Background: and Purpose Neuropsychiatric symptoms (NPS) are frequent in dementia and mild cognitive impairment (MCI), yet their reported associations with white matter hyperintensities (WMHs) remain inconsistent. We examined item-level associations between WMHs and NPS across Alzheimer’s disease dementia (ADD), dementia with Lewy bodies (DLB), and amnestic MCI (aMCI). Methods: This multicenter retrospective study involved 523 patients: 276 with ADD, 67 with DLB, and 180 with aMCI. Three-dimensional T1-weighted and T2–fluid-attenuated inversion recovery magnetic resonance images were processed with BAAD (Brain Anatomical Analysis using Diffeomorphic Deformation) software to quantify WMH volume (WMHV) and gray matter volume (GMV), normalized to total intracranial volume (TIV). NPS were assessed using the Neuropsychiatric Inventory. Multiple regression analyses were performed within each group, adjusting for GMV/TIV, age, sex, years of education, Clinical Dementia Rating–Sum of Boxes score, and institution. Results: In the aMCI group, higher WMHV/TIV was positively associated with depression, apathy, and disinhibition, and negatively with delusions. Subregional analyses revealed NPSspecific topographic patterns. No significant associations were detected in the ADD or DLB group. GMV/TIV was positively associated with delusions in the ADD group, but negatively associated with hallucinations in the DLB group. Conclusions Associations between WMHs and NPS were evident in the aMCI group but absent in the ADD and DLB groups, suggesting a stage-dependent effect. WMHs may contribute to NPS primarily in prodromal stages, whereas their influence may be overshadowed by neurodegenerative pathology in dementia. Clarifying the mechanisms underlying WMHs is critical for evaluating their potential as intervention targets.

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.

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: Signal transducer and activator of transcription 3 (STAT3) plays key roles in regulating cancer cell proliferation, survival, and metastasis. We aimed to determine the effects of YHO-1701, an oral STAT3 inhibitor, in ovarian cancer (OC). Methods: We evaluated the impact of YHO-1701 on cell growth in patient-derived cells (PDCs) and OC cell lines using standard cell proliferation assays. Spheroid models derived from PDCs were assessed using three-dimensional (3D) cell viability assays. Antitumor activity was performed in SKOV3 xenograft mice treated orally administrated YHO-1701 with 20 mg/kg.Changes in STAT3 signaling were analyzed by western blotting. The molecular mechanisms of STAT3 inhibition were investigated by sequencing RNA and analyzing pathways in the SKOV3 using a small interfering RNA targeting STAT3 (STAT3 siRNA) and YHO-1701. Results: YHO-1701 inhibited the growth of OC cell lines by preventing STAT3 dimerization and decreasing the expression of its downstream signaling molecule, survivin. The growth of PDCs and spheroids obtained from patients with primary and recurrent OCs was significantly inhibited. Antitumor effect was observed in the SKOV3 xenograft mice with YHO-1701. YHO-1701 induced apoptosis in OC cells. Additionally, p53 and/or MAPK signaling pathways were upregulated in SKOV3 cells incubated with YHO-1701 and in those with STAT3 siRNA. Conclusion Our results showed that YHO-1701 suppressed cell growth in PDCs of OC, accompanied by survivin inhibition, and a decrease in the number of peritoneal metastasis in the mice by YHO-1701, compared with those treated with control. Therefore, YHO-1701 could be a promising candidate agent for treating OC

The Japan Society of Gynecologic Oncology (JSGO) guideline for the treatment of uterine body neoplasm are revised from the 2018 guideline. This guideline aimed to provide standardized care for uterine body neoplasm, indicate appropriate current treatment methods for uterine body neoplasm, minimize variances in treatment methods among institutions, improve disease prognosis and treatment safety, reduce the economic and psychosomatic burden on patients by promoting the performance of appropriate treatment, and enhance mutual understanding between patients and healthcare professionals. The guidelines were prepared through the consensus of the JSGO guideline committee, based on a careful review of evidence from the literature searches and the medical health insurance system and actual clinical practice situations in Japan. The main features of the 2023 revision are as follows: 1) The Guidelines Formulation Committee members were asked to understand Minds' medical guideline development method in advance. 2) The clinical question (CQ) was changed to Patient, Intervention, Comparison, Outcome format as much as possible. 3) Introduced the "body of evidence," which summarizes the results of research reports collected for the CQs by outcome and study design, and the strength of evidence for each body of evidence was rated from levels A to D. 4) Introduction of systematic reviews in some CQs. 5) The strength of evidence, the balance of benefits and harms, value and hope for patients, and clinical applicability were considered while drafting recommendations. Herein, we present the English version of the JSGO guidelines 2023 for the treatment of uterine body neoplasm.

Objective: The wrong dose of high-risk drugs such as oral steroids is a serious issue that needs to be addressed. This study aims to determine the appropriate upper tolerable dose threshold and to develop a multi-variable logistic regression model to detect dose-errors in oral prednisolone tablets.Methods: Data on Prednisolone prescriptions were obtained from a single center. Out of the data collected, positive cases consisted of cases where dose-related modifications were made. A univariate logistic regression model was developed with the current daily dose. In the model, the Youden Index was used to determine the upper tolerable dose threshold. The investigation was done to determine whether the performance of the multivariate model was improved by adding clinical department and previous prescription information as variables.Results: Univariate models (AUC: 0.645) with only current daily doses and estimated optimal thresholds of 6 mg/day or 11 mg/day, respectively were determined to be appropriate. Including variables improved the performance of the predictive model; the best performing model (AUC: 0.840) was derived when the following variables were entered: “current daily dose,” “current prescription days,” “clinical department,” “daily dose of the previous prescription,” and “prescription days of the previous prescription”.Conclusion: A single upper tolerance limit is insufficient to determine dose adequacy for prednisolone tablets owing to their broad clinical dose range. Itmay be possible to develop a high-performance dose audit support model by adding information.

Methods: Nineteen volunteers (16 men, three women) lifted a 60-kg doll from a seated position to a standing position. The first transfer was performed without the HAL for Care Support, and the second was performed with the HAL for Care Support assistive robot. We evaluated transfer performance, the visual analog scale (VAS) score for lumbar fatigue, and electromyogram analyses of the trunk and hip. Results: Four participants (two men, two women) succeeded with the HAL for Care Support even though they were unable to perform the task without it. The mean lumbar fatigue VAS score for all participants without the HAL for Care Support was 62 mm, while that with it was 43 mm. With lumbar assistance from the HAL for Care Support, subjective lumbar fatigue during the transfer decreased significantly. A power analysis indicated adequate statistical power to detect a difference in the VAS score for lumbar fatigue (0.99). The activity of the left gluteus maximus alone increased significantly during transfers with the HAL for Care Support. No adverse events occurred during use of the HAL for Care Support for transfers. Conclusions The HAL for Care Support was able to reduce lumbar load in a simulated patient transfer.

Background/Aims: Endoscopic resection (ER) for superficial non-ampullary duodenal epithelial tumors (SNADETs) is challenging. Conventional endoscopic mucosal resection (CEMR) is also problematic due to the anatomical features of the duodenum. We compared the safety and efficacy of underwater endoscopic mucosal resection (UEMR) with those of CEMR through a retrospective analysis. Methods: Altogether, 44 consecutive patients with 46 SNADETs underwent ER (18 CEMR cases and 28 UEMR cases) between January 2016 and October 2019. We investigated the proportions of en bloc resection, R0 resection, complications, resection time, and total procedure time and compared the outcomes of patients from the CEMR group with those of patients from the UEMR group. Results: The median tumor size was 8.0 mm (range, 2.0–20.0 mm). The UEMR group showed a higher proportion of en bloc resection (96.4% vs. 72.2%, p<0.05) and significantly lower median resection time and total procedure time (4 min vs. 9.5 min, p<0.05 and 13 min vs. 19 min, p<0.05; respectively) than the CEMR group. No complications were observed. However, two patients treated with piecemeal resection in the CEMR group had residual tumors. Conclusions UEMR is a feasible therapeutic option for SNADETs. It can be recommended as a standard treatment.

Background/Aims: Endoscopic resection (ER) for superficial non-ampullary duodenal epithelial tumors (SNADETs) is challenging. Conventional endoscopic mucosal resection (CEMR) is also problematic due to the anatomical features of the duodenum. We compared the safety and efficacy of underwater endoscopic mucosal resection (UEMR) with those of CEMR through a retrospective analysis. Methods: Altogether, 44 consecutive patients with 46 SNADETs underwent ER (18 CEMR cases and 28 UEMR cases) between January 2016 and October 2019. We investigated the proportions of en bloc resection, R0 resection, complications, resection time, and total procedure time and compared the outcomes of patients from the CEMR group with those of patients from the UEMR group. Results: The median tumor size was 8.0 mm (range, 2.0–20.0 mm). The UEMR group showed a higher proportion of en bloc resection (96.4% vs. 72.2%, p<0.05) and significantly lower median resection time and total procedure time (4 min vs. 9.5 min, p<0.05 and 13 min vs. 19 min, p<0.05; respectively) than the CEMR group. No complications were observed. However, two patients treated with piecemeal resection in the CEMR group had residual tumors. Conclusions UEMR is a feasible therapeutic option for SNADETs. It can be recommended as a standard treatment.