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Although bispecific T-cell engager (BiTE) is a promising treatment for relapsed/refractory multiple myeloma (RRMM), it needs to be evaluated in a real-world setting. This study aimed to evaluate the efficacy and safety of BiTEs compared with a synthetic standard of care (SOC). From a multicenter registry database of 474 patients with RRMM who received third- or more advanced-line treatments between January 2021 and October 2023, 1:1 propensity score-matched BiTE cohort (n = 71) and SOC cohort (n = 71) were established. Matching was based on age, sex, number of prior therapies, international staging system at diagnosis, and baseline biochemical characteristics. Compared with the matched SOC cohort, the matched BiTE cohort demonstrated a significant improvement in median progression-free survival (PFS, 19.2 vs 5.4 months, hazard ratio (HR) = .50 [95% CI, .33 to .78], p < .01). However, the overall survival (OS) was not significantly different between the two cohorts. Safety profiles showed that 37 (52%) patients in the matched BiTE cohort experienced cytokine release syndrome, mostly grade 1 (n = 29, 41%), with rare occurrences of neurotoxicity (n = 4, 5.6%). Infections were significantly more common in the matched BiTE cohort compared with the matched SOC cohort (81% vs. 49%, p < .01). Non-B-cell mutation antigen (BCMA)-targeted BiTEs improved 6-month OS rates compared with BCMA-targeted BiTEs in monotherapy (94% [95% CI, 84 to 100] vs. 65% [95% CI, 45 to 95], p = .04) and combination with daratumumab (100% [95% CI, 100 to 100] vs. 77% [95% CI, 57 to 100], p = .20). Non-BCMA-targeted BiTEs also provided benefit for 6-month PFS rate compared with the BCMA-targeted BiTE cohort in monotherapy (76% [95% CI, 59 to 100] vs. 50% [95% CI, 31 to 82], p = .11) and combination with daratumumab (100% [95% CI, 100 to 100] vs. 69% [95% CI, 48 to 99], p = .10). Quantitative bias and sensitivity analyses confirmed the robustness of these results. This real-world data-based study underscores the potential of BiTEs to significantly enhance survival outcomes in patients with heavily treated RRMM and manageable safety profiles. The difference in clinical outcomes by BiTE targets warrants further investigation in larger clinical trials (ClinicalTrials.gov identifier: NCT06205823)., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Finding an adequate dose of the drug by revealing the dose-response relationship is very crucial and a challenging problem in the clinical development. The main concerns in dose-finding study are to identify a minimum effective dose (MED) in anesthesia studies and maximum tolerated dose (MTD) in oncology clinical trials. For the estimation of MED and MTD, we propose two modifications of Firth's logistic regression using reparametrization, called reparametrized Firth's logistic regression (rFLR) and ridge-penalized reparametrized Firth's logistic regression (RrFLR). The proposed methods are designed by directly reducing the small-sample bias of the maximum likelihood estimate for the parameter of interest. In addition, we develop a method on how to construct confidence intervals for rFLR and RrFLR using profile penalized likelihood. In the up-and-down biased-coin design, numerical studies confirm the superior performance of the proposed methods in terms of the mean squared error, bias, and coverage accuracy of confidence intervals., (© 2024 John Wiley & Sons Ltd.)

Background: Out-of-hospital cardiac arrest is a major public health concern in Korea. Identifying spatiotemporal patterns of out-of-hospital cardiac arrest incidence and survival outcomes is crucial for effective resource allocation and targeted interventions. Thus, this study aimed to investigate the spatiotemporal epidemiology of out-of-hospital cardiac arrest in Korea, with a focus on identifying high-risk areas and populations and examining factors associated with prehospital outcomes., Methods: We conducted this population-based observational study using data from the Korean out-of-hospital cardiac arrest registry from January 2009 to December 2021. Using a Bayesian spatiotemporal model based on the Integrated Nested Laplace Approximation, we calculated the standardized incidence ratio and assessed the relative risk to compare the spatial and temporal distributions over time. The primary outcome was out-of-hospital cardiac arrest incidence, and the secondary outcomes included prehospital return of spontaneous circulation, survival to hospital admission and discharge, and good neurological outcomes., Results: Although the number of cases increased over time, the spatiotemporal analysis exhibited a discernible temporal pattern in the standardized incidence ratio of out-of-hospital cardiac arrest with a gradual decline over time (1.07; 95% credible interval [CrI], 1.04-1.09 in 2009 vs. 1.00; 95% CrI, 0.98-1.03 in 2021). The district-specific risk ratios of survival outcomes were more favorable in the metropolitan and major metropolitan areas. In particular, the neurological outcomes were significantly improved from relative risk 0.35 (0.31-0.39) in 2009 to 1.75 (1.65-1.86) in 2021., Conclusion: This study emphasized the significance of small-area analyses in identifying high-risk regions and populations using spatiotemporal analyses. These findings have implications for public health planning efforts to alleviate the burden of out-of-hospital cardiac arrest in Korea., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Myeloid-derived suppressor cells (MDSCs) are bone marrow (BM)-derived immunosuppressive cells in the tumor microenvironment, but the mechanism of MDSC mobilization from the BM remains unclear. We investigated how BM stromal cell activation by PTH1R contributes to MDSC mobilization. PTH1R activation by parathyroid hormone (PTH) or PTH-related peptide (PTHrP), a tumor-derived counterpart, mobilized monocytic (M-) MDSCs from murine BM without increasing immunosuppressive activity. In vitro cell-binding assays demonstrated that α4β1 integrin and vascular cell adhesion molecule (VCAM)-1, expressed on M-MDSCs and osteoblasts, respectively, are key to M-MDSC binding to osteoblasts. Upon PTH1R activation, osteoblasts express VEGF-A and IL6, leading to Src family kinase phosphorylation in M-MDSCs. Src inhibitors suppressed PTHrP-induced MDSC mobilization, and Src activation in M-MDSCs upregulated two proteases, ADAM-17 and MMP7, leading to VCAM1 shedding and subsequent disruption of M-MDSC tethering to osteoblasts. Collectively, our data provide the molecular mechanism of M-MDSC mobilization in the bones of tumor hosts., (© 2023. The Author(s).)

Rationale and Objectives: To assess the diagnostic performances of prostate specific antigen (PSA) and PSA with prostate magnetic resonance imaging (MRI) to predict prostate cancer in patients with PSA ≤ 20 ng/mL., Materials and Methods: Patients suspected of prostate cancer with a PSA test and prebiopsy MRI were included (n = 881). Prostate biopsy results or follow-up clinical data for 2 years were used to determine the presence of prostate cancer. The diagnostic performance of PSA, MRI, and PSA with MRI (referred to as the protocol) was evaluated. The positive predictive value (PPV) and negative predictive value (NPV) of the MRI were calculated in subgroups of patients with specific ranges of PSA level., Results: Prostate cancer and CSC were diagnosed in 220 and 162 patients, respectively. Adding MRI to PSA could greatly improve specificity and PPV (0.833 and 0.567) for detecting CSC, compared to PSA ≥ 4 ng/mL alone (0.248 and 0.0219). Even though the sensitivity of the protocol (0.679) was lower than PSA (0.938), the NPV of the protocol was comparable to PSA (0.929 vs. 0.924). The protocol consistently showed the superior PPV and NVP to PSA only in not only patients within the gray zone of PSA, but also in patients with higher PSA., Conclusion: In conclusion, this longitudinal observational study confirmed that adding prebiopsy MRI to PSA was consistently beneficial in patients with PSA ≤ 20 ng/mL for avoiding unnecessary biopsy despite decrease in the sensitivity., (Copyright © 2022 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Background: Mammography screening has been proven to detect breast cancer at an early stage and reduce mortality; however, it has low accuracy in young women or women with dense breasts. Blood-based diagnostic tools may overcome the limitations of mammography. This study assessed the diagnostic performance of a three-protein signature in patients with suspicious breast lesions., Findings: This trial (MAST; KCT0004847) was a prospective multicenter observational trial. Three-protein signature values were obtained using serum and plasma from women with suspicious lesions for breast malignancy before tumor biopsy. Additionally, blood samples from women who underwent clear or benign mammography were collected for the assays. Among 642 participants, the sensitivity, specificity, and overall accuracy values of the three-protein signature were 74.4%, 66.9%, and 70.6%, respectively, and the concordance index was 0.698 (95% CI 0.656, 0.739). The diagnostic performance was not affected by the demographic features, clinicopathologic characteristics, and co-morbidities of the participants., Conclusions: The present trial showed an accuracy of 70.6% for the three-protein signature. Considering the value of blood-based biomarkers for the early detection of breast malignancies, further evaluation of this proteomic assay is warranted in larger, population-level trials. This Multi-protein Assessment using Serum to deTermine breast lesion malignancy (MAST) was registered at the Clinical Research Information Service of Korea with the identification number of KCT0004847 ( https://cris.nih.go.kr )., (© 2023. The Author(s).)

Susceptible-exposed-infectious-recovered (SEIR) models were applied to assess the effectiveness of non-pharmaceutical interventions (NPIs) and to study the dynamic behavior of the COVID-19 pandemic. Recently, SEIR models have evolved to address the change of human mobility by some NPIs for predicting the new confirmed cases. However, the models have serious limitations when applied to Seoul. Seoul has two representative quarantine policies, i.e. social distancing and the ban on gatherings. Effects of the two policies need to be reflected in different functional forms in the model because changes in human mobility do not fully reflect the ban on gatherings. Thus we propose a modified SEIR model to assess the effectiveness of social distancing, ban on gatherings and vaccination strategies. The application of the modified SEIR model was illustrated by comparing the model output with real data., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Multi-color flow cytometry is the standard approach for immunophenotyping clinical samples. With the recent advances in cancer immunotherapy, myeloid-derived suppressor cells (MDSC), immature myeloid-lineage cells in cancer patient blood and the tumor microenvironment, are highlighted as an important immune cell population that correlates with prognosis and therapeutic efficacy. In contrast to their clear functions and existence, immunophenotyping of MDSC is not consistent among investigators due to surface antigens overlapping with many normal hematopoietic lineage cell populations. We performed a clinical study and analyzed more than 1000 breast cancer patients blood samples to quantitate MDSC during breast cancer progression. In this methodology manuscript, we described detailed procedures for study design, sample logistics and handling, staining and flow cytometric analysis. This protocol used a 7-color fluorochrome-conjugated antibody panel to analyze polymorphonuclear (PMN)- and monocytic (M)-MDSC subsets simultaneously. The interim analysis results of this study showed that both PMN and M-MDSC populations are increased in patients with bone metastasis compared with patients with visceral organ metastasis. In conclusion, this work provides a versatile, comprehensive, and practical protocol to measure MDSC in patient blood samples., Competing Interests: Declaration of Competing Interest All authors declare no financial conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

This paper discusses our collaboration work with government officers in the health department of Seoul during the COVID-19 pandemic. First, we focus on short-term forecasting for the number of new confirmed cases and severe cases. Second, we focus on understanding how much of the current infections has been affected by external influx from neighborhood areas or internal transmission within the area. This understanding may be important because it is linked to the government policy determining non-pharmaceutical interventions. To obtain the decomposition of the effect, districts of Seoul should be considered simultaneously, and multivariate time series models are used. Third, we focus on predicting the number of new weekly confirmed cases for each district in Seoul. This detailed prediction may be important to the government policy on resource allocation. We consider an ensemble method to overcome poor prediction performance of simple models. This paper presents the methodological details and analysis results of the study., Competing Interests: The authors declare no competing interests., (© 2022 The Authors.)

Introduction: Owing to the coronavirus disease 19 pandemic, the demand for telemedicine has increased. However, the awareness of and experience with telemedicine among the Korean population have not been investigated. Therefore, we examined Korean outpatients' experience with and awareness of telemedicine. Methods: From December 2020 to March 2021, we conducted a survey exploring the awareness of and experience with telemedicine of outpatients who were consecutively enrolled by family physicians from four hospitals. The participants completed questionnaires on sociodemographic characteristics and knowledge, experience, satisfaction, preference, and future considerations concerning telemedicine. We evaluated factors associated with satisfaction with telemedicine experiences using multivariate logistic regression analysis. Results: Among the 563 study participants, 364 participants had experience with telemedicine. More than 95% of the telemedicine visits were performed by telephone consultation, and the most common disease type for telemedicine visits was chronic diseases (67.5%). Overall, 82.4% of the participants were satisfied with telemedicine. More than 90% of the participants were satisfied with telemedicine in terms of saving time and money relative to hospital visits, no risk of infection, and convenience. According to the multivariate logistic regression analysis, adults aged ≥65 years (odds ratio [OR] 3.53, 95% confidence interval [CI] 1.44-8.68), residents of a metropolitan city (OR 6.8, 95% CI 1.41-32.55), and those with knowledge of telemedicine (OR 2.96, 95% CI 1.21-7.26) were more likely to be satisfied with their telemedicine experience, compared with their counterparts. For chronic diseases, participants with telemedicine experience were significantly more likely to prefer telemedicine for revisits, compared with those with no telemedicine experience. Nonetheless, most respondents recognized that telemedicine requires improvement. Conclusions: Most Korean outpatients showed high satisfaction with telemedicine. Telemedicine may be considered in various medical situations in the future. Therefore, building a practical system for telemedicine and changes in the medical environment are required.

Background: The coronavirus disease 2019 (COVID-19) has taken millions of lives and disrupted living standards at individual, societal, and worldwide levels, causing serious consequences globally. Understanding its epidemic curve and spatio-temporal dynamics is crucial for the development of effective public health plans and responses and the allocation of resources. Thus, we conducted this study to assess the epidemiological dynamics and spatio-temporal patterns of the COVID-19 pandemic in Rwanda., Methods: Using the surveillance package in R software version 4.0.2, we implemented endemic-epidemic multivariate time series models for infectious diseases to analyze COVID-19 data reported by Rwanda Biomedical Center under the Ministry of Health from March 15, 2020 to January 15, 2021., Results: The COVID-19 pandemic occurred in two waves in Rwanda and showed a heterogenous spatial distribution across districts. The Rwandan government responded effectively and efficiently through the implementation of various health measures and intervention policies to drastically reduce the transmission of the disease. Analysis of the three components of the model showed that the most affected districts displayed epidemic components within the area, whereas the effect of epidemic components from spatial neighbors were experienced by the districts that surround the most affected districts. The infection followed the disease endemic trend in other districts., Conclusion: The epidemiological and spatio-temporal dynamics of COVID-19 in Rwanda show that the implementation of measures and interventions contributed significantly to the decrease in COVID-19 transmission within and between districts. This accentuates the critical call for continued intra- and inter- organization and community engagement nationwide to ensure effective and efficient response to the pandemic., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

Machine learning (ML) has been suggested to improve the performance of prediction models. Nevertheless, research on predicting the risk in patients with acute myocardial infarction (AMI) has been limited and showed inconsistency in the performance of ML models versus traditional models (TMs). This study developed ML-based models (logistic regression with regularization, random forest, support vector machine, and extreme gradient boosting) and compared their performance in predicting the short- and long-term mortality of patients with AMI with those of TMs with comparable predictors. The endpoints were the in-hospital mortality of 14,183 participants and the three- and 12-month mortality in patients who survived at discharge. The performance of the ML models in predicting the mortality of patients with an ST-segment elevation myocardial infarction (STEMI) was comparable to the TMs. In contrast, the areas under the curves (AUC) of the ML models for non-STEMI (NSTEMI) in predicting the in-hospital, 3-month, and 12-month mortality were 0.889, 0.849, and 0.860, respectively, which were superior to the TMs, which had corresponding AUCs of 0.873, 0.795, and 0.808. Overall, the performance of the predictive model could be improved, particularly for long-term mortality in NSTEMI, from the ML algorithm rather than using more clinical predictors.

Background: The survival rate of breast cancer survivors (BCSs) is > 90%. Particular issues are upper arm dysfunction caused by surgery and treatments. Physical activity has been recommended to improve shoulder function and quality of life (QoL) in BCSs. However, rehabilitation programs tend not to be continuous., Purpose: To explore the effectiveness of therapeutic inflatable ball self-exercise for improving shoulder function and QoL in breast cancer survivors (BCSs) following breast cancer surgery., Patients and Methods: Seventy-two BCSs were allocated to two groups, conventional self-exercise (CSE; n = 34; age, 48.9 ± 7.2 years) and therapeutic inflatable ball self-exercise (IBE; n = 38; age, 47.7 ± 8.9 years); 22 in the CSE and 23 in the IBE group completed the interventions. Both groups performed intervention for 12 weeks, three times per week and 15 min a day at least. Measurement was performed three times for shoulder range of motion (ROM), handgrip strength, Shoulder Pain and Disability Index (SPADI), and Functional Assessment of Cancer Therapy-Breast (FACT-B)., Result: Flexion and extension of shoulder ROM showed significant differences between the two groups at 12 weeks. Flexion and extension of shoulder ROM showed significant differences for t1-t2 (p = 0.02) and t0-t1 (p = 0.04). Abduction showed a significant difference for t0-t1 (p = 0.03), t1-t2 (p = 0.02), and t0-t2 (p = 0.01). CSE (7 points) and IBE (20 points) satisfied the MDC in FACT-B total score. The MDC of the SPADI total score was 13 points in the CSE group and 9 points in the IBE group., Conclusion: IBE would be more appropriate to start the rehabilitation for BCSs and CSE would be effective after the pain has improved.