1.Association between Osteoporosis and Skeletal Muscle Mass in Men
Masaya MIZUTANI ; Yawara EGUCHI ; Toru TOYOGUCHI ; Sumihisa ORITA ; Kazuhide INAGE ; Yasuhiro SHIGA ; Satoshi MAKI ; Junichi NAKAMURA ; Shigeo HAGIWARA ; Yasuchika AOKI ; Masahiro INOUE ; Masao KODA ; Hiroshi TAKAHASHI ; Tsutomu AKAZAWA ; Seiji OHTORI
Asian Spine Journal 2024;18(1):73-78
Methods:
This study included 99 men (mean age, 74.9 years; range, 28–93 years) who visited Qiball Clinic for BMD and body composition examinations. The osteoporosis group consisted of 24 patients (mean age, 72.5 years; range, 44–92 years), and the control group consisted of 75 individuals (mean age, 74.9 years; range, 28–93 years). Whole-body skeletal muscle mass was measured using a bioelectrical impedance analyzer. BMD was measured by dual X-ray absorptiometry. Skin autofluorescence (SAF), a marker of dermal AGE accumulation, was measured using a spectroscope. Osteoporosis was defined as a bone density T score of –2.5 or less. Physical findings, skeletal muscle mass, BMD, grip strength, and SAF were compared between the osteoporosis and control groups.
Results:
The osteoporosis group had significantly lower trunk muscle mass (23.1 kg vs. 24.9 kg), lower leg muscle mass (14.4 kg vs. 13.0 kg), and skeletal mass index (7.1 kg/m2 vs. 6.7 kg/m2) than the control group (all p<0.05). Lower limb muscle mass was identified as a risk factor for osteoporosis in men (odds ratio, 0.64; p=0.03).
Conclusions
Conservative treatment of osteoporosis in men will require an effective approach that facilitates the maintenance or strengthening of skeletal muscle mass, including exercise therapy with a focus on lower extremities and nutritional supplementation.
2.Postoperative norepinephrine versus dopamine in patients undergoing noncardiac surgery: a propensity-matched analysis using a nationwide intensive care database
Yoshitaka AOKI ; Mikio NAKAJIMA ; Sho SUGIMURA ; Yasuhito SUZUKI ; Hiroshi MAKINO ; Yukako OBATA ; Matsuyuki DOI ; Yoshiki NAKAJIMA
Korean Journal of Anesthesiology 2023;76(5):481-489
Background:
Choosing catecholamines, such as norepinephrine and dopamine, for perioperative blood pressure control is essential for anesthesiologists and intensivists. However, studies specific to noncardiac surgery are limited. Therefore, we aimed to evaluate the effects of postoperative norepinephrine and dopamine on clinical outcomes in adult noncardiac surgery patients by analyzing a nationwide intensive care patient database.
Methods:
The Japanese Intensive care PAtient Database (JIPAD) was used for this multicenter retrospective study. Adult patients in the JIPAD who received norepinephrine or dopamine within 24 h after noncardiac surgery in 2018–2020 were included. We compared the norepinephrine and dopamine groups using a one-to-one propensity score matching analysis. The primary outcome was in-hospital mortality. Secondary outcomes were intensive care unit (ICU) mortality, hospital length of stay, and ICU length of stay.
Results:
A total of 6,236 eligible patients from 69 ICUs were allocated to the norepinephrine (n = 4,652) or dopamine (n = 1,584) group. Propensity score matching was used to create a matched cohort of 1,230 pairs. No differences in the in-hospital mortality was found between the two propensity score matched groups (risk difference: 0.41%, 95% CI [−1.15, 1.96], P = 0.608). Among the secondary outcomes, only the ICU length of stay was significantly shorter in the norepinephrine group than in the dopamine group (median length: 3 vs. 4 days, respectively; P < 0.001).
Conclusions
In adult patients after noncardiac surgery, norepinephrine was not associated with decreased mortality but was associated with a shorter ICU length of stay than dopamine.
3.Evaluation of CD4+ cells infiltration as a prognostic factor in cervical intraepithelial neoplasia 2
Guanliang CHEN ; Takashi IWATA ; Masaki SUGAWARA ; Hiroshi NISHIO ; Yuki KATOH ; Iwao KUKIMOTO ; Daisuke AOKI
Journal of Gynecologic Oncology 2023;34(1):e2-
Objective:
To identify candidate predictors for the prognosis of cervical intraepithelial neoplasia 2 (CIN2) lesions and evaluate the prognostic value of the local immune response.
Methods:
One hundred fifteen CIN2 patients were enrolled. The percentage of p16-, minichromosome maintenance complex component 2- or apolipoprotein B mRNA editing enzyme catalytic subunit 3G (APOBEC3G)-positive cells was determined immunohistochemically. Tumor-infiltrating lymphocytes (TILs) in intertumoral lesions were scored using an automated system. CIN3 disease progression and regression rates were estimated by the Kaplan–Meier method. A case-control study was conducted to screen CIN2 prognostic factors in 10 regression and 10 progression patients. Selected factors were examined in a cohort study to determine their prognostic value for CIN2.
Results:
Among all participants, the cumulative progression and regression rates at 60 months were 0.477 and 0.510, respectively. In the case-control study, p16- and APOBEC3G-positive cells were higher in the progression group (p=0.043, p=0.023). Additionally, CD4+ cell infiltration was enhanced in the regression group (p=0.023). The cohort study revealed a significantly increased progression rate in patients with elevated p16-positive cells (p<0.001), and increased CD4+ TIL infiltration was associated with better regression (p=0.011). Kaplan–Meier analysis according to human papillomavirus (HPV) positivity revealed a greater CIN3 development risk in HPV16-positive patients than in HPV16-negative cases. Finally, multivariate analysis identified HPV16 infection and CD4+ TIL infiltration as independent prognostic factors in CIN2 regression.
Conclusion
CD4+ TIL infiltration in intertumoral lesions was related with CIN2 regression. Our findings suggest CD4+ TIL infiltration may be useful for the triage of CIN2 patients.
4.An attempt to establish real-world databases of poly(ADP-ribose) polymerase inhibitors for advanced or recurrent epithelial ovarian cancer: the Japanese Gynecologic Oncology Group
Muneaki SHIMADA ; Kosuke YOSHIHARA ; Terumi TANIGAWA ; Hiroyuki NOMURA ; Junzo HAMANISHI ; Satoe FUJIWARA ; Hiroshi TANABE ; Hiroaki KAJIYAMA ; Masaki MANDAI ; Daisuke AOKI ; Takayuki ENOMOTO ; Aikou OKAMOTO
Journal of Gynecologic Oncology 2023;34(3):e62-
The development of new treatments for gynecological malignancies has been conducted mainly through collaborative international phase III trials led by the United States and Europe. The survival outcomes of many gynecological malignancies have greatly improved as a result. Recent large-scale genome-wide association studies have revealed that drug efficacy and adverse event profiles are not always uniform. Thus, it is important to validate new treatment options in each country to safely and efficiently provide newly developed treatment options to patients with gynecological malignancies. The Japanese Gynecologic Oncology Group (JGOG) is conducting 5 cohort studies (JGOG 3026, 3027, 3028, 3030, and 3031) to establish real-world data (RWD) of poly(ADP-ribose) polymerase (PARP) inhibitor use in patients with advanced or recurrent epithelial ovarian cancer. The RWD constructed will be used to provide newly developed PARP inhibitors for women with advanced or recurrent ovarian cancer in a safer and more efficient manner as well as to develop further treatment options. In 2022, The JGOG, Korean Gynecologic Oncology Group, Chinese Gynecologic Cancer Society, and Taiwanese Gynecologic Oncology Group established the East Asian Gynecologic Oncology Trial Group to collaborate with East Asian countries in clinical research on gynecologic malignancies and disseminate new knowledge on gynecologic malignancies from Asia. The JGOG will conduct a collaborative integrated analysis of the RWD generated from Asian countries and disseminate real-world clinical knowledge regarding new treatment options that have been clinically implemented.
5.Improvements in Intractable Lumbar and LowerExtremity Symptoms after Systemic Administration of Tocilizumab, an Anti-interleukin-6 Receptor Antibody
Takeshi SAINOH ; Takeshi SAINOH ; Sumihisa ORITA ; Sumihisa ORITA ; Masayuki MIYAGI ; Masayuki MIYAGI ; Miyako SUZUKI-NARITA ; Miyako SUZUKI-NARITA ; Yoshihiro SAKUMA ; Yoshihiro SAKUMA ; Yasuhiro OIKAWA ; Yasuhiro OIKAWA ; Go KUBOTA ; Go KUBOTA ; Jun SATO ; Jun SATO ; Yasuhiro SHIGA ; Yasuhiro SHIGA ; Kazuki FUJIMOTO ; Kazuki FUJIMOTO ; Yawara EGUCHI ; Yawara EGUCHI ; Masao KODA ; Masao KODA ; Yasuchika AOKI ; Yasuchika AOKI ; Tsutomu AKAZAWA ; Tsutomu AKAZAWA ; Takeo FURUYA ; Takeo FURUYA ; Junichi NAKAMURA ; Junichi NAKAMURA ; Hiroshi TAKAHASHI ; Hiroshi TAKAHASHI ; Satoshi MAKI ; Satoshi MAKI ; Masahiro INOUE ; Masahiro INOUE ; Hideyuki KINOSHITA ; Hideyuki KINOSHITA ; Masaki NORIMOTO ; Masaki NORIMOTO ; Takashi SATO ; Takashi SATO ; Masashi SATO ; Masashi SATO ; Masahiro SUZUKI ; Masahiro SUZUKI ; Keigo ENOMOTO ; Keigo ENOMOTO ; Hiromitsu TAKAOKA ; Hiromitsu TAKAOKA ; Norichika MIZUKI ; Norichika MIZUKI ; Takashi HOZUMI ; Takashi HOZUMI ; Ryuto TSUCHIYA ; Ryuto TSUCHIYA ; Geundong KIM ; Geundong KIM ; Takuma OTAGIRI ; Takuma OTAGIRI ; Tomohito MUKAIHATA ; Tomohito MUKAIHATA ; Takahisa HISHIYA ; Takahisa HISHIYA ; Seiji OHTORI ; Seiji OHTORI ; Kazuhide INAGE ; Kazuhide INAGE
Asian Spine Journal 2022;16(1):99-106
Methods:
This prospective, single-arm study included 11 patients (eight men; mean age, 62.7 years) with ≥3-months’ chronic pain history due to lumbar disease. Subcutaneous TCZ injections were administered twice, at a 2-week interval. We evaluated low back pain, leg pain, and leg numbness using numeric rating scales and the Oswestry Disability Index (ODI; baseline and 6 months postinjection); serum IL-6 and tumor necrosis factor-α levels (baseline and 1 month postinjection); and clinical adverse events.
Results:
Intractable symptoms reduced after TCZ administration. Low back pain improved for 6 months. Improvements in leg pain and numbness peaked at 4 and 1 month, respectively. Improvements in ODI were significant at 1 month and peaked at 4 months. Serum IL-6 was increased at 1 month. IL-6 responders (i.e., patients with IL-6 increases >10 pg/mL) showed particularly significant improvements in leg pain at 2 weeks, 1 month, and 2 months compared with nonresponders. We observed no apparent adverse events.
Conclusions
Systemic TCZ administration improved symptoms effectively for 6 months, with peak improvements at 1–4 months and no adverse events. Changing serum IL-6 levels correlated with leg pain improvements; further studies are warranted to elucidate the mechanistic connections between lumbar disorders and inflammatory cytokines.
6.Usefulness of Simultaneous Magnetic Resonance Neurography and Apparent T2 Mapping for the Diagnosis of Cervical Radiculopathy
Keigo ENOMOTO ; Yawara EGUCHI ; Takashi SATO ; Masaki NORIMOTO ; Masahiro INOUE ; Atsuya WATANABE ; Takayuki SAKAI ; Masami YONEYAMA ; Yasuchika AOKI ; Sumihisa ORITA ; Miyako NARITA ; Kazuhide INAGE ; Yasuhiro SHIGA ; Tomotaka UMIMURA ; Masashi SATO ; Masahiro SUZUKI ; Hiromitsu TAKAOKA ; Norichika MIZUKI ; Geundong KIM ; Takashi HOZUMI ; Naoya HIROSAWA ; Takeo FURUYA ; Satoshi MAKI ; Junichi NAKAMURA ; Shigeo HAGIWARA ; Masao KODA ; Tsutomu AKAZAWA ; Hiroshi TAKAHASHI ; Kazuhisa TAKAHASHI ; Seiji OHTORI
Asian Spine Journal 2022;16(1):47-55
Methods:
A total of 14 patients with unilateral radicular symptoms and five healthy subjects were subjected to simultaneous apparent T2 mapping and neurography with nerve-sheath signal increased with inked rest-tissue rapid acquisition of relaxation enhancement signaling (SHINKEI-Quant) using a 3-Tesla magnetic resonance imaging. The Visual Analog Scale (VAS) score for neck pain and upper arm pain was used to evaluate clinical symptoms. T2 relaxation times of the cervical dorsal root ganglia of the brachial plexus were measured bilaterally from C4 to C8 in patients with radicular symptoms and from C5 to C8 in healthy controls. The T2 ratio was calculated as the affected side to unaffected side.
Results:
When comparing nerve roots bilaterally at each spinal level, no significant differences in T2 relaxation times were found between patients and healthy subjects. However, T2 relaxation times of nerve roots in the patients with unilateral radicular symptoms were significantly prolonged on the involved side compared with the uninvolved side (p<0.05). The VAS score for upper arm pain was not significantly correlated with the T2 relaxation times, but was positively correlated with the T2 ratio.
Conclusions
In patients with cervical radiculopathy, the SHINKEI-Quant technique can be used to quantitatively evaluate the compressed cervical nerve roots. The VAS score for upper arm pain was positively correlated with the T2 ratio. This suggests that the SHINKEI-Quant is a potential tool for the diagnosis of cervical nerve entrapment.
7.TP53 variants in p53 signatures and the clonality of STICs in RRSO samples
Tomoko AKAHANE ; Kenta MASUDA ; Akira HIRASAWA ; Yusuke KOBAYASHI ; Arisa UEKI ; Miho KAWAIDA ; Kumiko MISU ; Kohei NAKAMURA ; Shimpei NAGAI ; Tatsuyuki CHIYODA ; Wataru YAMAGAMI ; Shigenori HAYASHI ; Fumio KATAOKA ; Kouji BANNO ; Kokichi SUGANO ; Hajime OKITA ; Kenjiro KOSAKI ; Hiroshi NISHIHARA ; Daisuke AOKI
Journal of Gynecologic Oncology 2022;33(4):e50-
Objective:
Precursor lesions may be identified in fallopian tube tissue after risk-reducing salpingo-oophorectomy (RRSO) in patients with pathogenic variants of BRCA1/2. Serous tubal intraepithelial carcinoma (STIC) is considered a precursor of high-grade serous carcinoma, whereas the significance of the p53 signature remains unclear. In this study, we investigated the relationship between the p53 signature and the risk of ovarian cancer.
Methods:
We analyzed the clinicopathological findings and conducted DNA sequencing for TP53 variants of p53 signatures and STIC lesions isolated using laser capture microdissection in 13 patients with pathogenic variants of BRCA1/2 who underwent RRSO and 17 control patients with the benign gynecologic disease.
Results:
TP53 pathogenic variants were detected significantly higher in RRSO group than control (p<0.001). No difference in the frequency of p53 signatures were observed between groups (53.8% vs 29.4%; p=0.17). TP53 sequencing and next-generation sequencing analysis in a patient with STIC and occult cancer revealed 2 TP53 mutations causing different p53 staining for STICs and another TP53 mutation shared between STIC and occult cancer.
Conclusion
The sequence analysis for TP53 revealed 2 types of p53 signatures, one with a risk of progression to STIC and ovarian cancer with pathological variants in TP53 and the other with a low risk of progression without pathological variants in TP53 as seen in control.
8.Parent Artery Complex Coil Protection for Side-Branched Wide-Neck Aneurysms
Keisuke SATO ; Hiroshi AOKI ; Shinya JINGUJI ; Hiroki SETO ; Tsutomu KOBAYASHI
Neurointervention 2022;17(2):115-120
This study aimed to validate the usefulness of parent artery complex coil protection for the treatment of wide-neck, side-branched, and ruptured aneurysms. A microcatheter was first introduced into the aneurysmal sac, and another microcatheter was introduced into the parent artery or near the orifice of the branch artery. A framing coil was deployed partially from the first microcatheter, and a protection coil was deployed from the second microcatheter to prevent protrusion of the first framing coil to the parent artery and side branches. After the first framing coil insertion, the protection coil was withdrawn to confirm the stability of the framing coil and blood flow. The procedures with this technique were successful for 3 patients. Parent artery complex coil protection can be an effective and safe coil embolization technique for the preservation of parent and side branch arteries and an alternative method for emergent ruptured cases.
9.Clinical practice guidelines for the management of biliary tract cancers 2019: the 3rd English edition
Masato NAGINO ; Satoshi HIRANO ; Hideyuki YOSHITOMI ; Taku AOKI ; Katsuhiko UESAKA ; Michiaki UNNO ; Tomoki EBATA ; Masaru KONISHI ; Keiji SANO ; Kazuaki SHIMADA ; Hiroaki SHIMIZU ; Ryota HIGUCHI ; Toshifumi WAKAI ; Hiroyuki ISAYAMA ; Takuji OKUSAKA ; Toshio TSUYUGUCHI ; Yoshiki HIROOKA ; Junji FURUSE ; Hiroyuki MAGUCHI ; Kojiro SUZUKI ; Hideya YAMAZAKI ; Hiroshi KIJIMA ; Akio YANAGISAWA ; Masahiro YOSHIDA ; Yukihiro YOKOYAMA ; Takashi MIZUNO ; Itaru ENDO
Chinese Journal of Digestive Surgery 2021;20(4):359-375
The Japanese Society of Hepato-Biliary-Pancreatic Surgery launched the clinical practice guidelines for the management of biliary tract cancers (cholangiocarcinoma, gallbladder cancer, and ampullary cancer) in 2007, then published the 2nd version in 2014. In this 3rd version, clinical questions (CQs) were proposed on six topics. The recommendation, grade for recommendation, and statement for each CQ were discussed and finalized by an evidence-based approach. Recommendations were graded as grade 1 (strong) or grade 2 (weak) according to the concepts of the grading of recommendations assessment, development, and evaluation system. The 31 CQs covered the six topics: (1) prophylactic treatment, (2) diagnosis, (3) biliary drainage, (4) surgical treatment, (5) chemotherapy, and (6) radiation therapy. In the 31 CQs, 14 recommendations were rated strong and 14 recommendations weak. The remaining three CQs had no recommendation. Each CQ includes a statement of how the recommendations were graded. This latest guideline provides recommendations for important clinical aspects based on evidence. Future collaboration with the cancer registry will be key for assessing the guidelines and establishing new evidence.
10.Time-Course Changes in Bone Metabolism Markers and Density in Patients with Osteoporosis Treated with Romosozumab: A Multicenter Retrospective Study
Kazuhide INAGE ; Sumihisa ORITA ; Yawara EGUCHI ; Yasuhiro SHIGA ; Masao KODA ; Yasuchika AOKI ; Toshiaki KOTANI ; Tsutomu AKAZAWA ; Takeo FURUYA ; Junichi NAKAMURA ; Hiroshi TAKAHASHI ; Miyako SUZUKI-NARITA ; Satoshi MAKI ; Shigeo HAGIWARA ; Masahiro INOUE ; Masaki NORIMOTO ; Hideyuki KINOSHITA ; Takashi SATO ; Masashi SATO ; Keigo ENOMOTO ; Hiromitsu TAKAOKA ; Norichika MIZUKI ; Takashi HOZUMI ; Ryuto TSUCHIYA ; Geundong KIM ; Takuma OTAGIRI ; Tomohito MUKAIHATA ; Takahisa HISHIYA ; Seiji OHTORI
Yonsei Medical Journal 2021;62(9):829-835
Purpose:
In this multicenter retrospective observational study, we examined the early effects of romosozumab in patients with severe osteoporosis in terms of time-course changes in bone metabolism marker, improvement in bone density, and adverse effects.
Materials and Methods:
Patients with severe osteoporosis were included. We investigated the progress of TRACP 5b and P1NP before and 1–2 months after the administration of romosozumab. We also investigated the bone density of lumbar spine, femoral neck, and the entire femur, measured by the DXA method, before and 5–7 months after the administration of romosozumab.
Results:
A total of 70 patients (7 males and 63 females, age 75.0±3.6 years) participated in this study. Significant improvements in TRACP 5b and P1NP levels were observed before and 1–2 months after romosozumab administration. The average bone density of lumbar spine, femoral neck, and the entire femur were measured before and 5–7 months after romosozumab administration;and a significant increase only observed in the lumbar spine.
Conclusion
Consistent with the findings of previous clinical studies, romosozumab has both bone formation-enhancing and bone resorption effects (dual effect). In addition, romosozumab also demonstrated improvement in bone density from the early phase after the administration, though the result was only seen in the lumbar spine.

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