Identification and overcoming rituximab resistance in diffuse large B-cell lymphoma using next-generation sequencing

Background/Aims@#Although rituximab, an antiCD20 monoclonal antibody, has dramatically improved the clinical outcomes of diffuse large B-cell lymphoma, rituximab resistance remains a challenge. @*Methods@#We developed a rituximab-resistant cell line (RRCL) by sequential exposure to gradually increasing concentrations of rituximab in a rituximab-sensitive cell line (RSCL). When the same dose of rituximab was administered, RRCL showed a smaller decrease in cell viability and apoptosis than RSCL. To determine the differences in gene expression between RSCL and RRCL, we performed next-generation sequencing. @*Results@#In total, 1,879 differentially expressed genes were identified, and in the over-representation analysis of Consensus-PathDB, mitogen-activated protein kinase (MAPK) signaling pathway showed statistical significance. MAPK13, which encodes the p38δ protein, was expressed more than four-fold in RRCL. Western blot analysis revealed that phosphop38 expression mainwas increased in RRCL, and when p38 inhibitor was administered, phosphop38 expression was significantly decreased. Therefore, we hypothesized that p38 MAPK activation was associated with rituximab resistance. Previous studies have suggested that p38 is associated with NF-κB activation. Deferasirox has been reported to inhibit NF-κB activity and suppress phosphorylation of the MAPK pathway. Furthermore, it also has cytotoxic effects on various cancers and synergistic effects in overcoming drug resistance. In this study, we confirmed that deferasirox induced dose-dependent cytotoxicity in both RSCL and RRCL, and the combination of deferasirox and rituximab showed a synergistic effect in RRCL at all combination concentrations. @*Conclusions@#We suggest that p38 MAPK, especially p38δ, activation is associated with rituximab resistance, and deferasirox may be a candidate to overcome rituximab resistance.

Improved Intermediate Visual Function with New Monofocal Intraocular Lens in Combined Cataract and Vitrectomy Surgery for Retinal Disease

Purpose@#To evaluate the usefulness of a newly generated monofocal intraocular lens (IOL) in patients with various retinal diseases who underwent combined cataract and pars plana vitrectomy surgery. @*Methods@#This prospective observational study included 33 patients with various retinal diseases. Monocular best-corrected distance visual acuity (BCDVA), uncorrected distance visual acuity (UCDVA), uncorrected intermediate visual acuity (UCIVA), uncorrected near visual acuity (UCNVA), and contrast sensitivity were measured and compared with 40 age-matched patients in the standard monofocal IOL. @*Results@#The Eyhance IOL group demonstrated significantly better UCIVA at 6 months follow-up compared to the standard monofocal IOL group. No significant differences were observed between the two groups in contrast sensitivity, BCDVA, UCDVA, or UCNVA. The regression analysis showed a significant association between preoperative corrected distance visual acuity and improved UCIVA in the Eyhance IOL group. @*Conclusions@#The Eyhance ICB00 IOL proved to be a valuable option for patients with retinal diseases undergoing combined cataract surgery and vitrectomy. It effectively improved intermediate vision without compromising contrast sensitivity or distance visual acuity.

Comparison of interdental brush size and label information marketed in Korea / 대한구강보건학회지

Objectives@#This study compares the labeling information on the sizes of interdental brushes marketed in Korea to their actual sizes. Moreover, it analyzes the relationship between the size of the passage hole diameter (PHD), brush diameter, stem diameter, and stem length. @*Methods@#Among the commercially available interdental brushes in Korea, 171 interdental brushes, 3 in each size, were collected from 9 companies. The labels of the collected interdental brushes were researched, and the PHD was measured and compared. The correlation between the passage hole diameter, brush diameter, stem diameter, and stem length was analyzed. Multiple regression analysis was performed to verify the effect of brush diameter, stem diameter, and stem length on the determination of the PHD. @*Results@#The sizes of the interdental brushes were expressed using the ISO labeling or the Small, Medium, Large (S, M, L) labeling and indicated in units of 0.1. The concordance rate of the measured PHD and named PHD was 39.7%. The measured brush diameter, stem diameter, and stem length increased as the interdental brush size increased. There was a significant correlation (P<0.01) between PHD, brush diameter, stem diameter, and stem length. The order of variables with the most to least significant influence on PHD was stem diameter (β=0.528), brush diameter (β=0.404), and stem length (β=0.074). @*Conclusions@#This study shows that the label and actual size of interdental brushes did not match, and the concordance rate between the measured and labeled PHDs was low. Therefore, the interdental brush size labels among manufacturers should be standardized. Moreover, these manufacturers must provide the correct size information for the interdental brushes.

Effective Eradication Regimen and Duration According to the Clarithromycin Susceptibility of Helicobacter pylori Determined Using Dual Priming Oligonucleotide-Based Multiplex Polymerase Chain Reaction

Background/Aims@#Dual priming oligonucleotide-based multiplex polymerase chain reaction (DPO-PCR) has recently been used for both the detection of Helicobacter pylori and the identification of H. pylori 23S ribosomal RNA point mutations that cause clarithromycin resistance.The aim of this study was to investigate the duration of effective standard triple therapy in a clarithromycin susceptible group and of bismuth-based quadruple therapy in a resistant group based on DPO-PCR. @*Methods@#We retrospectively analyzed the electronic medical records of 184 patients who, between September 2019 and December 2020, received eradication therapy following detection of H. pylori, and the subsequent identification of the clarithromycin susceptibility of their H. pylori using DPO-PCR. Patients were treated with 7- or 14-day standard triple therapy in the clarithromycin susceptible group, whereas 7- or 14-day bismuth-based quadruple therapy in the clarithromycin resistance group. @*Results@#In the clarithromycin susceptible group, per-protocol analyses showed eradication rates of 87.5% (42/48; 95% confidence interval [CI], 77.1% to 95.8%) for 7-day therapy and 87.2% (41/47; 95% CI, 78.7% to 95.7%) for 14-day therapy (p=0.969). The eradication rates in the clarithromycin resistance group were 91.4% (32/35; 95% CI, 80.0% to 100.0%) for 7-day therapy and 90.3% (28/31; 95% CI, 77.4% to 100.0%) for 14-day therapy (p=0.876). There was no significant difference in the eradication rates, patient compliance, or rate of adverse events between the 7-and 14-day therapies for both groups. @*Conclusions@#Compared to the 14-day therapy, 7-day eradication therapy is sufficient after DPO-PCR-based clarithromycin susceptibility testing.

Long-Term Changes in the Mortality Rates of Thyroid Cancer in Korea: Analysis of Korean National Data from 1985 to 2020

Background@#Thyroid cancer mortality has been largely overlooked as relatively stable given the large gap between thyroid cancer incidence and mortality. This study evaluated long-term trends in age-standardized mortality rates (ASMRs) throughout Korea and compared them with mortality data reported by the Surveillance, Epidemiology, and End Results (SEER). @*Methods@#Cancer-specific mortality data from 1985 to 2020 were obtained from Statistics Korea. ASMRs from thyroid cancer were calculated based on the Korean mid-year resident registration population of 2005. We assessed SEER*Explorer and downloaded the mortality data. @*Results@#The ASMR increased from 0.19 to 0.77/100,000 between 1985 and 2002 but decreased continuously to 0.36/100,000 in 2020. The annual percent change (APC) in the ASMR between 1985 and 2003 and between 2003 and 2020 was 6.204 and −4.218, respectively, with similar patterns observed in both men and women. The ASMR of the SEER showed a modest increase from 1988 to 2016 and then stabilized. In subgroup analysis, the ASMR of the old age group (≥55 years) increased significantly from 0.82 in 1985 to 3.92/100,000 in 2002 (APC 6.917) but then decreased again to 1.86/100,000 in 2020 (APC −4.136). ASMRs according to the age group in the SEER showed a relatively stable trend even in the elderly group. @*Conclusion@#The ASMR of thyroid cancer in Korea had increased from 1985 to 2002 but has since been steadily decreasing. This trend was mainly attributed to elderly people aged 55 or over. The absolute APC value of Korea was much higher than that of the SEER.

CycloZ Improves Hyperglycemia and Lipid Metabolism by Modulating Lysine Acetylation in KK-Ay Mice

Background@#CycloZ, a combination of cyclo-His-Pro and zinc, has anti-diabetic activity. However, its exact mode of action remains to be elucidated. @*Methods@#KK-Ay mice, a type 2 diabetes mellitus (T2DM) model, were administered CycloZ either as a preventive intervention, or as a therapy. Glycemic control was evaluated using the oral glucose tolerance test (OGTT), and glycosylated hemoglobin (HbA1c) levels. Liver and visceral adipose tissues (VATs) were used for histological evaluation, gene expression analysis, and protein expression analysis. @*Results@#CycloZ administration improved glycemic control in KK-Ay mice in both prophylactic and therapeutic studies. Lysine acetylation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, liver kinase B1, and nuclear factor-κB p65 was decreased in the liver and VATs in CycloZ-treated mice. In addition, CycloZ treatment improved mitochondrial function, lipid oxidation, and inflammation in the liver and VATs of mice. CycloZ treatment also increased the level of β-nicotinamide adenine dinucleotide (NAD+), which affected the activity of deacetylases, such as sirtuin 1 (Sirt1). @*Conclusion@#Our findings suggest that the beneficial effects of CycloZ on diabetes and obesity occur through increased NAD+ synthesis, which modulates Sirt1 deacetylase activity in the liver and VATs. Given that the mode of action of an NAD+ booster or Sirt1 deacetylase activator is different from that of traditional T2DM drugs, CycloZ would be considered a novel therapeutic option for the treatment of T2DM.

Efficacy of a long-pulsed 1064-nm Nd:YAG laser in acute scar redness

Background@#The initial redness of the scar on a postoperative suture site is a natural phenomenon that fades over time. However, with a long period of redness, patients complain about cosmetic discomfort, and the possibility of pigmentation changes is induced. We investigated the use of a long-pulsed 1064 nm Nd:YAG laser as a noninvasive treatment for improving the redness of these scars. @*Methods@#A retrospective chart review was conducted on 36 patients who underwent excision of a nevus on the face. Fourteen patients received laser treatment and another 22 patients used only scar management ointment. Patients were followed up 1 week after the sutures were removed. The photographic images taken at the time of suture removal and 2 months later were reviewed. The evaluation was performed on a 7-point scale by adding the Japan Scar Workshop (JSW) scar scale’s redness and erythema scores. @*Results@#The average initial JSW scar scale score of the treatment group was 4.6, and that of the nontreatment group was 4.2. When the re-evaluation was performed 2 months later, the score of the treatment group decreased to 2.2 and that of the nontreatment group decreased to 3.1. The difference in the JSW scar scale between the treatment group and the nontreatment group according to laser performance was statistically significant (P=0.03). @*Conclusions@#The treatment method with a long-pulsed 1064 nm Nd:YAG laser that is less invasive and has a quick effect can be a good alternative for improving this initial scar redness.

Reliability and Validity of the Korean Version of the Duchenne Muscular Dystrophy Functional Ability Self-Assessment Tool

Objective@#To systematically translate the Duchenne muscular dystrophy Functional Ability Self-Assessment Tool (DMDSAT) into Korean and verify the reliability and validity of the Korean version (K-DMDSAT). @*Methods@#The original DMDSAT was translated into Korean by two translators and two pediatric physiatrists. A total of 88 patients with genetically confirmed Duchenne muscular dystrophy (DMD) participated in the study. They were evaluated using the K-DMDSAT once as a self-assessment and once by an interviewer. The interviewer evaluated the K-DMDSAT again 1 week later using a test-retest approach. The intraclass correlation coefficient (ICC) was used to verify the interrater and test-retest reliabilities. Pearson correlation analysis between the K-DMDSAT and the Brooke or Vignos scales were used to assess validity. @*Results@#The total score and all domains of the K-DMDSAT showed excellent interrater and test-retest reliability, with an ICC for total scores of 0.985 and 0.987, respectively. All domains had an ICC >0.90. From the Pearson correlation analysis, the total K-DMDSAT score was significantly correlated with the Vignos and Brooke scales (r=0.918 and 0.825, respectively; p<0.001), and each domain of K-DMDSAT showed significant correlation with either the Vignos or Brooke scales. @*Conclusion@#DMDSAT was systematically translated into Korean, and K-DMDSAT was verified to have excellent reliability and validity. K-DMDSAT can help clinicians easily describe and categorize various functional aspects of patients with DMD through the entire disease progression.

Short-term efficacy and safety analysis of TACE combined with TKI and PD-1 inhibitors in the treatment of initially unresectable hepatocellular carcinoma / 中华肝胆外科杂志

Objective:To evaluate the efficacy and safety of transhepatic arterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKI) and programmed death-1 (PD-1) inhibitors in the treatment of patients with initially unresectable hepatocellular carcinoma.Methods:The clinical data of 42 patients with initially unresectable hepatocellular carcinoma who were admitted to the Department of Hepatobiliary and Pancreatic Surgery of the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2022 were included. There were 31 males and 11 females, with a median age of 56 years old (range, 45-72 years old). All patients received TACE+ TKI+ PD-1 inhibitor combined treatment. The systemic treatment cycles were calculated by the regimen of immunotherapy. The timing of local treatment depends on tumor size, blood supply and treatment response. Patients were followed up through hospitalization, outpatient visits and telephone review. The Kaplan-Meier curves were obtained for survival analysis.Results:The dosing cycle to achieve optimal imaging response in the patients was 4 (3, 7) [ M( Q1, Q3)], with a systemic treatment time of 141 (65, 194) d [ M( Q1, Q3)] and 2 (1, 3) times [ M( Q1, Q3)] of local treatments. All patients were evaluated by modified response evaluation criteria in solid tumors criteria after treatment, including nine patients with complete response (CR), 21 with partial response, eight with stable disease, and four with progressive disease. Objective response rate and disease control rate were 71.4% (30/42) and 90.5% (38/42), respectively. Treatment-related adverse reactions occurred in 85.7% (36/42) of patients and grade Ⅲ or Ⅳ adverse reactions occurred in 16.7% (7/42). There was no level Ⅳ adverse reactions. All adverse reactions were controlled after dose reduction and symptomatic treatment. Thirteen patients (31.0%, 13/42) redeemed resectable after treatment and underwent radical surgery. Seven patients had pathological CR after surgery. In two patients, the pathological residual cancer tissue was less than 10%. The cumulative overall survival rates of the 42 patients at 6 months, 1 year, 1.5 years after treatment were 100%, 91.7%, and 65.0%, respectively. The postoperative 1-year survival rate of patients undergoing surgery after successful conversion was 83.3%. Conclusion:This study preliminarily showed the safety and efficacy of TACE, TKI, and PD-1 inhibitor combined therapy in patients with initially unresectable hepatocellular carcinoma.

Review of North Korean Reports on Cardiovascular Disease Research and Management

Purpose@#This study aimed to investigate the quality of medical care in North Korea using data from North Korean medical research. @*Materials and Methods@#This study included publications containing the keyword “medical” among North Korea’s consecutive publications and selected 415 papers related to heart disease, brain disease, and emergency medical care published at The North Korean Data Center of the Ministry of Unification (https://unibook.unikorea.go.kr). Among 40 research articles, we reviewed ten with representative epidemiological data for cardiovascular treatment, and the latest medical materials were selected and analyzed in detail. @*Results@#Few studies reported the experience of large-scale medical facilities or verified professional performance. Proof of the efficacy of the latest drugs was rare, although the treatment results of interventional therapy and conventional heart surgery were reported. Efforts to improve emergency medical care and innovation of treatment materials using new technologies were being actively studied. However, careful interpretation is required due to the lack of objectivity in research data and some deviation in the composition of patients included in the data. @*Conclusion@#Research of cardiovascular disease in North Korea is conducted at a very limited scope, although treatment results appear to be recorded. The management of cardiovascular disease and the establishment of an emergency medical system warrant global attention and cooperation for further improvement.

Combined use of shear-wave elastography and Doppler ultrasonography in equivocal fibroepithelial lesions of the breast diagnosed by core needle biopsy

Purpose@#The aim of this study was to evaluate the diagnostic value of shear-wave elastography (SWE) combined with Doppler ultrasonography (US) in selecting equivocal breast fibroepithelial lesions (FELs) for follow-up without further excision. @*Methods@#A retrospective analysis was conducted of 88 patients with equivocal breast FELs (FELs with the possibility of both fibroadenoma [FA] and phyllodes tumor [PT]) diagnosed by core needle biopsy (CNB). For post-CNB treatment, surgical or vacuum-assisted excision was performed on 88 equivocal FELs, of which 56 were diagnosed as FAs and 32 as PTs on histopathology. Mean elasticity (Emean) and vascularity were determined using SWE and Doppler US. The diagnostic performances of B-mode US, SWE, and Doppler US were calculated to differentiate FAs and PTs in the excised equivocal FELs. @*Results@#In the excised equivocal FELs diagnosed by CNB, FAs showed significantly lower median Emean values (36.4 vs. 66.7 kPa, P=0.005) and more frequent low vascularity (0–1 vessel flow signal) (P60.9 kPa and high vascularity (≥2 vessel flows) showed a sensitivity and negative predictive value of 100%, as well as better performance in other diagnostic values than B-mode US alone (Breast Imaging Reporting and Data System ≥4A) (all P<0.05). @*Conclusion@#Equivocal breast FELs showing both low elasticity and low vascularity were not upgraded to PTs upon further excision. Therefore, the combination of SWE and color Doppler US mode might help select patients with equivocal FELs for whom further excision is unnecessary.

Orientation of the ultrasound probe to identify the taller-than-wide sign of thyroid malignancy: a registry-based study with the Thyroid Imaging Network of Korea

Purpose@#Although the taller-than-wide (TTW) sign has been regarded as one of the most specific ultrasound (US) features of thyroid malignancy, uncertainty still exists regarding the US probe’s orientation when evaluating it. This study investigated which US plane would be optimal to identify the TTW sign based on malignancy risk stratification using a registry-based imaging dataset. @*Methods@#A previous study by 17 academic radiologists retrospectively analyzed the US images of 5,601 thyroid nodules (≥1 cm, 1,089 malignant and 4,512 benign) collected in the webbased registry of Thyroid Imaging Network of Korea through the collaboration of 26 centers. The present study assessed the diagnostic performance of the TTW sign itself and fine needle aspiration (FNA) indications via a comparison of four international guidelines, depending on the orientation of the US probe (criterion 1, transverse plane; criterion 2, either transverse or longitudinal plane). @*Results@#Overall, the TTW sign was more frequent in malignant than in benign thyroid nodules (25.3% vs. 4.6%). However, the statistical differences between criteria 1 and 2 were negligible for sensitivity, specificity, and area under the curve (AUC) based on the size effect (all P0.05, respectively). @*Conclusion@#A longitudinal US probe orientation provided little additional diagnostic value over the transverse orientation in detecting the TTW sign of thyroid nodules.

Incidence of Upper Respiratory Diseases During the COVID-19 Pandemic: A Nationwide Data-Based Epidemiological Study / 대한이비인후과학회지

Background and Objectives@#Nonpharmacologic interventions (NPIs), such as social distancing and preventive measures, were administered during the coronavirus disease (COVID-19) pandemic, which may influence the incidence of upper respiratory diseases (URDs). The present study compared the incidence of URDs during the COVID-19 pandemic and during the years prior to COVID-19, and investigated the effect of NPIs on URD in the nationwide general population.Subjects and Method This is an epidemiologic study based on the Korean National Health Insurance Database from March 2016 to February 2021. We compared the monthly incidence of URDs from March 2020 to February 2021 (12 months) with that of the past four years. A negative binomial regression model was used to evaluate the annual difference in the incidence of each URD and adjusting temperature, humidity, and the level of particulate matter 10 (PM10). @*Results@#The monthly incidence of ‘the five common URDs’ in 2020 was significantly lower than that in the past four years. The incidence of other chronic diseases, however, such as hypertension and diabetes mellitus, was comparable or higher in the past four years. Among the five common URDs, influenza virus infections decreased most dramatically, nearing 99%, from 296.4-377.1 per 100000 people during the period of 2016 to 2019 to 3.7 per 100000 people in 2020. @*Conclusion@#The present study shows that the incidence of ‘five common URDs’ significantly decreased during the era of COVID-19 in Korea. We believe that nationwide NPI might prevent the transmission of COVID-19 as well as other infectious sources associated with URDs.

De Novo Crescentic Glomerulonephritis Following COVID-19 Infection:A Pediatric Case Report

As the global coronavirus disease 2019 (COVID-19) pandemic continues to sweep across the globe, reports of kidney involvement in adult patients infected with COVID-19 have been documented, and recently, cases in the pediatric population have also been reported.This report highlights the case of an 11-year-old boy who developed acute kidney injury presenting as gross hematuria, proteinuria, and hypertension immediately after a COVID-19 infection. A renal biopsy allowed us to diagnose the patient with post-COVID-19 infectionassociated de novo crescentic immune-mediated glomerulonephritis. Oral prednisolone and cyclophosphamide treatments were initiated after methylprednisolone pulse therapy administration. Currently, the patient is receiving medical treatment for five weeks, and his renal function is gradually recovering. Previous studies have suggested that, although quite rare, a variety of kidney complications can occur after COVID-19 infection or vaccination, and it is recommended to monitor renal function through evaluation. Herein, we report a pediatric case of post-COVID-19 infection-associated de novo crescentic immune-mediated glomerulonephritis consistent with rapidly progressive glomerulonephritis.

Relationship between the High Fatty Liver Index and Risk of Fracture

Background/Aims@#The prevalence of nonalcoholic fatty liver disease (NAFLD) has increased rapidly as a consequence of more sedentary lifestyles and a Westernized diet. Fracture is a major clinical problem in older people, but few large-scale cohort studies have evaluated the relationship between NAFLD and fracture. Therefore, we aimed to determine whether the fatty liver index (FLI), which represents the severity of NAFLD, can predict fracture risk. @*Methods@#We analyzed the relationship between the FLI and incident fracture using multivariate Cox proportional hazards models and data for 180,519 individuals who underwent National Health check-ups in the Republic of Korea between 2009 and 2014. @*Results@#A total of 2,720 participants (1.5%) were newly diagnosed with fracture during the study period (median 4.6 years). The participants were grouped according to FLI quartiles (Q1, 0 to <5.653; Q2, 5.653 to <15.245; Q3, 15.245 to <37.199; and Q4 ≥37.199). The cumulative fracture incidence was significantly higher in the highest FLI group than in the lowest FLI group (Q4, 986 [2.2%] and Q1, 323 [0.7%]; p<0.001). The adjusted hazard ratio indicated that the highest FLI group was independently associated with a higher incidence of fracture (hazard ratio for Q4 vs Q1, 2.956; 95% confidence interval, 2.606 to 3.351; p<0.001). FLI was significantly associated with a higher incidence of fracture, independent of the baseline characteristics of the participants. @*Conclusions@#Our data imply that the higher the FLI of a Korean patient is, the higher their risk of osteoporotic fracture, independent of key confounding factors.

The Link between Mitochondrial Dysfunction and Sarcopenia: An Update Focusing on the Role of Pyruvate Dehydrogenase Kinase 4

Sarcopenia, defined as a progressive loss of muscle mass and function, is typified by mitochondrial dysfunction and loss of mitochondrial resilience. Sarcopenia is associated not only with aging, but also with various metabolic diseases characterized by mitochondrial dyshomeostasis. Pyruvate dehydrogenase kinases (PDKs) are mitochondrial enzymes that inhibit the pyruvate dehydrogenase complex, which controls pyruvate entry into the tricarboxylic acid cycle and the subsequent adenosine triphosphate production required for normal cellular activities. PDK4 is upregulated in mitochondrial dysfunction-related metabolic diseases, especially pathologic muscle conditions associated with enhanced muscle proteolysis and aberrant myogenesis. Increases in PDK4 are associated with perturbation of mitochondria-associated membranes and mitochondrial quality control, which are emerging as a central mechanism in the pathogenesis of metabolic disease-associated muscle atrophy. Here, we review how mitochondrial dysfunction affects sarcopenia, focusing on the role of PDK4 in mitochondrial homeostasis. We discuss the molecular mechanisms underlying the effects of PDK4 on mitochondrial dysfunction in sarcopenia and show that targeting mitochondria could be a therapeutic target for treating sarcopenia.

Diagnostic evolution of vestibular neuritis after long-term monitoring / Evolução diagnóstica da neurite vestibular após monitoração de longo prazo

Abstract Introduction The diagnosis of vestibular neuritis is based on clinical and laboratory findings after exclusion of other disease. There are occasional discrepancies between clinical impressions and laboratory results. It could be the first vertigo episode caused by other recurrent vestibular disease, other than vestibular neuritis. Objective This study aimed to analyze the clinical features and identify the diagnostic evolution of patients with clinically suspected vestibular neuritis. Methods A total of 201 patients clinically diagnosed with vestibular neuritis were included in this study. Clinical data on the symptoms and signs of vertigo along with the results of vestibular function test were analyzed retrospectively. Patients were categorized in terms of the results of caloric testing (CP - canal paresis) group; canal paresis ≥25%; (MCP -minimal canal paresis) group; canal paresis <25%). Clinical features were compared between the two groups and the final diagnosis was reviewed after long-term follow up of both groups. Results Out of 201 patients, 57 showed minimal canal paresis (CP < 25%) and 144 showed definite canal paresis (CP ≥ 25%). A total of 48 patients (23.8%) experienced another vertigo episode and were re-diagnosed. Recurring vestibular symptoms were seen more frequently in patients with minimal canal paresis (p = 0.027). Repeated symptoms were observed on the same affected side more frequently in the CP group. The proportion of final diagnosis were not different between two groups. Conclusions Patients with minimal CP are more likely to have recurrent vertigo than patients with definite CP. There was no significant difference in the distribution of the final diagnoses between two groups when the vertigo recurs.

Resumo Introdução O diagnóstico de neurite vestibular é baseado em achados clínicos e laboratoriais após exclusão de outra doença. Existem discrepâncias ocasionais entre a impressão clínica e os resultados laboratoriais. Pode ser o primeiro episódio de vertigem causado por outra doença vestibular recorrente, além da neurite vestibular. Objetivo Analisar as características clínicas e identificar a evolução diagnóstica de pacientes com suspeita clínica de neurite vestibular. Método Foram incluídos neste estudo 201 pacientes com diagnóstico clínico de neurite vestibular. Os dados clínicos sobre os sintomas e sinais de vertigem e os resultados dos testes de função vestibular foram analisados retrospectivamente. Os pacientes foram categorizados de acordo com os resultados das provas calóricos (Grupo PC: paresia do canal ≥ 25%; Grupo PMC: paresia mínima do canal < 25%). As características clínicas foram comparadas entre os dois grupos e o diagnóstico final foi revisado após o acompanhamento de longo prazo de ambos os grupos. Resultados De 201 pacientes, 57 apresentaram paresia mínima do canal (PC < 25%) e 144 apresentaram paresia definitiva do canal (PC ≥ 25%). Quarenta e oito pacientes (23,8%) apresentaram outro tipo de vertigem e foram diagnosticados novamente. Sintomas vestibulares recorrentes foram observados com mais frequência nos pacientes com paresia mínima do canal (p = 0,027). Sintomas recorrentes no mesmo lado afetado foram observados com mais frequência no Grupo PC. A proporção de diagnóstico final não foi diferente entre os dois grupos. Conclusão Os pacientes com paresia mínima do canal foram mais propensos a apresentar vertigem recorrente que os pacientes com paresia do canal definitiva. Não houve diferença significante na distribuição dos diagnósticos finais entre os dois grupos quando houve recorrência da vertigem.

Resting-state fMRI study of Parkinson disease patients with peak-dose dyskinesia: an ALFF analysis / 中华行为医学与脑科学杂志

Objective:To observe the characteristics of resting-state brain activity in Parkinson disease (PD) patients with peak-dose dyskinesia, and to explore its pathogenesis.Methods:From March 2017 to November 2019, totally 27 PD patients with peak-dose dyskinesia (dyskinetic group), and 29 PD patients without dyskinesia (non-dyskinetic group) treated in the First Affiliated Hospital of Nanjing Medical University and 27 healthy controls from the community were recruited.Resting-state functional magnetic resonance imaging (rs-fMRI) and clinical scale data were collected.SPSS 26.0 software and REST software were used for data analysis.The whole brain amplitude of low-frequency fluctuation (ALFF) values were compared among the three groups.Correlation analysis was performed between ALFF values of the significant brain regions and the scale scores.Finally, receiver operating characteristic (ROC) curve was used to evaluate the efficacy of ALFF values of significant brain regions in identifying three groups of subjects.Results:The peak-dose dyskinetic group showed decreased ALFF in right inferior frontal gyrus(MNI: x=36, y=21, z=30; x=36, y=18, z=30)and increased ALFF in right supplementary motor area (MNI: x=9, y=0, z=69; x=6, y=-3, z=72)(all P<0.05, Alphasim correction) compared with non-dyskinetic group and healthy controls.ALFF value in right inferior frontal gyrus was negatively correlated with unified dyskinesia rating scale (UDysRS) scores ( r=-0.47, P=0.018). The ALFF value of the right inferior frontal gyrus was more effective in identifying peak-dose dyskinetic patients from non-dyskinetic patients and healthy controls, and the area under the curve of right inferior frontal gyrus were 0.881 and 0.787 (both P<0.01), respectively. Conclusion:Abnormal spontaneous brain activity in right inferior frontal gyrus and right supplementary motor area can be the neurobiological basis of peak-dose dyskinesia in PD patients.The severity of peak-dose dyskinesia is associated with abnormal brain activity of right inferior frontal gyrus.The ALFF value of right inferior frontal gyrus is a potential imaging marker for identifying peak-dose dyskinetic patient.

Composite follicular lymphoma and classic Hodgkin lymphoma

Composite lymphoma is very rare and a combination of Hodgkin lymphoma and non-Hodgkin lymphoma and even histiocytic tumors can occur. Because of the unfamiliarity, not only can this cause diagnostic problems, but can also affect treatment plan. We report a case of composite lymphoma in a 40-year-old male. Initial biopsy showed a composite lymphoma of follicular lymphoma grade 1 and classic Hodgkin lymphoma. After chemotherapy, another lymph node was taken because of disease progression, which revealed follicular lymphoma, grade 3a without Hodgkin lymphoma component.

ACTG2 Variants in Pediatric Chronic Intestinal Pseudo-obstruction With Megacystis

Background/Aims@#Chronic intestinal pseudo-obstruction (CIPO) is a clinically heterogeneous syndrome characterized by compromised peristalsis and intestinal obstruction. Variants of actin gamma 2 (ACTG2), a protein crucial for correct enteric muscle contraction, have been found in CIPO patients. The aim of this study is to examine the clinical features and ACTG2 variants in Korean patients with CIPO. @*Methods@#From January 1995 to August 2020, 12 patients diagnosed with CIPO were included and genetic analysis testing of ACTG2 was performed. @*Results@#Heterozygous ACTG2 missense variants were found in 6 patients (50.0%). The p.Arg257Cys variant was found in 3 patients, and p.Arg63Gln and p.Arg178His variants were found in 1 patient each. A novel variant, p.Ile193Phe, was found in 1 patient. Three patients were diagnosed at birth, 2 at the age of 1 year, and 1 at 3 years of age. Abnormal prenatal genitourinary ultrasonographic findings were found in all 6 patients; microcolon was found in 4 patients (66.7%), and megacystis in all 6 patients. The pathology showed abnormal ganglion cells as well as myopathic findings. All patients are dependent on total parenteral nutrition and are to date alive. @*Conclusions@#ACTG2 variants are commonly found in Korean patients with CIPO. In CIPO patients with megacystis and abnormal prenatal ultrasonography, genetic testing of ACTG2 should be considered. Molecular diagnosis of CIPO is more important than pathologic diagnosis.