Papers - NAKASHIMA Hiroaki

Efficacy of Corticosteroid Addition to Selective Nerve Root Block for Lumbar Radiculopathy: A Multicenter Prospective Cohort Study Open Access

Ouchida Jun, Nakashima Hiroaki, Miyagi Masayuki, Inoue Gen, Nagata Keiji, Watanabe Kei, Terai Hidetomi, Yamato Yu, Nishida Norihiro, Suzuki Hidenori, Orita Sumihisa, Imagama Shiro, Miyakoshi Naohisa, Yamada Hiroshi, Hashizume Hiroshi, Matsuyama Yukihiro, Haro Hirotaka, Nakamura Masaya, Kaito Takashi, Yoshii Toshitaka, Project Committee of the Japanese Society for Spine Surgery and Related Research (JSSR)

Spine Surgery and Related Research   Vol. advpub ( 0 )   2026

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Language：English   Publisher：The Japanese Society for Spine Surgery and Related Research  

<p><b>Introduction:</b> The addition of corticosteroids to selective nerve root block (SNRB) is widely practiced for lumbar radiculopathy, yet robust evidence regarding its efficacy for functional outcomes remains limited. We evaluated whether adding corticosteroids to local anesthetic in SNRB relieves functional disability and improves quality of life in patients with lumbar radiculopathy.</p><p><b>Methods:</b> This multicenter, prospective cohort study enrolled 78 patients with single-level lumbar radiculopathy. Patients received fluoroscopy-guided SNRB with either corticosteroids (dexamethasone, betamethasone) plus 1% lidocaine (n = 64) or lidocaine alone (n = 14). The primary outcome was the Oswestry Disability Index (ODI) at 90 and 180 days. Secondary outcomes included visual analog scale (VAS) scores for leg pain, Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ), and minimal clinically important difference (MCID) achievement rates. Linear mixed-effects models were used for analysis.</p><p><b>Results:</b> The steroid group indicated significantly greater ODI improvement at 90 days (27.9 vs 47.1; mean difference, 19.2 points [95% confidence interval (CI), 6.8-31.6]; p = 0.002) and 180 days (29.0 vs 44.1; mean difference, 15.1 points [95% CI, 2.3-27.9]; p = 0.022), with large effect sizes (Cohen d >0.8). Significant improvements favoring corticosteroids were observed for VAS scores at 90 days (3.5 vs 5.7; p = 0.018) and 180 days (3.7 vs 5.9; p = 0.023) and multiple JOABPEQ domains. MCID achievement was significantly higher in the steroid group at 90 days (75.0% vs 33.3%; p = 0.043); the number needed to treat was 2.4. Adverse event rates were similar in the groups, and no serious adverse events occurred. Benefits plateaued between 90 and 180 days.</p><p><b>Conclusions:</b> Adding non-particulate corticosteroids to SNRB significantly relieved functional disability and pain and improved quality of life in patients with lumbar radiculopathy, with the most pronounced group differences occurring at 90 days and sustained through 180 days. Clinically, the 90-day timepoint is optimal for evaluating treatment success and determining the need for alternative treatments.</p>

DOI： 10.22603/ssrr.2025-0327

Open Access

CiNii Research

Cost-Effectiveness of Monotherapy versus Polypharmacy in Cervicobrachial Symptoms: A Nationwide Multicenter Analysis Open Access

Ito Sadayuki, Nakashima Hiroaki, Wakao Norimitsu, Furuya Takeo, Yoshii Toshitaka, Arima Hideyuki, Yamato Yu, Imagama Shiro, Imajo Yasuaki, Miyamoto Hiroshi, Inoue Gen, Miyagi Masayuki, Kanbara Shunsuke, Iizuka Yoichi, Chikuda Hirotaka, Watanabe Kei, Kobayashi Kazuyoshi, Tsushima Mikito, Miyazaki Masashi, Yagi Mitsuru, Suzuki Satoshi, Takahata Masahiko, Hongo Michio, Koda Masao, Nagata Keiji, Mori Kanji, Suzuki Akinobu, Kaito Takashi, Murotani Kenta, Miyakoshi Naohisa, Hashizume Hiroshi, Matsuyama Yukihiro, Kawakami Mamoru, Haro Hirotaka, The Project Committee of the Japanese Society for Spine Surgery and Related Research (JSSR)

Spine Surgery and Related Research   Vol. advpub ( 0 )   2026

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Language：English   Publisher：The Japanese Society for Spine Surgery and Related Research  

<p><b>Introduction: </b>Cervicobrachial symptoms are common causes of disability worldwide, yet the cost-effectiveness of combination therapy versus monotherapy remains unclear. In this nationwide multicenter study, we aimed to compare the economic value of multiple-drug therapy with that of monotherapy for cervicobrachial symptoms.</p><p><b>Methods: </b>This prospective observational study, conducted through the Japanese Society for Spine Surgery and Related Research, included 261 adults with cervicobrachial symptoms across 28 institutions (July 2020 to July 2022). Patients received monotherapy (n = 112) or multiple-drug therapy (n = 149) using five pre-specified agents: loxoprofen, celecoxib, acetaminophen, tramadol–acetaminophen, and pregabalin. The primary outcome was quality-adjusted life years (QALYs), calculated from monthly EuroQol 5-Dimension 5-Level assessments over six months. The secondary outcomes were drug costs and incremental cost-effectiveness ratios (ICERs), evaluated against Japan's reference threshold of ¥5,000,000 per QALY.</p><p><b>Results: </b>Mean QALY gains were similar between the monotherapy (0.00267 ± 0.00544) and multiple-drug therapy (0.00284 ± 0.00774) groups, with no statistically significant difference (p > 0.05). However, total drug costs were substantially higher with multiple-drug therapy (¥19,243 vs. ¥8,275). ICERs were more favorable for monotherapy (¥3,093,957/QALY) than for multiple-drug therapy (¥6,781,101/QALY). Among agents used as monotherapy, loxoprofen (¥744,409/QALY) and acetaminophen (¥781,293/QALY) showed the most favorable cost-effectiveness profiles, whereas tramadol–acetaminophen (¥6,370,451/QALY) and pregabalin (¥10,995,651/QALY) had the least favorable cost-effectiveness. Most QALY gains occurred during the first three months in both groups.</p><p><b>Conclusions: </b>Multiple-drug therapy approximately doubled pharmaceutical costs without providing additional QALY gains over six months. Monotherapy, particularly with non-steroidal anti-inflammatory drugs or acetaminophen, offers superior cost-effectiveness and should be prioritized as first-line treatment. These findings underscore the need for restraint in polypharmacy and provide real-world evidence to guide clinical decision-making and national healthcare policy.</p>

DOI： 10.22603/ssrr.2025-0304

Open Access

CiNii Research

Coherent Optical Transmitter Assessment Based on Noise Spectrum Measurement Using Probability-Maintained Notch Sequences Open Access

Li J., Ye T., Nakashima H., Hoshida T., Aoki Y., Tao Z., Mori Y., Hasegawa H.

Journal of Lightwave Technology     2026

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Publisher：Journal of Lightwave Technology  

A practical and accurate method for coherent optical transmitter assessment is crucial. Compared with conventional receiver-based methods which rely on expensive high-speed oscilloscopes and the specific receiver digital signal processing (DSP), spectrum analyzers offer a direct, robust, DSP independent and low-cost approach for transmitter assessment based on noise spectrum measurement in which the stimulus plays an important role. In this study, the probability-maintained (PM) notch sequence as a novel stimulus is proposed, whose probability density function is identical to that of a standard 64 array quadrature amplitude modulation signal and whose power spectral density has a deep notch of 25 dB. By applying the proposed PM notch sequence, the noise spectrum of the coherent optical transmitter can be measured using an optical spectrum analyzer, in which the regrowth frequency components in the notch region of a double-side PM notch indicate the nonlinear distortion while the spectrum difference between double-side and single-side PM notches reveals the in-phase/quadrature imbalance. The performance of the coherent optical transmitter is assessed by establishing an equivalent additive noise model based on the measured noise spectrum. The proposed method demonstrates an accuracy within 0.3 dB compared to the Q factor obtained by a coherent optical receiver.

DOI： 10.1109/JLT.2026.3670460

Open Access

Scopus

Dysfunctional variants of <i>ABCG2</i> create strong individual and population risks for progression of hyperuricemia: the potential for implementation of genome-personalized nursing Open Access

Nakayama, A; Hayano, K; Ueno, M; Miyoshi, Y; Nakashima, H; Shimizu, S; Hashimoto, I; Toba, M; Kikuchi, R; Takehana, N; Miura, M; Kawamura, Y; Toyoda, Y; Mizuno, T; Tanabe, R; Hamada, Y; Tamura, T; Kato, Y; Mitsuda, Y; Nakaoka, H; Yamamoto, K; Tsunoda, M; Shinomiya, N; Matsuo, H

HUMAN CELL   Vol. 39 ( 1 ) page： 22   2025.12

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Language：English   Publisher：Human Cell  

Gout, a common disease, develops after prolonged hyperuricemia with elevated serum uric acid (SUA) levels. Sex, overweight/obesity, heavy drinking, and aging all increase risk. Common dysfunctional variants (polymorphisms) in the ABCG2/BCRP gene are major genetic causes of gout/hyperuricemia. Early management would thus have potential benefits for public health. Several studies report the effectiveness of nurse-led care for gout management. We evaluate here the individual and population genetic effects of ABCG2 in 9244 Japanese study participants, in all of whom ABCG2 variants had a higher population-attributable fraction (PAF; approximately 30%) for progression of hyperuricemia than those for other typical environmental risk factors (overweight/obesity, heavy drinking, and aging). PAFs for aging in males and heavy drinking in females were not significant. All these factors also showed significant individual risk of increased SUA level, and ABCG2 variants had sufficient effect size to allow them to be converted into other environmental factors. To implement genome-personalized nursing, we then mapped onto the process a theoretical framework that is based on a psychological model from behavioral change theory. Because the present results for convertibility will improve the predictability of genetic effects, cognitive interventions by nurses based on individual variants could therefore encourage both inducements of behavioral change: efficacy expectations (self-efficacy) and outcome expectations. We conclude that the framework would function effectively based on cognitive interventions by nurses/paramedics. This theoretical framework has potential as a basis for implementing genome-personalized prevention, medicine and nursing of gout/hyperuricemia, and for optimizing nurse-led care.

DOI： 10.1007/s13577-025-01310-y

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PubMed

Unplanned reoperations due to implant-related complications in older versus non-older patients following adult spinal deformity surgery: A retrospective cohort study using a multi-center database.

Ouchida J, Nakashima H, Koshimizu H, Ito S, Segi N, Yamauchi I, Ohara T, Kanemura T, Shinjyo R, Imagama S

Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association     2025.12

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Language：English   Publisher：Journal of Orthopaedic Science  

Background: Adult spinal deformity (ASD) surgery involves instrumentation, which can lead to implant-related complications (IRCs) and unplanned returns to the operating room (UPROR). Older patients often have risk factors like osteoporosis and multiple comorbidities, but research on how age-related factors affect IRCs and UPROR across age groups is limited. The aim of this study was to evaluate the characteristics of UPROR due to IRCs between older and non-older patients following ASD surgery. Methods: A retrospective analysis of patients (≥20 years) who underwent spinal fusion with instrumentation from 2010 to 2019 based on a multi-center database. Medical records were reviewed to identify ASD diagnoses and details of IRCs, including UPROR timing. UPROR timing was classified as early (<30 days), intermediate (30–90 days), and late (>90 days) postoperatively. Patients were stratified into older (≥65 years) and non-older (<65 years) groups to compare the characteristics of UPROR between the groups. Results: IRCs occurred in 56 of 565 ASD cases (9.9 %) within 2 years postoperatively. UPROR was required in 38 patients (6.7 %), with implant breakage being the most frequent cause (23 cases), followed by screw malposition (14 cases). Screw-related complications predominated early, whereas implant breakage was most common in the late postoperative period. No significant differences in overall IRC or UPROR prevalence were observed between age groups. However, younger patients exhibited a higher rate of early UPROR (44.4 % vs. 20.0 % within 30 days). Conclusions: These findings highlight the distinct characteristics of IRCs between older and non-older patients, particularly in terms of UPROR timing. Understanding temporal patterns of these complications can inform surgical strategies and enhance patient outcomes by reducing UPROR.

DOI： 10.1016/j.jos.2025.12.001

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Skeletal muscle thickness and echo intensity may reflect the risk of malnutrition and physical dysfunction in acutely hospitalized older patients

Yoshiko, A; Nakashima, H; Nagae, M; Sakai, T; Matsui, Y; Umegaki, H

EUROPEAN GERIATRIC MEDICINE     2025.12

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Language：English   Publisher：European Geriatric Medicine  

Aim: This study aimed to investigate whether muscle quantity and quality are useful parameters for detecting sarcopenia-related malnutrition, decreased activity of daily living, and lower physical function in acutely hospitalized older patients. Findings: Malnutrition and lower physical function in hospitalized older patients may be detected using skeletal muscle thickness and echo intensity taken as parameters of muscle quantity and quality. Message: Skeletal muscle parameters obtained via ultrasound images provide important information for hospitalized older individuals.

DOI： 10.1007/s41999-025-01384-9

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A Multicenter Pivotal Study on the Artificial Intelligence System for Neoplastic Lesions Detection in Upper Gastrointestinal Endoscopy Open Access

Abe, S; Kitagawa, Y; Hatta, W; Maekita, T; Kato, M; Nagahara, A; Osawa, H; Dohi, O; Nakashima, H; Furukawa, K; Oka, S; Yokoyama, T; Ito, T; Oda, I

DIGESTIVE ENDOSCOPY   Vol. 37 ( 12 ) page： 1306 - 1314   2025.12

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Language：English   Publisher：Digestive Endoscopy  

Objectives: This pivotal study aimed to evaluate the performance of the CAD-EYE prototype in identifying esophageal squamous cell carcinoma (ESCC) and gastric neoplasm (GN) for regulatory approval of the Pharmaceuticals and Medical Devices Agency in Japan. Methods: This retrospective study utilized image datasets comprising 15 consecutive video frames captured using non-magnifying white-light imaging (WLI), blue laser/light imaging (BLI), and linked color imaging (LCI). The sensitivity and specificity of the CAD-EYE prototype for successful detection were calculated using the gold standard, which consists of image datasets of neoplastic lesions annotated by experienced endoscopists. Results: A total of 620, 679, and 682 ESCC datasets were analyzed in the WLI, BLI, and LCI groups, respectively. The sensitivity and specificity of ESCC detection were 85.9% [81.1%–90.6%] and 93.3% [90.8%–95.7%] in the WLI group, 97.6% [95.6%–99.7%] and 92.9% [90.6%–95.3%] in the BLI group, and 96.6% [94.2%–99.1%] and 93.2% [91.0%–95.5%] in the LCI group. The sensitivities for pT1a ESCC were 85.3%, 97.3%, and 97.2% in the WLI, BLI, and LCI groups, respectively. For GN, 841 WLI and 882 LCI datasets were analyzed. The sensitivity, specificity, and specificity in the detection flag of GN detection were 95.5% [92.8%–98.1%], 86.1%, and 85.4% [82.6%–88.2%] in the WLI group, and 93.9% [91.1%–96.7%], 94.4%, and 93.9% [92.0%–95.8%] in the LCI group, respectively. The sensitivities for pT1a early gastric cancer were 93.8% and 92.4% in the WLI and LCI groups, respectively. Conclusions: The CAD-EYE prototype demonstrated high sensitivity in detecting ESCC and GN, highlighting its potential as a promising tool for clinical applications.

DOI： 10.1111/den.70015

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PubMed

Efficacy and Safety of Mirogabalin as an Add-on to Nonsteroidal Anti-inflammatory Drugs for Neuropathic Pain Caused by Lumbar Disc Herniation: A Randomized Controlled Study (Miro-Hers). International journal Open Access

Hidenori Suzuki, Takashi Kaito, Hiroaki Nakashima, Hiroshi Takahashi, Shuhei Yamamoto, Shunsuke Tabata, Hiromitsu Toyoda

Pain and therapy   Vol. 14 ( 6 ) page： 1879 - 1898   2025.12

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Language：English   Publishing type：Research paper (scientific journal)  

INTRODUCTION: Lumbar disc herniation (LDH) is characterized by the displacement of intervertebral disc material with compression of adjacent nerve roots, leading to nociceptive and neuropathic pain in the lower limbs and lower back. The Miro-Hers study explored the efficacy and safety of mirogabalin add-on treatment in combination with nonsteroidal anti-inflammatory drugs (NSAIDs) compared with NSAIDs alone. We hypothesized that mirogabalin added on to NSAID therapy may reduce neuropathic pain due to LDH more than NSAIDs alone. METHODS: This was a multicenter, 8-week, randomized (1:1), open-label, parallel-group study conducted in Japan between March 2023 and September 2024. The study included participants with LDH diagnosed by magnetic resonance imaging who had inadequately controlled lower limb pain [numerical rating scale (NRS) score ≥ 4] despite NSAID treatment. The primary endpoint was the change in the NRS score for lower limb pain from baseline to Week 8. The secondary endpoints included quality of life, as assessed by the EuroQol 5 dimensions 5-level score (EQ-5D-5L), and NRS score for sleep disturbance. Safety endpoints included treatment-emergent adverse events (TEAEs) and adverse drug reactions (ADRs). RESULTS: Of the 182 participants screened and randomized, 90 in the mirogabalin add-on group and 89 in the NSAIDs alone group were included in the efficacy analysis. The reduction in NRS score for lower limb pain from baseline to Week 8 was significantly greater in the mirogabalin add-on group than in the NSAIDs alone group, with least squares mean changes of - 3.8 [95% confidence interval (CI): - 4.4, - 3.3] and - 2.2 (- 2.8, - 1.7), respectively [intergroup difference - 1.6 (- 2.4, - 0.8); P < 0.001]. EQ-5D-5L and NRS score for sleep disturbance both significantly improved over the study period with mirogabalin add-on treatment compared with NSAIDs alone [intergroup difference: 0.0653 (95% CI 0.0235, 0.1071); P = 0.002 and - 1.3 (- 1.9, - 0.7); P < 0.001, respectively]. No severe or serious TEAEs were observed. In the mirogabalin add-on group, ADRs were observed in 48.9% of participants, with somnolence (31.1%) and dizziness (18.9%) being the most common. CONCLUSION: The addition of mirogabalin to NSAIDs treatment significantly improved pain, quality of life, and sleep disturbance in patients with LDH, with no previously undocumented safety concerns identified. TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCTs061220102, registered 27/February/2023, https://jrct.mhlw.go.jp/en-latest-detail/jRCTs061220102 ).

DOI： 10.1007/s40122-025-00776-w

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PubMed

Periprosthetic femoral fractures following bipolar hemiarthroplasty: A descriptive multicenter study exploring associations with mortality and functional status. International journal

Koki Miyagawa, Yasuhiko Takegami, Hiroaki Nakashima, Kenichi Mishima, Kazuyoshi Kobayashi, Shiro Imagama

Injury   Vol. 56 ( 12 ) page： 112776 - 112776   2025.12

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BACKGROUND: Periprosthetic femoral fractures (PFFs) following bipolar hemiarthroplasty (BHA) represent a major complication in elderly patients with frailty and poor bone quality. However, limited data exist on the relationship between fracture type and clinical outcomes such as mortality and functional status in this population. METHODS: This multicenter retrospective study included 157 patients who sustained a PFF following BHA for femoral neck fractures between 2010 and 2023. Fractures were classified using the Vancouver classification. Clinical variables included age, sex, comorbidities (Charlson Comorbidity Index, CCI), dementia, coexisting fragility fractures, pre-injury mobility, and treatment modality. One-year mortality and postoperative functional outcomes were assessed using Kaplan-Meier survival analysis, the Parker Mobility Score (PMS), and Merle d'Aubigné score. RESULTS: The one-year mortality rate was 31.4 %. Higher mortality was significantly associated with CCI ≥2, dementia, and coexisting vertebral or pelvic fragility fractures (p < 0.05). In contrast, no significant differences in one-year mortality or postoperative functional scores were observed across Vancouver classification types or treatment methods. Functional recovery was similarly limited regardless of fracture type. CONCLUSION: In this multicenter retrospective cohort of patients with periprosthetic femoral fractures following bipolar hemiarthroplasty, the 1-year mortality was high at approximately 30 %. Outcomes appeared to be driven primarily by systemic factors-greater comorbidity burden, cognitive impairment, and concomitant fragility fractures. These findings underscore the importance of comprehensive geriatric assessment and proactive osteoporosis management in this vulnerable population.

DOI： 10.1016/j.injury.2025.112776

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Postoperative residual neuropathic pain prevents return to work after cervical OPLL surgery: nationwide multicenter study Open Access

Mori, K; Miyagi, M; Ikeda, S; Yokozeki, Y; Sakai, K; Endo, T; Takahata, M; Tsutsui, S; Kato, S; Egawa, S; Hirai, T; Maki, S; Hozumi, T; Nishida, N; Nakashima, H; Nakajima, H; Takahashi, H; Koda, M; Kusano, K; Imagama, S; Yoshii, T; Kawaguchi, Y; Yamazaki, M

SCIENTIFIC REPORTS   Vol. 15 ( 1 ) page： 42724   2025.11

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Language：English   Publisher：Scientific Reports  

Cervical ossification of the posterior longitudinal ligament of the spine (c-OPLL) is an intractable disease that impairs activities of daily living and quality of life. There are few reports on patients’ return to work (RTW) after surgery. The aim of this study was to investigate the RTW status and its associated factors after c-OPLL surgery through a nationwide multicenter questionnaire survey and to provide reference evidence for determining the future treatment of this disease. We were able to study 286 patients (205 males, 81 females) from 13 institutions. We analyzed RTW in 198 patients, excluding 88 patients who were unemployed before surgery. RTW was confirmed in 151 patients (124 males, 27 females), and RTW rate was 76.3%. Significant differences were observed between RTW + and—groups in age, body mass index, preoperative workload, and preoperative JOA score. Notably, this study was the first to demonstrate that postoperative residual neuropathic pain is a significant factor associated with RTW after c-OPLL surgery. The results of this study will provide useful information for determining future treatment plans for patients with an eye toward returning to work after surgery, and may also have an impact on surgical indications for this disease.

DOI： 10.1038/s41598-025-26781-9

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PubMed

miR-199a functions downstream of MeCP2 in neurons of<i> MECP2</i> duplication syndrome models Open Access

Akaba, Y; Takahashi, S; Adachi, S; Nishimura, M; Suzuki, K; Nakashima, H; Nakashima, K; Kira, R; Chong, PF; Sakai, Y; Hayashi, Y; Kushima, I; Mori, D; Arioka, Y; Okumura, H; Nakayama, A; Mizuno, S; Yamamoto, T; Osakada, F; Ozaki, N; Tsujimura, K

ISCIENCE   Vol. 28 ( 11 ) page： 113789   2025.11

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Language：English   Publisher：Iscience  

Duplication of the methyl-CpG-binding protein 2 (MECP2) gene causes MECP2 duplication syndrome (MDS), a severe neurodevelopmental disorder with an unclear pathology. We previously showed that MeCP2 promotes the processing of specific microRNAs (miRNAs), including miR-199a, to regulate neuronal functions. Here, we demonstrate that neurons derived from MDS model mice and patient-induced pluripotent stem cells (iPSCs) exhibit morphological abnormalities, such as abnormal dendrite outgrowth, enlarged soma size, increased glutamatergic synapse density, and hyperactivation of the mechanistic target of rapamycin (mTOR) signaling. MeCP2 overexpression increased miR-199a production in both models. Blocking miR-199a-5p improved soma size and mTOR activity, while inhibiting miR-199a-3p normalized dendritic outgrowth. Crossing MDS model mice with miR-199a-2 knockout mice ameliorated synaptic and mTOR abnormalities. Human MDS cortical organoids exhibited reduced neuronal activity, which was reversed by suppressing miR-199a-5p. These findings identify miR-199a as a key downstream mediator of MeCP2 in MDS, providing new insights into its molecular pathology.

DOI： 10.1016/j.isci.2025.113789

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Cost and outcome comparison between intradiscal condoliase injection and surgical treatment for lumbar disc herniation based on real-world data analysis. International journal Open Access

Naoki Segi, Hiroaki Nakashima, Takahiro Imaizumi, Sadayuki Ito, Jun Ouchida, Ippei Yamauchi, Yukihito Ode, Yasuhiro Nagatani, Yuya Okada, Yujiro Kagami, Shiro Imagama

Scientific reports   Vol. 15 ( 1 ) page： 40145 - 40145   2025.11

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Intradiscal condoliase injection therapy (ICIT) is a novel minimally invasive treatment for lumbar disc herniation (LDH). We aimed to compare adverse events, outcomes, and costs of ICIT versus surgery using health claims data. From the database for the period 2020 to 2023, 1,982 ICIT, 4,009 endoscopic discectomy, and 5,528 open discectomy records were extracted. Comparing each surgical group matched to the ICIT group revealed that ICIT had a significantly lower surgical site infection incidence (vs. endoscopic, 0.6% vs. 1.4%, P = 0.016; vs. open, 0.6% vs. 2.8%, P < 0.001), whereas the incidence of additional spine surgery within 90 days was significantly higher (4.9% vs. 2.5%, p < 0.001; 4.9% vs. 1.6%, p < 0.001). The total cost of ICIT group was < 50% of that of discectomy (352,271 vs. 807,550 JPY, P < 0.001; 352,271 vs. 866,642 JPY, P < 0.001). In the first month after treatment, ICIT was associated with the least amount of analgesic prescriptions (76.1% vs. 91.2%, P < 0.001; 76.1% vs. 96.2%, P < 0.001), whereas ICIT was associated with the most in the third month (25.6% vs. 16.0%, P < 0.001; 25.6% vs. 15.7%, P < 0.001). ICIT presents a viable, low-cost treatment alternative to surgery for LDH.

DOI： 10.1038/s41598-025-23988-8

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Effect of Preoperative Nutritional Status on Postoperative Clinical Outcomes of Patients with Metastatic Spinal Tumors: Japan Association of Spine Surgeons with Ambition Multicenter Study. International journal

Masafumi Kawai, Satoshi Kato, Noriaki Yokogawa, Takaki Shimizu, Satoru Demura, Yuki Shiratani, Akinobu Suzuki, Koji Tamai, Kenichiro Kakutani, Yutaro Kanda, Hiroyuki Tominaga, Ichiro Kawamura, Masayuki Ishihara, Masaaki Paku, Toru Funayama, Kousei Miura, Eiki Shirasawa, Hirokazu Inoue, Atsushi Kimura, Kazuo Nakanishi, Hirokatsu Sawada, Koji Matsumoto, Masahiro Funaba, Hidenori Suzuki, Koji Akeda, Norihiko Takegami, Takuya Iimura, Hiroshi Moridaira, Hideaki Nakajima, Tsutomu Oshigiri, Takashi Hirai, Bungo Otsuki, Kazu Kobayakawa, Haruki Funao, Koji Uotani, Shinji Tanishima, Koichi Sairyo, Ko Hashimoto, Chizuo Iwai, Shoji Seki, Masashi Miyazaki, Kazuyuki Watanabe, Toshio Nakamae, Takashi Kaito, Hiroaki Nakashima, Narihito Nagoshi, Shiro Imagama, Kota Watanabe, Gen Inoue, Takeo Furuya

Spine   Vol. 50 ( 22 ) page： 1571 - 1580   2025.11

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STUDY DESIGN: A multicenter prospective study. OBJECTIVE: To evaluate the effect of preoperative nutritional status, assessed using the Prognostic Nutritional Index (PNI), on clinical outcomes, including survival prognosis, postoperative complications, hospitalization duration, and functional prognosis, in patients with metastatic spinal tumors undergoing surgery. SUMMARY OF BACKGROUND DATA: Malnutrition is common in patients with cancer and is associated with poor clinical outcomes. However, data on the role of nutritional status in metastatic spinal tumors are limited. METHODS: We included 309 patients who underwent surgery for metastatic spinal tumors between October 2018 and March 2021. Patients were divided into two groups: normal nutrition (PNI ≥40) and malnutrition (PNI <40). Clinical outcomes, including 1-year mortality, postoperative complications, and functional improvements (performance status, Frankel grade, Barthel Index, Vitality Index, and EuroQol 5-Dimension 5-level), were compared using propensity score matching to adjust for confounding factors, such as age, sex, preoperative chemotherapy, performance status, primary tumor type, and visceral metastases. RESULTS: Thirty-six percent of patients were malnourished. After propensity score matching, the malnutrition group had a significantly higher mortality rate within 1 year than the normal nutrition group (55% vs. 31%, P<0.001) and showed limited physical improvement, including neurological recovery, 1 month postoperatively. However, improvements in motivation and quality of life (QOL) were comparable between the groups, and physical function recovery at 6 months was similar. No significant differences in postoperative complications or length of hospital stay were observed between the groups. CONCLUSION: Preoperative malnutrition was observed in 36% of patients with metastatic spinal tumors who underwent surgery and was associated with a poor postoperative survival prognosis and delayed physical recovery. However, surgical treatment improved motivation, QOL, and physical function 6 months after surgery. These findings highlight the importance of assessing the nutritional status preoperatively and considering both survival and functional prognoses when selecting surgical treatment for patients with malnutrition.

DOI： 10.1097/BRS.0000000000005487

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Association of Serum Creatinine-Cystatin C Ratio With Hospital-Associated Complications and Post-Discharge Mortality Open Access

Yamada, Y; Nakashima, H; Nagae, M; Watanabe, K; Fujisawa, C; Komiya, H; Tajima, T; Sakai, T; Satake, S; Umegaki, H

GERIATRICS & GERONTOLOGY INTERNATIONAL   Vol. 25 ( 11 ) page： 1564 - 1570   2025.11

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Language：English   Publisher：Geriatrics and Gerontology International  

Aim: To examine the associations of serum creatinine-cystatin C ratio (CCR) at admission with mortality at 3 months post-discharge and the incidence of hospital-associated complications (HAC). Methods: The study was conducted at 2 centers and included patients admitted to and discharged from geriatric wards between October 2019 and July 2023. Patient backgrounds were compared according to mortality at 3 months post-discharge. Next, logistic regression analysis was performed using mortality at 3 months post-discharge as the objective variable. Similarly, logistic regression analysis was performed with the incidence of HAC as the objective variable. Results: Two hundred thirty-one patients were included in the analysis. The death group had significantly lower CCR (p < 0.001). In logistic regression analysis adjusted for age and sex, a low CCR was associated with increased mortality (odds ratio 3.260, p = 0.003). This association remained significant even after additional adjustment for kidney function (odds ratio 2.710, p = 0.014). The lowest CCR quartile showed a similar trend with an increased risk of death at 3 months compared to the highest quartile, even after extensive adjustment for demographics, kidney function, comorbidities, frailty, and cognitive function (Odds Ratio 4.157, p = 0.086). On the other hand, no significant association was found between CCR and the incidence of HAC. Conclusions: A low CCR predicted higher post-discharge mortality after basic adjustment; although the association attenuated when frailty and cognition were included, a risk increase persisted for the lowest versus highest quartile. Measuring CCR in hospitalized older adults may be useful for early identification of patients at high risk of death.

DOI： 10.1111/ggi.70206

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Prognostic value of low estimated appendicular skeletal muscle mass in hospitalized older adults: A multicenter prospective observational study

Miyahara, S; Maeda, K; Satake, S; Nagae, M; Nakashima, H; Takeya, Y; Umeda-Kameyama, Y; Umegaki, H

ARCHIVES OF GERONTOLOGY AND GERIATRICS   Vol. 138   page： 105958   2025.11

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Language：English   Publisher：Archives of Gerontology and Geriatrics  

Background: Muscle mass assessment is essential for diagnosing sarcopenia and malnutrition. Various equations for estimating appendicular skeletal muscle mass (ASM) exist. Among these, equations based on basic clinical variables—age, sex, height, and weight—are potentially applicable to a broad range of patients. This study aimed to examine the validity of multiple ASM estimation equations in hospitalized older patients by investigating their associations with adverse outcomes, including mortality and functional decline. Methods: This study used data from the Japan Hospital Acquired Complications project, a multicenter observational study, and included patients aged ≥65 years. ASM was estimated at admission using four previously reported equations. The appendicular skeletal muscle mass index (ASMI) was calculated and classified as low based on predefined cut-off values. Multivariable logistic regression was used to assess association between low ASMI, in-hospital or 3-month post-discharge mortality, and in-hospital Clinical Frailty Scale (CFS) worsening. Results: A total of 1012 patients (mean age 83.9 ± 6.6 years; 57.4 % female) were analyzed. During hospitalization or within three months after discharge, 109 patients died. Low ASMI, as defined by several equations, was significantly associated with this mortality after adjusting for confounders. Additionally, low ASMI was significantly associated with in-hospital CFS worsening (n = 175), across all equations. Conclusions: Estimated ASM based on clinical information was associated with mortality and worsening frailty. These simple equations are widely applicable for assessing muscle mass and may contribute to facilitating the diagnosis of sarcopenia and malnutrition.

DOI： 10.1016/j.archger.2025.105958

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Association between the central sensitization inventory score and health-related quality of life in community-dwelling middle-aged and older adults. International journal Open Access

Naoki Segi, Hiroaki Nakashima, Ryotaro Oishi, Sadayuki Ito, Jun Ouchida, Ippei Yamauchi, Yasuhiro Nagatani, Taisuke Seki, Yasuhiko Takegami, Shinya Ishizuka, Yukiharu Hasegawa, Shiro Imagama

PloS one   Vol. 20 ( 10 ) page： e0335923   2025.10

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BACKGROUND: Central sensitization is an important factor associated with impaired health-related quality of life in patients with musculoskeletal disorders and community-dwelling older adults. However, health-related quality-of-life domains strongly associated with central sensitization in the general population remain unclear. This study aimed to examine the association between the Central Sensitization Inventory Part A scores and health-related quality of life using community health checkup data. METHODS: A total of 419 middle-aged and older adults (mean age, 64.4 ± 11.2 years; 59.4% female) were included. Participants completed a questionnaire survey on pain, including visual analogue scales (VASs) for lower-back and knee pain, and the Central Sensitization Inventory Part A. Additionally, participants completed the Short-Form 36-Item Health Survey, and three component-summary scores and eight subscales were calculated. Additionally, participants completed the 5-level EuroQol 5 dimensions, and health-state utility values were calculated. The correlation between the Central Sensitization Inventory Part A scores and these health-related quality-of-life measures was investigated. RESULTS: Central Sensitization Inventory Part A score ≥40 was observed in 2.6% participants. Significant moderate negative correlations were observed between the Central Sensitization Inventory Part A scores and EuroQol 5 dimensions health-state utility values (r = -0.631, P < 0.001), Short-Form 36 mental-component summary (r = -0.550, P < 0.001), body pain (r = -0.556, P < 0.001), general health (r = -0.556, P < 0.001), vitality (r = -0.610, P < 0.001), and mental health (r = -0.556, P < 0.001). Similar results were obtained for participants with Central Sensitization Inventory Part A scores <30. CONCLUSIONS: In community-dwelling middle-aged and older adults, Central Sensitization Inventory Part A scores were negatively correlated with health-related quality-of-life scores, even in participants with Central Sensitization Inventory Part A scores <30.

DOI： 10.1371/journal.pone.0335923

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Radiographic parameters of nonunion in Vancouver type C periprosthetic femoral fractures treated with plate fixation. International journal

Shimpei Takahashi, Yasuhiko Takegami, Hiroaki Nakashima, Kenichi Mishima, Toshiki Iwase, Shiro Imagama

Archives of orthopaedic and trauma surgery   Vol. 145 ( 1 ) page： 490 - 490   2025.10

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DOI： 10.1007/s00402-025-06088-0

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Machine Learning-Based Prediction of Quality of Life Improvement After Surgery for Spinal Metastases: A Prospective Multicenter Study. International journal

Kyota Kitagawa, Satoshi Maki, Yuki Shiratani, Akinobu Suzuki, Koji Tamai, Takaki Shimizu, Kenichiro Kakutani, Yutaro Kanda, Hiroyuki Tominaga, Ichiro Kawamura, Masayuki Ishihara, Masaaki Paku, Yohei Takahashi, Toru Funayama, Kousei Miura, Eiki Shirasawa, Hirokazu Inoue, Atsushi Kimura, Takuya Iimura, Hiroshi Moridaira, Hideaki Nakajima, Shuji Watanabe, Koji Akeda, Norihiko Takegami, Kazuo Nakanishi, Hirokatsu Sawada, Koji Matsumoto, Masahiro Funaba, Hidenori Suzuki, Haruki Funao, Tsutomu Oshigiri, Takashi Hirai, Bungo Otsuki, Kazu Kobayakawa, Koji Uotani, Koichi Sairyo, Shinji Tanishima, Ko Hashimoto, Chizuo Iwai, Daisuke Yamabe, Akihiko Hiyama, Shoji Seki, Kenji Kato, Masashi Miyazaki, Kazuyuki Watanabe, Toshio Nakamae, Takashi Kaito, Hiroaki Nakashima, Narihito Nagoshi, Satoshi Kato, Shiro Imagama, Kota Watanabe, Seiji Ohtori, Gen Inoue, Takeo Furuya

Spine   Vol. 50 ( 20 ) page： 1410 - 1419   2025.10

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STUDY DESIGN: A prospective multicenter cohort study. OBJECTIVE: To develop and validate machine learning models for predicting health-related quality of life (HRQoL) improvements in patients after one month and six months of surgery for spinal metastases. SUMMARY OF BACKGROUND DATA: The prediction of postoperative HRQoL of spinal metastases surgery remains understudied compared with studies of survival outcomes. METHODS: We analyzed data from 413 patients who underwent surgery for spinal metastases at 40 participating institutions in Japan. The primary outcome was HRQoL improvement, defined as an increase in the EuroQol 5-Dimension 5-Level (EQ-5D) utility value of ≥0.32 from baseline. We developed two models for 1-month (n=360) and 6-month (n=189) outcomes using various machine learning algorithms. Missing values were imputed, and feature selection was performed using recursive feature elimination with cross-validation. We split the data into training (80%) and test (20%) sets for each model. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), accuracy, precision, and F1-score. SHapley Additive exPlanations (SHAP) analysis was used to interpret feature importance. RESULTS: The 6-month model outperformed the 1-month model across all metrics. For 1-month predictions, Logistic Regression achieved an AUC of 0.8136 and an accuracy of 0.7639 on the test set. For 6-month predictions, Naive Bayes demonstrated an AUC of 0.8928 and an accuracy of 0.8684. The 1-month model used 12 features, while the 6-month model required seven. SHAP analysis revealed that EQ-5D Mobility was the most influential feature in both models. CONCLUSIONS: Our models demonstrate high predictive accuracy for HRQoL improvements following spinal metastases surgery, with superior performance of the 6-month model. These models could enhance clinical decision-making and patient counseling by providing personalized predictions of postoperative QoL. Future research should focus on external validation and integration of these models into clinical practice.

DOI： 10.1097/BRS.0000000000005367

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Age-Stratified Effect of Rivaroxaban Monotherapy for Atrial Fibrillation in Stable Coronary Artery Disease: A Post Hoc Analysis of the AFIRE Randomized Clinical Trial Open Access

Yamaguchi J., Arashi H., Hagiwara N., Yasuda S., Kaikita K., Akao M., Ako J., Matoba T., Nakamura M., Miyauchi K., Matsui K., Ogawa H., Nakamura A., Tamiya E., Yamamoto T., Suetake S., Noguchi T., Nakamura S., Matsumura A., Kojima J., Yamaguchi H., Suwa S., Yasu T., Nakajima A., Yamada T., Arai H., Hata Y., Sakanashi T., Tateishi H., Nakayama T., Nozaki Y., Okumura Y., Tokue M., Kuroki N., Maruyama Y., Suzuki H., Nishida Y., Ajioka M., Yumoto K., Shimizu S., Aoyama T., Shimomura H., Takeda T., Oshiro K., Sugishita N., Shibata Y., Otonari T., Shimizu M., Kihara H., Ogawa H., Ono A., Hazama M., Tsukahara K., Haruta S., Haruna T., Ito M., Fujii K., Atsuchi N., Sata M., Wakeyama T., Hasebe N., Kobayasi Y., Osato K., Hironaga K., Naganuma Y., Anzaki K., Okazaki S., Nakagawa Y., Tokuhiro K., Tanaka K., Momose T., Fukushima Y., Kametani R., Kawamitsu K., Saito Y., Akashi S., Kumagai K., Eshima K., Tobaru T., Seo T., Okuhara K., Kozuma K., Ikari Y., Takahashi T., Oiwa K., Michishita I., Fujikura H., Momomura S., Yamamoto Y., Otomo K., Matsubara T., Tashiro H., Inoue T., Ishihara M., Shiojima I., Tachibana E., Sumii K., Yamamoto N., Omura N., Nakamura T.

JAMA Cardiology   Vol. 10 ( 10 ) page： 990 - 999   2025.10

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Importance: Antithrombotic therapy is crucial for older patients with coronary artery disease (CAD) and atrial fibrillation (AF) who are at a high risk of bleeding and thrombotic events. Objective: To examine the age-stratified effects of rivaroxaban monotherapy compared with those of rivaroxaban plus antiplatelet agent combination therapy. Design, Setting, and Participants: This was a post hoc secondary analysis of the Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease (AFIRE) open-label randomized clinical trial. This was a multicenter study conducted in Japan from February 23, 2015, to July 31, 2018. Patients with AF and stable CAD who had undergone percutaneous coronary intervention or coronary artery bypass grafting 1 or more years earlier or who had angiographically confirmed CAD that did not require revascularization were enrolled. Participants were stratified into 4 groups by age (<70 years, 70-74 years, 75-79 years, and ≥80 years). Study data were analyzed from August 2024 to July 2025. Interventions: Rivaroxaban monotherapy or rivaroxaban plus antiplatelet agent therapy. Main Outcomes and Measures: The primary efficacy end point was a major adverse cardiovascular event, defined as a composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, or death from any cause. The primary safety end point was major bleeding. Results: This study included a total of 2215 participants (mean [SD] age, 74.3 [8.2] years; 1751 male [79.1%]). The incidence of primary efficacy end points per patient-year for rivaroxaban monotherapy vs rivaroxaban plus antiplatelet agent therapy was 3.2% vs 4.3% (<70 years), 3.2% vs 2.8% (70-74 years), 3.8% vs 5.3% (75-79 years), and 6.2% vs 10.3% (≥80 years). The hazard ratios were 0.74 (95% CI, 0.40-1.37) for those younger than 70 years, 1.16 (95% CI, 0.55-2.45) for those aged 70 to 74 years, 0.72 (95% CI, 0.41-1.26) for those aged 75 to 79 years, and 0.61 (95% CI, 0.40-0.93) for those 80 years and older (P for interaction =.51). For the primary safety end points, the incidence was 0.5% vs 2.3% (<70 years), 2.2% vs 2.4% (70-74 years), 1.1% vs 2.1% (75-79 years), and 2.9% vs 4.3% (≥80 years). The hazard ratios were 0.23 (95% CI, 0.06-0.79) for those younger than 70 years, 0.91 (95% CI, 0.39-2.15) for those aged 70 to 74 years, 0.52 (95% CI, 0.19-1.42) for those aged 75 to 79 years, and 0.67 (95% CI, 0.35-1.27) for those 80 years and older (P for interaction =.33). Conclusions and Relevance: Results of this post hoc analysis of the AFIRE randomized clinical trial reveal that rivaroxaban monotherapy reduced the risk of major cardiovascular events and major bleeding across the broad range of age in patients with AF and stable CAD. Possible age-related differences in trends, with more pronounced efficacy in older patients and more pronounced safety in younger patients, should be considered as hypothesis generating and require further research.

DOI： 10.1001/jamacardio.2025.2611

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HALP and FI-Lab Scores in Hospitalized Older Adults: A Retrospective Comparative Study of Adverse Outcomes

Nagae, M; Umegaki, H; Nakashima, H; Nishiuchi, T

JOURNAL OF GENERAL INTERNAL MEDICINE     2025.10

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Language：English   Publisher：Journal of General Internal Medicine  

Background: Early identification of poor prognosis in acutely hospitalized older adults is essential. Hemoglobin, albumin, lymphocyte, and platelet (HALP) scores have garnered attention as a predictor of poor prognosis in both cancer and non-cancer patients. The frailty index-laboratory (FI-lab) has also demonstrated utility as an indicator of unfavorable outcomes. Associations have been established between low HALP levels and high FI-lab scores with adverse outcomes. However, no study has yet compared these indicators to predict outcomes in hospitalized older adults. Methods: This retrospective cohort study involved older adults admitted to a 730-bed tertiary hospital. The study encompassed patients aged 65 years or older admitted to the general internal medicine department and discharged between August 2020 and July 2023. The HALP score and FI-lab were computed based on laboratory parameters derived from blood tests conducted upon admission. The study assessed outcomes including in-hospital mortality, in-hospital falls, discharge to home, and length of hospital stay. Results: A total of 1346 patients, of whom 11.6% died during hospitalization. The FI-lab score was more predictive of in-hospital death than the HALP score. In Cox regression survival analysis, higher FI-lab scores (hazard ratio 1.70, 95% confidence interval 1.47–1.96, p < 0.01) and lower HALP scores (hazard ratio 1.62, 95% confidence interval 1.12–2.33, p < 0.01) were significantly associated with in-hospital mortality. Moreover, higher FI-lab scores and low HALP scores were linked to a prolonged hospital stay and reduced likelihood of discharge. In contrast, none of these indicators was correlated with in-hospital falls. Conclusions: The FI-lab demonstrated superior predictive capability for in-hospital mortality compared to the HALP score. However, the HALP score also proved effective in forecasting adverse outcomes among older adults hospitalized in general internal medicine wards. Automatically calculable laboratory scores could offer significant value in caring for diverse older inpatients.

DOI： 10.1007/s11606-025-09889-6

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