1.Establishment of a Multilocus Sequence Typing Scheme for Pasteurella canis Using Isolates from Infected Humans and Diseased Companion Animals
Haruno YOSHIDA ; Jae-Seok KIM ; Takahiro MAEDA ; Mieko GOTO ; Yuzo TSUYUKI ; Kenichi SHIZUNO ; Takashi TAKAHASHI
Annals of Laboratory Medicine 2025;45(3):300-311
Background:
Multilocus sequence typing (MLST) is well-established for Pasteurella multocida but remains undeveloped for Pasteurella canis. We established MLST for P. canis using isolates from humans and companion animals in Japan and Korea to gain insights into its population biology.
Methods:
We analyzed 39 and 22 isolates from companion animals and humans, respectively. We selected seven housekeeping genes—adk, aroA, deoD, gdhA, g6pd, mdh, and pgi—used in P. multocida MLST. Primer pairs for PCR amplification and sequencing were designed based on conserved sites in 10 whole-genome sequences. We determined frag-ment sequences, variable sites, allelic profiles, and sequence types (STs) of each isolate. A phylogenetic tree of concatenated sequences was constructed using the goeBURST algo-rithm to identify STs and clonal complexes (CCs). ompAM, encoding outer membrane protein A, was genotyped for molecular characterization.
Results:
The sequenced fragment lengths and allele numbers of the seven genes wereHallym University College of Medicine, 424, 451, 483, 439, 429, 419, and 440 bp and 16, 13, 15, 18, 22, 19, and 18, respec-tively. ST1–ST47, including CC2, CC10, CC18, CC31, and CC33, were diversely distributed among the isolates from different hosts/countries. In the seven-gene phylogenetic tree, apart from P. multocida, all isolates clustered together. goeBURST diagrams revealed di-verse ST distributions among different hosts (animal/human) and countries (Japan/Ko-rea/others). We found clusters 1–4 in ompA genotyping, indicating that MLST discrimination is higher than ompA typing discrimination.
Conclusions
We established MLST for P. canis isolates from humans and companion ani-This is an Open Access article distributed under mals in Japan and Korea, thereby providing a robust tool for population biology studies.
3.Comparative Genomic Analysis of Staphylococcal Cassette Chromosome mec Type V Staphylococcus aureus Strains and Estimation of the Emergence of SCCmec V Clinical Isolates in Korea
Takashi TAKAHASHI ; Hyaekang KIM ; Han-Sung KIM ; Hyun Soo KIM ; Wonkeun SONG ; Jae-Seok KIM
Annals of Laboratory Medicine 2024;44(1):47-55
Background:
Staphylococcal cassette chromosome mec type V (SCCmec V) methicillin-resistant Staphylococcus aureus (MRSA) has been recovered from patients and livestock.Using comparative genomic analyses, we evaluated the phylogenetic emergence of SCCmec V after transmission from overseas donor strains to Korean recipient strains.
Methods:
Sixty-three complete MRSA SCCmec V genomes (including six Korean clinical isolates) were used to construct a phylogenetic tree. Single-nucleotide polymorphisms were identified using Snippy, and a maximum-likelihood-based phylogenetic tree was constructed using RAxML. The possible emergence of the most common ancestor was estimated using BactDating. To estimate mecA horizontal gene transfer (HGT) events, Rangerdtl was applied to 818 SCCmec V strains using publicly available whole-genome data.
Results:
The phylogenetic tree showed five major clades. German strains formed a major clade; their possible origin was traced to the 1980s. The emergence of Korean SCCmec V clinical isolates was traced to 2000–2010. mecA HGT events in Staphylococcus spp. were identified in seven strains. P7 (Hong Kong outbreak strain) served as the donor strain for two Korean sequence type (ST) 59 strains, whereas the other five recipient strains emerged from different SCCmec V donors.
Conclusions
Most Korean SCCmec V strains may have emerged during 2000–2010. A unique MRSA SCCmec V strain, ST72 (a Korean common type of community-associated MRSA), was also identified. The genomic dynamics of this clone with a zoonotic background should be monitored to accurately understand MRSA evolution.
4.Prevention of symptomatic pulmonary embolism for gynecologic malignancies with preoperative asymptomatic venous thromboembolism: GOTIC-VTE trial
Yoshifumi TAKAHASHI ; Hiroyuki FUJIWARA ; Kouji YAMAMOTO ; Masashi TAKANO ; Morikazu MIYAMOTO ; Kosei HASEGAWA ; Maiko MIWA ; Toyomi SATOH ; Hiroya ITAGAKI ; Takashi HIRAKAWA ; Mayuyo MORI-UCHINO ; Tomonori NAGAI ; Yoshinobu HAMADA ; Soichi YAMASHITA ; Hiroko YANO ; Tomoyasu KATO ; Keiichi FUJIWARA ; Mitsuaki SUZUKI ; On behalf of the GOTIC-VTE Trial Investigators
Journal of Gynecologic Oncology 2024;35(4):e37-
Objective:
In Japan, perioperative prophylaxis of pulmonary embolism (PE) in gynecologic cancer patients with preoperative asymptomatic venous thromboembolism (VTE) has not been well established yet. The GOTIC-VTE trial was a prospective, multi-center, single-arm clinical trial to investigate the prevention of postoperative symptomatic PE onset by seamless anticoagulant therapy from the preoperative period to 4 weeks after surgery instead of using intermittent pneumatic compression.
Methods:
Anticoagulant therapy was started immediately after asymptomatic VTE diagnosis and stopped preoperatively according to the rules of each institution. Unfractionated heparin administration was resumed within 12 hours postoperatively, and this was followed by the switch to low-molecular-weight heparin and subsequently, edoxaban; this cycle was continued for 28 days. Primary outcome was the occurrence of symptomatic PE in 28 days postoperatively. Secondary outcomes were the incidence of VTE-related events in 28 days and 6 months postoperatively and protocol-related adverse events.
Results:
Between February 2018 and September 2020, 99 patients were enrolled; of these, 82patients were assessed as the full analysis set, including 58 for ovarian cancer, fallopian tube, or peritoneal cancer; 21 for endometrial cancer; and 3 for cervical cancer. No symptomatic PE was observed within 28 days postoperatively; two patients had bleeding events (major bleeding and clinically relevant nonmajor bleeding) and three had grade 3 adverse events (increased alanine transaminase, aspartate aminotransferase, or gamma-glutamyl transferase).
Conclusion
The multifaceted perioperative management for gynecologic malignancies with asymptomatic VTE effectively prevented postoperative symptomatic PE.Trial Registration: JRCT Identifier: jRCTs031180124
5.Lenvatinib and pembrolizumab versus platinum doublet chemotherapy as second-line therapy for advanced or recurrent endometrial cancer
Yutaka YONEOKA ; Tsukuru AMANO ; Akimasa TAKAHASHI ; Hiroki NISHIMURA ; Mari DEGUCHI ; Hiroyuki YAMANAKA ; Yuji TANAKA ; Shunichiro TSUJI ; Takashi MURAKAMI
Obstetrics & Gynecology Science 2024;67(6):534-540
Objective:
There is no consensus on whether platinum doublet chemotherapy or lenvatinib and pembrolizumab (LEN/PEM) is superior for advanced or recurrent endometrial cancer. Thus, this study aimed to compare the prognosis and adverse events in patients with advanced or recurrent endometrial cancer treated with platinum doublet chemotherapy or LEN/PEM.
Methods:
We retrospectively reviewed the medical records of patients who received platinum doublet chemotherapy or LEN/PEM at our institution for advanced or recurrent endometrial cancer and had a history of platinum-based chemotherapy between January 2013 and August 2023.
Results:
During the study period, 11 regimens were identified in the platinum doublet chemotherapy group, and 11 regimens were identified in the LEN/PEM group. The objective response rates of the platinum doublet chemotherapy and LEN/ PEM groups were 36.4% and 54.5% (P=0.67), respectively. The 6-month progression-free survival (PFS) rates of the platinum doublet chemotherapy and LEN/PEM groups were 27.3% (95% confidence interval [CI], 13.8%-40.7%) and 70.0% (95% CI, 55.5%-84.5%), respectively. The differences were significant between the two groups. Multivariate analyses of histology, prior lines of chemotherapy, platinum-free intervals, and regimens revealed that the LEN/PEM group had significantly better PFS rates.
Conclusion
Treatment with LEN/PEM resulted in significantly longer PFS than that of treatment with platinum doublet chemotherapy in patients with advanced and recurrent endometrial cancer. However, further large-scale studies are required to validate these findings.
6.Prevention of symptomatic pulmonary embolism for gynecologic malignancies with preoperative asymptomatic venous thromboembolism: GOTIC-VTE trial
Yoshifumi TAKAHASHI ; Hiroyuki FUJIWARA ; Kouji YAMAMOTO ; Masashi TAKANO ; Morikazu MIYAMOTO ; Kosei HASEGAWA ; Maiko MIWA ; Toyomi SATOH ; Hiroya ITAGAKI ; Takashi HIRAKAWA ; Mayuyo MORI-UCHINO ; Tomonori NAGAI ; Yoshinobu HAMADA ; Soichi YAMASHITA ; Hiroko YANO ; Tomoyasu KATO ; Keiichi FUJIWARA ; Mitsuaki SUZUKI ; On behalf of the GOTIC-VTE Trial Investigators
Journal of Gynecologic Oncology 2024;35(4):e37-
Objective:
In Japan, perioperative prophylaxis of pulmonary embolism (PE) in gynecologic cancer patients with preoperative asymptomatic venous thromboembolism (VTE) has not been well established yet. The GOTIC-VTE trial was a prospective, multi-center, single-arm clinical trial to investigate the prevention of postoperative symptomatic PE onset by seamless anticoagulant therapy from the preoperative period to 4 weeks after surgery instead of using intermittent pneumatic compression.
Methods:
Anticoagulant therapy was started immediately after asymptomatic VTE diagnosis and stopped preoperatively according to the rules of each institution. Unfractionated heparin administration was resumed within 12 hours postoperatively, and this was followed by the switch to low-molecular-weight heparin and subsequently, edoxaban; this cycle was continued for 28 days. Primary outcome was the occurrence of symptomatic PE in 28 days postoperatively. Secondary outcomes were the incidence of VTE-related events in 28 days and 6 months postoperatively and protocol-related adverse events.
Results:
Between February 2018 and September 2020, 99 patients were enrolled; of these, 82patients were assessed as the full analysis set, including 58 for ovarian cancer, fallopian tube, or peritoneal cancer; 21 for endometrial cancer; and 3 for cervical cancer. No symptomatic PE was observed within 28 days postoperatively; two patients had bleeding events (major bleeding and clinically relevant nonmajor bleeding) and three had grade 3 adverse events (increased alanine transaminase, aspartate aminotransferase, or gamma-glutamyl transferase).
Conclusion
The multifaceted perioperative management for gynecologic malignancies with asymptomatic VTE effectively prevented postoperative symptomatic PE.Trial Registration: JRCT Identifier: jRCTs031180124
7.Lenvatinib and pembrolizumab versus platinum doublet chemotherapy as second-line therapy for advanced or recurrent endometrial cancer
Yutaka YONEOKA ; Tsukuru AMANO ; Akimasa TAKAHASHI ; Hiroki NISHIMURA ; Mari DEGUCHI ; Hiroyuki YAMANAKA ; Yuji TANAKA ; Shunichiro TSUJI ; Takashi MURAKAMI
Obstetrics & Gynecology Science 2024;67(6):534-540
Objective:
There is no consensus on whether platinum doublet chemotherapy or lenvatinib and pembrolizumab (LEN/PEM) is superior for advanced or recurrent endometrial cancer. Thus, this study aimed to compare the prognosis and adverse events in patients with advanced or recurrent endometrial cancer treated with platinum doublet chemotherapy or LEN/PEM.
Methods:
We retrospectively reviewed the medical records of patients who received platinum doublet chemotherapy or LEN/PEM at our institution for advanced or recurrent endometrial cancer and had a history of platinum-based chemotherapy between January 2013 and August 2023.
Results:
During the study period, 11 regimens were identified in the platinum doublet chemotherapy group, and 11 regimens were identified in the LEN/PEM group. The objective response rates of the platinum doublet chemotherapy and LEN/ PEM groups were 36.4% and 54.5% (P=0.67), respectively. The 6-month progression-free survival (PFS) rates of the platinum doublet chemotherapy and LEN/PEM groups were 27.3% (95% confidence interval [CI], 13.8%-40.7%) and 70.0% (95% CI, 55.5%-84.5%), respectively. The differences were significant between the two groups. Multivariate analyses of histology, prior lines of chemotherapy, platinum-free intervals, and regimens revealed that the LEN/PEM group had significantly better PFS rates.
Conclusion
Treatment with LEN/PEM resulted in significantly longer PFS than that of treatment with platinum doublet chemotherapy in patients with advanced and recurrent endometrial cancer. However, further large-scale studies are required to validate these findings.
8.Lenvatinib and pembrolizumab versus platinum doublet chemotherapy as second-line therapy for advanced or recurrent endometrial cancer
Yutaka YONEOKA ; Tsukuru AMANO ; Akimasa TAKAHASHI ; Hiroki NISHIMURA ; Mari DEGUCHI ; Hiroyuki YAMANAKA ; Yuji TANAKA ; Shunichiro TSUJI ; Takashi MURAKAMI
Obstetrics & Gynecology Science 2024;67(6):534-540
Objective:
There is no consensus on whether platinum doublet chemotherapy or lenvatinib and pembrolizumab (LEN/PEM) is superior for advanced or recurrent endometrial cancer. Thus, this study aimed to compare the prognosis and adverse events in patients with advanced or recurrent endometrial cancer treated with platinum doublet chemotherapy or LEN/PEM.
Methods:
We retrospectively reviewed the medical records of patients who received platinum doublet chemotherapy or LEN/PEM at our institution for advanced or recurrent endometrial cancer and had a history of platinum-based chemotherapy between January 2013 and August 2023.
Results:
During the study period, 11 regimens were identified in the platinum doublet chemotherapy group, and 11 regimens were identified in the LEN/PEM group. The objective response rates of the platinum doublet chemotherapy and LEN/ PEM groups were 36.4% and 54.5% (P=0.67), respectively. The 6-month progression-free survival (PFS) rates of the platinum doublet chemotherapy and LEN/PEM groups were 27.3% (95% confidence interval [CI], 13.8%-40.7%) and 70.0% (95% CI, 55.5%-84.5%), respectively. The differences were significant between the two groups. Multivariate analyses of histology, prior lines of chemotherapy, platinum-free intervals, and regimens revealed that the LEN/PEM group had significantly better PFS rates.
Conclusion
Treatment with LEN/PEM resulted in significantly longer PFS than that of treatment with platinum doublet chemotherapy in patients with advanced and recurrent endometrial cancer. However, further large-scale studies are required to validate these findings.
9.Lenvatinib and pembrolizumab versus platinum doublet chemotherapy as second-line therapy for advanced or recurrent endometrial cancer
Yutaka YONEOKA ; Tsukuru AMANO ; Akimasa TAKAHASHI ; Hiroki NISHIMURA ; Mari DEGUCHI ; Hiroyuki YAMANAKA ; Yuji TANAKA ; Shunichiro TSUJI ; Takashi MURAKAMI
Obstetrics & Gynecology Science 2024;67(6):534-540
Objective:
There is no consensus on whether platinum doublet chemotherapy or lenvatinib and pembrolizumab (LEN/PEM) is superior for advanced or recurrent endometrial cancer. Thus, this study aimed to compare the prognosis and adverse events in patients with advanced or recurrent endometrial cancer treated with platinum doublet chemotherapy or LEN/PEM.
Methods:
We retrospectively reviewed the medical records of patients who received platinum doublet chemotherapy or LEN/PEM at our institution for advanced or recurrent endometrial cancer and had a history of platinum-based chemotherapy between January 2013 and August 2023.
Results:
During the study period, 11 regimens were identified in the platinum doublet chemotherapy group, and 11 regimens were identified in the LEN/PEM group. The objective response rates of the platinum doublet chemotherapy and LEN/ PEM groups were 36.4% and 54.5% (P=0.67), respectively. The 6-month progression-free survival (PFS) rates of the platinum doublet chemotherapy and LEN/PEM groups were 27.3% (95% confidence interval [CI], 13.8%-40.7%) and 70.0% (95% CI, 55.5%-84.5%), respectively. The differences were significant between the two groups. Multivariate analyses of histology, prior lines of chemotherapy, platinum-free intervals, and regimens revealed that the LEN/PEM group had significantly better PFS rates.
Conclusion
Treatment with LEN/PEM resulted in significantly longer PFS than that of treatment with platinum doublet chemotherapy in patients with advanced and recurrent endometrial cancer. However, further large-scale studies are required to validate these findings.
10.Prevention of symptomatic pulmonary embolism for gynecologic malignancies with preoperative asymptomatic venous thromboembolism: GOTIC-VTE trial
Yoshifumi TAKAHASHI ; Hiroyuki FUJIWARA ; Kouji YAMAMOTO ; Masashi TAKANO ; Morikazu MIYAMOTO ; Kosei HASEGAWA ; Maiko MIWA ; Toyomi SATOH ; Hiroya ITAGAKI ; Takashi HIRAKAWA ; Mayuyo MORI-UCHINO ; Tomonori NAGAI ; Yoshinobu HAMADA ; Soichi YAMASHITA ; Hiroko YANO ; Tomoyasu KATO ; Keiichi FUJIWARA ; Mitsuaki SUZUKI ; On behalf of the GOTIC-VTE Trial Investigators
Journal of Gynecologic Oncology 2024;35(4):e37-
Objective:
In Japan, perioperative prophylaxis of pulmonary embolism (PE) in gynecologic cancer patients with preoperative asymptomatic venous thromboembolism (VTE) has not been well established yet. The GOTIC-VTE trial was a prospective, multi-center, single-arm clinical trial to investigate the prevention of postoperative symptomatic PE onset by seamless anticoagulant therapy from the preoperative period to 4 weeks after surgery instead of using intermittent pneumatic compression.
Methods:
Anticoagulant therapy was started immediately after asymptomatic VTE diagnosis and stopped preoperatively according to the rules of each institution. Unfractionated heparin administration was resumed within 12 hours postoperatively, and this was followed by the switch to low-molecular-weight heparin and subsequently, edoxaban; this cycle was continued for 28 days. Primary outcome was the occurrence of symptomatic PE in 28 days postoperatively. Secondary outcomes were the incidence of VTE-related events in 28 days and 6 months postoperatively and protocol-related adverse events.
Results:
Between February 2018 and September 2020, 99 patients were enrolled; of these, 82patients were assessed as the full analysis set, including 58 for ovarian cancer, fallopian tube, or peritoneal cancer; 21 for endometrial cancer; and 3 for cervical cancer. No symptomatic PE was observed within 28 days postoperatively; two patients had bleeding events (major bleeding and clinically relevant nonmajor bleeding) and three had grade 3 adverse events (increased alanine transaminase, aspartate aminotransferase, or gamma-glutamyl transferase).
Conclusion
The multifaceted perioperative management for gynecologic malignancies with asymptomatic VTE effectively prevented postoperative symptomatic PE.Trial Registration: JRCT Identifier: jRCTs031180124

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