1.Real-world efficacy and safety of bevacizumab single-maintenance therapy following platinum-paclitaxel chemotherapy plus bevacizumab in patients with advanced cervical cancer
Saki KOTAKA ; Eiji KONDO ; Yosuke KAWAI ; Kota OKAMOTO ; Yasuyuki KISHIGAMI ; Takaharu YAMAWAKI ; Kenji NAGAO ; Toru HIRATA ; Shiro SUZUKI
Journal of Gynecologic Oncology 2023;34(5):e60-
Objective:
Bevacizumab maintenance therapy following platinum-based combination chemotherapy for metastatic, recurrent, or persistent cervical cancer is not recommended as standard therapy. This pilot study aimed to evaluate the efficacy and safety of bevacizumab maintenance therapy and the contribution of the platinum-free interval to the efficacy of subsequent chemotherapy for advanced cervical cancer.
Methods:
We retrospectively identified 115 patients with metastatic, recurrent, or persistent cervical cancer treated with platinum-paclitaxel chemotherapy plus bevacizumab at 7 institutions between 2015 and 2020. The primary endpoints were overall survival (OS) and progression-free survival (PFS) in patients who received bevacizumab maintenance therapy and those who did not. We also analyzed the adverse events associated with bevacizumab and survival time from the start of subsequent chemotherapy in both groups.
Results:
Following platinum-paclitaxel plus bevacizumab chemotherapy, 34 patients received bevacizumab maintenance therapy and 81 patients did not. Of the 115 patients, 56 received chemotherapy for subsequent relapse. Although bevacizumab maintenance therapy prolonged PFS (median of 16.0 months vs. 9.0 months, p=0.041), significant differences were not observed in OS (p=0.374). Furthermore, bevacizumab maintenance therapy did not prolong OS and PFS after the start of subsequent chemotherapy (p=0.663 and p=0.136, respectively). Bevacizumab maintenance therapy significantly increased hypertension (p=0.035) and proteinuria (p=0.005) but did not cause complications leading to death.
Conclusion
Bevacizumab single-maintenance therapy for advanced cervical cancer can be considered in selected cases, such as those with acceptable bevacizumab-related side effects. The outcomes of our study will likely contribute to decision-making regarding practical treatment strategies.
2.Incidence and Characteristics of Clinical L5–S1 Adjacent Segment Degeneration after L5 Floating Lumbar Fusion: A Multicenter Study
Norihiko TAKEGAMI ; Koji AKEDA ; Junichi YAMADA ; Takao IMANISHI ; Tatsuhiko FUJIWARA ; Tetsushi KONDO ; Kenji TAKEGAMI ; Akihiro SUDO
Asian Spine Journal 2023;17(1):109-117
Methods:
In total, 306 patients who received L5 floating lumbar fusion were included in this study. Clinical L5–S1 ASD was defined as newly developed radiculopathy in relation to the L5–S1 segment. Patients’ medical records and imaging data were retrospectively analyzed. The risk factors for clinical ASD were assessed by an inverse probability of treatment weighting-adjusted logistic regression analysis.
Results:
Clinical L5–S1 ASD occurred in 17 patients (5.6%). The mean onset time of L5–S1 ASD was 12.9±7.5 months after the primary surgery. Among these patients, 10 (58.8%) presented with clinical L5–S1 ASD within 12 months. Reoperation was performed in three patients (1.0%). The severity of L5–S1 disk degeneration did not affect the occurrence of L5–S1 ASD. Logistic regression analysis showed that the number of fusion levels was a significant risk factor for clinical L5–S1 ASD.
Conclusions
The incidence and characteristics of clinical L5–S1 ASD after L5 floating lumbar fusion were retrospectively investigated. This study established that the number of fusion levels was a significant candidate factor for clinical L5–S1 ASD. Careful clinical follow-up is deemed necessary after L5 floating lumbar fusion surgery, especially for patients who received multiple-level fusions.
3.Efficacy and safety of filgotinib as induction and maintenance therapy for Japanese patients with moderately to severely active ulcerative colitis: a post-hoc analysis of the phase 2b/3 SELECTION trial
Toshifumi HIBI ; Satoshi MOTOYA ; Tadakazu HISAMATSU ; Fumihito HIRAI ; Kenji WATANABE ; Katsuyoshi MATSUOKA ; Masayuki SARUTA ; Taku KOBAYASHI ; Brian G FEAGAN ; Chantal TASSET ; Robin BESUYEN ; Chohee YUN ; Gerald CRANS ; Jie ZHANG ; Akira KONDO ; Mamoru WATANABE
Intestinal Research 2023;21(1):110-125
Background/Aims:
The safety and efficacy of filgotinib, a once-daily oral Janus kinase 1 preferential inhibitor, were evaluated in Japanese patients with ulcerative colitis (UC) in the phase 2b/3 SELECTION trial.
Methods:
SELECTION (NCT02914522) was a randomized, placebo-controlled trial comprising 2 induction studies and a maintenance study. Adults with moderately to severely active UC were randomized in induction study A (biologic-naïve) or B (biologic-experienced) to receive filgotinib 200 mg, 100 mg, or placebo once daily for 11 weeks. Patients in clinical remission or Mayo Clinic score response at week 10 entered the 47-week maintenance study. Efficacy and safety outcomes were assessed in Japanese patients enrolled in Japan.
Results:
Overall, 37 and 72 Japanese patients were enrolled in Japan in induction studies A and B, respectively, and 54 entered the maintenance study. Numerically higher proportions of filgotinib 200 mg-treated than placebo-treated patients achieved clinical remission in induction study A (4/15 [26.7%] vs. 0/6 [0%]) and the maintenance study (5/20 [25.0%] vs. 0/9 [0%]), but not induction study B (1/29 [3.4%] vs. 1/14 [7.1%]). Both doses were well tolerated, and no new safety signals were noted. Herpes zoster was reported in 1 filgotinib 200 mg-treated patient in each of induction study A (2.3%, 1/44) and the maintenance study (5.0%, 1/20).
Conclusions
These data, alongside those of the overall SELECTION population, suggest the potential of filgotinib 200 mg as a viable treatment option for Japanese patients with UC. Owing to small patient numbers, data should be interpreted cautiously.
4.Nutrition Improvement of Pediatric Cancer Patients through Hospital Meals and Nutrition education in Cambodia
Ayana UEDA ; Natsuki KAWAI ; Maiko KOJIRO ; Sho SATO ; Shusei WADA ; Kenji SHINKAI ; Eriko KONDO
Journal of International Health 2023;38(1):1-11
Introduction NPO Japan Heart opened a children’s medical center in Cambodia in 2018 to treat pediatric cancer. In many public hospitals in Cambodia, patients’ meals must be prepared by their families with little knowledge about hygiene and nutrition, so patients may not always receive sufficient nutrition for their treatment. We considered a hygienic and nutritious diet essential for effective pediatric cancer treatment. Therefore, the “Japan Heart Children’s Medical Center Meal Project” was launched. The objectives of this study were as follows; (1) to describe that patients receive hygienic and nutritious meals during their hospitalization and after discharge, (2) to measure the effects of providing hospital meals and nutrition education by Cambodian staff who are not qualified dietitians, and to clarify the changes in the nutritional status of pediatric cancer patients as a result of these activities.Methods The target group was pediatric cancer patients and their families. Japanese dietitians and chefs conducted study sessions, created menu standards based on the Minimum Dietary Diversity (MDD) , and trained local staff to provide meals and nutrition education. To provide hospital meals, local staff conducted hygiene management, prepared menus based on standards, and measured eating rates. They also provided nutrition education to the patients and their families, and connected survey before and after education. Nutrition assessment was conducted based on WHO Growth Chart BMI for age by measuring height and weight.Results The MDD achievement rate for the menu increased from 72% to 100% (after intervention 1week-2 week (January, 2020)), and the eating rate increased from 45.9% to a maximum of 80.5% (April, 2020-January, 2022). Surveys before and after nutrition education showed that 89.1% of patient families improved their knowledge and awareness. Height and weight were assessed by BMI, and the percentage of patients with ≤−2SD decreased from 28.1% at admission to 15.9% at discharge. Conclusions In Cambodia where there is no dietitian system, it is important to do activities with contents that is feasible for local staff who have never studied nutrition. In order to further support treatment from the nutritional aspect, it is desirable to develop nutritional human resources in Cambodia.
5.Segmental Arteries and Veins at Higher Lumbar Levels Can Intersect the Adjacent Caudal Intervertebral Disc in the Anterior Part of the Spinal Column: A Cadaveric Analysis
Kiyoshi YAGI ; Nobuyuki SUZUKI ; Jun MIZUTANI ; Kenji KATO ; Akira KONDO ; Yuya WASEDA ; Yuta GOTO ; Hideki MURAKAMI
Asian Spine Journal 2022;16(1):1-8
Methods:
Five formalin-embalmed human cadavers were used. We assessed the proportion of segmental arteries and veins that intersected the IVD in the L2–L5 range and their course on the anterior part of the spinal column.
Results:
The segmental arteries and veins commonly intersect the anterior part of the IVD (artery, 28.1%; vein, 42.1%). Seven of 10 (70%) segmental arteries at L2 intersected the IVD, but only one artery intersected the IVD at L3 and L4. The proportions of segmental veins that intersected the IVD were 60%, 50%, and 16.7% at L2, L3, and L4, respectively.
Conclusions
The segmental arteries and veins frequently intersect the IVD in the anterior part of the spinal column. Therefore, it is necessary to consider these individual anatomical features to prevent vascular damage during lateral lumbar interbody fusion surgery.
7.p38 Mitogen-Activated Protein Kinase Is Involved in Interleukin-6 Secretion from Human Ligamentum Flavum–Derived Cells Stimulated by Tumor Necrosis Factor-α
Kiyoshi YAGI ; Yuta GOTO ; Kenji KATO ; Nobuyuki SUZUKI ; Akira KONDO ; Yuya WASEDA ; Jun MIZUTANI ; Yohei KAWAGUCHI ; Yuji JOYO ; Yuko WAGURI-NAGAYA ; Hideki MURAKAMI
Asian Spine Journal 2021;15(6):713-720
Methods:
HFCs were obtained from patients with LSS who underwent surgery. HFCs were stimulated by tumor necrosis factor-α (TNF-α) and a p38 MAP kinase inhibitor, SB203580. Phosphorylation of the p38 MAP kinase was analyzed by western blotting. The concentration of interleukin-6 (IL-6) in the conditioned medium was measured by enzyme-linked immunoassay and IL-6 messenger RNA expression levels were determined by real-time polymerase chain reaction.
Results:
TNF-α induced the phosphorylation of p38 MAP kinase in a time-dependent manner, which was suppressed by the p38 MAP kinase inhibitor, SB203580. TNF-α also stimulated IL-6 release in both a time- and dose-dependent manner. On its own, SB203580 did not stimulate IL-6 secretion from HFCs; however, it dramatically suppressed the degree of IL-6 release stimulated by TNF-α from HFCs.
Conclusions
This is the first report suggesting that TNF-α stimulates the gene expression and protein secretion of IL-6 via p38 MAP kinase in HFCs. A noted association between tissue hypertrophy and inflammation suggests that the p38 MAP kinase inflammatory pathway may be a therapeutic molecular target for LSS.
8.Current Status and Issues of Education on Radiation Health Risk Science
Naoki MATSUDA ; Yoshishige URATA ; Masanobu KITAGAWA ; Masahiko AOKI ; Yoshio HOSOI ; Kenji NEMOTO ; Akira OHTSURU ; Tomonori ISOBE ; Hideyuki SAKURAI ; Kiyoshi MIYAKAWA ; Ryoichi YOSHIMURA ; Reiko KANDA ; Takashi KONDO ; Shunichi TAKEDA ; Takeshi TOUDO ; Kazuo AWAI ; Teruhisa TSUZUKI ; Takeshi NAGAYASU
Medical Education 2019;50(6):581-587
In accordance with the new model-core-curriculum for medical education, the current status of education about the science of radiation health was surveyed in all medical schools in Japan. Among the four learning points related to the “Biological effects of radiation and radiation hazards” , about half of the schools covered issues on “radiation and human body” and the “effect of medical radiation exposure” in one, or less than one, 60-minutes class, but did not touch on “radiation risk communication” and “radiological disaster medicine” . A significant deviation of human resources was also observed between schools. Learning tools such as presentation files and video content were preferred as education support materials. Therefore, development and distribution of the learning tools, especially in “radiation risk communication” and “radiological disaster medicine” , may be a first step to promoting high-quality education on the science of radiation health risk in each school’s curriculum.
9.Comparison of the Perception between Pharmacy Students and Practicing Pharmacists in the Acquisition of Physical Assessment Skills
Toru OTORI ; Tomomi INOUE ; Koichi HOSOMI ; William FIGONI ; Manabu KITAKOJI ; Hiroko HACHIKEN ; Hiroyuki NAKAGAWA ; Keiko TAKASHIMA ; Hisami KONDO ; Tsugumi TAKADA ; Kenji MATSUYAMA ; Shozo NISHIDA
Japanese Journal of Social Pharmacy 2018;37(2):127-133
The expansion of home medical care and the growth in sales of OTC, coupled with Japan’s aging society and the need to reduce medical costs has broadened the role of the pharmacist to include physical assessment. In response, the Kindai University Faculty of Pharmacy, implemented the Physical Assessment Practical Training Course (PAPTC) to improve the physical assessment skills of pharmacy students and practicing pharmacists. In order to investigate pharmacy students’ and practicing pharmacists’ perceptions of PAPTC, a questionnaire using a five-part, forced- choice Lykert type scale was conducted. The results of the questionnaire were analyzed using factor analysis and cluster analysis. The total number of respondents was 456. Three hundred thirteen of the respondents were students, and 143 of the respondents were practicing pharmacists. Factor analysis revealed four factors which we titled, “Physical Assessment Skills”, “Physical Assessment Course”, “Pharmacist Jobs” and, “Knowledge Required by Pharmacist”. Subsequently, cluster analysis identified two distinct groups. Group A which constituted primarily of pharmacy students, and Group B which consisted primarily of practicing pharmacists. Each group displayed notable differences in perceptions related to PAPTC. These differences may be influenced by perceptions toward “skills” and/or “knowledge”. These findings suggest that in order to better address the motivational needs of the participants, PAPTC should be divided into two courses. One, for knowledge-based instruction, and other for skill-based practice.
10.Oxidized human serum albumin as a possible correlation factor for atherosclerosis in a rural Japanese population: the results of the Yakumo Study.
Ryosuke FUJII ; Jun UEYAMA ; Arisa AOI ; Naohiro ICHINO ; Keisuke OSAKABE ; Keiko SUGIMOTO ; Koji SUZUKI ; Nobuyuki HAMAJIMA ; Kenji WAKAI ; Takaaki KONDO
Environmental Health and Preventive Medicine 2018;23(1):1-1
BACKGROUND:
The effect of the redox state of human serum albumin (HSA) on the antioxidant properties of the entire body has been a focus of recent research. The usefulness of HSA redox state as a biomarker for reducing oxidative stress has been investigated in clinical settings; however, evidence for its significance as a health index in non-clinical settings is yet to be established. This study aimed to examine the associations between HSA redox state and the atherosclerotic indices of carotid intima-media thickness (IMT) and plaque formation in a rural Japanese population.
METHODS:
We conducted a cross-sectional study as part of a health check-up program in the rural area of Hokkaido, Japan, at the end of August 2013. A total of 281 residents (124 men and 157 women) were included in the final analysis. Lifestyle-related data were obtained through a self-reported questionnaire, and ultrasound examinations were performed to measure IMT and determine plaque formation. The high-performance liquid chromatography postcolumn bromocresol green method was used to separate HSA into human nonmercaptalbumin and human mercaptalbumin (HMA).
RESULTS:
We found a significant negative relationship between the fraction of HMA [f(HMA)] and IMT (standardized β = - 0.132, p = 0.03). Moreover, f(HMA) was significantly associated with plaque formation (p < 0.01) with an odds ratio of 0.89 (95% confidence interval, 0.81-0.97) for every 10% increment in f(HMA).
CONCLUSIONS
We found that the HSA redox state, as determined by f(HMA), was associated with atherosclerotic indices in Japanese subjects. These results suggest that the HSA redox state indicates the risk of developing atherosclerosis.
Adult
;
Aged
;
Aged, 80 and over
;
Atherosclerosis
;
epidemiology
;
etiology
;
Biomarkers
;
Carotid Intima-Media Thickness
;
statistics & numerical data
;
Cross-Sectional Studies
;
Female
;
Humans
;
Japan
;
epidemiology
;
Male
;
Middle Aged
;
Oxidation-Reduction
;
Risk Factors
;
Serum Albumin
;
metabolism
;
Serum Albumin, Human
;
metabolism


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