Nystagmus in Ramsay Hunt syndrome with or without dizziness.

BACKGROUND: The presence of dizziness has been reported as a negative prognostic factor for recovery of facial palsy in Ramsay Hunt syndrome (RHS). The aim of this study was to investigate the incidence and patterns of nystagmus in RHS patients without dizziness, and discuss possible mechanisms. We also compared the severity and prognosis of facial palsy between RHS patients with and without dizziness. METHODS: From January 2014 to January 2019, 36 patients diagnosed with RHS (27 with dizziness and 9 without dizziness) were included. Patterns of nystagmus were examined and categorized using video-nystagmography. House-Brackmann(HB) grade of facial palsy was compared between RHS patients with and without dizziness. RESULTS: Not only RHS patients with dizziness exhibited nystagmus in most cases (96%, 26 of 27) but also as many as 67% (6 of 9) of RHS patients without dizziness exhibited nystagmus, though the intensity was remarkably weak. In both groups of RHS with and without dizziness, direction-fixed nystagmus and direction-changing positional nystagmus were observed. Initial HB grade and recovery of facial palsy after treatment were not significantly different between RHS with and without dizziness. CONCLUSION: Various patterns of nystagmus including direction-fixed and positional direction-changing nystagmus were observed in RHS patients, and inflammation of the vestibular nerve and inner ear end organs may be responsible for the production of nystagmus in these patients. The results support that the evaluation of vestibular function may be necessary even in RHS patients who do not complain of dizziness or vertigo.

Effectiveness and Satisfaction Degree of Transconjunctival-Approach Lower Blepharoplasty Combined With Pinch Skin Excision Technique.

The purpose of this study was to evaluate and compare the effectiveness and satisfaction of transconjunctival-approach lower blepharoplasty combined with a pinch skin excision technique between young patients (younger than 60 years of age) and elderly patients (older than 60 years of age) in Korea. The medical records of 69 patients who underwent transconjunctival-approach lower blepharoplasty combined with a pinch skin excision technique from January 2003 to February 2018 were reviewed. Success rate postoperative complications, and degree of satisfaction with the surgical technique were evaluated and statistically compared between the 2 different age groups. All 69 patients were satisfied with the final result. The average success rate of surgery was 96.7% in the young patients (group A) and 97.4% in the elderly patients (group B) during the mean follow-up period of 6 months. There were 3 cases reported as having persistent complications (2 cases in group A and 1 patient in group B). The satisfaction rating between groups A and B showed no statistically significant difference (P = 0.430). We confirmed lower-eyelid fat prolapse and dermatochalasis can be effectively corrected using transconjunctival lower blepharoplasty with a pinch skin excision technique in patients regardless of age.

The Effect of Upper Aging Blepharoplasty on Upper and Lower Eyelid Position.

PURPOSE: Change in eyelid position after upper blepharoplasty is an important factor that can affect postoperative patient satisfaction. However, no one has investigated eyelid changes during follow-up for upper eyelid surgery. Thus, the purpose of this study was to investigate position changes in the upper and lower eyelids during the follow-up period after upper blepharoplasty in Korean. METHODS: The authors retrospectively reviewed the clinical records of patients who underwent upper blepharoplasty for uncomplicated upper eyelid dermatochalasis. Digital photographs were taken preoperatively, immediately after surgery, and at 1 week postoperative, 1 month postoperative, and 3 months postoperative. Our main-effect variables were marginal reflex distance (MRD) 1 and 2 and palpebral fissure height (PFH), which were measured from digital photographs using ImageJ software. RESULTS: We enrolled 180 eyes from 90 patients (M: 35 and F: 55) with a mean age of 63.8 ± 10.3 years. The eyelid measurements (MRD1, MRD2, PFH) taken preoperatively, immediately after surgery, and 1 week, 1 month, and 3 months postoperative were, respectively: MRD1 (mm): 2.56 ± 1.08, 1.91 ± 0.86, 2.21 ± 1.02, 2.66 ± 1.01, 2.75 ± 0.99; MRD2 (mm): 4.91 ± 0.93, 4.62 ± 0.87, 4.68 ± 0.90, 4.87 ± 0.86, 4.91 ± 0.83; and PFH (mm): 7.48 ± 1.64, 6.53 ± 1.46, 6.89 ± 1.53, 7.52 ± 1.51, 7.65 ± 1.49. All postoperative measurements for MRD1 and PFH were significantly different from the preoperative measurement, except for measurements taken 1 month postoperative. MRD2 measurements differed significantly from the preoperative measurements immediately after surgery and 1 week postoperative. Among age, preoperative PFH, and amount of skin-muscle resection, only preoperative PFH significantly affected PFH changes immediately after surgery and at 3 months postoperative (OR 0.636, 95% CI 0.478-0.847, OR 0.506, 95% CI 0.386-0.663). CONCLUSION: All eyelid measurements (MRD1, MRD2, and PFH) decreased 1 week postoperatively from values immediately after surgery, but MRD1 and PFH increased slightly 3 months postoperative. We note that postoperative changes in PFH may be large in patients with large PFH before blepharoplasty. It should also be noted that reverse ptosis of the lower eyelid occurs immediately after upper eyelid surgery.

Construction of a database for published phase II/III drug intervention clinical trials for the period 2009-2014 comprising 2,326 records, 90 disease categories, and 939 drug entities.

OBJECTIVES: To construct a database of published clinical drug trials suitable for use 1) as a research tool in accessing clinical trial information and 2) in evidence-based decision-making by regulatory professionals, clinical research investigators, and medical practitioners. MATERIALS: Comprehensive information obtained from a search of design elements and results of clinical trials in peer reviewed journals using PubMed (http://www.ncbi.nlm.ih.gov/pubmed). METHOD: The methodology to develop a structured database was devised by a panel composed of experts in medical, pharmaceutical, information technology, and members of Ministry of Food and Drug Safety (MFDS) using a step by step approach. A double-sided system consisting of user mode and manager mode served as the framework for the database; elements of interest from each trial were entered via secure manager mode enabling the input information to be accessed in a user-friendly manner (user mode). Information regarding methodology used and results of drug treatment were extracted as detail elements of each data set and then inputted into the web-based database system. RESULTS: Comprehensive information comprising 2,326 clinical trial records, 90 disease states, and 939 drugs entities and concerning study objectives, background, methods used, results, and conclusion could be extracted from published information on phase II/III drug intervention clinical trials appearing in SCI journals within the last 10 years. The extracted data was successfully assembled into a clinical drug trial database with easy access suitable for use as a research tool. The clinically most important therapeutic categories, i.e., cancer, cardiovascular, respiratory, neurological, metabolic, urogenital, gastrointestinal, psychological, and infectious diseases were covered by the database. Names of test and control drugs, details on primary and secondary outcomes and indexed keywords could also be retrieved and built into the database. The construction used in the database enables the user to sort and download targeted information as a Microsoft Excel spreadsheet. CONCLUSION: Because of the comprehensive and standardized nature of the clinical drug trial database and its ease of access it should serve as valuable information repository and research tool for accessing clinical trial information and making evidence-based decisions by regulatory professionals, clinical research investigators, and medical practitioners.

Population pharmacokinetics of cyclosporine in hematopoietic stem cell transplant patients: consideration of genetic polymorphisms.

BACKGROUND: Cyclosporine (CsA), which is used for graft-versus-host disease prophylaxis in allogeneic hematopoietic stem cell transplant (allo-HSCT), has a narrow therapeutic range and large interindividual and intraindividual pharmacokinetic variability. Nevertheless, population pharmacokinetic (PopPK) studies of CsA in allo-HSCT are scarce. OBJECTIVE: The goal of our study was to build a PopPK model of CsA in allo-HSCT in consideration of demographic, clinical, and genetic polymorphisms data. METHODS: A total of 34 adult allo-HSCT patients who received CsA were enrolled prospectively. Demographic, clinical, and CYP3A5 *1/*3, CYP2C19 *1/*2/*3, ABCB1 3435C>T, 1236C>T, 2677G>T/A, ABCC2 -24C>T, 1249G>A, VDR Bsml, Apal polymorphisms data were collected. A PopPK modeling was conducted with NONMEM program. RESULTS: A 1-compartment model with a 2-transit absorption compartment model was developed. After the stepwise covariate model building process, weight was incorporated into clearance (CL) as a power function model with the exponent value of 0.419. The final typical estimate of CL was 21.2 L/h; volume of distribution was 430 L; logit-transformed bioavailability was 1.49 (bioavailability: 81%); and transit compartment rate was 2.87/h. None of the genetic polymorphisms in CYP3A5, CYP2C19, ABCB1, ABCC2, and VDR were significant covariates in the pharmacokinetics of CsA. CONCLUSIONS: In our study, it was observed that weight had a significant effect on CL. Genetic polymorphisms did not affect CsA pharmacokinetics. Prospective studies with a larger number of participants is needed to validate the results of this study.

Advances in the Immunology of the Host-Parasite Interactions in African Trypanosomosis, including Single-Cell Transcriptomics.

Trypanosomes are single-celled extracellular parasites that infect mammals, including humans and livestock, causing global public health concerns and economic losses. These parasites cycle between insect vectors, such as tsetse flies and vertebrate hosts, undergoing morphological, cellular, and biochemical changes. They have remarkable immune evasion mechanisms to escape the host's innate and adaptive immune responses, such as surface coat antigenic variation and the induction of the loss of specificity and memory of antibody responses, enabling the prolongation of infection. Since trypanosomes circulate through the host body in blood and lymph fluid and invade various organs, understanding the interaction between trypanosomes and tissue niches is essential. Here, we present an up-to-date overview of host-parasite interactions and survival strategies for trypanosomes by introducing and discussing the latest studies investigating the transcriptomics of parasites according to life cycle stages, as well as host cells in various tissues and organs, using single-cell and spatial sequencing applications. In recent years, this information has improved our understanding of trypanosomosis by deciphering the diverse populations of parasites in the developmental process, as well as the highly heterogeneous immune and tissue-resident cells involved in anti-trypanosome responses. Ultimately, the goal of these approaches is to gain an in-depth understanding of parasite biology and host immunity, potentially leading to new vaccination and therapeutic strategies against trypanosomosis.

Population pharmacokinetics analysis of cyclophosphamide with genetic effects in patients undergoing hematopoietic stem cell transplantation.

PURPOSE: To build a population pharmacokinetic (PK) model of cyclophosphamide (CY) and its metabolite, 4-hydroxycyclophosphamide (HCY), in patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT) and to identify covariates, including genetic polymorphisms, which affect CY and HCY PK parameters. METHOD: The study cohort comprised 21 patients undergoing HSCT who received CY intravenously between 2009 and 2011. Clinical characteristics and CY and HCY concentration data were collected for all patients, and ABCB1, ABCC2, GSTA1, GSTM1, GSTP1, GSTT1, CYP2B6, CYP2C19, and CYP3A5 genotyping was performed. A hypothetical enzyme compartment was conducted using the NONMEM program. RESULTS: A population PK analysis showed that the ABCC2 1249 genotype and aspartate aminotransferase levels significantly affected non-induced clearance (CL UI) and induced clearance (CL I) of CY, respectively. The final estimate of the mean CL UI and CL I of CY was 15.5 and 0.683 L/h, respectively, and the mean volume of distribution (V 1) of CY was 88.0 L. The inter-individual variability for CL UI, CL I, and V 1 of CY was 52.8, 200, and 18.0 %, respectively. Additionally, the CL UI of CY was significantly decreased to approximately 51 % in patients with the 1249 GA heterozygous genotype compared to those with the 1249 GG wild-type genotype (p < 0.05). There were only three heterozygous GA variants of ABCC2 1249 in the study patients. CONCLUSIONS: The population PK model developed in this study implies an influence of genetic factors on the clearance of CY. Clearance was moderately reduced in patients with the ABCC2 1249GA heterozygous genotype.

Neutrophil metalloproteinase driven spleen damage hampers infection control of trypanosomiasis.

Recent blood transcriptomic analysis of rhodesiense sleeping sickness patients has revealed that neutrophil signature genes and activation markers constitute the top indicators of trypanosomiasis-associated inflammation. Here, we show that Trypanosoma brucei infection results in expansion and differentiation of four splenic neutrophil subpopulations, including Mki67+Birc5+Gfi1+Cebpe+ proliferation-competent precursors, two intermediate immature subpopulations and Cebpb+Spi1+Irf7+Mcl1+Csf3r+ inflammation reprogrammed mature neutrophils. Transcriptomic scRNA-seq profiling identified the largest immature subpopulation by Mmp8/9 positive tertiary granule markers. We confirmed the presence of both metalloproteinases in extracellular spleen homogenates and plasma. During infection, these enzymes digest extracellular matrix components in the absence of sufficient TIMP inhibitory activity, driving remodeling of the spleen follicular architecture. Neutrophil depletion prevents the occurrence of organ damage, resulting in increased plasma cell numbers and prolonged host survival. We conclude that trypanosomiasis-associated neutrophil activation is a major contributor to the destruction of the secondary lymphoid architecture, required for maintaining an efficient adaptive immune response.

Association of Tumor Necrosis Factor Inhibitors with the Risk of Nontuberculous Mycobacterial Infection in Patients with Rheumatoid Arthritis: A Nationwide Cohort Study.

Tumor necrosis factor inhibitors (TNFi) are proposed as a risk factor for nontuberculous mycobacteria (NTM) infection. Limited research investigates NTM infection risk in rheumatoid arthritis (RA) patients treated with TNFi compared to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), considering other concurrent or prior non-TNFi antirheumatic drugs. We aimed to evaluate the NTM infection risk associated with TNFi using a real-world database. Patients with RA treated with TNFi or csDMARDs between 2005 and 2016 were identified utilizing the Korean National Health Insurance Service database. To minimize potential bias, we aligned the initiation year of csDMARDs for both TNFi and csDMARD users and tracked them from their respective treatment start dates. The association of TNFi with NTM infection risk was estimated in a one-to-one matched cohort using a multivariable conditional Cox regression analysis. In the matched cohort (n = 4556), the incidence rates of NTM infection were 2.47 and 3.66 per 1000 person-year in TNFi and csDMARD users. Compared to csDMARDs, TNFi did not increase the risk of NTM infection (adjusted hazard ratio (aHR) 0.517 (95% confidence interval, 0.205-1.301)). The TNFi use in RA patients was not associated with an increased risk of NTM infection compared to csDMARDs. Nevertheless, monitoring during TNFi treatment is crucial.

CYP3A5 polymorphism effect on cyclosporine pharmacokinetics in living donor renal transplant recipients: analysis by population pharmacokinetics.

BACKGROUND: Cyclosporine is often used to prevent allograft rejection in renal transplant recipients. However, cyclosporine has a narrow therapeutic window and large variability in its pharmacokinetics. Individual characteristics and genetic polymorphisms can cause the variation. Hence, it is important to determine the cause(s) of the variation in cyclosporine pharmacokinetics. To our knowledge, this is the first reported population pharmacokinetic study of cyclosporine in living donor renal transplant recipients that considered the genetic polymorphism as a covariate. OBJECTIVE: To build a population pharmacokinetic model of cyclosporine in living donor renal transplant recipients and identify covariates including CYP3A5*3, ABCB1 genetic polymorphisms that affect cyclosporine pharmacokinetic parameters. METHODS: Clinical characteristics and cyclosporine concentration data for 69 patients who received cyclosporine-based immunosuppressive therapy after living donor renal transplantation were collected retrospectively for up to 400 postoperative days. CYP3A5*1/*3 and ABCB1C1236T, G2677T/A, C3435T geno-typing was performed. A population pharmacokinetic analysis was conducted using a NONMEM program. After building the final model, 1000 bootstrappings were performed to validate the final model. RESULTS: In total, 2034 blood samples were collected. A 1-compartment open model with first-order absorption and elimination was chosen to describe the pharmacokinetics of cyclosporine. A population pharmacokinetic analysis showed that postoperative days, sex, and CYP3A5 genotype significantly affected the pharmacokinetics of cyclosporine. The final estimate of mean clearance was 56 L/h, and the mean volume of distribution was 4650 L. The interindividual variability for these parameters was 22.98% and 51.48%, respectively. CONCLUSIONS: Using the present model to calculate the dose of cyclosporine with CYP3A5 genotyping can be possible for the patients whose cyclosporine concentration is not within the therapeutic range even with therapeutic drug monitoring.

Development and Degeneration of Retinal Ganglion Cell Axons in Xenopus tropicalis.

Neurons make long-distance connections via their axons, and the accuracy and stability of these connections are crucial for brain function. Research using various animal models showed that the molecular and cellular mechanisms underlying the assembly and maintenance of neuronal circuitry are highly conserved in vertebrates. Therefore, to gain a deeper understanding of brain development and maintenance, an efficient vertebrate model is required, where the axons of a defined neuronal cell type can be genetically manipulated and selectively visualized in vivo. Placental mammals pose an experimental challenge, as time-consuming breeding of genetically modified animals is required due to their in utero development. Xenopus laevis, the most commonly used amphibian model, offers comparative advantages, since their embryos ex utero during which embryological manipulations can be performed. However, the tetraploidy of the X. laevis genome makes them not ideal for genetic studies. Here, we use Xenopus tropicalis, a diploid amphibian species, to visualize axonal pathfinding and degeneration of a single central nervous system neuronal cell type, the retinal ganglion cell (RGC). First, we show that RGC axons follow the developmental trajectory previously described in X. laevis with a slightly different timeline. Second, we demonstrate that co-electroporation of DNA and/or oligonucleotides enables the visualization of gene function-altered RGC axons in an intact brain. Finally, using this method, we show that the axon-autonomous, Sarm1-dependent axon destruction program operates in X. tropicalis. Taken together, the present study demonstrates that the visual system of X. tropicalis is a highly efficient model to identify new molecular mechanisms underlying axon guidance and survival.

Employee Perspectives on Onsite Health Clinics in Semiconductor Company in South Korea.

(1) Background: Onsite clinics are increasingly common features of corporate health promotion programs. These clinics allow employers to offer convenient care to employees at their workplaces, which can lead to reduced healthcare expenditure and improved productivity. The objective of this study was to build basic data by qualitatively exploring employees' experiences and perspectives on onsite clinics in a semiconductor company, as one part of the project to examine and improve the health management system of a large semiconductor company in Korea. (2) Methods: This study adopted the methodology of "Consolidated Criteria for Reporting Qualitative Research" (COREQ-32 checklist). Semi-structured interviews were conducted for this study over a two-month period. For data analysis, a codebook was developed and the constant comparative method was used. (3) Results: Most employees perceived convenience and a sense of belonging as the benefits of onsite clinics, while barriers to the use of onsite clinics included a lack of communication, concerns about confidentiality, and a provider-centered system. Promotion of onsite clinic services and affiliated physicians, employee-centered service provisions, and trust-building in healthcare information privacy were considered necessary to strengthen the role of onsite clinics as a primary care provider in the workplace. (4) Conclusions: The results of this qualitative study help us to gain a better understanding of employees' perspectives on the onsite clinic's service and roles.

Vision-Threatening Ocular Adverse Events after Vaccination against Coronavirus Disease 2019.

A single-center retrospective observational case series was conducted. This case series enrolled patients who showed ophthalmic manifestations within one week after COVID-19 vaccination at Korea University Guro Hospital in Seoul, Korea, from May 2021 to January 2022. The medical records of patients who complained of ocular symptoms and showed ophthalmic adverse events within one week after COVID-19 vaccination were reviewed. Seventeen eyes from 16 patients with a mean age of 63.8 (range 33-83) years were included in the case series, and all symptoms developed within 1-7 days following inoculation. Retinal vein occlusion in nine eyes (52.9%), retinal artery occlusion in one eye (5.9%), newly developed anterior uveitis in one eye (5.9%), exacerbation of previously diagnosed panuveitis in two eyes (11.8%), and angle-closure attack with high intraocular pressure in four eyes (23.5%) were included. Twelve patients (75%) had been vaccinated with the AstraZeneca (AZD1222) and four (25%) with the Pfizer (BNT162b2) vaccines. Of these, 10 patients (62.5%) experienced ocular disease exacerbation after the first dose, 4 (25%) after the second dose, and 2 (12.5%) after the third dose (booster shot). Eleven patients (64.7%) underwent tests for hematological abnormalities, and three of them tested positive for anti-PF4 antibodies, but no abnormal findings were noted. A causal relationship between vaccination and the ocular manifestations could not be determined, which is a limitation of this study. However, clinicians should consider the effect of COVID-19 vaccination on ophthalmic disease. Further studies are required to elucidate the possible effects of COVID-19 vaccination on the eye.

The risk of newly diagnosed cancer in patients with rheumatoid arthritis by TNF inhibitor use: a nationwide cohort study.

BACKGROUND: Tumor necrosis factor (TNF) inhibitors use in patients with rheumatoid arthritis (RA) has raised safety concerns about cancer risk, but study results remain controversial. This largest nationwide study to date compared cancer risk in TNF inhibitor users to non-biologic disease-modifying anti-rheumatic drug (nbDMARD) users in Korean patients with RA. METHODS: Data on all the eligible patients diagnosed with RA between 2005 and 2016 were retrieved from the Korean National Health Information Database. The one-to-one matched patients consisted of the matched cohort. The risks for developing all-type and site-specific cancers were estimated using incidence and incidence rate (IR) per 1000 person-years. Adjusted hazard ratio (HR) and 95% confidence interval (CI) were estimated using a Cox regression model. RESULTS: Of the 22,851 patients in the before matching cohort, 4592 patients were included in the matched cohort. Treatment with TNF inhibitors was consistently associated with a lower risk of cancer than in the nbDMARD cohort (IR per 1000 person-years, 6.5 vs. 15.6; adjusted HR, 0.379; 95% CI, 0.255-0.563). The adjusted HR (95% CI) was significantly lower in the TNF inhibitor cohort than the nbDMARD cohort for gastrointestinal cancer (0.432; 0.235-0.797), breast cancer (0.146; 0.045-0.474), and genitourinary cancer (0.220; 0.059-0.820). CONCLUSIONS: The use of TNF inhibitors was not associated with an increased risk of cancer development, and rather associated with a lower cancer incidence in Korean patients with RA. Cautious interpretation is needed not to oversimplify the study results as cancer-protective effects of TNF inhibitors. A further study linking claims and clinical data is needed to confirm our results.

Nystagmus in adult patients with acute otitis media or otitis media with effusion without dizziness.

The present study aimed to investigate the incidence and patterns of nystagmus in adult patients with acute otitis media (AOM) or otitis media with effusion (OME) without dizziness or vertigo, and discuss possible mechanisms. From February 2018 to November 2018, 34 consecutive patients with AOM or OME without dizziness were included. Nystagmus was examined with video Frenzel glasses. Of 34 adult AOM or OME patients without dizziness, nystagmus was observed in 28 patients (82%). In unilateral AOM or OME (n = 30), the most commonly observed nystagmus pattern was irritative-type direction-fixed nystagmus (n = 13), followed by paretic-type direction-fixed nystagmus (n = 8), and direction-changing positional nystagmus (n = 4). In bilateral AOM or OME (n = 4), direction-fixed nystagmus and direction-changing positional nystagmus were observed in two and one patients, respectively. Nystagmus was observed in as many as 82% of adult AOM or OME patients even though they did not complain of dizziness, and the pattern of nystagmus was either direction-fixed or direction-changing. Direct effect of inflammatory mediators penetrated from the middle ear and biochemical alteration in the inner ear fluids due to blood-perilymph barrier dysfunction may result in the presence of nystagmus in AOM or OME patients without dizziness.

Factors Influencing Workplace Health Promotion Interventions for Workers in the Semiconductor Industry According to Risk Levels of Chronic Disease.

(1) Background: This study aimed to analyze the risk of chronic diseases including hypertension, diabetes, and dyslipidemia in workers of a semiconductor manufacturing company and the factors associated with their participation in workplace health promotion (WHP) programs. (2) Methods: Subjects were workers in a semiconductor and liquid crystal display company in South Korea who had undergone regular health checkups. Data from regular health checkups and WHP interventions were analyzed. Health risk was classified based on the diagnosed disease, in-house classification criteria, and pooled cardiovascular risk score. (3) Results: The baseline characteristics of 39,073 participants included the following: male, 67.8%; between 30 and 40 years of age, 74.1%; <2 h of physical activities, 65.9%. Workers at risk of chronic diseases accounted for 22.2%, and 20.1% were suspicious cases of chronic diseases. Body mass index, and cholesterol level were relatively high in workers with the burden of chronic diseases. The participation rate in WHP programs was 28.8% in a high-risk group among workers at risk of chronic diseases. More participation was shown in male, older age groups, production work type, and single-person household. (4) Conclusions: Because of the low participation rate in WHP activities among workers with the burden of chronic diseases, it is necessary to establish measures to encourage their participation.

Prevalence and characteristics of S-point bleeding compared to non S-point bleeding in severe epistaxis.

INTRODUCTION: Stamm's S-point is gaining importance as a bleeding focus in severe epistaxis. However, prevalence and features of S-point bleeding compared to non S-point bleeding have not been studied. OBJECTIVE: To investigate the characteristics of patients with S-point bleeding among those with severe epistaxis and to compare the factors involved in the treatment of epistaxis. METHODS: We retrospectively analyzed medical records of 268 patients admitted to the otorhinolaryngology department of Konkuk University Hospital and Chung-Ang University Hospital with epistaxis of which the bleeding focus clarified. Patients with anterior nasal bleeding (n=129) were excluded. The study was conducted at the department of otorhinolaryngology from January 2008 to August 2019. Collected data included patients' demographic information, bleeding focus, body mass index underlying medical and sinonasal diseases, laboratory test results (initial hemoglobin, platelet count, and triglyceride level), use of anticoagulants, direction of epistaxis, initial and final treatments, and need for blood transfusion. RESULTS: The prevalence of S-point bleeding was 28.8% of non-anterior bleeding cases. Mean body mass index score was lower in the S-point group (23.41±3.71) compared to the non S-point group (24.93±3.97) (p=0.039). Underweight patients tended to show a greater incidence of S-point bleeding (15.0%) than non S-point bleeding (2.0%) (p=0.010). Incidence of anemia was higher in the S-point group (67.5%) than in the non S-point group (36.4%). Anemia (Odds ratio [OR]: 3.635; 95% confidence interval [CI]: 1.669-7.914, p=0.001) and underweight (body mass index<18.5, OR: 8.559, CI: 1.648-44.445, p=0.011) were significantly associated with S-point bleeding. CONCLUSION: Prevalence of S-point bleeding was significant, underlining the importance of examining the S-point in patients with severe epistaxis. Patients with S-point bleeding had lower body mass index scores and a higher incidence of anemia than those with non S-point bleeding.

UXT chaperone prevents proteotoxicity by acting as an autophagy adaptor for p62-dependent aggrephagy.

p62/SQSTM1 is known to act as a key mediator in the selective autophagy of protein aggregates, or aggrephagy, by steering ubiquitinated protein aggregates towards the autophagy pathway. Here, we use a yeast two-hybrid screen to identify the prefoldin-like chaperone UXT as an interacting protein of p62. We show that UXT can bind to protein aggregates as well as the LB domain of p62, and, possibly by forming an oligomer, increase p62 clustering for its efficient targeting to protein aggregates, thereby promoting the formation of the p62 body and clearance of its cargo via autophagy. We also find that ectopic expression of human UXT delays SOD1(A4V)-induced degeneration of motor neurons in a Xenopus model system, and that specific disruption of the interaction between UXT and p62 suppresses UXT-mediated protection. Together, these results indicate that UXT functions as an autophagy adaptor of p62-dependent aggrephagy. Furthermore, our study illustrates a cooperative relationship between molecular chaperones and the aggrephagy machinery that efficiently removes misfolded protein aggregates.

Comorbid Cupulolithiasis Is Rare in Patients With Horizontal Semicircular Canal Canalolithiasis.

OBJECTIVES: Considering that otolith particles pass through the canal until attaching to the cupula in the canal-side horizontal semicircular canal (HSCC) cupulolithiasis, comorbidity of HSCC canalolithiasis and cupulolithiasis may occur. We aimed to investigate the incidence of comorbidity of cupulolithiasis in patients with HSCC canalolithiasis and to improve treatment efficacy. STUDY DESIGN: Retrospective study. SETTING: Tertiary referral academic center. PATIENTS: Ninety-seven consecutive patients with HSCC canalolithiasis between March 2017 and March 2019 were included. MAIN OUTCOME MEASURES: Coexistence of HSCC cupulolithiasis was hierarchically investigated. 1) Spontaneous reversal of initial nystagmus is observed bilaterally in a head-roll test (HRT), 2) nystagmus is in the same direction at each of the three times the supine position was tested, and 3) both bowing and leaning nystagmus with opposite direction are observed. RESULTS: Of 97 patients with HSCC canalolithiasis, 2 patients (2%) had comorbid HSCC cupulolithiasis. CONCLUSIONS: Although coexistence of HSCC canalolithiasis and cupulolithiasis should be considered when spontaneous reversal of nystagmus direction is observed without position change during a HRT, the incidence of coexistence is very low. However, canalith repositioning maneuvers for both canalolithiasis and cupulolithiasis should be performed in cases with comorbidity.