Background/Aims: Duodenal invasion (DI) is a risk factor for early recurrent biliary obstruction (RBO) in endoscopic retrograde cholangiopancreatography-guided biliary drainage (ERCP-BD). Endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) may reduce early RBO in cases of asymptomatic DI, even when ERCP is possible. Methods: We enrolled 56 patients with pancreatic cancer and asymptomatic DI who underwent EUS-HGS (n=25) or ERCP-BD (n=31). Technical and clinical success, early (<3 months) and overall RBO rates, time to RBO (TRBO), and adverse events were compared between the EUS-HGS and ERCP-BD groups. Risk factors for early RBO were also evaluated. Results: Baseline characteristics were similar between the groups. Both procedures demonstrated 100% technical and clinical success rates, with a similar incidence of adverse events (48% vs. 39%, p=0.59). While the median TRBO was comparable (5.7 vs. 8.8 months, p=0.60), EUS-HGS was associated with a lower incidence of early RBO compared to ERCP-BD (8% vs. 29%, p=0.09). The major causes of early RBO in ERCP-BD were sludge and food impaction, rarely occurring in EUS-HGS. EUS-HGS was potentially reduced early RBO (odds ratio, 0.32; p=0.07). Conclusions EUS-HGS can be a viable option for treating pancreatic cancer with asymptomatic DI.

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.

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.

Background/Aims: Duodenal invasion (DI) is a risk factor for early recurrent biliary obstruction (RBO) in endoscopic retrograde cholangiopancreatography-guided biliary drainage (ERCP-BD). Endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) may reduce early RBO in cases of asymptomatic DI, even when ERCP is possible. Methods: We enrolled 56 patients with pancreatic cancer and asymptomatic DI who underwent EUS-HGS (n=25) or ERCP-BD (n=31). Technical and clinical success, early (<3 months) and overall RBO rates, time to RBO (TRBO), and adverse events were compared between the EUS-HGS and ERCP-BD groups. Risk factors for early RBO were also evaluated. Results: Baseline characteristics were similar between the groups. Both procedures demonstrated 100% technical and clinical success rates, with a similar incidence of adverse events (48% vs. 39%, p=0.59). While the median TRBO was comparable (5.7 vs. 8.8 months, p=0.60), EUS-HGS was associated with a lower incidence of early RBO compared to ERCP-BD (8% vs. 29%, p=0.09). The major causes of early RBO in ERCP-BD were sludge and food impaction, rarely occurring in EUS-HGS. EUS-HGS was potentially reduced early RBO (odds ratio, 0.32; p=0.07). Conclusions EUS-HGS can be a viable option for treating pancreatic cancer with asymptomatic DI.

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.

Background/Aims: Duodenal invasion (DI) is a risk factor for early recurrent biliary obstruction (RBO) in endoscopic retrograde cholangiopancreatography-guided biliary drainage (ERCP-BD). Endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) may reduce early RBO in cases of asymptomatic DI, even when ERCP is possible. Methods: We enrolled 56 patients with pancreatic cancer and asymptomatic DI who underwent EUS-HGS (n=25) or ERCP-BD (n=31). Technical and clinical success, early (<3 months) and overall RBO rates, time to RBO (TRBO), and adverse events were compared between the EUS-HGS and ERCP-BD groups. Risk factors for early RBO were also evaluated. Results: Baseline characteristics were similar between the groups. Both procedures demonstrated 100% technical and clinical success rates, with a similar incidence of adverse events (48% vs. 39%, p=0.59). While the median TRBO was comparable (5.7 vs. 8.8 months, p=0.60), EUS-HGS was associated with a lower incidence of early RBO compared to ERCP-BD (8% vs. 29%, p=0.09). The major causes of early RBO in ERCP-BD were sludge and food impaction, rarely occurring in EUS-HGS. EUS-HGS was potentially reduced early RBO (odds ratio, 0.32; p=0.07). Conclusions EUS-HGS can be a viable option for treating pancreatic cancer with asymptomatic DI.

BACKGROUND: Many factors are associated with the development and progression of liver fat and fibrosis; however, genetics and the gut microbiota are representative factors. Moreover, recent studies have indicated a link between host genes and the gut microbiota. This study investigated the effect of patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 (C > G), which has been reported to be most involved in the onset and progression of fatty liver, on liver fat and fibrosis in a cohort study related to gut microbiota in a non-fatty liver population. METHODS: This cohort study included 214 participants from the health check-up project in 2018 and 2022 who had non-fatty liver with controlled attenuation parameter (CAP) values <248 dB/m by FibroScan and were non-drinkers. Changes in CAP values and liver stiffness measurement (LSM), liver-related items, and gut microbiota from 2018 to 2022 were investigated separately for PNPLA3 rs738409 CC, CG, and GG genotypes. RESULTS: Baseline values showed no difference among the PNPLA3 rs738409 genotypes for any of the measurement items. From 2018 to 2022, the PNPLA3 rs738409 CG and GG genotype groups showed a significant increase in CAP and body mass index; no significant change was observed in the CC genotype group. LSM increased in all genotypes, but the rate of increase was highest in the GG genotype, followed by the CG and CC genotypes. Fasting blood glucose levels increased in all genotypes; however, HOMA-IR (Homeostasis Model Assessment of Insulin Resistance) increased significantly only in the GG genotype. HDL (high-density lipoprotein) and LDL (low-density lipoprotein) cholesterol levels significantly increased in all genotypes, whereas triglycerides did not show any significant changes in any genotype. As for the gut microbiota, the relative abundance of Feacalibacterium in the PNPLA3 rs738409 GG genotype decreased by 2% over 4 years, more than 2-fold compared to CC and GG genotypes. Blautia increased significantly in the CC group. CONCLUSION The results suggest that PNPLA3 G-allele carriers of non-fatty liver develop liver fat and fibrosis due to not only obesity and insulin resistance but also the deterioration of gut microbiota, which may require a relatively long course of time, even years.
Humans ; Gastrointestinal Microbiome ; Male ; Female ; Membrane Proteins/metabolism* ; Lipase/genetics* ; Middle Aged ; Liver Cirrhosis/epidemiology* ; Cohort Studies ; Genotype ; Adult ; Non-alcoholic Fatty Liver Disease/microbiology* ; Polymorphism, Single Nucleotide ; Acyltransferases ; Phospholipases A2, Calcium-Independent

Our extensive basic research on photodynamic therapy (PDT) application in models of intracranial malignant astrocytoma led to its clinical application for intracranial malignant astrocytoma in Japan. Having considered the safety and effectiveness of this pathology, we initiate a first-in-human clinical study of PDT for spinal cord malignant astrocytoma. This study has an open-label, single-arm design. The initial follow-up period is 12 months, at the end of which we will quantify survival after PDT for spinal cord malignant astrocytoma as primary objective. The secondary objective is to quantify the overall progression-free survival of treated patients and the percentage of patients surviving 6 months after PDT without recurrence. Twenty patients suffering from spinal cord malignant astrocytoma will be recruited. In particular, 10 of those should be newly diagnosed World Health Organization grade 4. After obtaining consent, each patient will receive a single intravenous injection of talaporfin sodium (40 mg/m2) 1 day before tumor resection. One day after completing tumor removal, the residual lesion and/or resection cavity will be irradiated using a 664-nm semiconductor laser with a radiation power density of 150 mW/cm2 and a radiation energy density of 27 J/cm2. The procedure will be performed 22–26 hours after talaporfin sodium administration. This study protocol has been reviewed and approved by the Certified Committee in the Japanese Ministry of Health, Labor, and Welfare University Hospital Medical Information Network Clinical Trials Registry (Japan Registry of Clinical Trials number, jRCT2021220040).

Our extensive basic research on photodynamic therapy (PDT) application in models of intracranial malignant astrocytoma led to its clinical application for intracranial malignant astrocytoma in Japan. Having considered the safety and effectiveness of this pathology, we initiate a first-in-human clinical study of PDT for spinal cord malignant astrocytoma. This study has an open-label, single-arm design. The initial follow-up period is 12 months, at the end of which we will quantify survival after PDT for spinal cord malignant astrocytoma as primary objective. The secondary objective is to quantify the overall progression-free survival of treated patients and the percentage of patients surviving 6 months after PDT without recurrence. Twenty patients suffering from spinal cord malignant astrocytoma will be recruited. In particular, 10 of those should be newly diagnosed World Health Organization grade 4. After obtaining consent, each patient will receive a single intravenous injection of talaporfin sodium (40 mg/m2) 1 day before tumor resection. One day after completing tumor removal, the residual lesion and/or resection cavity will be irradiated using a 664-nm semiconductor laser with a radiation power density of 150 mW/cm2 and a radiation energy density of 27 J/cm2. The procedure will be performed 22–26 hours after talaporfin sodium administration. This study protocol has been reviewed and approved by the Certified Committee in the Japanese Ministry of Health, Labor, and Welfare University Hospital Medical Information Network Clinical Trials Registry (Japan Registry of Clinical Trials number, jRCT2021220040).

Our extensive basic research on photodynamic therapy (PDT) application in models of intracranial malignant astrocytoma led to its clinical application for intracranial malignant astrocytoma in Japan. Having considered the safety and effectiveness of this pathology, we initiate a first-in-human clinical study of PDT for spinal cord malignant astrocytoma. This study has an open-label, single-arm design. The initial follow-up period is 12 months, at the end of which we will quantify survival after PDT for spinal cord malignant astrocytoma as primary objective. The secondary objective is to quantify the overall progression-free survival of treated patients and the percentage of patients surviving 6 months after PDT without recurrence. Twenty patients suffering from spinal cord malignant astrocytoma will be recruited. In particular, 10 of those should be newly diagnosed World Health Organization grade 4. After obtaining consent, each patient will receive a single intravenous injection of talaporfin sodium (40 mg/m2) 1 day before tumor resection. One day after completing tumor removal, the residual lesion and/or resection cavity will be irradiated using a 664-nm semiconductor laser with a radiation power density of 150 mW/cm2 and a radiation energy density of 27 J/cm2. The procedure will be performed 22–26 hours after talaporfin sodium administration. This study protocol has been reviewed and approved by the Certified Committee in the Japanese Ministry of Health, Labor, and Welfare University Hospital Medical Information Network Clinical Trials Registry (Japan Registry of Clinical Trials number, jRCT2021220040).