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1.
Norio Itokawa Masanori Atsukawa Akihito Tsubota Noritomo Shimada Hidenori Toyoda Koichi Takaguchi Atsushi Hiraoka Tomonori Senoh Mai Koeda Yuji Yoshida Tomomi Okubo Taeang Arai Korenobu Hayama Ai Nakagawa-Iwashita Chisa Kondo Katsuhiko Iwakiri 《Internal medicine (Tokyo, Japan)》2021,60(4):507
Objective Pegylated-interferon monotherapy is the standard treatment for patients with chronic hepatitis B; however, the factors associated with its therapeutic effects remain unclear. Methods Patients with chronic hepatitis B were treated with pegylated interferon α-2a for 48 weeks. We evaluated the kinetics of hepatitis B surface antigen (HBsAg) during treatment and follow-up periods and the factors associated with an HBsAg response (defined as a change in HBsAg of ≥-1 log IU/mL from baseline). Results The study population comprised 50 patients. The median baseline levels of hepatitis B virus DNA and HBsAg were 5.00 and 3.40 log IU/mL. The median values of HBsAg reduction from baseline were -0.44 (n=48), -0.41 (n=40), and -0.68 (n=11) log IU/mL at the end of treatment and at 48 and 144 weeks post-treatment, respectively. The rates of HBsAg response were 24.0% and 22.5% at the end of treatment and at 48 weeks post-treatment, respectively. A multivariate analysis identified HBsAg <3.00 log IU/mL as an independent baseline factor contributing to the HBsAg response at the end of treatment and 48 weeks post-treatment (p=1.07×10-2 and 4.42×10-2, respectively). There were significant differences in the reduction of the HBsAg levels at 12 weeks of treatment and in the incidence of serum ALT increase during treatment between patients with and without an HBsAg response. Conclusion These findings suggest that the baseline HBsAg level, HBsAg kinetics at 12 weeks of treatment, and ALT increase during treatment are important factors contributing to the HBsAg response in pegylated interferon α-2a monotherapy for patients with chronic hepatitis B. 相似文献
2.
Kazuko Sakai Takayuki Takahama Mototsugu Shimokawa Koichi Azuma Masayuki Takeda Terufumi Kato Haruko Daga Isamu Okamoto Hiroaki Akamatsu Shunsuke Teraoka Akira Ono Tatsuo Ohira Toshihide Yokoyama Nobuyuki Yamamoto Kazuhiko Nakagawa Kazuto Nishio 《Molecular oncology》2021,15(1):126
The WJOG8815L phase II clinical study involves patients with non‐small cell lung cancer (NSCLC) that harbored the EGFR T790M mutation, which confers resistance to EGFR tyrosine kinase inhibitors (TKIs). The purpose of this study was to assess the predictive value of monitoring EGFR genomic alterations in circulating tumor DNA (ctDNA) from patients with NSCLC that undergo treatment with the third‐generation EGFR‐TKI osimertinib. Plasma samples of 52 patients harboring the EGFR T790M mutation were obtained pretreatment (Pre), on day 1 of treatment cycle 4 (C4) or cycle 9 (C9), and at diagnosis of disease progression or treatment discontinuation (PD/stop). CtDNA was screened for EGFR‐TKI‐sensitizing mutations, the EGFR T790M mutation, and other genomic alterations using the cobas EGFR Mutation Test v2 (cobas), droplet digital PCR (ddPCR), and targeted deep sequencing. Analysis of the sensitizing—and T790M—EGFR mutant fractions (MFs) was used to determine tumor mutational burden. Both MFs were found to decrease during treatment, whereas rebound of the sensitizing EGFR MF was observed at PD/stop, suggesting that osimertinib targeted both T790M mutation‐positive tumors and tumors with sensitizing EGFR mutations. Significant differences in the response rates and progression‐free survival were observed between the sensitizing EGFR MF‐high and sensitizing EGFR MF‐low groups (cutoff: median) at C4. In conclusion, ctDNA monitoring for sensitizing EGFR mutations at C4 is suitable for predicting the treatment outcomes in NSCLC patients receiving osimertinib (Clinical Trial Registration No.: UMIN000022076).
Abbreviations
- CIs
- confidence intervals
- ctDNA
- circulating tumor DNA
- ddPCR
- droplet digital PCR
- EGFR
- epidermal growth factor receptor
- MFs
- mutant fractions
- NGS
- next‐generation sequencing
- NSCLC
- non‐small cell lung cancer
- ORR
- overall response rate
- OS
- overall survival
- PD
- progressive disease
- PFS
- progression‐free survival
- PR
- partial response
- SD
- stable disease
- TKI
- tyrosine kinase inhibitor
3.
4.
Mayuko Kinoshita Haruka Kaneko Lizu Liu Masashi Nagao Ryo Sadatsuki 《Modern rheumatology / the Japan Rheumatism Association》2019,29(1):157-164
Objectives: To examine the factors associated with increase in lumbar spine bone mineral density (LS-BMD) by bisphosphonates (BPs) with active vitamin D analog (aVD).Methods: Two independent postmenopausal osteoporotic patients treated by BPs with aVD for 24 months (Study 1: n?=?93, Study 2: n?=?99) were retrospectively analyzed.Results: In Study 1, LS-BMD of the patients significantly increased for 24 m (5.4%, p?.001). A multiple regression analysis among baseline characteristics revealed that serum calcium (sCa: 8.5–10.5?mg/dL) was associated with an increased LS-BMD by treatment (r2: 0.088, p?=?.02). While average sCa of the patients was 9.2?mg/dL before treatment, it increased time-dependently to 9.6?mg/dL for 24 m by treatment. As each patient had their LS-BMD five times during the study, there were four instances of %LS-BMD in each patient, resulting in 372 instances of %LS-BMD in Study 1. The smallest Akaike’s information criterion value for the most appropriate cut-off levels of sCa for %LS-BMD by treatment every 6 m was 9.3?mg/dL. The %LS-BMD by treatment for 6 m during 24 m period in patients with sCa ≥9.3?mg/dL (1.5%) was significantly higher than that in patients with sCa <9.3?mg/dL (0.8%, p?=?.038). The results of Study 2 were similar to those of Study 1, confirming the phenomena observed.Conclusion: sCa was associated with an increased LS-BMD by BPs with aVD. 相似文献
5.
Kensuke Kudou Hiroshi Saeki Yuichiro Nakashima Shun Sasaki Tomoko Jogo Kosuke Hirose Qingjiang Hu Yasuo Tsuda Koichi Kimura Ryota Nakanishi Nobuhide Kubo Koji Ando Eiji Oki Tetsuo Ikeda Yoshihiko Maehara 《American journal of surgery》2019,217(4):757-763
Background
There were few studies assessed the postoperative sarcopenia in patients with cancers. The objective of present study was to assess whether postoperative development of sarcopenia could predict a poor prognosis in patients with adenocarcinoma of esophagogastric junction, (AEG) and upper gastric cancer (UGC).Methods
Patients with AEG and UGC who were judged as non-sarcopenic before surgery were reassessed the presence of postoperative development of sarcopenia 6 months after surgery. Patients were divided into the development group or non-development group, and clinicopathological factors and prognosis between these two groups were analyzed.Results
The 5-year overall survival rates were significantly poorer in the development group than non-development group (68.0% vs. 92.6%, P?=?0.0118). Multivariate analyses showed that postoperative development of sarcopenia was an independent prognostic factor for poor overall survival (P?=?0.0237).Conclusions
Postoperative development of sarcopenia was associated with a poor prognosis in patients with AEG and UGC. 相似文献6.
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8.
Akiko Kaneshima Sayaka Yamaguchi Takuya Miyagi Yoshiyuki Kariya Tsuyoshi Awazawa Tokiko Ohshiro Nobuyuki Hyakuna Koichi Nakanishi Kenzo Takahashi 《The Journal of dermatology》2019,46(9):812-815
A 3‐month‐old boy developed small papules on his trunk. After the papules increased in number, the patient was diagnosed with Langerhans cell histiocytosis based on the pathological findings. He was referred to our department for further examination. Upon initial examination, the papules and nodules were scattered on his back, abdomen and lumbar region. Because he did not present with any organ involvement except the skin, he was diagnosed with single‐system and skin‐limited Langerhans cell histiocytosis. Skin rashes were treated with a topical steroid and started regressing 3 months after onset. All papules disappeared 6 months after onset. In this boy, the Langerhans cell histiocytosis tumor cells expressed phosphorylated extracellular signal‐regulated kinases. In Langerhans cell histiocytosis, BRAF V600E and other genes are known to mutate to act as driver mutations in stem cells of the myeloid dendritic cell lineage. Consequently, extracellular signal‐regulated kinases are continuously activated, which contributes to Langerhans cell histiocytosis carcinogenesis. 相似文献
9.
Yoshihiro Goto Takahiro Suzuki Yoko Suzuki Kazushi Anzawa Takashi Mochizuki Takashi Tamura Koichi Makimura Masahiro Aoshima Taisuke Ito Yoshiki Tokura 《The Journal of dermatology》2019,46(9):794-797
We report a case of kerion celsi due to Trichophyton tonsurans. An 18‐year‐old male student judo practitioner had alopecic patches, black dots and subcutaneous abscesses on the right temporal region. The damaged hair represented endothrix infection with T. tonsurans, as assessed by mycological examinations. He was treated with oral itraconazole without any therapeutic effect, followed by terbinafine with good effect. A skin biopsy showed neutrophil, lymphocyte and histiocyte infiltration into the dermis and subcutaneous tissue with abscesses around a number of dilated hair follicles. Immunostaining showed that the expression level of human β‐defensin 2 (HBD‐2) was decreased in the epidermis of the alopecic and adjacent skin. Because interleukin (IL)‐17A generally induces HBD‐2 production by epidermal keratinocytes, we also immunohistochemically investigated IL‐17A expression. Unexpectedly, many IL‐17A‐bearing cells were found around destructed hair follicles, indicating that IL‐17A expression was not attenuated, but rather increased in the skin lesion. Our case suggests that IL‐17A‐upregulated antimicrobial peptide expression is disordered in kerion celsi, and severe inflammation with IL‐17A may cause tissue damage and resultant scar. 相似文献
10.