COVID-19 vaccination-related myocarditis: a Korean nationwide study.

AIMS: A comprehensive nationwide study on the incidence and outcomes of COVID-19 vaccination-related myocarditis (VRM) is in need. METHODS AND RESULTS: Among 44 276 704 individuals with at least 1 dose of COVID-19 vaccination, the incidence and clinical courses of VRM cases confirmed by the Expert Adjudication Committee of the Korea Disease Control and Prevention Agency were analyzed. COVID-19 VRM was confirmed in 480 cases (1.08 cases per 100 000 persons). Vaccination-related myocarditis incidence was significantly higher in men than in women (1.35 vs. 0.82 per 100 000 persons, P < 0.001) and in mRNA vaccines than in other vaccines (1.46 vs. 0.14 per 100 000 persons, P < 0.001). Vaccination-related myocarditis incidence was highest in males between the ages of 12 and 17 years (5.29 cases per 100 000 persons) and lowest in females over 70 years (0.16 cases per 100 000 persons). Severe VRM was identified in 95 cases (19.8% of total VRM, 0.22 per 100 000 vaccinated persons), 85 intensive care unit admission (17.7%), 36 fulminant myocarditis (7.5%), 21 extracorporeal membrane oxygenation therapy (4.4%), 21 deaths (4.4%), and 1 heart transplantation (0.2%). Eight out of 21 deaths were sudden cardiac death (SCD) attributable to VRM proved by an autopsy, and all cases of SCD attributable to VRM were aged under 45 years and received mRNA vaccines. CONCLUSION: Although COVID-19 VRM was rare and showed relatively favorable clinical courses, severe VRM was found in 19.8% of all VRM cases. Moreover, SCD should be closely monitored as a potentially fatal complication of COVID-19 vaccination.

Sudden Occurrence of Pacemaker Capture Failure during Irreversible Electroporation Ablation for Prostate Cancer in Post-COVID-19 Patient: A Case Report.

Irreversible electroporation (IRE) ablation is a novel treatment option for localized prostate cancer. Here, we present a case of an abrupt and fatal arrhythmia during the IRE procedure in a prostate cancer patient with an implanted permanent pacemaker. A 78-year-old male patient with a pacemaker due to sick sinus syndrome and syncope was scheduled for IRE prostate ablation surgery under general anesthesia. He had a history of recovering from coronavirus disease 2019 (COVID-19) after having been vaccinated against it and recovered without sequalae. Pacemaker interrogation and reprogramming to asynchronous AOO mode was carried out before surgery, however, sinus pause occurred repeatedly during ablation pulse delivery. After the first sinus pause of 2.25 s there was a decrease in continuous arterial blood pressure (ABP). During the delivery of the second and third pulses, identical sinus pauses were observed due to failure to capture. However, the atrial-paced rhythm recovered instantly, and vital signs became acceptable. Although sinus pause recovered gradually, the duration thereof was increased by the delivery of more IRE pulses, with a subsequent abrupt decrease seen in blood pressure. The pacemaker was urgently reprogrammed to DOO mode, after which there were no further pacing failures and no hemodynamic adverse events. For patients with pacemakers, close cardiac monitoring in addition to the interrogation of the pacemaker during the electromagnetic interference (EMI) procedure is recommended, especially in the case of having a disease that may aggravate cardiac vulnerability, such as COVID-19.

Comparing Results of Five SARS-CoV-2 Antibody Assays Before and After the First Dose of ChAdOx1 nCoV-19 Vaccine among Health Care Workers.

Reliable results regarding serologic positivity for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody before and after AstraZeneca (AZ) vaccination are essential for estimating the efficacy of vaccination. We assessed positivity rates and associated factors using five SARS-CoV-2 antibody assays. A total of 228 paired serum samples (456 samples) were obtained from 228 participants. After baseline sampling, the second sampling was conducted between 11 and 28 days after the first dose of the AZ vaccine. Sera were tested using five SARS-CoV-2 antibody assays, including two surrogate virus neutralization tests. A questionnaire on the symptoms, severity, and duration of adverse reactions was completed by all participants. The overall positivity rates for SARS-CoV-2 antibody were 84.6% for the Roche assay, 92.5% for the Abbott assay, 75.4% for the Siemens assay, 90.7% for the SD Biosensor assay, and 66.2% for the GenScript assay after the first dose of the AZ vaccine. The positivity rates and antibody titers of sera obtained between 21 and 28 days were significantly higher than those obtained between 11 and 20 days in all five assays. More-severe adverse reactions and longer durations of adverse reactions were related to higher SARS-CoV-2 antibody levels. The agreements and correlations among the assays applied were substantial (к, 0.73 to 0.95) and strong (ρ, 0.83 to 0.91). A single dose of the AZ vaccine led to high positivity rates based on the five assays. Days after vaccination and adverse reactions could help estimate serologic conversion rates. The results should be interpreted cautiously considering the assays and cutoffs applied. Our findings could inform decisions regarding vaccination and laboratory settings and could thus contribute to the control of the spread of SARS-CoV-2 infection.

Comparison of the Results of Five SARS-CoV-2 Antibody Assays before and after the First and Second ChAdOx1 nCoV-19 Vaccinations among Health Care Workers: a Prospective Multicenter Study.

Reliable results for serological positivity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody after the second dose of AstraZeneca (AZ) vaccination are important to estimate the real efficacy of vaccination. We evaluated positivity rates and changes in semiquantitative antibody titers before and after the first and second ChAdOx1 nCoV-19 vaccinations using five SARS-CoV-2 antibody assays, including two surrogate virus neutralization tests. A total of 674 serum samples were obtained from 228 participants during three blood sampling periods. A questionnaire on symptoms, severity, and adverse reaction duration was completed by participants after the second vaccination. The overall positive rates for all assays were 0.0 to 0.9% before vaccination, 66.2 to 92.5% after the first vaccination, and 98.2 to 100.0% after the second vaccination. Median antibody titers in five assays after the second dose of vaccination were increased compared to those after the first dose (106.4-fold increase for Roche total antibody, 3.6-fold for Abbott IgG, 3.6-fold for Siemens, 1.2-fold for SD Biosensor V1 neutralizing antibody, and 2.2-fold for GenScript neutralizing antibody). Adverse reactions were reduced after the second dose in 89.9% of participants compared to after the first dose. Overall, the second vaccination led to almost 100% positivity rates based on these SARS-CoV-2 antibody assays. The results should be interpreted with caution, considering the characteristics of the applied assays. Our findings could inform decisions regarding vaccination and the use of immunoassays, thus contributing to SARS-CoV-2 pandemic control.

Evaluation of Combined Cancer Markers With Lactate Dehydrogenase and Application of Machine Learning Algorithms for Differentiating Benign Disease From Malignant Ovarian Cancer.

BACKGROUND: The differential diagnosis of ovarian cancer is important, and there has been ongoing research to identify biomarkers with higher performance. This study aimed to evaluate the diagnostic utility of combinations of cancer markers classified by machine learning algorithms in patients with early stage ovarian cancer, which has rarely been reported. METHODS: In total, 730 serum samples were assayed for lactate dehydrogenase (LD), neutrophil-to-lymphocyte ratio (NLR), human epididymis protein 4 (HE4), cancer antigen 125 (CA125), and risk of ovarian malignancy algorithm (ROMA). Among them, 53 were diagnosed with early stage ovarian cancer, and the remaining 677 were diagnosed with benign disease. RESULTS: The areas under the receiver operating characteristic curves (ROC-AUCs) of the ROMA, HE4, CA125, LD, and NLR for discriminating ovarian cancer from non-cancerous disease were .707, .680, .643, .657, and .624, respectively. ROC-AUC of the combination of ROMA and LD (.709) was similar to that of single ROMA in the total population. In the postmenopausal group, ROC-AUCs of HE4 and CA125 combined with LD presented the highest value (.718). When machine learning algorithms were applied to ROMA combined with LD, the ROC-AUC of random forest was higher than that of other applied algorithms in the total population (.757), showing acceptable performance. CONCLUSION: Our data suggest that the combinations of ovarian cancer-specific markers with LD classified by random forest may be a useful tool for predicting ovarian cancer, particularly in clinical settings, due to easy accessibility and cost-effectiveness. Application of an optimal combination of cancer markers and algorithms would facilitate appropriate management of ovarian cancer patients.

Immature granulocyte percentage for prediction of sepsis in severe burn patients: a machine leaning-based approach.

BACKGROUND: Of the existing sepsis markers, immature granulocytes (IG) most frequently reflect the presence of an infection. The importance of IG as an early predictor of sepsis and bacteremia is evaluated differently for each study. This study aimed to evaluate the effectiveness of the Sysmex XN series' IG% as an independent prognostic indicator of sepsis using machine learning. METHODS: A total of 2465 IG% results from 117 severe burn patients in the intensive care unit of one institution were retrospectively analyzed. We evaluated the IG% for sepsis using the receiver operating characteristic, logistic regression, and partial dependence plot analyses. Clinical characteristics and other laboratory markers associated with sepsis, including WBC, procalcitonin, and C-reactive protein, were compared with the IG% values. RESULTS: Twenty-six of the 117 patients were diagnosed with sepsis. The median IG% value was 2.6% (95% CI: 1.4-3.1). The area under the receiver operating characteristic curve was 0.77 (95% CI: 0.78-0.84) and the optimal cut-off value was 3%, with a sensitivity of 76.9% and specificity of 68.1%. The partial dependence plot of IG% on predicting sepsis showed that an IG% < 4% had low predictability, but increased thereafter. The interaction plot of IG% and C-reactive protein showed an increase in sepsis probability at an IG% of 6% and C-reactive protein of 160 mg/L. CONCLUSIONS: IG% is moderately useful for predicting sepsis. However, since it can be determined from routine laboratory test results and requires no additional intervention or cost, it could be particularly useful as an auxiliary marker.

Evaluation of the dosimetric effect of scattered protons in clinical practice in passive scattering proton therapy.

The present study verified and evaluated the dosimetric effects of protons scattered from a snout and an aperture in clinical practice, when a range compensator was included. The dose distribution calculated by a treatment planning system (TPS) was compared with the measured dose distribution and the dose distribution calculated by Monte Carlo simulation at several depths. The difference between the measured and calculated results was analyzed using Monte Carlo simulation with filtration of scattering in the snout and aperture. The dependence of the effects of scattered protons on snout size, beam range, and minimum thickness of the range compensator was also investigated using the Monte Carlo simulation. The simulated and measured results showed that the additional dose compared with the results calculated by the TPS at shallow depths was mainly due to protons scattered by the snout and aperture. This additional dose was filtered by the structure of the range compensator so that it was observed under the thin region of the range compensator. The maximum difference was measured at a depth of 16 mm (8.25%), with the difference decreasing with depth. Analysis of protons contributing to the additional dose showed that the contribution of protons scattered from the snout was greater than that of protons scattered from the aperture when a narrow snout was used. In the Monte Carlo simulation, this effect of scattered protons was reduced when wider snouts and longer-range proton beams were used. This effect was also reduced when thicker range compensator bases were used, even with a narrow snout. This study verified the effect of scattered protons even when a range compensator was included and emphasized the importance of snout-scattered protons when a narrow snout is used for small fields. It indicated that this additional dose can be reduced by wider snouts, longer range proton beams, and thicker range compensator bases. These results provide a better understanding of the additional dose from scattered protons in clinical practice.

Seroprevalence of Anti-SARS-CoV-2 Antibodies among Outpatients in Southwestern Seoul, Korea.

Serosurveillance studies reveal the actual disease burden and herd immunity level in the population. In Seoul, Korea, a cross-sectional investigation showed 0.07% anti-severe acute respiratory syndrome coronavirus-2 antibody seropositivity among 1,500 outpatients of the university hospitals. Low seroprevalence reflects well-implemented social distancing. Serosurveillance should be repeated as the pandemic progresses.

Currently Applied Molecular Assays for Identifying ESR1 Mutations in Patients with Advanced Breast Cancer.

Approximately 70% of breast cancers, the leading cause of cancer-related mortality worldwide, are positive for the estrogen receptor (ER). Treatment of patients with luminal subtypes is mainly based on endocrine therapy. However, ER positivity is reduced and ESR1 mutations play an important role in resistance to endocrine therapy, leading to advanced breast cancer. Various methodologies for the detection of ESR1 mutations have been developed, and the most commonly used method is next-generation sequencing (NGS)-based assays (50.0%) followed by droplet digital PCR (ddPCR) (45.5%). Regarding the sample type, tissue (50.0%) was more frequently used than plasma (27.3%). However, plasma (46.2%) became the most used method in 2016-2019, in contrast to 2012-2015 (22.2%). In 2016-2019, ddPCR (61.5%), rather than NGS (30.8%), became a more popular method than it was in 2012-2015. The easy accessibility, non-invasiveness, and demonstrated usefulness with high sensitivity of ddPCR using plasma have changed the trends. When using these assays, there should be a comprehensive understanding of the principles, advantages, vulnerability, and precautions for interpretation. In the future, advanced NGS platforms and modified ddPCR will benefit patients by facilitating treatment decisions efficiently based on information regarding ESR1 mutations.

Incidence of Severe Chronic Neutropenia in South Korea and Related Clinical Manifestations: A National Health Insurance Database Study.

Background and objectives: Severe chronic neutropenia (SCN) is a condition in which absolute neutrophil counts remain at a low level (under 500/µL) over months or years. Because of the rare onset of SCN, its epidemiology, prognosis, and clinical manifestations have not yet been fully understood. In particular, large-cohort studies in Asian countries are still insufficient. Therefore, in this study, national health insurance data was used to investigate the epidemiologic features and prognosis of SCN in South Korea. MATERIALS AND METHODS: The data from the Health Insurance Review and Assessment database recorded between 1 January 2011 and 31 December 2015 were explored. SCN was defined based on the ICD-10 code, registry of benefit extension policy, and inclusion criteria of the study. After identifying patients with SCN, annual incidence and their co-morbidities were analyzed. RESULTS: Among the initially identified patients with severe neutropenia (N = 2145), a total of 367 patients had SCN and were enrolled. The annual incidence rate of SCN ranged from 0.12 to 0.17 per 100,000 person-year (PY) during the study period. The highest incidence was observed in pediatric patients aged between 0 to 9 years (N = 156), followed by women in their fifties (N = 43). The total incidence rate was 0.17 in females and 0.12 in males (Relative risk (RR): 1.43, 95%, CI: 1.16-1.76). The most common accompanying condition was mild respiratory infection, but about 3.2% of patients progressed to hematologic malignancy after an average of 2.4 years. CONCLUSIONS: This nationwide population-based epidemiological study showed that incidence of SCN is higher in pediatrics and middle-aged women. As progression to hematologic malignancy was significantly higher in the age of in 45-49 year olds, careful follow-up is necessary in this group. However, since this study lacks the molecular information, these finding need to be interpreted with great caution.

Two-dimensional in vivo rectal dosimetry during high-dose-rate brachytherapy for cervical cancer: a phantom study.

BACKGROUND: The aim of the present study was to verify the dosimetric accuracy of two-dimensional (2D) in vivo rectal dosimetry using an endorectal balloon (ERB) with unfoldable EBT3 films for high-dose-rate (HDR) brachytherapy for cervical cancer. The clinical applicability of the technique was discussed. MATERIAL AND METHODS: ERB inflation makes the EBT3 films unrolled, whereas its deflation makes them rolled. Patient-specific quality assurance (pQA) tests were performed in 20 patient plans using an Ir-192 remote afterloading system and a water-filled cervical phantom with the ERB. The dose distributions measured in ERBs were compared with those of the treatment plans. RESULTS: The absolute dose profiles measured by the ERBs were in good agreement with those of treatment plans. The global gamma passing rates were 96-100% and 91-100% over 20 pQAs under the criteria of 3%/3 mm and 3%/2 mm, respectively, with a 30% low-dose threshold. Dose-volume histograms of the rectal wall were obtained from the measured dose distributions and showed small volume differences less than 2% on average from the patients' plans over the entire dose interval. The positioning error of the applicator set was detectable with high sensitivity of 12% dose area variation per mm. Additionally, the clinical applicability of the ERB was evaluated in volunteers, and none of them felt any pain when the ERB was inserted or removed. CONCLUSIONS: The 2D in vivo rectal dosimetry using the ERB with EBT3 films was effective and might be clinically applicable for HDR brachytherapy for cervical and prostate cancers to monitor treatment accuracy and consistency as well as to predict rectal toxicity.

Case Report of Kidney Paired Donation (KPD) with Desensitization: the Strategy and Experience of 3-Way KPD in Samsung Medical Center.

As the need for the organ donation increases, strategies to increase kidney transplantation (KT) through expanded living donation have become essential. These include kidney paired donation (KPD) programs and desensitization in incompatible transplantations. KPD enables kidney transplant candidates with incompatible living donors to join a registry with other incompatible pairs in order to find potentially compatible living donor. Positive cross match and ABO incompatible transplantation has been successfully accomplished in selective cases with several pre-conditionings. Patients who are both difficult-to-match due to broad sensitization and hard-to-desensitize because of donor conditions can often be successfully transplanted through a combination of KPD and desensitization. According to the existing data, KPD can increase the number of KTs from living donors with excellent clinical results. This is also a cost-effective treatment as compared with dialysis and desensitization protocols. We carried out 3-way KPD transplantation with one highly sensitized, positive cross match pair and with two ABO incompatible pairs. Herein we report our first successful 3-way KPD transplantation in a single center. To maximize donor-recipient matching and minimize immunologic risk, KPD programs should use proper algorithms with desensitization to identify optimal donor with simultaneous two-, three- or more complex multi-way exchanges.

Optimal dose of dabigatran for the prevention of thromboembolism with minimal bleeding risk in Korean patients with atrial fibrillation.

AIMS: We aim to determine the optimal dose of dabigatran in Korean patients with atrial fibrillation (AF). METHODS AND RESULTS: We analysed 1834 patients with non-valvular AF, classified into a warfarin group (n = 990), dabigatran 150 mg group (D150, n = 294), and 110 mg group (D110, n = 550). The D110 group was further classified into patients concordant (co-D110, n = 367) and patients discordant (di-D110, n = 183) with guidelines to dose reduction. Propensity-matched 1-year clinical outcomes were then compared. Efficacy outcomes were defined as thromboembolism composed of new-onset stroke or systemic embolism. Safety outcomes were major bleeding. Both D150 and D110 had comparable efficacies as warfarin. However, only D110 significantly lowered the risk of major bleeding [hazard ratio (HR) 0.19, 95% confidence interval (CI) 0.07-0.55, P = 0.002]. In a subgroup analysis according to guideline-concordant indications for dose reduction, both co-D110 and di-D110 displayed a comparable efficacy as warfarin. Both co-D110 (HR 0.22, 95% CI 0.06-0.76, P = 0.017) and di-D110 (HR 0.11, 95% CI 0.02-0.81, P = 0.030) significantly lowered incidences of major bleeding. There were no differences in the efficacy and safety between di-D110 and D150, and net clinical outcomes were similar. CONCLUSION: Although D150 and D110 had a comparable efficacy, only D110 lowered the risk of major bleeding in Korean AF patients compared with warfarin. Even the guideline-discordant use of dabigatran 110 mg demonstrated a similar efficacy and safety compared with D150. However, further prospective randomized trials are needed in order to comprehensively evaluate whether D150 or D110 is the optimal dosage in Asian patients with AF.

Association of HLA Types with Non-Specific Binding of Negative Control Beads in Luminex Panel Reactive Antibody (PRA) Screening Assay.

BACKGROUND: Luminex panel reactive antibody (PRA) screening assays using microbeads are widely used for organ transplantation. Anti-HLA serum reactivity is calculated by correcting for non-specific binding to the negative control (NC) beads. High mean fluorescence intensity (MFI) value of NC beads are observed in some patients and can result in false negative results in the PRA screening assay. We analyzed the clinical characteristics and HLA types of those patients with high MFI values of NC beads. METHODS: Sixty-six patients with high MFI values of NC beads (> 300) in the PRA LABScreen Mixed assay (One Lambda) tested were included as the high NC group. Age and gender matched controls with low MFI values of NC beads (< 100) (n = 132), tested with PRA, were selected as the low NC group and 207 healthy Koreans were used as normal controls. Association of clinical characteristics and HLA types with the high NC group were analyzed using Chi-square test or Fischer's exact test, as appropriate. RESULTS: The proportion of patients with underlying liver disease was higher in the high NC group compared to the low NC group (18.1% vs. 1.5%, p < 0.001, OR = 14.2). The seropositivity of anti-nuclear antibody and rheumatoid factor, the frequency of use of intravenous immunoglobulin G, anti-thymocyte globulin, and rituximab showed no difference between two groups. The phenotype frequency (PF) of HLA-B46 was higher in the high NC group than in the low NC group (8.0% vs. 3.2%, p = 0.036, OR = 2.8). The PF of HLA-B7 was lower in the high NC group than in the healthy controls (0.0% vs. 6.5%, p = 0.008, OR = 0.1). The PF of HLA-DR1 was lower in the high NC group than in the low NC group (0.8% vs. 6.6%, p = 0.015, OR = 0.1) or healthy controls (0.8% vs. 7.4%, p = 0.003, Pc = 0.042, OR = 0.1). CONCLUSIONS: Increased non-specific binding to NC beads was associated with underlying liver disease and HLAB46. HLA-B7 and HLA-DR1 were related to a lower chance of non-specific binding to NC beads. The mechanism of those associations, such as differences in non-specific antibody response according to HLA phenotype or underlying disease, needs to be elucidated in further studies.

Outcome of living donor liver transplantation using right liver allografts with multiple arterial supply.

A right liver graft with multiple hepatic artery (HA) stumps can be found in approximately 5% of living donor liver transplantation (LDLT) using a right lobe graft. From January 2000 to June 2014, 1149 patients underwent LDLT procedures. Thirty patients with LDLT using a right lobe graft with multiple HA stumps and 149 patients with LDLT using a right lobe graft with a single HA stump were enrolled. These patients were divided into 3 groups: single HA (group 1, n = 149), multiple HAs with total reconstruction (group 2, n = 19), and multiple HAs with selective partial reconstruction (group 3, n = 11). Selective partial reconstruction was performed only when pulsatile back-bleeding was confirmed after larger HA reconstruction and sufficient intrahepatic arterial flow was confirmed by Doppler ultrasound (DUS). In group 2, the donor HAs were smaller (P < .001), and HA reconstruction took longer (P < .001). However, there was no significant difference among the groups regarding the arterial complication rate, biliary complication rate, and patient and graft survival. In conclusion, selective partial reconstruction of HA stumps for LDLT using a right lobe graft was feasible when intrahepatic arterial communication was confirmed by pulsatile back-bleeding from the smaller artery and DUS. Liver Transplantation 22 1649-1655 2016 AASLD.

Size dependent bipolar resistance switching of NiO nanodots for low-power and multi-state operation.

NiO nanodots of various sizes were fabricated via anodic oxidation induced through atomic force microscopy (AFM) nanolithography on an 18 nm thick Ni thin film, and their resistance switching properties were investigated using conductive AFM. We found that NiO nanodots with a medium size of around 15 nm height showed clear bipolar resistance switching. A threshold switching was observed in the NiO nanodots with a larger size due to having a much thinner bottom Ni layer left after oxidation. By adjusting the range of the sweeping voltage, the high resistance state can be controlled to realize multi-state switching. The power consumption during the switching process induced by the AFM tip was found to be lower than the reported power values of the NiO thin film- or NiO nanowires-based resistance switching devices.

Kv 11.1 Expression Is Associated With Malignancy of Canine Mammary Gland Tumors.

BACKGROUND/AIM: The expression level of the voltage-dependent potassium channel Kv 11.1 was shown to be associated with the clinicopathological features, aggressiveness, and prognosis of human breast cancer. Canine mammary gland tumor (cMGT) is the most common tumor type in intact female dogs; however, the significance of Kv 11.1 in cMGT is unknown. The aim of this study was to identify Kv 11.1 expression in 57 benign and malignant cMGT tissues from dogs and to investigate the correlation of Kv 11.1 expression with the clinicopathological parameters and prognosis of cMGT. MATERIALS AND METHODS: A total of 57 samples were collected from cMGTs surgically resected at the Veterinary Medical Teaching Hospital, Seoul National University and subjected to immunohistochemistry assay using rabbit anti-Kv 11.1 polyclonal antibody. Immunohistochemical staining results were evaluated as the sum of intensity and percentage scores. The correlation between immunohistochemistry scores and clinicopathological parameters was investigated. RESULTS: Immunohistochemical analysis revealed that Kv 11.1 immunoreactivity was higher in benign cMGTs than in malignant cMGTs. Kv 11.1 expression was significantly associated with tumor malignancy (p<0.001), tumor size (p<0.001), histological grade (p<0.05), and age at the time of mastectomy (p<0.05). CONCLUSION: This study presents the first evidence of Kv 11.1 expression in cMGTs and indicates an inverse correlation between Kv 11.1 expression and tumor malignancy. Kv 11.1 expression can be used as a prognostic biomarker and a tool for the management of cMGTs.

Clinical performance of the Roche Cobas Liat SARS-CoV-2 & influenza A/B assay: A systematic review and meta-analysis.

Respiratory tract infections caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses are persistent and critical. The Cobas Liat SARS-CoV-2 & influenza A/B assay (Multiplex Liat), the FDA-authorized point-of-care reverse transcriptase polymerase chain reaction (RT-PCR) assay, has a turnaround time of 20 min and high accuracy. This study evaluates the pooled performance of this assay to provide practical information. This meta-analysis was registered in PROSPERO (registration number: CRD42023467579). A systematic literature search was conducted within PubMed, Ovid-EMBASE, and the Cochrane Library for articles evaluating the accuracy of the Multiplex Liat assay through September 2023. A random-effects model was used to calculate the pooled diagnostic values with real-time RT-PCR (rRT-PCR) as a reference test. A total of 4,705 samples from eight studies were included in the primary meta-analysis. The overall pooled sensitivity and specificity of Multiplex Liat were 100.0 % (95 % confidence interval [CI] = 96.7 %-100.0 %) and 99.7 % (95 % CI = 98.7 %-99.9 %), respectively. The presence of variants of concern or in-house rRT-PCR assays as reference standards did not significantly affect the pooled diagnostic performance of the Multiplex Liat. When 5,333 samples from nine studies were assessed for sensitivity, the pooled sensitivity was 100.0 % (95 % CI = 85.8 %-100.0 %) without a significant difference. This meta-analysis demonstrates the usefulness of Multiplex Liat for the detection of SARS-CoV-2 based on pooled diagnostic values. These practical findings may facilitate appropriate settings for the diagnosis and management of patients with respiratory tract infections.

Modified application of SAMe-TT2R2 scoring system in Asian patients with atrial fibrillation for the selection of oral anticoagulants.

BACKGROUND/AIMS: The SAMe-TT2R2 score is used for assessing anticoagulation control (AC) quality with warfarin. However, it is hard to apply SAMe-TT2R2 score in Asian patients with atrial fibrillation (AF), because it has not been proven in those populations. This study aimed to validate the SAMe-TT2R2 score in Asian patients with AF and suggest a modified SAMe- TT2R2 score for this population. METHODS: We analyzed 710 Korean patients with AF who were using warfarin. The AC quality was assessed as the mean time in therapeutic range (TTR). Each component of SAMe-TT2R2 score was evaluated for the relationship with AC. Further clinical factors that predict AC were analyzed. Identified factors were re-assorted and constructed as SA2Me-TTR scoring system. RESULTS: Of the components of the SAMe-TT2R2 score, female, age, and rhythm control were associated with AC. Heart failure and renal insufficiency were newly identified factors associated with AC. The modified SA2Me-TTR score was reconstructed with the relevant risk factors (S, female gender, 1 point; A, age < 60 yr, 2 points; Me, medical history of heart failure, 1 point; T, treatment for rhythm control, 1 point; T, history of stroke or transient ischemic attack, 1 point; R, renal insufficiency, 1 point). The modified SA2Me-TTR score demonstrated an excellent relationship with the grading of AC. The modified SA2Me-TTR score ≤ 1 identified patients with good AC (hazard ratio 2.46, 95% CI 1.75-3.47). CONCLUSION: The modified SA2Me-TTR score was useful for guiding oral anticoagulants selection in Asian patients with AF.

Analysis of Anti-Angiogenesis-Related Adverse Events Associated with Vascular Endothelial Growth Factor Receptor-Tyrosine Kinase Inhibitors (VEGFR-TKIs) in Patients with Metastatic Renal Cell Carcinoma.

BACKGROUND: Limited studies have evaluated anti-angiogenesis-related adverse events involving oral vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs) in metastatic renal cell carcinoma using real-world data. OBJECTIVE: This study aimed to investigate the incidence, patterns, and impact on the dose intensity of anti-angiogenesis-related adverse events associated with the use of VEGFR-TKIs in patients with metastatic renal cell carcinoma using real-world data. METHODS: This cross-sectional study included patients with a diagnosis of metastatic renal cell carcinoma who received axitinib, cabozantinib, pazopanib, sorafenib, and sunitinib at a tertiary hospital in South Korea. We categorized the patients into those who had not previously received a VEGFR-TKI (VEGFR-TKI-naive) and those who had previously received a VEGFR-TKI (VEGFR-TKI-experienced). Anti-angiogenesis-related adverse events were defined as hypertension, proteinuria, bleeding, thrombosis, hypothyroidism, and left ventricular dysfunction, which were rated "possible" or higher based on a causality assessment scale. RESULTS: Among a total of 988 patients, 674 patients were VEGFR-TKI-naïve and 314 patients were VEGFR-TKI-experienced. Anti-angiogenesis-related adverse events of any grade and severe adverse events occurred in 65.1 and 34.6% of VEGFR-TKI-naïve patients and 54.8 and 36.0% of VEGFR-TKI-experienced patients, respectively. Regardless of treatment history, the most common adverse event was hypertension, with 48.6% in VEGFR-TKI-naïve patients and 35.0% in VEGFR-TKI-experienced patients. For VEGFR-TKI-experienced patients, the overall rate of anti-angiogenesis-related adverse events for sorafenib (24.3%) was lower than that for other VEGFR-TKIs (p < 0.05). Patients experiencing anti-angiogenesis-related adverse events were 1.6 times more likely to receive a low relative dose intensity. CONCLUSIONS: More than half and more than one-third of patients with renal cell carcinoma receiving VEGFR-TKIs experienced any and severe anti-angiogenesis-related adverse events, respectively. The relative dose intensity of VEGFR-TKI treatment was associated with anti-angiogenesis-related adverse events.