Hamanomachi Hospital

Individuals with locomotive syndrome (LS) have muscle weakness and reduced motor function due to musculoskeletal disorders that cause reduced mobility and physical function. In Japan, musculoskeletal disorders are the most common reason for requiring home support or nursing care, highlighting the need for preventing and ameliorating LS. Middle-aged and older adults sometimes encounter difficulty making a habit of exercise therapy (the mainstay of LS treatment). We investigated whether digital therapeutics (DTx) can prevent or ameliorate LS in middle-aged and older adults. We conducted a prospective, longitudinal, nonrandomized, single-group study of Japanese aged 40 years and older who were eligible for LS checkups (N=47). Each participant underwent an 8-week locomotion training intervention based on DTx supervised by medical staff. We objectively assessed the participants' subjective and objective motor abilities and motor awareness with the Timed Up and Go (TUG) test, 25-question Geriatric Locomotive Function Scale (GLFS-25), and Behavioral Regulation in Exercise Questionnaire-3 at baseline (before the DTx), an interim point (4 wk after the DTx initiation), and a final evaluation (8 wk post-DTx initiation). We compared the scores of the 3 tests at the 3 time points as dependent variables in a 3-factor ANOVA with Bonferroni correction (significance defined as 0.05/3=0.0167). No increase in amotivation to exercise or refusal to exercise was observed. Significant improvements at 8 weeks versus the baseline were observed in the TUG scores (baseline: 9.0, 95% CI 8.4-9.6; 8 wk: 7.5, 95% CI 7.1-8.0; P=.001) and GLFS-25 results (baseline: 18.7, 95% CI 14.5-22.8; 8 wk: 11.7, 95% CI 8.8-14.7; P=.004). The Behavioral Regulation in Exercise Questionnaire-3 and its subscale data did not differ significantly at any assessment time point. These results indicate that an 8-week locomotive training intervention using DTx significantly improved middle-aged and older adults' TUG and GLFS-25 scores and will help prevent and ameliorate LS and establish better exercise habits among them.

The feasibility of total body irradiation (TBI) delivery using the TomoDirect mode of a TomoTherapy system has been demonstrated. In clinical practice, TomoTherapy-based TBI is typically performed in two parts: upper and lower body. This study aimed to evaluate the dosimetric impact of varying port numbers on dose evaluation indices for lower body irradiation using TomoDirect and to compare these results with those of TomoHelical in a simulation setting. Sixteen patients who underwent myeloablative TBI using TomoHelical between October 2017 and March 2021 were retrospectively analyzed. TomoDirect plans with 2 to 12 ports at approximately equal beam angles were generated (modulation factor=1.5, field width=5.0cm, pitch=0.500). TomoHelical plans used identical parameters except for a pitch of 0.397. The prescribed dose was 12Gy in six fractions. Dose indices (D2, D98, D50, homogeneity index [HI]) and beam-on time were compared. In TomoDirect plans, all dose evaluation indices worsened as the number of ports increased up to five, but changes became minimal beyond eight ports. D2 was significantly improved in all TomoDirect plans compared with those of TomoHelical plan. D98 was significantly lower for the three- and five-port TomoDirect plans, and no TomoDirect plan achieved higher D98 than TomoHelical. The D50 and HI were significantly improved in all TomoDirect plans except the five-port configuration. The two-port TomoDirect plan achieved the most favorable dose indices and the shortest beam-on time. The two-port TomoDirect approach with anterior-posterior beam configuration provides an efficient and clinically reasonable option for lower-body irradiation, offering improved dose homogeneity and reduced treatment time compared with TomoHelical.

Chemotherapy-induced neutropenia has been identified as a potential prognostic marker for multiple cancers. However, only one retrospective study, NN-2301, has investigated the relationship between neutropenia and treatment effects of nanoliposomal irinotecan/5-fluorouracil/folinic acid (NFF) in pancreatic cancer. In this prospective study, we aimed to clarify whether NFF-induced neutropenia could serve as a prognostic marker in pancreatic cancer. Data were analyzed from the prospective cohort of the NAPOLEON-2 trial, an observational study involving patients with unresectable pancreatic cancer treated with NFF. Neutropenia severity was categorized into three cutoffs: Cutoff A (Grade [Gr] 0 vs. Gr 1-4), cutoff B (Gr 0-1 vs. Gr 2-4), and Cutoff C (Gr 0-2 vs. Gr 3-4), using the Common Terminology Criteria for Adverse Events version 5.0, owing to conformity with previous studies and simplicity. The primary endpoint was overall survival (OS); progression-free survival (PFS) was the secondary endpoint. The neutropenic groups included Gr 1, 2, 3, and 4, with 79, 23, 34, and 7 patients, respectively. At each cutoff, OS and PFS were significantly better in the severe neutropenia groups. Higher neutropenia grades correlated with improved OS (log-rank trend test: χ2 = 8.62, p < .01). Multivariate Cox regression analysis revealed significant differences for all cutoffs: adjusted hazard ratios were 0.57 (95% confidence interval [CI] 0.40-0.83) (Cutoff A), 0.53 (95% CI 0.36-0.78) (Cutoff B), and 0.52 (95% CI 0.34-0.80) (Cutoff C). NFF-induced neutropenia is a valuable prognostic marker in pancreatic cancer and may guide treatment selection.

Fragility hip fracture (FHF) has been frequently seen in trauma of older people, resulted in decreased mobility and a loss of independence. This study retrospectively assessed the long-term health-related quality of life (HRQOL) and living arrangement in older patients following FHF, and evaluated the factors associating with long-term EuroQol 5D (EQ5D) for 5years or more. This study included 203 Japanese patients (male 26, female 177) with FHF over the age of 60years. We examined the long-term EQ5D and life style at final follow-up, and identified the factors affecting with EQ5D. The mean age at baseline of 79years, the mean observation duration was 6years, and the average value of EQ5D at final follow-up was 0.65. Multivariate analysis presented that EQ5D at final follow-up was significantly predicted by serum albumin, trochanteric fracture, comorbidity stroke, higher BI at post-admission, less length of stay hospital, and living at home at final follow-up. The people living at home at final follow-up (148/203 [72.9%]) was less than the people at baseline (190/203 [93.6%]). In multivariate analysis, the people living at home at final follow-up were younger age at baseline, and higher BI at post-admission. In conclusion the long-term EQ5D after FHF was decreased in patients with lower serum albumin at baseline, with trochanteric fracture, with stroke comorbidity, and with lower BI at post-admission. The people living at home after FHF were young age at baseline and high BI at post-admission.

Both anti-thymocyte globulin (ATG) and post-transplant cyclophosphamide (PTCy) have shown prophylactic effects on graft-versus-host disease (GVHD) in multiple phase III studies. We conducted a comparative study of for low dose ATG (thymoglobulin) versus PTCy for GVHD prophylaxis in peripheral blood stem cell transplantation (PBSCT). The ATG (n = 67) and PTCy (n = 40) groups included patients enrolled in multicenter phase II studies (JSCT-ATG15 and JSCT-PTCY19, respectively). The probability of GVHD-free and relapse-free survival at 2 years as the primary endpoint was not significantly different between these two groups (57.9% for ATG vs. 67.8% for PTCy, P = 0.49). Both neutrophil and platelet engraftments were both significantly shorter in the ATG group than in the PTCy group (neutrophils: median 13 days vs. 15 days, P = 0.007; platelets: median 20 days vs. 27 days, P = 0.007). The cumulative incidences of acute and chronic GVHD, relapse, non-relapse mortality, and off-immunosuppressant use were similar between these two groups. The probabilities of overall and progression-free survival were 83.4% and 70.0% in the ATG group and 76.5% and 75.2% in the PTCy group, respectively, with no significant differences. These data indicate that low dose ATG and PTCy are equivalent for GVHD prophylaxis for PBSCT.

Umbilical cord blood transplantation (CBT) is accepted as an effective treatment for acute myeloid leukemia (AML), and reduced-intensity conditioning (RIC), rather than myeloablative conditioning (MAC) regimens allowed elderly patients to be treated safely. However, appropriate intensities of conditioning regimens are still unclear, especially for middle-aged patients. To compare outcomes after RIC and MAC regimens, we analyzed AML patients aged 16 years or older in the Japanese registry database, who underwent single cord unit CBT between 2010-2019. Median ages of the RIC group (n = 1353) and the MAC group (n = 2101) were 59 and 51 years (P < 0.001), respectively. 5-year overall survival (OS) after MAC was superior to that of RIC (38.3% vs 27.7%, P < 0.001) with lower incidence of relapse (33.9% vs 37.4%, P = 0.029) and better neutrophil engraftment (84.7% vs 75.9%, P < 0.001). Detailed subgroup analysis revealed that age at transplantation is the most important factor affecting 5-year OS in RIC and MAC. This analysis identified a threshold of 55 years, beyond which the superiority of MAC disappeared, irrespective of other factors such as disease status or performance status. In conclusion, RIC may be preferable for patients aged 56 or older in CBT for AML due to higher potential toxicities.

Understanding differences in clinical outcomes between PBSCT and BMT is important, and this study compared outcomes of HLA-matched related PBSCT and BMT using reduced-intensity conditioning (RIC) in adult acute myeloid leukemia (AML) patients. Data from 402 patients who underwent either PBSCT (n=294) or BMT (n=108) between 2000 and 2022 were analyzed using the Japanese nationwide registry database. The primary endpoint was overall survival (OS), and secondary endpoints included disease-free survival (DFS), non-relapse mortality (NRM), and GVHD. Results indicated no significant difference in 3-year OS (44.6% for PBSCT vs. 46.9% for BMT, HR 1.173, P=0.299) and DFS (42.1%vs. 41.8%, HR 1.073, P=0.639). PBSCT was more beneficial for avoiding relapse (20.3%vs. 12.4%, HR, 0.715, P=0.059). However, PBSCT was associated with higher NRM (20.3%vs. 12.4%, HR 1.801, P=0.025) due to more frequent, chronic GVHD (HR 1.889, P=0.035). Subgroup analysis did not reveal specific patient groups that benefited more from PBSCT or BMT. Incidence of extensive chronic GVHD and NRM has improved in PBSCT recipients in recent years (2014-2022). We conclude that related PBSCT with RIC regimens offers comparable prognosis to BMT for adult AML patients. Further optimization of prophylactic strategies for chronic GVHD is required to improve outcomes after PBSCT.

This study aims to compare the antiemetic efficacy of a four-drug combination with that of a standard three-drug combination in Japanese breast cancer patients, who received their first cycle of anthracycline and cyclophosphamide combination therapy and were treated with granisetron, dexamethasone, and aprepitant with or without 2.5 mg olanzapine. This retrospective observational study was performed at Hamanomachi Hospital using the electronic medical records of 71 patients who were divided into two groups, ie, the four- and three-drug groups comprising 31 and 40 patients, respectively. The complete response (CR: no emesis and no use of rescue medications) rate in the delayed phase (24 – 120 h after the start of chemotherapy) was 77.4％ and 47.5％ in the four- and three-drug groups (P = 0.014), respectively. A multivariable logistic regression analysis showed that the four-drug group was significantly associated with an increased odds of CR achievement in the delayed phase (odds ratio: 5.61, 95％ confidence interval: 1.63 – 19.3). Additionally, daytime somnolence had 41.2％ incidence in 72 h after chemotherapy administration, but 32.4％ of patients continued. These findings suggest that the antiemetic efficacy of the four-drug combination is superior to that of the standard three-drug combination.