1.Mechanism of Action and Pharmacokinetics of Approved Bispecific Antibodies
Seong Min CHOI ; Ju-Hee LEE ; Soyeon KO ; Soon-Sun HONG ; Hyo-Eon JIN
Biomolecules & Therapeutics 2024;32(6):708-722
		                        		
		                        			
		                        			 Bispecific antibodies represent a significant advancement in therapeutic antibody engineering, offering the ability to simultaneously target two distinct antigens. This dual-targeting capability enhances therapeutic efficacy, especially in complex diseases, such as cancer and autoimmune disorders, where drug resistance and incomplete target coverage are prevalent challenges.Bispecific antibodies facilitate immune cell engagement and disrupt multiple signaling pathways, providing a more comprehensive treatment approach than traditional monoclonal antibodies. However, the intricate structure of bispecific antibodies introduces unique pharmacokinetic challenges, including issues related to their absorption, distribution, metabolism, and excretion, which can significantly affect their efficacy and safety. This review provides an in-depth analysis of the structural design, mechanisms of action, and pharmacokinetics of the currently approved bispecific antibodies. It also highlights the engineering innovations that have been implemented to overcome these challenges, such as Fc modifications and advanced dimerization techniques, which enhance the stability and half-life of bispecific antibodies. Significant progress has been made in bispecific antibody technology;however, further research is necessary to broaden their clinical applications, enhance their safety profiles, and optimize their incorporation into combination therapies. Continuous advancements in this field are expected to enable bispecific antibodies to provide more precise and effective therapeutic strategies for a range of complex diseases, ultimately improving patient outcomes and advancing precision medicine. 
		                        		
		                        		
		                        		
		                        	
2.Mechanism of Action and Pharmacokinetics of Approved Bispecific Antibodies
Seong Min CHOI ; Ju-Hee LEE ; Soyeon KO ; Soon-Sun HONG ; Hyo-Eon JIN
Biomolecules & Therapeutics 2024;32(6):708-722
		                        		
		                        			
		                        			 Bispecific antibodies represent a significant advancement in therapeutic antibody engineering, offering the ability to simultaneously target two distinct antigens. This dual-targeting capability enhances therapeutic efficacy, especially in complex diseases, such as cancer and autoimmune disorders, where drug resistance and incomplete target coverage are prevalent challenges.Bispecific antibodies facilitate immune cell engagement and disrupt multiple signaling pathways, providing a more comprehensive treatment approach than traditional monoclonal antibodies. However, the intricate structure of bispecific antibodies introduces unique pharmacokinetic challenges, including issues related to their absorption, distribution, metabolism, and excretion, which can significantly affect their efficacy and safety. This review provides an in-depth analysis of the structural design, mechanisms of action, and pharmacokinetics of the currently approved bispecific antibodies. It also highlights the engineering innovations that have been implemented to overcome these challenges, such as Fc modifications and advanced dimerization techniques, which enhance the stability and half-life of bispecific antibodies. Significant progress has been made in bispecific antibody technology;however, further research is necessary to broaden their clinical applications, enhance their safety profiles, and optimize their incorporation into combination therapies. Continuous advancements in this field are expected to enable bispecific antibodies to provide more precise and effective therapeutic strategies for a range of complex diseases, ultimately improving patient outcomes and advancing precision medicine. 
		                        		
		                        		
		                        		
		                        	
3.Mechanism of Action and Pharmacokinetics of Approved Bispecific Antibodies
Seong Min CHOI ; Ju-Hee LEE ; Soyeon KO ; Soon-Sun HONG ; Hyo-Eon JIN
Biomolecules & Therapeutics 2024;32(6):708-722
		                        		
		                        			
		                        			 Bispecific antibodies represent a significant advancement in therapeutic antibody engineering, offering the ability to simultaneously target two distinct antigens. This dual-targeting capability enhances therapeutic efficacy, especially in complex diseases, such as cancer and autoimmune disorders, where drug resistance and incomplete target coverage are prevalent challenges.Bispecific antibodies facilitate immune cell engagement and disrupt multiple signaling pathways, providing a more comprehensive treatment approach than traditional monoclonal antibodies. However, the intricate structure of bispecific antibodies introduces unique pharmacokinetic challenges, including issues related to their absorption, distribution, metabolism, and excretion, which can significantly affect their efficacy and safety. This review provides an in-depth analysis of the structural design, mechanisms of action, and pharmacokinetics of the currently approved bispecific antibodies. It also highlights the engineering innovations that have been implemented to overcome these challenges, such as Fc modifications and advanced dimerization techniques, which enhance the stability and half-life of bispecific antibodies. Significant progress has been made in bispecific antibody technology;however, further research is necessary to broaden their clinical applications, enhance their safety profiles, and optimize their incorporation into combination therapies. Continuous advancements in this field are expected to enable bispecific antibodies to provide more precise and effective therapeutic strategies for a range of complex diseases, ultimately improving patient outcomes and advancing precision medicine. 
		                        		
		                        		
		                        		
		                        	
4.Impact of Social Support during Diagnosis and Treatment on Disease Progression in Young Patients with Breast Cancer: A Prospective Cohort Study
Danbee KANG ; Seri PARK ; Hyo Jung KIM ; Seok Won KIM ; Jeong Eon LEE ; Jonghan YU ; Se Kyung LEE ; Ji-Yeon KIM ; Seok Jin NAM ; Juhee CHO ; Yeon Hee PARK
Cancer Research and Treatment 2024;56(1):125-133
		                        		
		                        			 Purpose:
		                        			We evaluated the association between changes in social support after cancer treatment and recurrence-free survival (RFS) in such patients using a prospective cohort study. 
		                        		
		                        			Materials and Methods:
		                        			Data were obtained from a prospective cohort study (NCT03131089) conducted at Samsung Medical Center (2013-2021). The primary outcome measure was RFS. Social support was measured using the social and family well-being (SFWB) domain of the Functional Assessment of Cancer Therapy-General. We calculated the changes in SFWB scores before and during treatment and the hazard ratio for RFS by comparing such changes. 
		                        		
		                        			Results:
		                        			The mean±standard deviation (SD) age of the patients was 35±3.9 years, and 71.5% and 64.8% of the patients were married and had children, respectively. The mean±SD SFWB score at baseline was 20.5±5.0 out of 26. After cancer treatment, 35.9%, 10.3%, and 53.8% of the participants had increasing, unchanged, and decreasing SFWB scores, respectively. The decreasing SFWB score group had a higher risk of mortality or recurrence than the increasing group. Risk factors for the decreasing score were the presence of children during diagnosis. 
		                        		
		                        			Conclusion
		                        			In this cohort, changes in social support after treatment were associated with RFS in young patients with breast cancer. Health professionals should develop family interventions to help them receive proper social support. 
		                        		
		                        		
		                        		
		                        	
5.Differences in the incidence, characteristics, and outcomes of patients with acute kidney injury in the medical and surgical intensive care units
Yeji LEE ; Taeil KIM ; Dong Eon KIM ; Eun Mi JO ; Da Woon KIM ; Hyo Jin KIM ; Eun Young SEONG ; Sang Heon SONG ; Harin RHEE
Kidney Research and Clinical Practice 2024;43(4):518-527
		                        		
		                        			
		                        			 Though acute kidney injury (AKI) is a prevalent complication in critically ill patients, knowledge on the epidemiological differences and clinical characteristics of patients with AKI admitted to medical and surgical intensive care units (ICUs) remains limited. Methods: Electronic medical records of patients in ICUs in Pusan National University Hospital and Pusan National University Hospital Yangsan, from January 2011 to December 2020, were retrospectively analyzed. Different characteristics of AKI between patients were analyzed. The contribution of AKI to the in-hospital mortality rate was assessed using a Cox proportional hazards model. Results: A total of 7,150 patients were included in this study. AKI was more frequent in medical (48.7%) than in surgical patients (19.7%), with the severity of AKI higher in medical patients. In surgical patients, hospital-acquired AKI was more frequent (51.0% vs. 49.0%), whereas community-acquired AKI was more common in medical patients (58.5% vs. 41.5%). 16.9% and 5.9% of medical and surgical patients died in the hospital, respectively. AKI affected patient groups to different degrees. In surgical patients, AKI patients had 4.778 folds higher risk of mortality (95% confidence interval [CI], 3.577–6.382; p < 0.001) than non-AKI patients; whereas in medical AKI patients, it was 1.239 (95% CI, 1.051–1.461; p = 0.01). Conclusion: While the prevalence of AKI itself is higher in medical patients, the impact of AKI on mortality was stronger in surgical patients compared to medical patients. This suggests that more attention is needed for perioperative patients to prevent and manage AKI. 
		                        		
		                        		
		                        		
		                        	
6.The role of nafamostat mesylate anticoagulation in continuous kidney replacement therapy for critically ill patients with bleeding tendencies: a retrospective study on patient outcomes and safety
Taeil KIM ; Dong Eon KIM ; Eun Mi JO ; Yeji LEE ; Da Woon KIM ; Hyo Jin KIM ; Eun Young SEONG ; Sang Heon SONG ; Harin RHEE
Kidney Research and Clinical Practice 2024;43(4):469-479
		                        		
		                        			
		                        			 Continuous kidney replacement therapy (CKRT) is crucial in the management of acute kidney injury in intensive care units (ICUs). Nonetheless, the optimal anticoagulation strategy for patients with bleeding tendencies remains debated. This study aimed to evaluate patient outcomes and safety of nafamostat mesylate (NM) compared with no anticoagulation (NA) in critically ill patients with bleeding tendencies who were undergoing CKRT. Methods: This retrospective study enrolled 2,313 patients who underwent CKRT between March 2013 and December 2022 at the third affiliated hospital in South Korea. After applying the exclusion criteria, 490 patients were included in the final analysis, with 245 patients in the NM and NA groups each, following 1:1 propensity score matching. Subsequently, in-hospital mortality, incidence of bleeding complications, agranulocytosis, hyperkalemia, and length of hospital stay were assessed. Results: No significant differences were observed between the groups regarding the lengths of hospital and ICU stays or the incidence of agranulocytosis and hyperkalemia. The NM group showed a smaller decrease in hemoglobin levels during CKRT (–1.90 g/dL vs. –2.39 g/dL) and less need for blood product transfusions than the NA group. Furthermore, the NM group exhibited a survival benefit in patients who required transfusion of all three blood products. Conclusion: NM is an effective and safe anticoagulant for CKRT in critically ill patients, especially those requiring transfusion of all three blood products. Although these findings are promising, further multicenter studies are needed to validate them and explore the mechanisms underlying the observed benefits. 
		                        		
		                        		
		                        		
		                        	
7.Disseminated herpes zoster with vagus nerve involvement in a kidney transplant recipient: a case report
Dong Eon KIM ; Da Woon KIM ; Hyo Jin KIM ; Harin RHEE ; Sang Heon SONG ; Eun Young SEONG
Kosin Medical Journal 2024;39(2):138-143
		                        		
		                        			
		                        			 Herpes zoster virus infection is common and results in significant morbidity in patients who have undergone solid organ transplantation. Herpes zoster can involve the cranial nerves, and vagus nerve involvement is an infrequent primary manifestation of herpes zoster. Here, we describe a rare presentation of disseminated herpes zoster infection with vagus nerve involvement in a kidney transplant recipient. A 62-year-old man who had undergone kidney transplantation 3 years prior presented to our clinic with sore throat and hoarseness, followed by multiple vesicular-pustular rashes on the face and trunk. Flexible laryngoscopy revealed left paramedian vocal cord paralysis with multiple ulcerative lesions extending from the left pyriform sinus to the epiglottis. Computed tomography of the neck, abdomen, and chest revealed no significant abnormalities that could have caused vocal cord paralysis. We confirmed the diagnosis of disseminated herpes zoster after herpes zoster laryngitis based on positive blood tests and polymerase chain reaction for varicella zoster virus antibodies. The skin rashes and laryngeal ulcers rapidly resolved after treatment with intravenous acyclovir and high-dose steroids. The patient still had persistent dysphagia and microaspiration as assessed by a video fluoroscopic swallowing study, but showed improvement in dysphagia in response to swallowing rehabilitation therapy. This case provides valuable insights into the presenting symptoms of disseminated herpes zoster, which can cause acute vagus neuritis in solid organ transplantation recipients. 
		                        		
		                        		
		                        		
		                        	
8.Quality of life in patients with diabetic nephropathy: findings from the KNOW-CKD (Korean Cohort Study forOutcomes in Patients with Chronic Kidney Disease) cohort
Hyunsuk KIM ; Joongyub LEE ; Gwang Ho CHOI ; Hae Min JEONG ; Seok hyung KIM ; Jae Eon GU ; Jeong-Ju YOO ; Miyeun HAN ; Hyo-Jin KIM ; Su-Ah SUNG ; Seung Hyeok HAN ; Yeong Hoon KIM ; Jong-Woo YOON ; Jongho HEO ; Kook-Hwan OH
Kidney Research and Clinical Practice 2022;41(1):43-57
		                        		
		                        			
		                        			 Diabetic nephropathy (DN) can affect quality of life (QoL) because it requires arduous lifelong management. This study analyzed QoL differences between DN patients and patients with other chronic kidney diseases (CKDs). Methods: The analysis included subjects (n = 1,766) from the KNOW-CKD (Korean Cohort Study for Outcomes in Patients with Chronic Kidney Disease) cohort who completed the Kidney Disease Quality of Life Short Form questionnaire. After implementing propensity score matching (PSM) using factors that affect the QoL of DN patients, QoL differences between DN and non-DN participants were examined. Results: Among all DN patients (n = 390), higher QoL scores were found for taller subjects, and lower scores were found for those who were unemployed or unmarried, received Medical Aid, had lower economic status, had higher platelet counts or alkaline phosphatase levels, or used clopidogrel or insulin. After PSM, the 239 matched DN subjects reported significantly lower patient satisfaction (59.9 vs. 64.5, p = 0.02) and general health (35.3 vs. 39.1, p = 0.04) than the 239 non-DN subjects. Scores decreased in both groups during the 5-year follow-up, and the scores in the work status, sexual function, and role-physical domains were lower among DN patients than non-DN patients, though those differences were not statistically significant. Conclusion: Socioeconomic factors of DN were strong risk factors for impaired QoL, as were high platelet, alkaline phosphatase, and clopidogrel and insulin use. Clinicians should keep in mind that the QoL of DN patients might decrease in some domains compared with non-DN CKDs. 
		                        		
		                        		
		                        		
		                        	
9.Predictive factors of drainage volume and drain duration after the inframammary approach to nipple-areolar-complex sparing mastectomy and implant-based breast reconstruction
Yoon Soo KIM ; Ho Sung KIM ; Eon Ju PARK ; Hyo Young KIM ; Hong Il KIM ; Jin Hyung PARK ; Chang Wan JEON ; Hyung Suk YI
Archives of Aesthetic Plastic Surgery 2021;27(1):23-30
		                        		
		                        			 Background:
		                        			The placement of a closed suction drain is indispensable for preventing serious infections; however, closed suction drains are inevitably accompanied by increases in local infections, pain, and length of hospital stay, and delays in breast cancer treatment including postoperative chemotherapy and radiotherapy. We analyzed predictive factors of total drainage volume and duration. 
		                        		
		                        			Methods:
		                        			Among patients who were diagnosed with primary breast cancer between January 2016 and December 2017, we retrospectively analyzed those who underwent immediate implant-based breast reconstruction. Factors that could affect the total volume and duration of drainage, including lipo-prostaglandin E1 use, preoperative chemotherapy, resected breast issue weight, age, body mass index (BMI), serum white blood cell count, erythrocyte sedimentation rate, and C-reactive protein (CRP) level, were analyzed. 
		                        		
		                        			Results:
		                        			The mean volume and duration of drainage were 1,213.6 mL and 14.8 days respectively. BMI and CRP on postoperative day (POD) 1 were correlated with the total drainage volume. Age, BMI, and resected breast tissue weight were correlated with the drainage duration. Multiple regression analysis showed that CRP level on POD 1, age, and resected breast tissue weight significantly affected the drainage duration. Multiple regression analysis also showed that the total drainage volume was significantly affected by BMI and CRP level on POD 1. 
		                        		
		                        			Conclusions
		                        			The factors found to affect the duration of drainage in patients undergoing implant-based breast reconstruction were CRP on POD 1, age, resected breast tissue weight, and BMI. The CRP level on POD 1 and BMI influenced the total volume of drainage. 
		                        		
		                        		
		                        		
		                        	
10.The Clinical Characteristics and Outcomes of Patients with Moderate-to-Severe Coronavirus Disease 2019 Infection and Diabetes in Daegu, South Korea
Mi Kyung KIM ; Jae-Han JEON ; Sung-Woo KIM ; Jun Sung MOON ; Nan Hee CHO ; Eugene HAN ; Ji Hong YOU ; Ji Yeon LEE ; Miri HYUN ; Jae Seok PARK ; Yong Shik KWON ; Yeon-Kyung CHOI ; Ki Tae KWON ; Shin Yup LEE ; Eon Ju JEON ; Jin-Woo KIM ; Hyo-Lim HONG ; Hyun Hee KWON ; Chi Young JUNG ; Yin Young LEE ; Eunyeoung HA ; Seung Min CHUNG ; Jian HUR ; June Hong AHN ; Na-young KIM ; Shin-Woo KIM ; Hyun Ha CHANG ; Yong Hoon LEE ; Jaehee LEE ; Keun-Gyu PARK ; Hyun Ah KIM ; Ji-Hyun LEE
Diabetes & Metabolism Journal 2020;44(4):602-613
		                        		
		                        			
		                        			  Coronavirus disease 2019 (COVID-19) is a global pandemic that had affected more than eight million people worldwide by June 2020. Given the importance of the presence of diabetes mellitus (DM) for host immunity, we retrospectively evaluated the clinical characteristics and outcomes of moderate-to-severe COVID-19 in patients with diabetes. We conducted a multi-center observational study of 1,082 adult inpatients (aged ≥18 years) who were admitted to one of five university hospitals in Daegu because of the severity of their COVID-19-related disease. The demographic, laboratory, and radiologic findings, and the mortality, prevalence of severe disease, and duration of quarantine were compared between patients with and without DM. In addition, 1:1 propensity score (PS)-matching was conducted with the DM group. Compared with the non-DM group ( DM is a significant risk factor for COVID-19 severity and mortality. Our findings imply that COVID-19 patients with DM, especially if elderly, require special attention and prompt intensive care.
		                        		
		                        	
            
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