MNK/eIF4E inhibition overcomes anlotinib resistance in non‐small cell lung cancer

alexandrossfakianakis shared this article with you from Inoreader MNK/eIF4E inhibition overcomes anlotinib resistance in non‐small cell lung cancer via Fundamental & Clinical Pharmacology Abstract Anlotinib is approved for refractory cases in advanced non-small-cell lung cancer (NSCLC). This is a novel oral multitarget tyrosine kinase inhibitor, but patients inevitably face prospects of drug resistance during the treatment process. Using anlotinib-resistant NSCLC models, this work investigated the underlying molecular mechanism and systematically addressed the issue of anlotinib resistance. We demonstrated that expression and activity of eukaryotic translation initiation factor 4E (eIF4E) were upregulated in NSCLC cells due to prolonged exposure to anlotinib. eIF4E depletion resulted in significant effects to anlotinib-resistant cells, showing proliferation inhibition and apoptosis inducement. We further showed that MAP kinase interacting serine/threonine kinase (MNK)-dependent eIF4E inhibition by cercosporamide was active against anlotinib-resistant cells and significantly augmented anlotinib's efficacy in parental NSCLC cells. Importantly, observations from in-vitro exp eriments are consistent in in vivo anlotinib-resistant and anlotinib-sensitive NSCLC cancer xenograft mouse models. Our work is the first to reveal that eIF4E is involved intimately in anlotinib resistance development in NSCLC, and this eIF4E activation can be reversed by cercosporamide or other MNK inhibitors. View on Web

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Nonpharmaceutical interventions for COVID‐19 disrupt the dynamic balance between influenza A virus and human immunity

alexandrossfakianakis shared this article with you from Inoreader Nonpharmaceutical interventions for COVID‐19 disrupt the dynamic balance between influenza A virus and human immunity via Journal of Medical Virology Abstract Background During the COVID-19 epidemic, nonpharmaceutical interventions (NPIs) blocked the transmission route of respiratory diseases. This study aimed to investigate the impact of NPIs on the influenza A virus (IAV) outbreak. Methods The present study enrolled all children with respiratory tract infections who came to the Children's Hospital of Zhejiang University between January 2019 and July 2022. A direct immunofluorescence assay kit detected IAV. Virus isolation and Sanger sequencing were performed. Results From June to July 2022, in Hangzhou, China, the positive rate of IAV infection in children has increased rapidly, reaching 30.41%, and children over three years old are the main infected population, accounting for 75% of the total number of infected children. Influenza A (H3N2) viruses are representative strains during this period. In this outbreak, H3N2 was isolated from a cluster of its own and is highly homologous with A/South_Dakota /22/2022 (2021-2022 northern hemisphere). Between isolated influenza A(H3N2) viruses and A/South_Dakota/22/2022, the nucleotide homology of the HA gene ranged from 97.3% to 97.5%; the amino acid homology was 97% - 97.2%, and the genetic distance of nucleotides ranged from 0.05 to 0.052. Compared with A/South_Dakota/22/2022, the isolated H3N2 showed S156H, N159Y, I160T, D186S, S198P, I48T, S53D, and K171N mutations. There was no variation in 13 key amino acid sites associated with neuraminidase inhibitor resistance in NA protein. Conclusion Long-term NPIs have significantly affected the evolution and transmission of the influenza virus and human immunity, breaking the dynamic balance between the influenza A virus and human immunity. This article is protected by copyright. All rights reserved. View on Web

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The association between serum 25‐hydroxyvitamin D and the prevalence of herpes simplex virus

alexandrossfakianakis shared this article with you from Inoreader The association between serum 25‐hydroxyvitamin D and the prevalence of herpes simplex virus via Journal of Medical Virology Abstract Objective Previous studies have reported a potential anti-infection effect for vitamin D. However, the relationship between vitamin D status and herpes simplex virus (HSV) infection has not yet been evaluated. Therefore, this study aimed to determine the association between serum 25-hydroxyvitamin D [25(OH)D] and infection with HSV types 1 and 2 (HSV-1 and HSV-2). Methods Data were collected from the National Health and Nutrition Examination Survey (NHANES) from 2007-2016. The association between 25(OH)D and HSV prevalence was evaluated using propensity score matching (PSM) and univariate and multivariate logistic regression analyses. Results Overall, 14174 participants were included in the final analysis. Before PSM, 8639 (60.9%) had positive HSV-1 and 2636 (18.6%) had HSV-2. The HSV-1 and HSV-2 positive groups had more females and older individuals (P<0.05). The HSV-2 patients had lower 25(OH)D levels than those with HSV-1. Age and g ender did not differ in the groups after PSM (P>0.05). The 25(OH)D level was significantly lower in the HSV-1 and HSV-2 groups than in the non-HSV infection groups. Multivariate logistic regression showed that serum 25(OH)D level was negatively associated with HSV-1 and HSV-2 infection (OR=0.730 and 0.691, P<0.001, respectively). Vitamin D deficiency was an independent risk factor for both HSV-1 and HSV-2 (adjusted OR=2.205 and 2.704, P<0.001, respectively). Conclusion Lower serum 25(OH)D levels correlated significantly with increased HSV-1 and HSV-2 infection risk This article is protected by copyright. All rights reserved. View on Web

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Drilling‐ and withdrawing‐related thermal effects of implant site preparation for ceramic and stainless steel twist drills in standardized bovine bone

alexandrossfakianakis shared this article with you from Inoreader Drilling‐ and withdrawing‐related thermal effects of implant site preparation for ceramic and stainless steel twist drills in standardized bovine bone via Clinical Implant Dentistry and Related Research Abstract Introduction Excessive surgical trauma is believed to be among the most important causes for early implant losses. As thermal injury to the bone is not only dependent on the amount of generated heat but also on the tissue exposure time, and the greatest temperature increase was found within the withdrawing period, the entire osteotomy procedure with the parameters contributing to thermal damage is of particular clinical relevance. The aim of this study was to investigate the thermal performance of metal-based and ceramic implant drills regarding the temperature exposure time during the whole osteotomy process. Materials and Methods This investigation consisted of 240 individual preparations in total, comprising two different drilling depths (10 and 16 mm), two irrigation methods (external and without irrigation), two implant drill materials (stainless steel and zirconia), and three consecutive drill diameters per material (2.0/2.2, 2.8, and 3.5 mm) with 10 identical repetitions. Real-time multichannel temperature measurement was conducted during automated drilling procedures in standardized bovine bone specimens. Results The maximum temperature changes were highly associated with the time period of passive drill withdrawing (p ≤ 0.05), irrespective of drill material, drilling depth, or drill diameter. Statistically significant differences in temperature generation between stainless steel and ceramic drills were observed in irrigated testing sites at both drilling depths with smaller drill diameters (2.0/2.2 and 2.8 mm, p ≤ 0.05). Conclusion Results of this in vitro study could demonstrate a strong association between the highest temperature increase and the passive withdrawing time period in both investigated drill materials. Considering these findings and the resulting thermal bone damage due to the whole surgical procedure, high overall temperatures in combination with a prolonged heat exposure time may impact the future osseointegration process. View on Web

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The use of electrodermal activity in pulpal diagnosis and dental pain assessment

alexandrossfakianakis shared this article with you from Inoreader The use of electrodermal activity in pulpal diagnosis and dental pain assessment via International Endodontic Journal Abstract Abstract Aims To explore whether electrodermal activity (EDA) can serve as a complementary tool for pulpal diagnosis (Aim 1) and an objective metric to assess dental pain before and after local anaesthesia (Aim 2). Methodology A total of 53 subjects (189 teeth) and 14 subjects (14 teeth) were recruited for Aim 1 and Aim 2, respectively. We recorded EDA using commercially available devices, PowerLab and Galvanic Skin Response (GSR) Amplifier, in conjunction with cold and electric pulp testing (EPT). Participants rated their level of sensation on a 0-10 visual analogue scale (VAS) after each test. We recorded EPT-stimulated EDA activity before and after the administration of local anaesthesia for participants who required root canal treatment (RCT) due to painful pulpitis. The raw data were converted to the time-varying index of sympathetic activity (TVSymp), a sensitive and specific parameter of EDA. Statistical analysis was performed using Python 3.6 and its Scikit-post hoc library. Results EDA activity was upregulated by the stimuli of cold and EPT testing in normal pulp. TVSymp signals were significantly increased in vital pulp compared to necrotic pulp by both, cold test and EPT. Teeth that exhibited intensive sensitivity to cold with or without lingering pain had increased peak numbers of TVSymp than teeth with mild sensation to cold. Pre- and post-anaesthesia EDA activity and VAS scores were recorded in patients with painful pulpitis. Post-anaesthesia EDA signals were significantly lower compared to pre-anaesthesia levels. Approximately 71 % of patients (10 out of 14 patients) experienced no pain during treatment and reported VAS score zero or 1. Majority of patients (10 out of 14) showed the reduction of TVSymp after the administration of anaesthesia. Two out of three patients who experienced increased pain during root canal treatment (post-treatment VAS > pre-treatment VAS) exhibited increased post-anaesthesia TVSymp. Conclusions Our data show promising results for using EDA in pulpal diagnosis and for assessing dental pain. While our testing was limited to subjects who had adequate communication skills, our future goal is to be able to use this technology to aid in the endodontic diagnosis of patients who have limited communication ability. View on Web

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Safety of day‐case endoscopic sinus surgery

alexandrossfakianakis shared this article with you from Inoreader Safety of day‐case endoscopic sinus surgery in England: An observational study using an administrative dataset via Clinical Otolaryngology Abstract Introduction As elective surgical services recover from the COVID-19 pandemic a movement towards day-case surgery may reduce waiting lists. However, evidence is needed to show that day-case surgery is safe for endoscopic sinus surgery (ESS). The aim of this study was to investigate the safety of day-case ESS in England. Design Secondary analysis of administrative data. Methods We extracted data from the Hospital Episodes Statistics database for the five years from 1st April 2014 to 31st March 2019. Patients undergoing elective ESS procedure aged ≥ 17 years were included. Exclusion criteria included malignant neoplasm, complex systemic disease and trans-sphenoidal pituitary surgery. The primary outcome was readmission within 30 days post-discharge. Multilevel, multivariable logistic regression modelling was used to compare outcomes for those operated on as day-cases and those with an overnight stay after adjusting for demographic, frailty, comorbidity and procedural covariates. Results Data were available for 49,223 patients operated on across 129 NHS hospital trusts. In trusts operating on more than 50 patients in the study period, rates of day-case surgery varied from 20.6% to 100%. Rates of day-case surgery increased from 64.0% in 2014/15 to 78.7 % in 2018/19. Day-case patients had lower rates of 30-day emergency readmission (odds ratio 0.71, 95% confidence interval 0.62 to 0.81). Outcomes for patients operated on in trusts with ≥80% day-case rates compared to patients operated on in trusts with <50% rates of day-case surgery were similar. Conclusions Our data support the view that ESS can safely be performed as day-case surgery in most cases, although it will not be suitable for all patients. There appears to be scope to increase rates of day-case ESS in some hospital trusts in England. View on Web

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Neck management of pathological N1 oral squamous cell carcinoma: a retrospective study

alexandrossfakianakis shared this article with you from Inoreader Neck management of pathological N1 oral squamous cell carcinoma: a retrospective study via International Journal of Oral and Maxillofacial Surgery via MedWorm.com This study was performed to compare the effects of neck dissection procedures on the prognosis of patients with pathological N1 (pN1) oral squamous cell carcinoma (OSCC), analyse factors affecting the prognosis, and provide a neck management strategy for clinical N1 (cN1) oral cancer. The study patients were divided into two groups according to the neck dissection: a selective neck dissection (SND) group (n  = 85) and a radical or modified radical neck dissection (RND/MRND) group (n = 22). There was no statistically significant difference in recurrence rates at local, regional, and distant sites between the SND and RND/MRND groups. (Source: International Journal of Oral and Maxillofacial Surgery) View on Web

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Abnormal TSH Prior to Surgery in Children with Graves' Disease Predicts Abnormal TSH Following Thyroidectomy

alexandrossfakianakis shared this article with you from Inoreader Abnormal TSH Prior to Surgery in Children with Graves' Disease Predicts Abnormal TSH Following Thyroidectomy via The Laryngoscope Objective To identify variables that are associated with poor compliance to thyroid hormone replacement therapy in children after total thyroidectomy. Method A retrospective cohort study of children who underwent total thyroidectomy by high-volume pediatric otolaryngologists between 1/2014 and 9/2021. Postoperative poor compliance was characterized by at least three separate measurements of high TSH levels not associated with radioactive iodine treatment. Results There were 100 patients, ages 3–20 years old who met inclusion criteria; 44 patients underwent thyroidectomy for cancer diagnosis, and 56 for Graves' disease. The mean follow-up time was 36.5 months (range 3.0–95.6 months). Overall, 42 patients (42%) were found to have at least three measurements of high TSH during follow-up, and 29 patients (29%) were diagnosed with clinical hypothyroidism. Sex, race, income, insurance type, and benign versus malignant etiology for thyroidectomy were not associated with adherence to therapy. Multivariate regression analysis identified patients with Graves' disease and hyperthyroidism at the time of surgery and Hispanic ethnicity to be associated with postoperative clinical hypothyroidism (OR 9.38, 95% CI 2.16–49.2, p = 0.004 and OR 6.15, 95% CI 1.21–36.0, p = 0.033, respectively). Conclusions Preoperative hyperthyroidism in patients with Graves' disease and Hispanic ethnicity were predictors of postoperative TSH abnormalities. Preoperative counseling for patients and their families on the implications of total thyroidectomy and the need for life-long medications postoperatively is necessary. Efforts should be made to evaluate and improve adherence to therapy pre-and postoperatively in patients with Graves' disease. Level of Evidence 4 Laryngoscope, 2022 View on Web

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Absolute lymphocyte count recovery following initial acute myelogenous leukemia therapy: Implications for adoptive cell therapy

alexandrossfakianakis shared this article with you from Inoreader Absolute lymphocyte count recovery following initial acute myelogenous leukemia therapy: Implications for adoptive cell therapy via Pediatric Blood & Cancer Abstract Background An adequate absolute lymphocyte count (ALC) is an essential first step in autologous chimeric antigen receptor (CAR) T-cell manufacturing. For patients with acute myelogenous leukemia (AML), the intensity of chemotherapy received may affect adequate ALC recovery required for CAR T-cell production. We sought to analyze ALC following each course of upfront therapy as one metric for CAR T-cell manufacturing feasibility in children and young adults with AML. Procedure ALC data were collected from an observational study of patients with newly diagnosed AML between the ages of 1 month and 21 years who received treatment between the years of 2006 and 2018 at one of three hospitals in the Leukemia Electronic Abstraction of Records Network (LEARN) consortium. Results Among 193 patients with sufficient ALC data for analysis, the median ALC following induction 1 was 1715 cells/μl (interquartile range: 1166–2388), with successive decreases in ALC with each subsequent course. Similarly, the proportion of patients achieving an ALC >400 cells/μl decreased following each course, ranging from 98.4% (190/193) after course 1 to 66.7% (22/33) for patients who received a fifth course of therapy. Conclusions There is a successive decline of ALC recovery with subsequent courses of chemotherapy. Despite this decline, ALC values are likely sufficient to consider apheresis prior to the initiation of each course of upfront therapy for the majority of newly diagnosed pediatric AML patients, thereby providing a window of opportunity for T-cell collection for those patients identified at high risk of relapse or with refractory disease. View on Web

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