Deep Learning-based Prediction of Axial Length Using Ultra-widefield Fundus Photography

Purpose@#To develop a deep learning model that can predict the axial lengths of eyes using ultra-widefield (UWF) fundus photography. @*Methods@#We retrospectively enrolled patients who visited the ophthalmology clinic at the Seoul National University Hospital between September 2018 and December 2021. Patients with axial length measurements and UWF images taken within 3 months of axial length measurement were included in the study. The dataset was divided into a development set and a test set at an 8:2 ratio while maintaining an equal distribution of axial lengths (stratified splitting with binning). We used transfer learning-based on EfficientNet B3 to develop the model. We evaluated the model’s performance using mean absolute error (MAE), R-squared (R2), and 95% confidence intervals (CIs). We used vanilla gradient saliency maps to illustrate the regions predominantly used by convolutional neural network. @*Results@#In total, 8,657 UWF retinal fundus images from 3,829 patients (mean age, 63.98 ±15.25 years) were included in the study. The deep learning model predicted the axial lengths of the test dataset with MAE and R2 values of 0.744 mm (95% CI, 0.709–0.779 mm) and 0.815 (95% CI, 0.785–0.840), respectively. The model’s accuracy was 73.7%, 95.9%, and 99.2% in prediction, with error margins of ±1.0, ±2.0, and ±3.0 mm, respectively. @*Conclusions@#We developed a deep learning-based model for predicting the axial length from UWF images with good performance.

Voretigene Neparvovec for the Treatment of RPE65-associated Retinal Dystrophy: Consensus and Recommendations from the Korea RPE65-IRD Consensus Paper Committee

Mutations in the RPE65 gene, associated with Leber congenital amaurosis, early-onset severe retinal dystrophy, and retinitis pigmentosa, gained growing attention since gene therapy for patients with RPE65-associated retinal dystrophy is available in clinical practice. RPE65 gene accounts for a very small proportion of patients with inherited retinal degeneration, especially Asian patients. Because RPE65-associated retinal dystrophy shares common clinical characteristics, such as early-onset severe nyctalopia, nystagmus, low vision, and progressive visual field constriction, with retinitis pigmentosa by other genetic mutations, appropriate genetic testing is essential to make a correct diagnosis. Also, fundus abnormalities can be minimal in early childhood, and the phenotype is highly variable depending on the type of mutations in RPE65-associated retinal dystrophy, which makes a diagnostic difficulty. The aim of this paper is to review the epidemiology of RPE65-associated retinal dystrophy, mutation spectrum, genetic diagnosis, clinical characteristics, and voretigene neparvovec, a gene therapy product for the treatment of RPE65-related retinal dystrophy.

Standardized Imaging and Reporting for Thyroid Ultrasound: Korean Society of Thyroid Radiology Consensus Statement and Recommendation

Ultrasonography (US) is a primary imaging modality for diagnosing nodular thyroid disease and has an essential role in identifying the most appropriate management strategy for patients with nodular thyroid disease. Standardized imaging techniques and reporting formats for thyroid US are necessary. For this purpose, the Korean Society of Thyroid Radiology (KSThR) organized a task force in June 2021 and developed recommendations for standardized imaging technique and reporting format, based on the 2021 KSThR consensus statement and recommendations for US-based diagnosis and management of thyroid nodules. The goal was to achieve an expert consensus applicable to clinical practice.

Current situation and control strategies of H9N2 avian influenza in South Korea

The H9N2 avian influenza (AI) has become endemic in poultry in many countries since the 1990s, which has caused considerable economic losses in the poultry industry. Considering the long history of the low pathogenicity H9N2 AI in many countries, once H9N2 AI is introduced, it is more difficult to eradicate than high pathogenicity AI. Various preventive measures and strategies, including vaccination and active national surveillance, have been used to control the Y439 lineage of H9N2 AI in South Korea, but it took a long time for the H9N2 virus to disappear from the fields. By contrast, the novel Y280 lineage of H9N2 AI was introduced in June 2020 and has spread nationwide. This study reviews the history, genetic and pathogenic characteristics, and control strategies for Korean H9N2 AI. This review may provide some clues for establishing control strategies for endemic AIV and a newly introduced Y280 lineage of H9N2 AI in South Korea.

Two Case Reports of Chronic Inflammatory Demyelinating Polyneuropathy After COVID-19Vaccination

The occurrence of chronic inflammatory demyelinating polyneuropathy (CIDP) related to coronavirus disease 2019 (COVID-19) has rarely been reported. We describe two patients who were diagnosed with CIDP after COVID-19 vaccination. A 72-year-old man presented with a progressive tingling sensation and weakness below both knees for two weeks. He had been vaccinated against COVID-19 (mRNA-1273 vaccine) a month before the appearance of symptoms. Demyelinating polyneuropathy was observed in the nerve conduction studies (NCS). Intravenous immunoglobulin (IVIg) was administered under the diagnosis of GuillainBarré syndrome (GBS), and his symptoms were improved. However, his symptoms relapsed at 10 weeks from the onset. Oral prednisolone, azathioprine, and IVIg were administered as treatment. The second case was a 50-year-old man who complained of a bilateral leg tingling sensation and gait disturbance lasting four weeks. He had received the Ad26.COV2.S vaccine against COVID-19 five weeks prior. Demyelinating polyneuropathy was observed in the NCS. He was treated with oral prednisolone, azathioprine, and IVIg for CIDP because his symptoms had lasted for more than 12 weeks from the onset. A causal relationship has not been established between COVID-19 vaccination and CIDP; however, CIDP may follow COVID-19 vaccination. As CIDP treatment is different from that for GBS, clinicians should closely monitor patients diagnosed with GBS associated with COVID-19 whether they deteriorate after initial treatment.

Diagnostic Performance of Ultrasound-Based Risk Stratification Systems for Thyroid Nodules: A Systematic Review and Meta-Analysis

Background@#This study investigated the diagnostic performance of biopsy criteria in four society ultrasonography risk stratification systems (RSSs) for thyroid nodules, including the 2021 Korean (K)-Thyroid Imaging Reporting and Data System (TIRADS). @*Methods@#The Ovid-MEDLINE, Embase, Cochrane, and KoreaMed databases were searched and a manual search was conducted to identify original articles investigating the diagnostic performance of biopsy criteria for thyroid nodules (≥1 cm) in four widely used society RSSs. @*Results@#Eleven articles were included. The pooled sensitivity and specificity were 82% (95% confidence interval [CI], 74% to 87%) and 60% (95% CI, 52% to 67%) for the American College of Radiology (ACR)-TIRADS, 89% (95% CI, 85% to 93%) and 34% (95% CI, 26% to 42%) for the American Thyroid Association (ATA) system, 88% (95% CI, 81% to 92%) and 42% (95% CI, 22% to 67%) for the European (EU)-TIRADS, and 96% (95% CI, 94% to 97%) and 21% (95% CI, 17% to 25%) for the 2016 K-TIRADS. The sensitivity and specificity were 76% (95% CI, 74% to 79%) and 50% (95% CI, 49% to 52%) for the 2021 K-TIRADS1.5 (1.5-cm size cut-off for intermediate-suspicion nodules). The pooled unnecessary biopsy rates of the ACR-TIRADS, ATA system, EU-TIRADS, and 2016 K-TIRADS were 41% (95% CI, 32% to 49%), 65% (95% CI, 56% to 74%), 68% (95% CI, 60% to 75%), and 79% (95% CI, 74% to 83%), respectively. The unnecessary biopsy rate was 50% (95% CI, 47% to 53%) for the 2021 K-TIRADS1.5. @*Conclusion@#The unnecessary biopsy rate of the 2021 K-TIRADS1.5 was substantially lower than that of the 2016 K-TIRADS and comparable to that of the ACR-TIRADS. The 2021 K-TIRADS may help reduce potential harm due to unnecessary biopsies.

Autophagy Enhancers Regulate Cholesterol-Induced Cytokine Secretion and Cytotoxicity in Macrophages

Objective@#Hypercholesterolaemia transforms macrophages into lipid-laden foam cells in circulation, which can activate the immune response. Compromised autophagy and inflammatory cytokines are involved in the pathogenesis and progression of metabolic diseases.The aim of this study was to identify the role of autophagy as a modulator of the inflammatory response and cytotoxicity in macrophages under hypercholesterolaemic conditions. @*Methods@#High cholesterol-induced cytokine secretion and alteration of autophagyassociated molecules were confirmed by cytokine array and western blot analysis, respectively. To confirm whether autophagic regulation affects high cholesterol-induced cytokine release and cytotoxicity, protein levels of autophagic molecules, cell viability, and cytotoxicity were measured in cultured macrophages treated autophagy enhancers. @*Results@#Cholesterol treatment increased cytokine secretion, cellular toxicity, and lactate dehydrogenase release in lipopolysaccharide (LPS)-primed macrophages. Concomitantly, altered levels of autophagy-related molecules were detected in LPS-primed macrophages under hypercholesterolaemic conditions. Treatment with autophagy enhancers reversed the secretion of cytokines, abnormally expressed autophagy-associated molecules, and cytotoxicity of LPS-primed macrophages. @*Conclusion@#Autophagy enhancers inhibit inflammatory cytokine secretion and reduce cytotoxicity under metabolic disturbances, such as hypercholesterolaemia. Modulation of autophagy may be a novel approach to control the inflammatory response observed in metabolic diseases.

Loss of Neutralizing Activity of Tixagevimab/Cilgavimab (Evusheld™) Against Omicron BN.1, a Dominant Circulating Strain Following BA.5During the Seventh Domestic Outbreak in Korea in Early 2023

Tixagevimab/cilgavimab is a monoclonal antibody used to prevent coronavirus disease 2019 among immunocompromised hosts and maintained neutralizing activity against early omicron variants. Omicron BN.1 became a dominant circulating strain in Korea early 2023, but its susceptibility to tixagevimab/cilgavimab is unclear. We conducted plaque reduction neutralization test (PRNT) against BN.1 in a prospective cohort (14 patients and 30 specimens). BN.1 PRNT was conducted for one- and three-months after tixagevimab/ cilgavimab administration and the average PRNT ND 50 of each point was lower than the positive cut-off value of 20 (12.9 ± 4.5 and 13.2 ± 4.2, respectively, P = 0.825). In the paired analyses, tixagevimab/cilgavimab-administered sera could not actively neutralize BN.1 (PRNT ND 50 11.5 ± 2.9, P = 0.001), compared with the reserved activity against BA.5 (ND 50 310.5 ± 180.4). Unlike virus-like particle assay, tixagevimab/cilgavimab was not active against BN.1 in neutralizing assay, and would not be effective in the present predominance of BA.2.75 sublineages.

Factors affecting the ongoing pregnancy rate in women with repeated implantation failure undergoing an endometrial receptivity array / 대한생식의학회지

Objective@#In this retrospective study, we analyzed factors influencing the ongoing pregnancy rate (PR) in women with repeated implantation failure (RIF) undergoing embryo transfer with endometrial receptivity array (ERA). @*Methods@#Eighty-three consecutive personalized embryo transfers (pETs) with ERA, from 54 women with RIF, were selected from June 2020 to April 2022. Vitrified blastocyst transfer was timed based on ERA results. @*Results@#The ongoing PR per pET was 33.7%. Using ERA, the endometrium was identified as pre-receptive in 26 cycles, early receptive in 25 cycles, receptive in 31 cycles, and late receptive in one cycle. With cycles categorized into three receptivity phases (pre-receptive, early receptive, or receptive), no significant differences were found in the clinical PR (27.3%, 55.6%, and 40%, respectively) or ongoing PR (9.1%, 55.6%, and 40%, respectively) after a single blastocyst transfer. Similarly, no significant differences were observed in the clinical PR or ongoing PR after the transfer of two or more blastocysts. Among women with ongoing pregnancy relative to those without, age at first pET was significantly lower (35 years vs. 39 years, p=0.001), while blastocyst score (23 vs. 18, p=0.012) and the proportion of blastocyst scores >18 (71.4% vs. 38.9%, p=0.005) were significantly higher. In multiple logistic regression analysis, the woman’s age (odds ratio [OR], 0.814; 95% confidence interval [CI], 0.706 to 0.940; p=0.005) and blastocyst score >18 (OR, 3.052; 95% CI, 1.075 to 8.665; p=0.036) were identified as significant factors influencing ongoing pregnancy. @*Conclusion@#In pET with ERA, ongoing pregnancy was closely associated with woman’s age and blastocyst quality.

Korean Clinical Practice Guidelines: Current Status of Adherence to the RIGHT Checklist

Background@#The Korean Academy of Medical Sciences (KAMS) has been utilizing AGREE II to audit the quality of clinical practice guidelines (CPGs) developed in Korea. Monitoring the RIGHT Checklist adherence could help monitor the quality status and discover areas for improvement of CPG development. @*Methods@#We included 129 CPGs from the past 5 years and assessed each item of the RIGHT Checklist. STATA version 15.0 was used for statistical analysis. @*Results@#Among the seven sections of the RIGHT checklist, sections with a full compliance rate over 60% were ‘basic information’ (65%) and ‘background’ (66%). The other sections’ mean full compliance rates were ‘Evidence’ 52%, ‘Recommendation’ 35%, ‘Review and quality assurance’ 25% and ‘Funding, declaration and management of interest’ 17%. Sections with a partial compliance rate over 60% were ‘Recommendation’ (60%) and ‘Funding, declaration and management of interest’ (70%). Non-compliance was highest in the ‘Review and quality assurance’ (17%) domain. In comparison between groups 1 (under median group) and 2 (over median group), group 2 showed a tendency to have multi-stakeholder involvement and present sufficient information on financial resources and conflict of interest declarations. For the CPGs developmental methodology aspect, group 2 provided more pertinent information than group 1 about supporting evidence-making and the process from evidence to recommendation. @*Conclusion@#This study evaluated adherence to the RIGHT Checklist of CPGs developed in Korea. It can provide helpful information to develop strategic plans for enhancing the capabilities of developing CPGs in Korea.

Letter to the Editor: Effectiveness of the Varicella Vaccine Among Korean Children: Suggestions for Future Research

no abstract available

Sinkihwan-gamibang ameliorates puromycin aminonucleoside-induced nephrotic syndrome / 中国天然药物

Nephrotic syndrome (NS) is a kidney disease characterized by hypertriglyceridemia, massive proteinuria, hypo-albuminemia and peripheral edema. Sinkihwan-gamibang (SKHGMB) was recorded in a traditional Chinese medical book named "Bangyakhappyeon ()" and its three prescriptions Sinkihwan, Geumgwe-sinkihwan, and Jesaeng-sinkihwan belong to Gamibang. This study confirmed the effect of SKHGMB on renal dysfunction in an NS model induced by puromycin aminonucleoside (PAN). The experimental NS model was induced in male Sprague Dawley (SD) rats through injection of PAN (50 mg·kg-1)via the femoral vein. SKHGMB not only reduced the size of the kidneys increased due to PAN-induced NS, but also decreased proteinuria and ascites. In addition, SKHGMB significantly ameliorated creatinine clearance, creatinine, and blood urea nitrogen. SKHGMB relieved glomeruli dilation and tubules fibrosis in the glomeruli of the NS model. SKHGMB inhibited the protein and mRNA levels of the NLRP3 inflammasome including NLRP3, ASC, and pro-caspase-1 in NS rats. SKHGMB reduced the protein and mRNA levels of fibrosis regulators in NS rats. The results indicated that SKHGMB exerts protective effects against renal dysfunction by inhibiting of renal inflammation and fibrosis in NS rats.

Adverse Events Associated with the Use of Leukocyte Reduction Filters and Blood Transfusion Sets: Experience of a Single Institute in Korea and Status of Adverse Event Reporting in Korea and the United States / 대한수혈학회지

Background@#Leukocyte reduction filters (LRF) and blood transfusion sets (BTS) are frequently used medical devices to prevent blood transfusion-related adverse reactions. This study attempted to analyze these medical devices related adverse events reported by an institution for 10 years and to understand the status of such reports in Korea and the United States (U.S.). @*Methods@#From January 2013 to October 2022, adverse events reported at Soonchunhyang university Bucheon hospital (SCHBC) were analyzed. From 2016 to 2022, adverse events registered in the Korean Medical Device Information Portal and the Total Product Life Cycle (TPLC) database of the U.S. were collected and evaluated using the International Medical Device Regulators Forum (IMDRF) code for medical device problems, clinical signs, and symptoms or conditions. @*Results@#A total of 12, 47, and 1,422 events were identified in SCHBC, Korea, and the U.S., respectively. The medical device problems reported in BTS included fluid leakage, breakage, disconnection, and no flow. In LRF, device or reagent problems, coagulation of device or device components, and filtration problems were reported. Most of the clinical signs and symptoms or conditions were not applicable (98.1%, 1,453/1,481), but hypotension and hemolysis were reported in LRF. @*Conclusion@#To improve the safety of transfusion-related medical devices such as LRF and BTS, proper attention needs to be paid to adverse events and all medical institutions should participate in the reporting of such events.The various adverse events and associated IMDRF codes included in this study would help enable reporting of adverse events and improve patient safety.

Radiofrequency ablation of recurrent thyroid cancers: anatomy-based management

Although differentiated thyroid cancer has an excellent prognosis and low mortality, its recurrence rate has been reported to be very high. While surgery is recommended as the standard treatment for recurrent thyroid cancer, reoperation may increase the incidence of complications due to fibrosis and anatomical distortion. In patients with high surgical risk or those who refuse repeated surgery, ultrasonography-guided ablation techniques including radiofrequency ablation, ethanol ablation, and laser ablation are suggested as alternative treatments. In this manuscript, we introduce an anatomy-based management concept for radiofrequency ablation for recurrent thyroid cancer, and present a review of the relevant literature, including indications, basic techniques, clinical outcomes, and complications.

A Rapid Assessing Method of Drug Susceptibility Using Flow Cytometry for Mycobacterium tuberculosis Isolates Resistant to Isoniazid, Rifampin, and Ethambutol / 결핵및호흡기질환

Background@#The current conventional drug susceptibility test (DST) for Mycobacterium tuberculosis (Mtb) takes several weeks of incubation to obtain results. As a rapid method, molecular DST requires only a few days to get the results but does not fully cover the phenotypic resistance. A new rapid method based on the ability of viable Mtb bacilli to hydrolyze fluorescein diacetate to free fluorescein with detection of fluorescent mycobacteria by flow cytometric analysis, was recently developed. @*Methods@#To evaluate this cytometric method, we tested 39 clinical isolates which were susceptible or resistant to isoniazid (INH) or rifampin (RIF), or ethambutol (EMB) by phenotypic or molecular DST methods and compared the results. @*Results@#The susceptibility was determined by measuring the viability rate of Mtb and all the isolates which were tested with INH, RIF, and EMB showed susceptibility results concordant with those by the phenotypic solid and liquid media methods. The isolates having no mutations in the molecular DST but resistance in the conventional phenotypic DST were also resistant in this cytometric method. These results suggest that the flow cytometric DST method is faster than conventional agar phenotypic DST and may complement the results of molecular DST. @*Conclusion@#In conclusion, the cytometric method could provide quick and more accurate information that would help clinicians to choose more effective drugs.

Salmonella enterica serotype Choleraesuis infection in weaned pigs: a first clinicopathological case report from Korea

Salmonella enterica serotype Choleraesuis causes swine paratyphoid, with clinical findings of enterocolitis and septicemia. However, the clinicopathological features of S. Choleraesuis infections in pigs have not been reported in Korea. We describe the pathological findings of two weaned pigs with S. Choleraesuis infections, presenting with diarrhea, cough, and sudden death. Pathological examination indicated severe necrotic colitis in pig 1 and septicemic lesions in pig 2. Multidrug-resistant S. Choleraesuis was isolated from the pigs’ lungs and intestinal contents. Further research is required for the surveillance of S. Choleraesuis infections in pigs and the virulence estimation in the S. Choleraesuis isolates.

Renal Infarction in Vascular Ehlers-Danlos Syndrome / 대한내과학회지

Renal infarction is a condition caused by sudden disturbance of renal arterial blood flow, which occurs frequently in cardioembolic disease, renal artery injury (trauma, Marfan syndrome, rarely Ehlers-Danlos syndrome), and in association with a hypercoagulable state. Ehlers-Danlos syndrome is a rare hereditary connective tissue disease characterized by skin fragility, hyperelasticity, hypermobility of small joints, and easy bruising. Among the subtypes, vascular Ehlers-Danlos syndrome is a very rare genetic disease caused by a mutation in the COL3A1 gene. As blood vessels are fragile due dysfunctional collagen synthesis, complications of bleeding due to arterial dissection or rupture are common in patients with this disease. Here, we report a case of vascular Ehlers-Danlos syndrome diagnosed based on a renal infarction caused by thrombus and renal artery injury; we also present a review of the relevant literature.

Aqueous extract of freeze-dried Protaetia brevitarsis larvae promotes osteogenesis by activating β-catenin signaling

Objective: To investigate the effect of an aqueous extract of Protaetia brevitarsis (AEPB) on osteogenesis using preosteoblast MC3T3-E1 cells and zebrafish larvae. Methods: Flow cytometric analysis was used to measure the cytotoxicy. Alkaline phosphatase activity was detetmined using p-nitrophenyl phosphate as a substrate. Calcium deposition was detected using alizarin red staining along with osteogenic marker expression in preosteoblast MC3T3E1 cells. In addition, vertebral formation in zebrafish larvae was detected using calcein staining and osteogenic gene expression. Results: AEPB highly promoted the expression of osteogenic markers including runt-related transcription factor 2, osterix, and alkaline phosphatase, along with elevated levels of mineralization in MC3T3-E1 cells. Moreover, AEPB accelerated vertebral formation in zebrafish larvae accompanied by upregulated expression of osteogenic genes. FH535, an inhibitor of Wnt/β-catenin, suppressed AEPB-induced osteogenic gene expression and vertebral formation, indicating that AEPB stimulates osteogenesis by activating the Wnt/β-catenin signaling pathway. Conclusions: AEPB stimulates osteoblast differentiation and bone formation by activating β-catenin. Therefore, AEPB is a promising material that induces osteogenesis, and is useful for the treatment of bone resorption diseases.

Aqueous extract of freeze-dried Protaetia brevitarsis larvae promotes osteogenesis by activating β-catenin signaling

Objective: To investigate the effect of an aqueous extract of Protaetia brevitarsis (AEPB) on osteogenesis using preosteoblast MC3T3-E1 cells and zebrafish larvae. Methods: Flow cytometric analysis was used to measure the cytotoxicy. Alkaline phosphatase activity was detetmined using p-nitrophenyl phosphate as a substrate. Calcium deposition was detected using alizarin red staining along with osteogenic marker expression in preosteoblast MC3T3E1 cells. In addition, vertebral formation in zebrafish larvae was detected using calcein staining and osteogenic gene expression. Results: AEPB highly promoted the expression of osteogenic markers including runt-related transcription factor 2, osterix, and alkaline phosphatase, along with elevated levels of mineralization in MC3T3-E1 cells. Moreover, AEPB accelerated vertebral formation in zebrafish larvae accompanied by upregulated expression of osteogenic genes. FH535, an inhibitor of Wnt/β-catenin, suppressed AEPB-induced osteogenic gene expression and vertebral formation, indicating that AEPB stimulates osteogenesis by activating the Wnt/β-catenin signaling pathway. Conclusions: AEPB stimulates osteoblast differentiation and bone formation by activating β-catenin. Therefore, AEPB is a promising material that induces osteogenesis, and is useful for the treatment of bone resorption diseases.

Booster BNT162b2 COVID-19 Vaccination Increases Neutralizing Antibody Titers Against the SARS-CoV-2 Omicron Variant in Both Young and Elderly Adults

Concerns about the effectiveness of current vaccines against the rapidly spreading severe acute respiratory syndrome-coronavirus-2 omicron (B.1.1.529) variant are increasing. This study aimed to assess neutralizing antibody activity against the wild-type (BetaCoV/Korea/ KCDC03/2020), delta, and omicron variants after full primary and booster vaccinations with BNT162b2. A plaque reduction neutralization test was employed to determine 50% neutralizing dilution (ND 50 ) titers in serum samples. ND 50 titers against the omicron variant (median [interquartile range], 5.3 [50 titers than the detection threshold (50 titers against BetaCoV/Korea/KCDC03/2020, delta, and omicron, although titers against omicron remained lower than those against the other variants (P < 0.001). Our study suggests that booster vaccination with BNT162b2 significantly increases humoral immunity against the omicron variant.