1.Early Rehabilitation Interventions by Physical Therapists for Severe COVID-19 Patients Were Associated With Decreased Incidence of Post-ICU Physical Impairment
Shinya OKU ; Junji HATAKEYAMA ; Keibun LIU ; Kentaro TOJO ; Masafumi IDEI ; Shigeaki INOUE ; Kazuma YAMAKAWA ; Takeshi NISHIDA ; Shinichiro OHSHIMO ; Satoru HASHIMOTO ; Shuhei MARUYAMA ; Yoshitaka OGATA ; Daisuke KAWAKAMI ; Hiroaki SHIMIZU ; Katsura HAYAKAWA ; Yuji FUJINO ; Taku OSHIMA ; Tatsuya FUCHIGAMI ; Hironori YAWATA ; Kyoji OE ; Akira KAWAUCHI ; Hidehiro YAMAGATA ; Masahiro HARADA ; Yuichi SATO ; Tomoyuki NAKAMURA ; Kei SUGIKI ; Takahiro HAKOZAKI ; Satoru BEPPU ; Masaki ANRAKU ; Noboru KATO ; Tomomi IWASHITA ; Hiroshi KAMIJO ; Yuichiro KITAGAWA ; Michio NAGASHIMA ; Hirona NISHIMAKI ; Kentaro TOKUDA ; Osamu NISHIDA ; Kensuke NAKAMURA
Annals of Rehabilitation Medicine 2025;49(1):49-59
		                        		
		                        			 Objective:
		                        			To implement early rehabilitation interventions by physical therapists is recommended. However, the effectiveness of early rehabilitation for severe coronavirus disease 2019 (COVID-19) patients in the prevention of post-intensive care syndrome (PICS) is unclear. We analyzed a multicenter prospective observational study (Post-Intensive Care outcomeS in patients with COronaVIrus Disease 2019) to examine the association between early rehabilitation interventions and PICS physical impairment. 
		                        		
		                        			Methods:
		                        			An analysis was performed on COVID-19 patients who were admitted to intensive care units (ICUs) between March 2020 and March 2021, and required mechanical ventilation. The primary outcome was the incidence of PICS physical impairment (Barthel Index≤90) after one year. Multivariate logistic regression analysis was used to estimate the association between early rehabilitation interventions and PICS physical impairment by adjusting ICU mobility scale (IMS) during seven-day following ICU admission, and clinically relevant risk factors. 
		                        		
		                        			Results:
		                        			The analysis included 259 patients, 54 of whom developed PICS physical impairment one year later. In 81 patients, physical therapists intervened within seven days of ICU admission. There was no significant difference in mean IMS by day seven of admission between the early and non-early rehabilitation patients (0.70 and 0.61, respectively). Multivariate logistic regression analysis showed that early rehabilitation interventions were significantly associated with a low incidence of PICS physical impairment (odds ratio, 0.294; 95% confidence interval, 0.123–0.706; p=0.006). 
		                        		
		                        			Conclusion
		                        			Early rehabilitation interventions by physical therapists were an independent factor associated with the decreased development of PICS physical impairment at one year, even though early rehabilitation had no significant effect on IMS. 
		                        		
		                        		
		                        		
		                        	
2.Early Rehabilitation Interventions by Physical Therapists for Severe COVID-19 Patients Were Associated With Decreased Incidence of Post-ICU Physical Impairment
Shinya OKU ; Junji HATAKEYAMA ; Keibun LIU ; Kentaro TOJO ; Masafumi IDEI ; Shigeaki INOUE ; Kazuma YAMAKAWA ; Takeshi NISHIDA ; Shinichiro OHSHIMO ; Satoru HASHIMOTO ; Shuhei MARUYAMA ; Yoshitaka OGATA ; Daisuke KAWAKAMI ; Hiroaki SHIMIZU ; Katsura HAYAKAWA ; Yuji FUJINO ; Taku OSHIMA ; Tatsuya FUCHIGAMI ; Hironori YAWATA ; Kyoji OE ; Akira KAWAUCHI ; Hidehiro YAMAGATA ; Masahiro HARADA ; Yuichi SATO ; Tomoyuki NAKAMURA ; Kei SUGIKI ; Takahiro HAKOZAKI ; Satoru BEPPU ; Masaki ANRAKU ; Noboru KATO ; Tomomi IWASHITA ; Hiroshi KAMIJO ; Yuichiro KITAGAWA ; Michio NAGASHIMA ; Hirona NISHIMAKI ; Kentaro TOKUDA ; Osamu NISHIDA ; Kensuke NAKAMURA
Annals of Rehabilitation Medicine 2025;49(1):49-59
		                        		
		                        			 Objective:
		                        			To implement early rehabilitation interventions by physical therapists is recommended. However, the effectiveness of early rehabilitation for severe coronavirus disease 2019 (COVID-19) patients in the prevention of post-intensive care syndrome (PICS) is unclear. We analyzed a multicenter prospective observational study (Post-Intensive Care outcomeS in patients with COronaVIrus Disease 2019) to examine the association between early rehabilitation interventions and PICS physical impairment. 
		                        		
		                        			Methods:
		                        			An analysis was performed on COVID-19 patients who were admitted to intensive care units (ICUs) between March 2020 and March 2021, and required mechanical ventilation. The primary outcome was the incidence of PICS physical impairment (Barthel Index≤90) after one year. Multivariate logistic regression analysis was used to estimate the association between early rehabilitation interventions and PICS physical impairment by adjusting ICU mobility scale (IMS) during seven-day following ICU admission, and clinically relevant risk factors. 
		                        		
		                        			Results:
		                        			The analysis included 259 patients, 54 of whom developed PICS physical impairment one year later. In 81 patients, physical therapists intervened within seven days of ICU admission. There was no significant difference in mean IMS by day seven of admission between the early and non-early rehabilitation patients (0.70 and 0.61, respectively). Multivariate logistic regression analysis showed that early rehabilitation interventions were significantly associated with a low incidence of PICS physical impairment (odds ratio, 0.294; 95% confidence interval, 0.123–0.706; p=0.006). 
		                        		
		                        			Conclusion
		                        			Early rehabilitation interventions by physical therapists were an independent factor associated with the decreased development of PICS physical impairment at one year, even though early rehabilitation had no significant effect on IMS. 
		                        		
		                        		
		                        		
		                        	
3.Early Rehabilitation Interventions by Physical Therapists for Severe COVID-19 Patients Were Associated With Decreased Incidence of Post-ICU Physical Impairment
Shinya OKU ; Junji HATAKEYAMA ; Keibun LIU ; Kentaro TOJO ; Masafumi IDEI ; Shigeaki INOUE ; Kazuma YAMAKAWA ; Takeshi NISHIDA ; Shinichiro OHSHIMO ; Satoru HASHIMOTO ; Shuhei MARUYAMA ; Yoshitaka OGATA ; Daisuke KAWAKAMI ; Hiroaki SHIMIZU ; Katsura HAYAKAWA ; Yuji FUJINO ; Taku OSHIMA ; Tatsuya FUCHIGAMI ; Hironori YAWATA ; Kyoji OE ; Akira KAWAUCHI ; Hidehiro YAMAGATA ; Masahiro HARADA ; Yuichi SATO ; Tomoyuki NAKAMURA ; Kei SUGIKI ; Takahiro HAKOZAKI ; Satoru BEPPU ; Masaki ANRAKU ; Noboru KATO ; Tomomi IWASHITA ; Hiroshi KAMIJO ; Yuichiro KITAGAWA ; Michio NAGASHIMA ; Hirona NISHIMAKI ; Kentaro TOKUDA ; Osamu NISHIDA ; Kensuke NAKAMURA
Annals of Rehabilitation Medicine 2025;49(1):49-59
		                        		
		                        			 Objective:
		                        			To implement early rehabilitation interventions by physical therapists is recommended. However, the effectiveness of early rehabilitation for severe coronavirus disease 2019 (COVID-19) patients in the prevention of post-intensive care syndrome (PICS) is unclear. We analyzed a multicenter prospective observational study (Post-Intensive Care outcomeS in patients with COronaVIrus Disease 2019) to examine the association between early rehabilitation interventions and PICS physical impairment. 
		                        		
		                        			Methods:
		                        			An analysis was performed on COVID-19 patients who were admitted to intensive care units (ICUs) between March 2020 and March 2021, and required mechanical ventilation. The primary outcome was the incidence of PICS physical impairment (Barthel Index≤90) after one year. Multivariate logistic regression analysis was used to estimate the association between early rehabilitation interventions and PICS physical impairment by adjusting ICU mobility scale (IMS) during seven-day following ICU admission, and clinically relevant risk factors. 
		                        		
		                        			Results:
		                        			The analysis included 259 patients, 54 of whom developed PICS physical impairment one year later. In 81 patients, physical therapists intervened within seven days of ICU admission. There was no significant difference in mean IMS by day seven of admission between the early and non-early rehabilitation patients (0.70 and 0.61, respectively). Multivariate logistic regression analysis showed that early rehabilitation interventions were significantly associated with a low incidence of PICS physical impairment (odds ratio, 0.294; 95% confidence interval, 0.123–0.706; p=0.006). 
		                        		
		                        			Conclusion
		                        			Early rehabilitation interventions by physical therapists were an independent factor associated with the decreased development of PICS physical impairment at one year, even though early rehabilitation had no significant effect on IMS. 
		                        		
		                        		
		                        		
		                        	
4.Prognostic Factors after Surgical Treatment for Spinal Metastases
Kazuhiro MUROTANI ; Shunsuke FUJIBAYASHI ; Bungo OTSUKI ; Takayoshi SHIMIZU ; Takashi SONO ; Eijiro ONISHI ; Hiroaki KIMURA ; Yasuyuki TAMAKI ; Naoya TSUBOUCHI ; Masato OTA ; Ryosuke TSUTSUMI ; Tatsuya ISHIBE ; Shuichi MATSUDA
Asian Spine Journal 2024;18(3):390-397
		                        		
		                        			 Methods:
		                        			A retrospective multicenter study was conducted. The study participants included 345 patients who underwent surgery for spinal metastases from 2010 to 2020 at nine referral spine centers in Japan. Data for each patient were extracted from medical records. To identify the factors predicting survival prognosis after surgery, univariate analyses were performed using a Cox proportional hazards model. 
		                        		
		                        			Results:
		                        			The mean age was 65.9 years. Common primary tumors were lung (n=72), prostate (n=61), and breast (n=39), and 67.8% (n=234) presented with osteolytic lesions. The epidural spinal cord compression scale score 2 or 3 was recognized in 79.0% (n=271). Frankel grade A paralysis accounted for 1.4% (n=5), and 73.3% (n=253) were categorized as intermediate or high risk according to the new Katagiri score. The overall survival rates were -71.0% at 6 months, 57.4% at 12, and 43.3% at 24. In the univariate analysis, Frankel grade A (hazard ratio [HR], 3.59; 95% confidence interval [CI], 1.23–10.50; p<0.05), intermediate risk (HR, 3.34; 95% CI, 2.10–5.32; p<0.01), and high risk (HR, 7.77; 95% CI, 4.72–12.8; p<0.01) in the new Katagiri score were significantly associated with poor survival. On the contrary, postoperative chemotherapy (HR, 0.23; 95% CI, 0.15–0.36; p<0.01), radiation therapy (HR, 0.43; 95% CI, 0.26–0.70; p<0.01), and both adjuvant therapy (HR, 0.21; 95% CI, 0.14–0.32; p<0.01) were suggested to improve survival. 
		                        		
		                        			Conclusions
		                        			Surgical indications for patients with Frankel grade A or intermediate or high risk in the new Katagiri score should be carefully considered because of poor survival. Chemotherapy or radiation therapy should be considered after surgery for better survival. 
		                        		
		                        		
		                        		
		                        	
5.Clinical Features and Surgical Outcomes of Lower Lumbar Osteoporotic Vertebral Collapse with Symptomatic Stenosis: A Surgical Strategy from a Multicenter Case Series
Takayoshi SHIMIZU ; Shunsuke FUJIBAYASHI ; Soichiro MASUDA ; Hiroaki KIMURA ; Tatsuya ISHIBE ; Masato OTA ; Yasuyuki TAMAKI ; Eijiro ONISHI ; Hideo ITO ; Bungo OTSUKI ; Koichi MURATA ; Shuichi MATSUDA
Asian Spine Journal 2022;16(6):906-917
		                        		
		                        			 Methods:
		                        			We investigated patients who underwent surgical intervention for LL-OVC (L3, L4, and/or L5) with symptomatic foraminal and/or central stenosis from eight spine centers. Only patients with a minimum follow-up duration of 1 year were included. We developed new criteria to grade vertebral collapse severity (grade 1, 0%–25%; grade 2, 25%–50%; grade 3, 50%–75%; and grade 4, 75%–100%). The clinical features and outcomes were compared based on the collapse grade and surgical procedures performed (i.e., decompression alone, posterior lateral fusion [PLF], lateral interbody fusion [LIF], posterior/transforaminal interbody fusion [PLIF/TLIF], or vertebral column resection [VCR]). 
		                        		
		                        			Results:
		                        			In this study, 59 patients (average age, 77.4 years) were included. The average follow-up period was 24.6 months. The clinical outcome score (Japanese Orthopaedic Association score) was more favorable in the LIF and PLIF/TLIF groups than in the decompression alone, PLF, and VCR groups. The use of VCR was associated with a high rate of revision surgery (57.1%). No significant difference in clinical outcomes was observed between the collapse grades; however, grade 4 collapse was associated with a high rate of revision surgery (40.0%). 
		                        		
		                        			Conclusions
		                        			When treating LL-OVC, appropriate instrumented reconstruction with rigid intervertebral stability is necessary. According to our newly developed criteria, LIF may be a surgical option for any collapse grade. The use of VCR for grade 4 collapse is associated with a high rate of revision. 
		                        		
		                        		
		                        		
		                        	
6.Functional Analysis of Induced Human Ballooned Hepatocytes in a Cell Sheet-Based Three Dimensional Model
Botao GAO ; Katsuhisa SAKAGUCHI ; Tetsuya OGAWA ; Yuki KAGAWA ; Hirotsugu KUBO ; Tatsuya SHIMIZU
Tissue Engineering and Regenerative Medicine 2021;18(2):217-224
		                        		
		                        			BACKGROUND:
		                        			Ballooned hepatocytes (BH) are a key histological hallmark of nonalcoholic steatohepatitis (NASH), yet their consequences for liver-specific functions are unknown. 
		                        		
		                        			METHODS:
		                        			In our previous study, an experimental model of human induced-BHs (iBH) has been successfully developed based on cell sheet technology. This study aimed to determine the functions of iBHs in the primary human hepatocyte/ normal human dermal fibroblast (PHH/NHDF) co-culture cell sheets. Normal hepatocytes in the PHH/3T3-J2 co-culture cell sheets were set as a control, since 3T3-J2 murine embryonic fibroblasts have exhibited previously long term maintenance of PHH functions. 
		                        		
		                        			RESULTS:
		                        			It was found that, albumin secretion was not affected in iBHs, but urea synthesis as well as cytochrome P450 enzyme (CYP) activities including CYP1A2 and CYP3A4, were significantly reduced in iBHs. Besides, loss of bile canaliculi was observed in iBHs. These findings are consistent with clinical studies of human NASH. In addition, PHH/ NHDF cell sheets demonstrated two fold higher TGF-b1 secretion compared with PHH/3T3-J2 cell sheets. Furthermore, treatment with a TGF-b inhibitor and a semi-synthetic bile acid analogue (obeticholic acid, phase 3 trial of NASH therapy) ameliorated the histological appearance of established iBHs. 
		                        		
		                        			CONCLUSION
		                        			In summary, this study demonstrates the priority of iBHs in recapitulating not only histology but also clinically relevant hepatic dysfunctions in human NASH and suggests TGF-b and bile acid related signal pathway may play important roles in the formation of iBHs.
		                        		
		                        		
		                        		
		                        	
7.Functional Analysis of Induced Human Ballooned Hepatocytes in a Cell Sheet-Based Three Dimensional Model
Botao GAO ; Katsuhisa SAKAGUCHI ; Tetsuya OGAWA ; Yuki KAGAWA ; Hirotsugu KUBO ; Tatsuya SHIMIZU
Tissue Engineering and Regenerative Medicine 2021;18(2):217-224
		                        		
		                        			BACKGROUND:
		                        			Ballooned hepatocytes (BH) are a key histological hallmark of nonalcoholic steatohepatitis (NASH), yet their consequences for liver-specific functions are unknown. 
		                        		
		                        			METHODS:
		                        			In our previous study, an experimental model of human induced-BHs (iBH) has been successfully developed based on cell sheet technology. This study aimed to determine the functions of iBHs in the primary human hepatocyte/ normal human dermal fibroblast (PHH/NHDF) co-culture cell sheets. Normal hepatocytes in the PHH/3T3-J2 co-culture cell sheets were set as a control, since 3T3-J2 murine embryonic fibroblasts have exhibited previously long term maintenance of PHH functions. 
		                        		
		                        			RESULTS:
		                        			It was found that, albumin secretion was not affected in iBHs, but urea synthesis as well as cytochrome P450 enzyme (CYP) activities including CYP1A2 and CYP3A4, were significantly reduced in iBHs. Besides, loss of bile canaliculi was observed in iBHs. These findings are consistent with clinical studies of human NASH. In addition, PHH/ NHDF cell sheets demonstrated two fold higher TGF-b1 secretion compared with PHH/3T3-J2 cell sheets. Furthermore, treatment with a TGF-b inhibitor and a semi-synthetic bile acid analogue (obeticholic acid, phase 3 trial of NASH therapy) ameliorated the histological appearance of established iBHs. 
		                        		
		                        			CONCLUSION
		                        			In summary, this study demonstrates the priority of iBHs in recapitulating not only histology but also clinically relevant hepatic dysfunctions in human NASH and suggests TGF-b and bile acid related signal pathway may play important roles in the formation of iBHs.
		                        		
		                        		
		                        		
		                        	
8.Reference Data, Characteristics and Related Factors of Quality of Life Assessed by a Questionnaire of Patient’s Behavior Survey in the General Population in Japan
Satoko ITO ; Megumi SHIMIZU ; Kazuki SATO ; Masashi KATO ; Daisuke FUJISAWA ; Akemi NAITO ; Tatsuya MORITA ; Mitsunori MIYASHITA
Palliative Care Research 2020;15(2):135-146
		                        		
		                        			
		                        			To decide the policy to promote palliative care properly, a new questionnaire has been added to Patient’s behavior survey to assess Quality of Life (QOL) of inpatients and outpatients in Japan. The aim of this study was to survey QOL score of general population in Japan by using a questionnaire of patient’s behavior survey. A large nationwide postal survey was conducted from January through February 2013 in Japan. A total of 2400 subjects were selected randomly from among members of the general population who were 20 to 79 years of age and lived in Japan. A total of 978 (41.1%) questionnaires were analyzed, and reference data of QOL score weighted by the national standard value of sex-age group population were calculated. Correlation coefficients were calculated between QOL score and SF-8TM, Patient Health Questionnaire-9 (PHQ-9), Eastern Cooperative Oncology Group Performance Status (ECOG), Memorial Symptom Assessment Scale (MSAS) score. In addition, sociodemographic factors related to QOL score were evaluated. From the perspectives of public health and administrative policy, the results of this survey will provide important basic data to evaluate patient’s behavior survey broadly and continuously with the goal of establishing a palliative care system in Japan.
		                        		
		                        		
		                        		
		                        	
9.Symptom Prevalence, Severity, and Distress Assessed by Memorial Symptom Assessment Scale (MSAS) in the General Population in Japan
Satoko Ito ; Megumi Shimizu ; Akemi Naito ; Kazuki Sato ; Daisuke Fujisawa ; Satoru Tsuneto ; Tatsuya Morita ; Mitsunori Miyashita
Palliative Care Research 2017;12(4):761-770
Understanding the symptoms of the general population has an important role in assessing and improving the quality of palliative care systems. However, there are no reliable epidemiological data on the symptoms of the general population in Japan. The aim of this study was to survey the actual status of the symptoms experienced by the general population in Japan. A large nationwide postal survey was conducted from January through February 2013 in Japan. A total of 2400 subjects were selected randomly from among members of the general population who were 20 to 79 years of age and lived in Japan. The Memorial Symptom Assessment Scale (MSAS) was used to multi-dimensionally evaluate symptoms experienced within the past week, and the Short Form 8™ (SF-8™) was used to assess the health-related quality of life (QOL). A total of 978 (41.1%) self-completed questionnaires were analyzed. The prevalences, severity rates, and distress rates of 35 physical and psychological symptoms were analyzed according to sex and age group. In addition, the relation between symptom severity and the health-related QOL score was evaluated. From the perspectives of public health and administrative policy, the results of this survey will most likely provide important basic data, with the ultimate goal of establishing a palliative care system in Japan.
10.The oncologists' views toward end-of-life discussions
Akiko Tarumi ; Saki Mimatsu ; Tatsuya Morita ; Akemi Naito ; Yasunari Sakamoto ; Takuji Okusaka ; Chikako Shimizu
Palliative Care Research 2016;11(1):301-305
		                        		
		                        			
		                        			End-of-life discussion with patients with advanced cancer is one of the important factors to determine the patient quality of life and their families' grief. The primary aim of this study is to collect Japanese medical oncologists' views toward end-of-life discussion. A context analysis of free comments of the questionnaire survey was conducted. Questionnaires were mailed to 864 medical oncologists, and 490 responses were obtained. A content analysis identified 420 free comments. As barriers of end-of-life discussion for oncologists, three types of barriers were emerged: 1) issues relating to patient and family (e.g., [individuality of the patient and family], [difficulty of acceptance of illness progression]), 2) issues relating to medical professionals (e.g., [a lack of psychological support], [difference in beliefs about end-of-life discussion among medical professionals]), and 3) health care systems (e.g., [a lack of time and human resources], [a lack of education and research]). The findings of this study may be useful to improve mutual understanding of oncologists and palliative care physicians when performing the end-of-life discussion in collaboration.
		                        		
		                        		
		                        		
		                        	
            

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