Risk factors for the long-term persistent genitourinary toxicity after stereotactic body radiation therapy for localized prostate cancer: A single-center, retrospective study of 306 patients.

OBJECTIVES: To identify risk factors for the long-term persistent genitourinary toxicity (GUT) after stereotactic body radiation therapy (SBRT) for localized prostate cancer (PCa). METHODS: A total of 306 patients who underwent SBRT at our institution between March 2017 and April 2022 were retrospectively evaluated. SBRT was performed at 35 Gy in five fractions over 5 or 10 days. Factors related to the long-term persistence of acute GUT after SBRT were analyzed. RESULTS: During the median follow-up period of 39.1 months, 203 (66%) patients experienced any grade of acute GUT, which remained in 78 (26%) patients 6 months after SBRT. Multivariate analysis revealed that age ≥75 years was consistently a significant independent risk factor for any grade of acute GUT 6, 12, and 24 months after SBRT (hazard ratio [HR] 2.31, p = 0.010; HR 2.84, p = 0001; and HR 3.05, p = 0.009, respectively). Older age was not a significant risk factor for the development of grade ≥2 acute GUT. The duration of acute GUT was significantly longer in the older group than in the nonolder group (median duration = 234 vs. 61 days, p < 0.001), and the incidence of persistent GUT was significantly more frequent in the older group beyond 6 months after SBRT. CONCLUSIONS: Older age is a significant independent risk factor for the long-term persistent GUT after SBRT for localized PCa.

Validity of identification algorithms combining diagnostic codes with other measures for acute ischemic stroke in MID-NET®.

PURPOSE: We aimed to develop a reliable identification algorithm combining diagnostic codes with several treatment factors for inpatients with acute ischemic stroke (AIS) to conduct pharmacoepidemiological studies using the administrative database MID-NET® in Japan. METHODS: We validated 11 identification algorithms based on 56 different diagnostic codes (International Classification of Diseases, Tenth Revision; ICD-10) using Diagnosis Procedure Combination (DPC) data combined with information on AIS therapeutic procedures added as "AND" condition or "OR" condition. The target population for this study was 366 randomly selected hospitalized patients with possible cases of AIS, defined as relevant ICD-10 codes and diagnostic imaging and prescription or surgical procedure, in three institutions between April 1, 2015 and March 31, 2017. We determined the positive predictive values (PPVs) of these identification algorithms based on comparisons with a gold standard consisting of chart reviews by experienced specialist physicians. Additionally, the sensitivities of them among 166 patients with the possible cases of AIS at a single institution were evaluated. RESULTS: The PPVs were 0.618 (95% confidence interval [CI]: 0.566-0.667) to 0.909 (95% CI: 0.708-0.989) and progressively increased with adding or limiting information on AIS therapeutic procedures as "AND" condition in the identification algorithms. The PPVs for identification algorithms based on diagnostic codes I63.x were >0.8. However, the sensitivities progressively decreased to a maximum of ~0.2 after adding information on AIS therapeutic procedures as "AND" condition. CONCLUSIONS: The identification algorithms based on the combination of appropriate ICD-10 diagnostic codes in DPC data and other AIS treatment factors may be useful to studies for AIS at a national level using MID-NET®.

Perioperative Clinical Course Variables Associated with Length of Hospital Stay after Primary Intracranial Meningioma Resection.

The relationship between perioperative clinical course variables and postoperative length of hospital stay (LOS) in patients undergoing primary intracranial meningioma resection has not been fully elucidated. We therefore aimed to identify the perioperative clinical course variables that predict postoperative LOS in such patients. We retrospectively collected data concerning demographics, tumor characteristics, and perioperative clinical course variables in 76 patients who underwent primary intracranial meningioma resection between January 2010 and December 2019, and tested for associations with postoperative LOS. Univariate analyses showed that younger age, fewer days to postoperative initiation of standing/walking, preoperative independence in activities of daily living (ADL), and ADL independence one week after surgery were associated with shorter postoperative LOS. Multiple regression analyses with these factors identified that days to stand/walk initiation and ADL independence one week after surgery were associated with postoperative LOS. Based on these results, we conclude that rehabilitation programs that promote early mobilization and the early acquisition of independence may reduce postoperative LOS in patients who undergo primary intracranial meningioma resection.

Risk factors and predictive model for incidence of difficult ureter during retrograde ureteroscopic lithotripsy.

OBJECTIVE: Difficult ureter can be a challenge for accessing upper urinary tract during lithotripsy. In this study, we evaluated the risk factors for the incidence of difficult ureter in retrograde ureteroscopic lithotripsy. Moreover, we aimed to develop a predictive model for the incidence of difficult ureter. METHODS: We retrospectively reviewed consecutive retrograde ureteroscopic lithotripsies performed at our institution between 2009 and 2021. A total of 1010 renal units were evaluated: 449 units with renal stones only and 561 units with ureteral stones, with or without renal stones. RESULTS: The overall incidence of difficult ureter was 5.9%, with a higher incidence in the renal alone stone group than in the ureteral stone group (7.8% vs 4.5%, P = 0.026). Multivariate regression analysis revealed three risk factors for the incidence of difficult ureter: absence of stone history (odds ratio 5.67, 95% confidence interval 2.40-13.4, and P < 0.001), age ≤45 years (odds ratio 3.61, 95% confidence interval 2.05-6.37, and P < 0.001), and renal stone only (odds ratio 2.11, 95% confidence interval 1.22-3.64, and P = 0.008). A simple model using these three risks enabled the stratification of the incidence rate of difficult ureter, with the incidence of high-risk cases being 12.7%. CONCLUSIONS: The greatest risk factor for the incidence of difficult ureter was the absence of stone history, followed by age 45 years or younger, and having only renal stones. In high-risk cases of difficult ureter, the possibility of secondary lithotripsy should be explained to the patients.

Long-term Multidisciplinary Rehabilitation Efficacy in Older Patients After Traumatic Brain Injury: Assessed by the Functional Independence Measure.

Instances of traumatic brain injury (TBI) in the elderly have been increasing along with the aging of popula-tions. In the present study, we examined the effect of aging on long-term multidisciplinary in-patient rehabili-tation efficacy after TBI. Sixty-three patients with physical and cognitive impairments after TBI were enrolled in this study. Patients were divided into 4 age groups (≤ 24, 25-44, 45-64, ≥ 65 years) and the clinical charac-teristics and rehabilitation efficacy of each age group were determined. Functional disability was evaluated using motor and cognitive Functional Independence Measure (FIM) scores. Rehabilitation efficacy was assessed by FIM gains during rehabilitation and compared among the groups. There were no statistically significant dif-ferences in motor and cognitive FIM gains among the age groups. However, cognitive FIM gain was limited in a subset of ≥ 65 patients, and initial cognitive measures could not predict cognitive FIM improvement. These results indicate that chronological age is insufficient to accurately predict rehabilitation efficacy in older TBI patients, and that such patients should be considered candidates for intensive rehabilitation programs based on these results. Accurate prognostication of rehabilitation efficacy with continuing data collection is important when using rehabilitation resources for older TBI patients.

[Points to Note about Neuropsychological Impairment in the Acute Management of Traumatic Brain Injury].

Neuropsychological impairment after traumatic brain injury(TBI)is occasionally difficult to diagnose and called "invisible or hidden impairment," especially when physical impairment is mild. Patients and their family do not recognize the impairment during hospitalization and even after discharge. However, they manifest many problems when they return to real life and society. Here, we have presented the characteristics and tips to diagnose neuropsychological impairment after TBI that are important for clinical neurosurgeons working at acute care hospitals. They are as follows: 1)In the emergency room, accurate evaluation of the consciousness state is the first step. 2)In the acute phase after TBI, do not mix up acute symptomatic seizure and post-traumatic epilepsy. 3)Soon after stabilization of the general condition, detailed radiological examinations should be performed to detect organic brain damages with MRI including DWI, FLAIR, T2*, and SWI. 4)At discharge, it is necessary to provide information about neuropsychological impairment to the patients and their family members. Neurosurgeons should diagnose and treat the patients with accurate understanding of neuropsychological impairment in the acute management of TBI.

A rare case of BRAF V600E-mutated epithelioid glioblastoma with a sarcomatous component.

Epithelioid glioblastoma is a rare subtype of glioblastoma, but the coexistence of a sarcomatous component is even rarer. An 80-year-old woman was admitted to our hospital with somnolence. Magnetic resonance imaging revealed a cystic lesion with a solid component in the left temporal-parietal lobe. Histopathological examination of the resected tumor revealed three components; namely, typical glioblastoma, sarcomatous and epithelioid components at a ratio of about 5:3:2. All components were immunohistochemically positive for vimentin and mutated BRAF (V600E) and showed focal expression of glial fibrillary acidic protein and cytokeratin AE1/AE3, but they were negative for isocitrate dehydrogenase 1. Genetic analysis revealed that both the sarcomatous and epithelioid components harbored BRAF T1799A (V600E) mutation and homozygous deletion of cyclin-dependent kinase inhibitor 2A/B. We diagnosed this tumor as epithelial glioblastoma with a sarcomatous component. Our results indicate that even when the epithelial component is not dominant, immunohistochemical and genetic investigation of BRAF mutations is useful for the diagnosis of glioblastoma subtypes. In particular, although the prognosis of epithelial glioblastoma is poor, potentially effective targeted therapies for BRAF V600E-mutated tumors are available.

Persistent restoration to the immunosupportive tumor microenvironment in glioblastoma by bevacizumab.

Although vascular endothelial growth factor (VEGF) promotes the immunosuppressive microenvironment, the efficacy of bevacizumab (Bev) on tumor immunity has not been fully investigated. The present study used 47 glioblastoma tissues obtained at 3 different settings: tumors of initial resection (naïve Bev group), tumors resected following Bev therapy (effective Bev group), and recurrent tumors after Bev therapy (refractory Bev group). The paired samples of the initial and post-Bev recurrent tumors from 9 patients were included. The expression of programmed cell death-1 (PD-1)/PD ligand-1 (PD-L1), CD3, CD8, Foxp3, and CD163 was analyzed by immunohistochemistry. The PD-L1+ tumor cells significantly decreased in the effective or refractory Bev group compared with the naïve Bev group (P < .01 for each). The PD-1+ cells significantly decreased in the effective or refractory Bev group compared with the naïve Bev group (P < .01 for each). The amount of CD3+ and CD8+ T cell infiltration increased in the refractory Bev group compared with the naïve Bev group (CD3, P < .01; CD8, P = .06). Both Foxp3+ regulatory T cells and CD163+ tumor-associated macrophages significantly decreased in the effective or refractory Bev group compared with the naïve Bev group (Foxp3, P < .01 for each; CD163, P < .01 for each). These findings were largely confirmed by comparing paired initial and post-Bev recurrent tumors. Bevacizumab restores the immunosupportive tumor microenvironment in glioblastomas, and this effect persists during long-term Bev therapy.

Histidine-rich Glycoprotein Could Be an Early Predictor of Vasospasm after Aneurysmal Subarachnoid Hemorrhage.

Cerebral vasospasm (CVS) is a major contributor to the high morbidity and mortality of aneurysmal subarachnoid hemorrhage (aSAH) patients. We measured histidine-rich glycoprotein (HRG), a new biomarker of aSAH, in cerebrospinal fluid (CSF) to investigate whether HRG might be an early predictor of CVS. A total of seven controls and 14 aSAH patients (8 males, 6 females aged 53.4±15.4 years) were enrolled, and serial CSF and serum samples were taken. We allocated these samples to three phases (T1-T3) and measured HRG, interleukin (IL)-6, fibrinopeptide A (FpA), and 8-hydroxy-2'-deoxyguanosine (8OHdG) in the CSF, and the HRG in serum. We also examined the release of HRG in rat blood incubated in artificial CSF. In contrast to the other biomarkers examined, the change in the CSF HRG concentration was significantly different between the nonspasm and spasm groups (p<0.01). The rat blood/CSF model revealed a time course similar to that of the human CSF samples in the non-spasm group. HRG thus appears to have the potential to become an early predictor of CVS. In addition, the interaction of HRG with IL-6, FpA, and 8OHdG may form the pathology of CVS.

Development of a powered variable-stiffness exoskeleton device for elbow rehabilitation.

Robot-assisted movement training by means of exoskeleton devices has been proven to be an effective method for post-stroke patients to recover their motor function. However, in order to be used in home-based rehabilitation, the kinematic structure of a wearable exoskeleton device should provide portability and make allowances for the natural joint range of motion for the user. Additionally, the actuated stiffness of the target joint is desired to be adjustable in accordance with the specific impairment level of the patient's upper limb. In this paper, we present a novel portable exoskeleton device which could provide support for rehabilitation patients with variable actuated stiffness in the elbow joint. It has five passive degrees of freedom to guarantee the user's natural joint range of motion and intra-subject variability, as well as an integrated variable stiffness actuator (VSA) which can adjust the joint stiffness independently by moving the pivot position. An elbow power-assist trial with different actuated joint stiffnesses was tested on a healthy subject to evaluate the functionality of the proposed device. By regulating the joint stiffness, the proposed device could provide variable power assistance for the wearer's elbow movements.

A marker-based contactless catheter-sensing method to detect surgeons' operations for catheterization training systems.

It is challenging to position a catheter or a guidewire within a patient's complicated and delicate vascular structure due to the lack of intuitive visual feedback by only manipulating the proximal part of the surgical instruments. Training is therefore critical before an actual surgery because any mistake due to the surgeon's inexperience can be fatal for the patient. The catheter manipulation skills of experienced surgeons can be useful as input for training novice surgeons. However, few research groups focused on designs with consideration of the contactless catheter motion measurement, which allows obtaining expert surgeons' catheter manipulation trajectories whilst still allowing them to employ an actual catheter and apply conventional pull, push and twist of the catheter as used in bedside intravascular interventional surgeries. In this paper, a novel contactless catheter-sensing method is proposed to measure the catheter motions by detecting and tracking a passive marker with four feature-point groups. The passive marker is designed to allow simultaneously sensing the translational and rotational motions of the input catheter. Finally, the effectiveness of the proposed contactless catheter-sensing method is validated by conducting a series of comparison experiments. The accuracy and error analysis are quantified based on the absolute error, relative error, mean absolute error, and the success rate of the detection.

Design and performance evaluation of collision protection-based safety operation for a haptic robot-assisted catheter operating system.

The robot-assisted catheter system can increase operating distance thus preventing the exposure radiation of the surgeon to X-ray for endovascular catheterization. However, few designs have considered the collision protection between the catheter tip and the vessel wall. This paper presents a novel catheter operating system based on tissue protection to prevent vessel puncture caused by collision. The integrated haptic interface not only allows the operator to feel the real force feedback, but also combines with the newly proposed collision protection mechanism (CPM) to mitigate the collision trauma. The CPM can release the catheter quickly when the measured force exceeds a certain threshold, so as to avoid the vessel puncture. A significant advantage is that the proposed mechanism can adjust the protection threshold in real time by the current according to the actual characteristics of the blood vessel. To verify the effectiveness of the tissue protection by the system, the evaluation experiments in vitro were carried out. The results show that the further collision damage can be effectively prevented by the CPM, which implies the realization of relative safe catheterization. This research provides some insights into the functional improvements of safe and reliable robot-assisted catheter systems.

Performance evaluation of a robot-assisted catheter operating system with haptic feedback.

In this paper, a novel robot-assisted catheter operating system (RCOS) has been proposed as a method to reduce physical stress and X-ray exposure time to physicians during endovascular procedures. The unique design of this system allows the physician to apply conventional bedside catheterization skills (advance, retreat and rotate) to an input catheter, which is placed at the master side to control another patient catheter placed at the slave side. For this purpose, a magnetorheological (MR) fluids-based master haptic interface has been developed to measure the axial and radial motions of an input catheter, as well as to provide the haptic feedback to the physician during the operation. In order to achieve a quick response of the haptic force in the master haptic interface, a hall sensor-based closed-loop control strategy is employed. In slave side, a catheter manipulator is presented to deliver the patient catheter, according to position commands received from the master haptic interface. The contact forces between the patient catheter and blood vessel system can be measured by designed force sensor unit of catheter manipulator. Four levels of haptic force are provided to make the operator aware of the resistance encountered by the patient catheter during the insertion procedure. The catheter manipulator was evaluated for precision positioning. The time lag from the sensed motion to replicated motion is tested. To verify the efficacy of the proposed haptic feedback method, the evaluation experiments in vitro are carried out. The results demonstrate that the proposed system has the ability to enable decreasing the contact forces between the catheter and vasculature.

Blood Glucose Variability: A Strong Independent Predictor of Neurological Outcomes in Aneurysmal Subarachnoid Hemorrhage.

PURPOSE: In patients with aneurysmal subarachnoid hemorrhage (SAH), increased glucose variability (GV) is associated with increased mortality and cerebral infarction; however, there are no reports demonstrating an association between GV and neurological outcome. This study investigated whether GV had an independent effect on neurological outcomes in patients with SAH in the intensive care unit. MATERIALS AND METHODS: Consecutive adult patients hospitalized with SAH between January 1, 2009, and May 31, 2015 (N = 122) were retrospectively reviewed. Univariate/multivariate analyses were performed to identify independent predictors of poor neurological outcome. Patients were divided according to the mean glucose level (80-139 vs 140-200 mg/dL) and further subdivided using quartiles (Q) of the standard deviation (SD, representing variability) of the glucose level (Q1, Q2 + 3, and Q4). RESULTS: Unfavorable neurological outcomes occurred in 44.2% of the patients. On multiple regression analysis, age, Hunt and Kosnik grade, SD of glucose (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.02-1.17; P < .01), and minimum blood glucose level (OR, 0.95; 95% CI, 0.91-0.99; P < .01) were significantly associated with unfavorable neurological outcomes. Both groups (mean glucose levels: 80-139 and 140-200 mg/dL groups) had increasing unfavorable neurological outcomes with increasing SD of glucose (Q1, 15.0%; Q2 + 3, 40.0%; Q4, 52.4% and Q1, 44.4%; Q2 + 3, 50%; Q4, 88.9% in the 80-139 and 140-200 mg/dL groups, respectively). Patients with minimum glucose of <90 mg/dL comprised >50% of unfavorable neurological outcome. CONCLUSION: Increased GV was an independent predictor of unfavorable neurological outcomes in patients with SAH.

Flow-metabolism uncoupling in the cervical spinal cord of ALS patients.

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease. In ALS, both glucose consumption and neuronal intensity reportedly decrease in the cerebral motor cortex when measured by positron emission tomography (PET). In this study, we evaluated cervical spinal glucose metabolism, blood flow, and neuronal intensity of 10 ALS patients with upper extremity (U/E) atrophy both with 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) PET and 11C-flumazenil (11C-FMZ) PET. On the ipsilateral side of C5 and T1 levels, 18F-FDG uptake increased significantly (*p < 0.05), and was correlated with the rate of progression of the ALS FRS-R-U/E score (R = 0.645, *p = 0.041). Despite this hyperglucose metabolism, the 11C-FMZ PET study did not show a coupled increase of spinal blood flow even though neuronal intensity did not decrease. These results indicate a strong correlation between hyperglucose metabolism and ALS progression alongside the uncoupling of flow-metabolism. This mechanism, which could result in subsequent motor neuronal death, may be a potential therapeutic target for ALS.

Expression of 58-kD Microspherule Protein (MSP58) is Highly Correlated with PET Imaging of Tumor Malignancy and Cell Proliferation in Glioma Patients.

BACKGROUND/AIMS: The nucleolar 58-kDa microspherule protein (MSP58) has important transcriptional regulation functions and plays a crucial role in the tumorigenesis and progression of cancers. 3'-deoxy-3'-[18F]fluorothymidine (FLT) has emerged as a promising positron emission tomography (PET) tracer for evaluating tumor malignancy and cell proliferation. METHODS: In the present study, the expression of MSP58 was evaluated by immunohistochemistry and the corresponding PET image was examined using FLT-PET in 55 patients with various grades of gliomas. RESULTS: The immunoreactivity score (IRS) of MSP58 increased with tumor grade with grade IV gliomas exhibiting the highest expression and showed a highly significant positive correlation with the Ki-67 index (r = 0.65, P < 0.001). The IRS of MSP58 in the tumor showed a highly significant positive correlation with corresponding FLT uptake value (r = 0.61, P < 0.001). The correlation between MSP58 expression and glioma malignancy was also confirmed by immunofluorescence, RT-PCR and western blot analysis. FLT uptake value also exhibited a highly significant positive correlation with the Ki-67 index (r = 0.59, P < 0.001). Kaplan-Meier analysis revealed that MSP58 expression has a significant prognostic ability for the overall survival time similar to that found in the uptake value of FLT-PET. CONCLUSION: These results indicate that MSP58 plays an important role in cell proliferation and will be one of the potential candidates of molecular therapy targeting proliferation. FLT-PET might be used as an early measure of treatment response in the proliferation-targeted therapy.

d-Allose Attenuates Overexpression of Inflammatory Cytokines after Cerebral Ischemia/Reperfusion Injury in Gerbil.

BACKGROUND: The present study investigates the effects of d-allose, a rare sugar, on the inflammatory response after transient forebrain ischemia in the gerbil and whether it reduces oxidative stress (8-hydroxyl-2'-deoxyguanosine levels) and behavioral deficits. METHODS: Transient forebrain ischemia was induced by occlusion of the bilateral common carotid arteries for 5 minutes. d-Allose was intraperitoneally injected immediately after ischemia (400 mg/kg). Inflammatory cytokines and oxidative damage in the hippocampus and behavioral deficits were examined 3 days after ischemia. RESULTS: d-Allose administration reduced ischemia-induced cytokine production, oxidative stress, and behavioral deficits (motor and memory related). CONCLUSIONS: The present results suggest that d-allose reduces brain injury after transient global ischemia by suppressing inflammation as well as by inhibiting oxidative stress.