cases of MBM were identified between 2011 and 2015. Six treatment cohorts were identified: stereotactic radiosurgery (SRS) + IT, SRS alone, whole brain radiotherapy (WBRT) + IT, WBRT alone, IT alone, and none. Concurrent therapy was defined as IT given within 28 days before or after RT; nonconcurrent defined as IT administered within 28–90 days of RT. The co‐primary outcomes were propensity score‐adjusted overall survival by treatment regimen and overall survival by RT and IT timing. Results Median overall survival (mOS) was performed for each treatment category; SRS +IT 15.77 m; (95%CI 12.13–21.29), SRS alone (9.33 m; 95%CI: 8.0–11.3), IT alone (7.29 m; 95%CI: 5.35–12.91), WBRT +IT (4.89 m; 95%CI: 3.65–5.92), No RT or IT (3.29 m; 95%CI: 2.96–3.75), and WBRT alone (3.12 m; 95%CI 2.79–3.52). By propensity score matching, mOS for SRS +IT (15.5 m; 95%CI: 11.5–20.2) was greater than SRS alone (10.1 m; 95%CI: 8.4–11.8) (p = 0.010), and median survival for WBRT +IT (4.6 m; 95%CI: 3.4–5.6) was greater than WBRT alone (2.9 m; 95%CI: 2.5–3.5) (p < 0.001). In the SRS +IT group, 24‐month landmark survival was 47% (95%CI; 42–52) for concurrent versus 37% (95%CI; 30–44) for nonconcurrent (p = 0.40). Conclusion Those who received IT in addition to WBRT and SRS experienced longer survival compared to RT modalities alone, while those receiving concurrent SRS and IT trended toward improved survival versus nonconcurrent therapy. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Targeting YAP‐p62 signaling axis suppresses the EGFR‐TKI‐resistant lung adenocarcinoma

xloma.fota13 shared this article with you from Inoreader Targeting YAP‐p62 signaling axis suppresses the EGFR‐TKI‐resistant lung adenocarcinoma Via Cancer Medicine The accumulated p62 by autophagy inhibitor, chloroquine has oncogenic functions in EGFR‐TKI resistant lung adenocarcinoma. Hippo effector YAP regulates p62 transcription through ERK, and YAP inhibition significantly suppresses the expression of p62. We suggest that targeting YAP‐p62 signaling axis can be useful to overcome the EGFR‐TKI resistance in lung adenocarcinoma. Abstract Background Despite the progress of advanced target therapeutic agents and immune checkpoint inhibitors, EGFR‐TKI resistance is still one of the biggest obstacles in treating lung cancer. Clinical studies with autophagy inhibitors are actively underway to overcome drug resistance. Methods We used PC9, PC9/GR, and HCC827/GR cell lines to evaluate the activation of autophagy and EGFR‐TKI resistance. Chloroquine was applied as an autophagic blocker and verteporfin was utilized as a YAP inhibitor. Results In this study, we tried to reveal the effect of autophagy adaptor p62 which is accumulated by autophagy inhibitor in EGFR‐TKI‐resistant lung adenocarcinoma. We identified that p62 has oncogenic functions that induce cell proliferation and invasion of EGFR‐TKI‐resistant lung adenocarcinoma. Interestingly, we found for the first time that YAP regulates p62 transcription through ERK, and YAP inhibition can suppress the expression of oncogenic p62. We also confirmed that the expressions of p62 and YAP have a positive correlation in EGFR‐mutant lung adenocarcinoma patients. To block cell survival via perturbing YAP‐p62 axis, we treated EGFR‐TKI‐resistant lung cancer cells with YAP inhibitor verteporfin. Remarkably, verteporfin effectively caused the death of EGFR‐TKI‐resistant lung cancer cells by decreasing the expressions of p62 with oncogenic function, YAP, and its target PD‐L1. So, the cumulative effect of oncogenic p62 should be considered when using autophag y inhibitors, especially drugs that act at the last stage of autophagy such as chloroquine and bafilomycin A1. Conclusion Finally, we suggest that targeting YAP‐p62 signaling axis can be useful to suppress the EGFR‐TKI‐resistant lung cancer. Therefore, drug repurposing of verteporfin for lung cancer treatment may be valuable to consider because it can inhibit critical targets: p62, YAP, and PD‐L1 at the same time. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Plasmodium falciparum FIKK9.1 is a monomeric serine–threonine protein kinase with features to exploit as a drug target

xloma.fota13 shared this article with you from Inoreader Plasmodium falciparum FIKK9.1 is a monomeric serine–threonine protein kinase with features to exploit as a drug target Via Chemical Biology & Drug Design FIKK‐9.1 kinase is monomeric with a native molecular weight of 60 ± 1.6 kDa. The C‐terminal domain of protein has a well‐defined pocket to bind ATP. FIKK protein binds ATP with a K d of 45.6 ± 2.4 µM. FIKK‐9.1 has 23 pockets to serve potential docking sites for substrates. Peptide P277 is fitting nicely into the binding pocket. FIKK‐9.1 is phosphorylating spectrin, ankyrin, band 3 in the IRBC. FIKK 9.1 can be exploited in drug discovery and diagnostics. Abstract FIKK‐9.1 is essential for parasite survival, but its structural and biochemical characterization will enable us to understand its role in the parasite life cycle. The recombinant FIKK9.1 kinase is monomeric with a native molecular weight of 60 ± 1.6 kDa. Structural characterization of FIKK9.1 kinase reveals that it consists of two domains: N‐terminal FHA like domain and C‐terminal kinase domain. The C‐terminal domain has a well‐defined pocket, but it displayed RMSD deviation of 1.38–3.2 Å from host kinases. ITC analysis indicates that ATP binds to the protein with a K d of 45.6 ± 2.4 µM. Mutational studies confirm the role of Val‐244, Met‐245, Lys‐320, 324, and Glu‐366 for ATP binding. Co‐localization studies revealed FIKK9.1 in the parasite cytosol with a component trafficked to the apicoplast and also to IRBC. FIKK9.1 has 23 pockets to serve as potential docking sites for substrates. Correlation analysis of peptides from the combinatorial library concluded that peptide P277 (MFDFHYTLGPMWGTL) was fitting nicely into the binding pocket. The peptide P277 picked up candidates from parasite and key players from RBC cytoskeleton. Interestingly, FIKK9.1 is phosphorylating spectrin, ankyrin, and band‐3 from RBC cytoskeleton. Our study highlights the structural and biochemical features of FIKK9.1 to exploit it as a drug target. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Administrative coding in electronic health care record‐based research of NAFLD: an expert panel consensus statement

xloma.fota13 shared this article with you from Inoreader Administrative coding in electronic health care record‐based research of NAFLD: an expert panel consensus statement Via Hepatology Abstract Background and aims Electronic health record (EHR)‐based research allows the capture of large amounts of data, which is necessary in nonalcoholic fatty liver disease (NAFLD), where the risk of clinical liver outcomes is generally low. The lack of consensus on which International Classification of Disease (ICD) codes should be used as exposures and outcomes limits comparability and generalizability of results across studies. We aimed to establish consensus among a panel of experts on ICD codes that could become the reference standard and provide guidance around common methodological issues. Approach and results Researchers with an interest in EHR‐based NAFLD research were invited to collectively define which administrative codes are most appropriate for documenting exposures and outcomes. We used a modified Delphi approach to reach consensus on several commonly encountered methodological challenges in the field. After two rounds of revision, a high level of agreement (>67%) was reached on all items considered. Full consensus was achieved on a comprehensive list of administrative codes to be considered for inclusion and exclusion criteria in defining exposures and outcomes in EHR‐based NAFLD research. We also provide suggestions on how to approach commonly encountered methodological issues and identify areas for future research. Conclusions This expert panel consensus statement can help harmonize and improve generalizability of EHR‐based NAFLD research. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.