1.Phase 1/2a Study of Rivoceranib, a Selective VEGFR-2 Angiogenesis Inhibitor, in Patients with Advanced Solid Tumors
Yoon-Koo KANG ; Min-Hee RYU ; Yong Sang HONG ; Chang-Min CHOI ; Tae Won KIM ; Baek-Yeol RYOO ; Jeong Eun KIM ; John R. WEIS ; Rachel KINGSFORD ; Cheol Hee PARK ; Seong JANG ; Arlo MCGINN ; Theresa L. WERNER ; Sunil SHARMA
Cancer Research and Treatment 2024;56(3):743-750
Purpose:
This study aimed to report the results from an early-phase study of rivoceranib, an oral tyrosine kinase inhibitor highly selective for vascular endothelial growth factor receptor 2, in patients with advanced solid tumors.
Materials and Methods:
In this open-label, single-arm, dose-escalating, multicenter three-part phase 1/2a trial, patients had advanced solid tumors refractory to conventional therapy. Part 1 evaluated the safety and pharmacokinetics of five ascending once-daily doses of rivoceranib from 81 mg to 685 mg. Part 2 evaluated the safety and antitumor activity of once-daily rivoceranib 685 mg. Part 3 was conducted later, due to lack of maximum tolerated dose determination in part 1, to evaluate the safety and preliminary efficacy of once-daily rivoceranib 805 mg in patients with unresectable or advanced gastric cancer.
Results:
A total of 61 patients were enrolled in parts 1 (n=25), 2 (n=30), and 3 (n=6). In parts 1 and 2, patients were white (45.5%) or Asian (54.5%), and 65.6% were male. The most common grade ≥ 3 adverse events were hypertension (32.7%), hyponatremia (10.9%), and hypophosphatemia (10.9%). The objective response rate (ORR) was 15.2%. In part 3, dose-limiting toxicities occurred in two out of six patients: grade 3 febrile neutropenia decreased appetite, and fatigue. The ORR was 33%.
Conclusion
The recommended phase 2 dose of rivoceranib was determined to be 685 mg once daily, which showed adequate efficacy with a manageable safety profile (NCT01497704 and NCT02711969).
2.Taxonomy of Botryotrichum luteum sp. nov. based on Morphology and Phylogeny Isolated from Soil in Korea
Jung-Joo RYU ; Kallol DAS ; Seong-Keun LIM ; Soo-Min HONG ; Seung-Yeol LEE ; Hee-Young JUNG
Mycobiology 2023;51(2):72-78
In this study, a fungal strain KNUF-22-025 belonging to the genus Botryotrichum was isolated from the soil in Korea. The cultural and morphological characteristics of this strain differed from those of closely related species. On malt extract agar, strain KNUF-22-025 showed slower growth than most of the related species, except B. domesticum. The conidia size (9.6– 21.1 Â 9.9–18.4 mm) of strain KNUF-22-025 was larger than those of B. piluliferum, B. domesticum, and B. peruvianum but smaller than those of B. atrogriseum and B. iranicum. Conidiophores in strain KNUF-22-025 (137 mm) were longer than those in other closely related species but shorter than those in B. atrogriseum. Multi-locus analysis of molecular markers, such as ITS, 28S ribosomal DNA, RBP2, and TUB2 revealed that strain KNUF-22-025 was distinct from other Botryotrichum species. Thus, this strain is proposed as a novel species based on morphological characteristics along with molecular phylogeny and named Botryotrichum luteum sp. nov.
3.Molecular Phylogeny and Morphology of Tolypocladium globosum sp. nov.Isolated from Soil in Korea
Kallol DAS ; Jung-Joo RYU ; Soo-Min HONG ; Seong-Keun LIM ; Seung-Yeol LEE ; Hee-Young JUNG
Mycobiology 2023;51(2):79-86
In this study, fungal strains designated as KNUF-22-14A and KNUF-22-15A were isolated from soil samples in Korea. These two strains were identified based on cultural and morphological characteristics as well as phylogenetic analyses and were found to be morphologically and phylogenetically identical. Upon their morphological comparison with closely related species, such as Tolypocladium album, T. amazonense, T. endophyticum, T. pustulatum,and T. tropicale, a difference in the size of short phialides [0.6–2.4(–9.3) Â 0.8–1.4 mm] was observed. Meanwhile, these strains had larger conidia (1.2–3.0 Â 1.2–3.0 mm) than T. album, T.amazonense, T. endophyticum, and T. tropicale and smaller conidia than T. pustulatum. Phylogenetic analyses using a multi-locus datasets based on ITS, LSU, and SSU showed that KNUF-22-14A and KNUF-22-15A formed a distinct cluster from previously identified Tolypocladium species. Thus, these fungal strains isolated from soil in Korea are proposed as a novel species according to their characteristics and are named Tolypocladium globosum sp. nov.
4.Molecular and Morphological Characteristics of a New Species Collected from an Insect (Cicindela transbaicalica) in Korea
Ju-Heon LEE ; Leonid N. TEN ; Seong-Keun LIM ; Jung-Joo RYU ; Diane AVALOS-RUIZ ; Seung-Yeol LEE ; Hee-Young JUNG
Mycobiology 2022;50(3):181-187
To exploit insect-derived fungi, insects were collected from seven different regions in Korea, including Gyeongbuk, Goryeong, and several fungi were isolated from them. A fungal strain designated 21-64-D was isolated from riparian tiger beetle (Cicindela transbaicalica) and morphologically identified as a species belonging to the genus Oidiodendron. Phylogenetic analysis using the nucleotide sequences of internal transcribed spacer (ITS) regions and the partial sequence of the large subunit of the nuclear ribosomal RNA (LSU) gene revealed the distinct phylogenetic position of the isolate among recognized Oidiodendron species including its closest neighbors O. chlamydosporicum, O. citrinum, O. maius, and O. pilicola. The hyphal and conidial morphology of the strain, particularly club-shaped hyphae, clearly differentiated it from its close relatives. Results indicated that 21-64-D is a novel species in the genus Oidiodendron, for which the name Oidiodendron clavatum sp. nov. is proposed.
5.Clinical Practice Guideline for Postoperative Rehabilitation in Older Patients With Hip Fractures
Kyunghoon MIN ; Jaewon BEOM ; Bo Ryun KIM ; Sang Yoon LEE ; Goo Joo LEE ; Jung Hwan LEE ; Seung Yeol LEE ; Sun Jae WON ; Sangwoo AHN ; Heui Je BANG ; Yonghan CHA ; Min Cheol CHANG ; Jung-Yeon CHOI ; Jong Geol DO ; Kyung Hee DO ; Jae-Young HAN ; Il-Young JANG ; Youri JIN ; Dong Hwan KIM ; Du Hwan KIM ; In Jong KIM ; Myung Chul KIM ; Won KIM ; Yun Jung LEE ; In Seok LEE ; In-Sik LEE ; JungSoo LEE ; Chang-Hyung LEE ; Seong Hoon LIM ; Donghwi PARK ; Jung Hyun PARK ; Myungsook PARK ; Yongsoon PARK ; Ju Seok RYU ; Young Jin SONG ; Seoyon YANG ; Hee Seung YANG ; Ji Sung YOO ; Jun-il YOO ; Seung Don YOO ; Kyoung Hyo CHOI ; Jae-Young LIM
Annals of Rehabilitation Medicine 2021;45(3):225-259
Objective:
The incidence of hip fractures is increasing worldwide with the aging population, causing a challenge to healthcare systems due to the associated morbidities and high risk of mortality. After hip fractures in frail geriatric patients, existing comorbidities worsen and new complications are prone to occur. Comprehensive rehabilitation is essential for promoting physical function recovery and minimizing complications, which can be achieved through a multidisciplinary approach. Recommendations are required to assist healthcare providers in making decisions on rehabilitation post-surgery. Clinical practice guidelines regarding rehabilitation (physical and occupational therapies) and management of comorbidities/complications in the postoperative phase of hip fractures have not been developed. This guideline aimed to provide evidence-based recommendations for various treatment items required for proper recovery after hip fracture surgeries. Methods Reflecting the complex perspectives associated with rehabilitation post-hip surgeries, 15 key questions (KQs) reflecting the complex perspectives associated with post-hip surgery rehabilitation were categorized into four areas: multidisciplinary, rehabilitation, community-care, and comorbidities/complications. Relevant literature from four databases (PubMed, EMBASE, Cochrane Library, and KoreaMed) was searched for articles published up to February 2020. The evidence level and recommended grade were determined according to the grade of recommendation assessment, development, and evaluation method. Results A multidisciplinary approach, progressive resistance exercises, and balance training are strongly recommended. Early ambulation, weigh-bearing exercises, activities of daily living training, community-level rehabilitation, management of comorbidities/complication prevention, and nutritional support were also suggested. This multidisciplinary approach reduced the total healthcare cost.
Conclusion
This guideline presents comprehensive recommendations for the rehabilitation of adult patients after hip fracture surgery.
6.Clinical Practice Guideline for Postoperative Rehabilitation in Older Patients With Hip Fractures
Kyunghoon MIN ; Jaewon BEOM ; Bo Ryun KIM ; Sang Yoon LEE ; Goo Joo LEE ; Jung Hwan LEE ; Seung Yeol LEE ; Sun Jae WON ; Sangwoo AHN ; Heui Je BANG ; Yonghan CHA ; Min Cheol CHANG ; Jung-Yeon CHOI ; Jong Geol DO ; Kyung Hee DO ; Jae-Young HAN ; Il-Young JANG ; Youri JIN ; Dong Hwan KIM ; Du Hwan KIM ; In Jong KIM ; Myung Chul KIM ; Won KIM ; Yun Jung LEE ; In Seok LEE ; In-Sik LEE ; JungSoo LEE ; Chang-Hyung LEE ; Seong Hoon LIM ; Donghwi PARK ; Jung Hyun PARK ; Myungsook PARK ; Yongsoon PARK ; Ju Seok RYU ; Young Jin SONG ; Seoyon YANG ; Hee Seung YANG ; Ji Sung YOO ; Jun-il YOO ; Seung Don YOO ; Kyoung Hyo CHOI ; Jae-Young LIM
Annals of Rehabilitation Medicine 2021;45(3):225-259
Objective:
The incidence of hip fractures is increasing worldwide with the aging population, causing a challenge to healthcare systems due to the associated morbidities and high risk of mortality. After hip fractures in frail geriatric patients, existing comorbidities worsen and new complications are prone to occur. Comprehensive rehabilitation is essential for promoting physical function recovery and minimizing complications, which can be achieved through a multidisciplinary approach. Recommendations are required to assist healthcare providers in making decisions on rehabilitation post-surgery. Clinical practice guidelines regarding rehabilitation (physical and occupational therapies) and management of comorbidities/complications in the postoperative phase of hip fractures have not been developed. This guideline aimed to provide evidence-based recommendations for various treatment items required for proper recovery after hip fracture surgeries. Methods Reflecting the complex perspectives associated with rehabilitation post-hip surgeries, 15 key questions (KQs) reflecting the complex perspectives associated with post-hip surgery rehabilitation were categorized into four areas: multidisciplinary, rehabilitation, community-care, and comorbidities/complications. Relevant literature from four databases (PubMed, EMBASE, Cochrane Library, and KoreaMed) was searched for articles published up to February 2020. The evidence level and recommended grade were determined according to the grade of recommendation assessment, development, and evaluation method. Results A multidisciplinary approach, progressive resistance exercises, and balance training are strongly recommended. Early ambulation, weigh-bearing exercises, activities of daily living training, community-level rehabilitation, management of comorbidities/complication prevention, and nutritional support were also suggested. This multidisciplinary approach reduced the total healthcare cost.
Conclusion
This guideline presents comprehensive recommendations for the rehabilitation of adult patients after hip fracture surgery.
7.The clinical and economic burden of community-onset complicated skin and skin structure infections in Korea
Yong Kyun CHO ; Heung Jeong WOO ; Shin Woo KIM ; In-Gyu BAE ; Young Goo SONG ; Hee Jin CHEONG ; Hyuck LEE ; Sang Hoon HAN ; Hee Jung CHOI ; Chisook MOON ; Seong Yeol RYU ; Jian HUR ; Ja Cob LEE ; Yu Mi JO ; Young Joo KIM
The Korean Journal of Internal Medicine 2020;35(6):1497-1506
Background/Aims:
To investigate epidemiologic characteristics, clinical and economic burdens, and factors associated with mortality in complicated skin and skin structure infection (cSSSI) patients in Korea.
Methods:
A retrospective, observational, nationwide study was conducted between April to July 2012 at 14 tertiary-hospitals in Korea. Eligible patients were hospitalized adults with community acquired cSSSI, who underwent surgical intervention and completed treatment between November 2009 and October 2011. Data on demography, clinical characteristics, outcomes and medical resource utilization were collected through medical record review. Direct medical costs were calculated by multiplying quantities of resources utilized by each unit price in Korea.
Results:
Of 473 patients enrolled, 449 patients (except 24 patients with no record on surgical intervention) were eligible for analysis. Microbiological testing was performed on 66.1% of patients and 8.2% had multiple pathogens. Among culture confirmed pathogens (n = 297 patients, 340 episodes), 76.2% were gram-positive (Staphylococcus aureus; 41.2%) and 23.8% were gram-negative. The median duration of hospital stay was 16 days. Among treated patients, 3.3% experienced recurrence and 4.2% died in-hospital. The mean direct medical costs amounted to $4,195/ person, with the greatest expenses for hospitalization and antibiotics. The in-hospital mortality and total medical costs were higher in combined antibiotics therapy than monotherapy (p < 0.05). Charlson’s comorbidity index ≥ 3, standardized early warning scoring ≥ 4, sub-fascia infections and combined initial therapy, were all found to be associated with higher mortality.
Conclusions
Korean patients with community-onset cSSSI suffer from considerable clinical and economic burden. Efforts should be made to reduce this burden through appropriate initial treatment.
8.Molecular Epidemiology of Ciprofloxacin-Resistant Escherichia coli Isolated from Community-Acquired Urinary Tract Infections in Korea
Bongyoung KIM ; Mi-Ran SEO ; Jieun KIM ; Yeonjae KIM ; Seong-Heon WIE ; Moran KI ; Yong Kyun CHO ; Seungkwan LIM ; Jin Seo LEE ; Ki Tae KWON ; Hyuck LEE ; Hee Jin CHEONG ; Dae Won PARK ; Seong Yeol RYU ; Moon-Hyun CHUNG ; Hyunjoo PAI
Infection and Chemotherapy 2020;52(2):194-203
Background:
Escherichia coli is the predominant causative pathogen for community-acquired urinary tract infections (UTIs), and the increase in fluoroquinolone-resistant E. coli is of great concern in Korea. The objectives of this study were to investigate the genotypic characteristics and molecular epidemiology of ciprofloxacin-resistant (CIP-R) E. coli isolated from community-acquired UTIs in Korea.
Materials and Methods:
E. coli samples isolated from the blood or urine were collected from patients with community-acquired acute pyelonephritis aged 15 years and more who were admitted to 12 Korean hospitals from 1st April 2010 to 29th February 2012. Phylogenetic typing, multilocus sequence typing, and molecular characterization of β-lactamase and plasmidmediated quinolone resistance determinants were performed for CIP-R E. coli isolates.
Results:
A total of 569 E. coli isolates were collected, and 122 (21.4%) isolates were CIP-R isolates. The most prevalent sequence type (ST) was ST131 (28.7%, 35/122), followed by ST393 (14.7%, 18/122), ST1193 (13.1%, 16/122), ST38 (9.0%, 11/122), and ST405 (8.2%, 10/122). The antimicrobial resistance rates of ST131 to cefepime (22.9%, 8/35), ST38 to gentamicin (100%, 11/11), and ST405 to cefotaxime (66.7%, 6/9) were significantly higher than the resistance rates of all other STs combined. Notably, 40% (4/10) of ST405 clones produced extendedspectrum β-lactamases and were co-resistant to trimethoprim/sulfamethoxazole. aac(6′)-1b-cr (20%, 7/35) and CTX-M-14 (40%, 4/10) were more frequently observed in ST131 and ST405 compared with other clones, respectively.
Conclusions
Among the CIP-R uropathogenic E. coli isolates in this study, ST131, ST38, and ST405 were specifically associated with antimicrobial resistance.
9.Unusual Presentation of Subcutaneous Phaeohyphomycosis by Alternaria alternate
Ji Yeon LEE ; Miri HYUN ; Hyun Ah KIM ; Seong Yeol RYU
Annals of Dermatology 2019;31(5):563-566
The Alternaria species are dematiaceous fungi. Human infection due to dematiaceous fungi is uncommon. Most reported cases of alternariosis have occurred in patients with immunodeficiency. The majority of cases were solid-organ transplantation recipients. Cutaneous alternariosis lesions are usually asymptomatic solitary nodules, plaques of ulcers or subcutaneous cysts. Here we report a case of a 77-year-old female who presented with hemorrhagic skin necrosis in right arm that had developed from hemorrhagic bullae. Her prior medical history included iatrogenic Cushing's syndrome, hypertension, interstitial lung disease and congestive heart failure. Following administration of itraconazole, her lesions improved.
Aged
;
Alternaria
;
Alternariosis
;
Arm
;
Cushing Syndrome
;
Female
;
Fungi
;
Heart Failure
;
Humans
;
Hypertension
;
Itraconazole
;
Lung Diseases, Interstitial
;
Necrosis
;
Phaeohyphomycosis
;
Skin
;
Ulcer
10.Comparison of Escherichia coli and Klebsiella pneumoniae Acute Pyelonephritis in Korean Patients
Miri HYUN ; Ji Yeon LEE ; Hyun ah KIM ; Seong Yeol RYU
Infection and Chemotherapy 2019;51(2):130-141
BACKGROUND:
Escherichia coli and Klebsiella pneumoniae are two of the most common causes of urinary tract infection. The purpose of this study was to compare clinical characteristics and antimicrobial susceptibility of acute pyelonephritis (APN) between E. coli and K. pneumoniae.
MATERIALS AND METHODS:
We retrospectively reviewed medical records of patients with APN due to E. coli and K. pneumoniae between February 2014 and October 2017.
RESULTS:
A total 329 patients were enrolled; 258 cases of E. coli and 71 cases of K. pneumoniae. Among them, 219 cases were categorized into community-onset APN; 194 cases of E. coli and 25 cases of K. pneumoniae, and 110 patients were categorized into healthcare-associated APN; 64 cases of E. coli and 46 cases of K. pneumoniae. Catheter-associated APN was more frequently observed in K. pneumoniae in both community-onset and healthcare-associated APN. Neurogenic bladder, obstructive uropathy, urinary tract stone, bacteremia, and severe APN were more related to E. coli in healthcare-associated APN. In multivariate analysis, urinary catheter was more associated with K. pneumoniae (odds ratio [OR] 9.643, 95% confidence intervals [CI] 4.919-18.904, P = 0.001) and neurogenic bladder was more associated with E. coli (OR 3.765, 95% CI 1.112-12.772, P = 0.033). Extended-spectrum β-lactamase (ESBL) production was observed in 29.0% of E. coli in community-onset APN. Among ESBL, antimicrobial susceptibility of piperacillin/tazobactam was significantly higher in E. coli and ciprofloxacin was significantly higher in K. pneumoniae.
CONCLUSION
K. pneumoniae were more associated with urinary catheter while E. coli tended to be more associated with urogenital problems. ESBL positivity showed no significance in healthcare-associated APN. In community-onset APN, ESBL producing E. coli was more observed than K. pneumoniae.

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