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Background: The optimal target for partial pressure of arterial carbon dioxide (PaCO₂) remains uncertain in patients undergoing veno-arterial extracorporeal membrane oxygenation (VA-ECMO) following out-of-hospital cardiac arrest (OHCA)., Research Question: Are PaCO₂ levels associated with functional outcomes in patients receiving VA-ECMO after OHCA?, Study Design: and Methods: This multicenter, registry-based observational study, conducted from 2014 to 2020, included non-traumatic adult OHCA patients on VA-ECMO with PaCO₂ levels measured within six hours of initiation (initial PaCO₂ set) and at 18-30 hours post-initiation (24-hour PaCO₂ set). PaCO₂ levels were categorized into five groups: hypocapnia (<30 mmHg), low normocapnia (30-<40 mmHg), high normocapnia (40-<50 mmHg), mild hypercapnia (50-<60 mmHg), and moderate to severe hypercapnia (≥60 mmHg). The primary outcome was the favorable functional outcome at 30 days, analyzed using multivariable logistic regression. PaCO₂ trajectories from initial to 24-hour levels were also explored., Results: A total of 1,454 and 572 patients were analyzed in the initial and 24-hour PaCO₂ sets, respectively. Compared to high normocapnia, low normocapnia was associated with worse functional outcomes in both initial and 24-hour PaCO₂ analyses, with adjusted odds ratios of 0.59 (95% CI, 0.38-0.89) for initial low normocapnia and 0.56 (95% CI, 0.33-0.95) for 24-hour low normocapnia. Other categories were similarly associated with worse functional outcomes in both PaCO₂ analyses. In exploratory analyses, trajectories ending in high normocapnia demonstrated higher proportions of the favorable functional outcome than those ending in low normocapnia, regardless of initial PaCO₂ levels., Interpretation: In non-traumatic adult OHCA patients on VA-ECMO, high normocapnia was associated with better functional outcomes than low normocapnia in both initial and 24-hour PaCO₂ analyses. These findings suggest a hypothesis that maintaining high normocapnia levels, irrespective of initial PaCO 2 , may improve functional outcomes for patients on VA-ECMO after OHCA., (Copyright © 2025. Published by Elsevier Inc.)

Pain perception is not solely determined by noxious stimuli, but also varies due to other factors, such as beliefs about pain and its uncertainty. A widely accepted theory posits that the brain integrates prediction of pain with noxious stimuli, to estimate pain intensity. This theory assumes that the estimated pain value is adjusted to minimize surprise, mathematically defined as errors between predictions and outcomes. However, it is still unclear whether the represented surprise directly influences pain perception or merely serves to update this estimate. In this study, we empirically examined this question using virtual reality. In the task, participants reported felt pain via VAS after their arm was stimulated by noxious heat and thrusted into by a virtual knife actively. To manipulate surprise level, the visual threat suddenly disappeared randomly, and noxious heat was presented in the on- or post-action phases. We observed that a transphysical surprising event, created by sudden disappearance of a visual threat cue combined with delayed noxious heat, amplified pain intensity. Subsequent model-based analysis using Bayesian theory revealed significant modulation of pain by the Bayesian surprise value. These results illustrated a real-time computational process for pain perception during a single task trial, suggesting that the brain anticipates pain using an efference copy of actions, integrates it with multimodal stimuli, and perceives it as a surprise., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2025. Published by Elsevier B.V.)

Background: Collecting blood cultures from indwelling arterial catheters is an attractive option in critically ill adult patients when peripheral venipuncture is difficult. However, whether the contamination proportion of blood cultures from arterial catheters is acceptable compared with that from venipuncture is inconclusive., Research Question: Is contamination of blood cultures from arterial catheters noninferior to that from venipuncture in critically ill adult patients with suspected bloodstream infection?, Study Design and Methods: In this multicenter prospective diagnostic study conducted at five hospitals, we enrolled episodes of paired blood culture collection, each set consisting of blood drawn from an arterial catheter and another by venipuncture, were obtained from critically ill adult patients with cilinical indication. The primary measure was the proportion of contamination, defined as the number of false-positive results relative to the total number of procedures done. The reference standard for true bloodstream infection was blinded assessment by infectious disease specialists. We examined the noninferiority hypothesis that the contamination proportion of blood cultures from arterial catheters did not exceed that from venipuncture by 2.0%., Results: Of 1,655 episodes of blood culture from December 2018 to July 2021, 590 paired blood culture episodes were enrolled, and 41 of the 590 episodes (6.9%) produced a true bloodstream infection. In blood cultures from arterial catheters, 33 of 590 (6.0%) were positive, and two of 590 (0.3%) were contaminated; in venipuncture, 36 of 590 (6.1%) were positive, and four of 590 (0.7%) were contaminated. The estimated difference in contamination proportion (arterial catheter - venipuncture) was -0.3% (upper limit of one-sided 95% CI, +0.3%). The upper limit of the 95% CI did not exceed the predefined margin of +2.0%, establishing noninferiority (P for noninferiority < .001)., Interpretation: Obtaining blood cultures from arterial catheters is an acceptable alternative to venipuncture in critically ill patients., Clinical Trial Registration: University Hospital Medical Information Network Center (UMIN-CTR); No.: UMIN000035392; URL: https://center6.umin.ac.jp/., (Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: We aimed to investigate the association between blood urea nitrogen to creatinine ratio (BCR) and survival with favourable neurological outcomes in patients with out-of-hospital cardiac arrest (OHCA)., Methods: This prospective, multicentre, observational study conducted in Osaka, Japan enrolled consecutive OHCA patients transported to 16 participating institutions from 2012 through 2019. We included adult patients with non-traumatic OHCA who achieved a return of spontaneous circulation and whose blood urea nitrogen and creatinine levels on hospital arrival were available. Based on BCR values, they were divided into: 'low BCR' (BCR <10), 'normal BCR' (10 ≤ BCR < 20), 'high BCR' (20 ≤ BCR < 30), and 'very high BCR' (BCR ≥ 30). We evaluated the association between BCR values and neurologically favourable outcomes, defined as cerebral performance category score of 1 or 2 at one month after OHCA., Results: Among 4415 eligible patients, the 'normal BCR' group had the highest favourable neurological outcome [19.4 % (461/2372)], followed by 'high BCR' [12.5 % (141/1127)], 'low BCR' [11.2 % (50/445)], and 'very high BCR' groups [6.6 % (31/471)]. In the multivariable analysis, adjusted odds ratios for 'low BCR', 'high BCR', and 'very high BCR' compared with 'normal BCR' for favourable neurological outcomes were 0.58 [95 % confidence interval (CI 0.37-0.91)], 0.70 (95 % CI 0.49-0.99), and 0.40 (95 % CI 0.21-0.76), respectively. Cubic spline analysis indicated that the association between BCR and favourable neurological outcomes was non-linear (p for non-linearity = 0.003). In subgroup analysis, there was an interaction between the aetiology of arrest and BCR in neurological outcome (p for interaction <0.001); favourable neurological outcome of cardiogenic OHCA patients was lower when the BCR was higher or lower, but not in non-cardiogenic OHCA patients., Conclusions: Both higher and lower BCR were associated with poor neurological outcomes compared to normal BCR, especially in cardiogenic OHCA patients., Competing Interests: Declaration of competing interest All the authors declare that they have no potential conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background & Aims: Although refeeding syndrome (RFS) has been recognized as a potentially fatal metabolic complication, the definition of RFS has remained unclear. Recently, European researchers suggested an evidence-based and consensus-supported algorithm that consisted of a new RFS risk classification and treatment strategies for medical inpatients. The classification was based on the National Institute for Health and Clinical Excellence (NICE) criteria for patients at risk of developing RFS. In this study, we aimed to investigate the frequency of each applied new risk group and the association between the new classification and mortality in critically ill patients., Methods: This cohort study was conducted at a Japanese metropolitan tertiary-care university hospital from December 2016 to December 2018. We included critically ill adult patients who were admitted to the intensive care unit (ICU) via the emergency department and who stayed in the ICU for 24 h or longer. We applied the new risk classification based on the NICE RFS risk factors on ICU admission. The main exposure was risk classification of RFS: no risk, low risk, high risk, or very high risk. The primary outcome was in-hospital mortality censored at day 30 after ICU admission. We performed a multivariable analysis using Cox proportional hazard regression., Results: We analyzed 542 patients who met the eligibility criteria. The prevalence of the four RFS risk classification groups was 25.8% for no risk, 25.7% for low risk, 46.5% for high risk, and 2.0% for very high risk. The 30-day mortality was 5.0%, 7.2%, 16.3%, and 27.3%, respectively (log-rank trend test: p < 0.001). In the multivariable Cox regression, adjusted hazard ratios with no risk group as a reference were 1.28 (95% CI 0.48-3.38) for low risk, 2.81 (95% CI 1.24-6.35) for high risk, and 3.17 (95% CI 0.78-12.91) for very high risk., Conclusions: Approximately half the critically ill patients were categorized as high or very high risk based on the new risk classification. Furthermore, as the risk categories progressed, the 30-day in-hospital mortality increased. Early recognition of patients at risk of developing RFS may improve patient outcomes through timely and optimal nutritional treatment., Competing Interests: Conflicts of interest The authors declare they have no competing interests., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Case Presentation: A 47-year-old man was admitted to the ICU with acute hypercapnic respiratory failure caused by a severe asthma attack. He had a history of asthma, atrial septal defect, chronic heart failure, and atrial fibrillation. He underwent surgical closure of the atrial septal defect at 7 years of age and was asymptomatic until 38 years of age when he developed congestive heart failure because of structural cardiac abnormalities, including left ventricular systolic dysfunction, biatrial enlargement, and mild mitral and tricuspid regurgitation. After ICU admission, he received ventilator management for asthma, IV prednisone, beta-2 agonist via inhalation, and ceftriaxone. Enteral feeding was provided since the day of admission. Hypercapnia gradually improved over 3 days. He remained alert and could communicate through writing during ventilator management until the third day in the ICU. Enteral feeding was titrated up to 32 kcal/kg/d with 1.6 g/kg/d of protein. Despite the recovery from the initial respiratory failure, he became inactive and lethargic on the fourth day in the ICU. ICU-acquired delirium was suspected, and administration of sedatives and analgesics was discontinued. On the following day, he was unresponsive to stimuli., (Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Survival in patients with bladder cancer has only moderately improved over the past 2 decades. A potential reason for this is nonadherence to clinical guidelines and best practice, leading to wide variations in care. Common quality indicators (QIs) are needed to quantify adherence to best practice and provide data for benchmarking and quality improvement., Objective: To produce an evidence- and consensus-based list of QIs for the management of bladder cancer., Methods: A modified Delphi method was used to develop the indicator list. Candidate indicators were extracted from the literature and rated by a 27-member Canadian expert panel in several rounds until consensus was reached on the final list of indicators. In rounds with numeric ratings, a frequency analysis was performed., Results: A total of 86 indicators were rated, 52 extracted from the literature and 34 suggested by the panel. After iterative rounds of ratings and discussion, a final list of 60 QIs spanning several disciplines and phases of the cancer care continuum was developed., Conclusions: This is the first study to comprehensively produce common QIs representing structure, process, and outcome measures in bladder cancer management. Though developed in Canada, these indicators can be used in other countries with slight modifications to track performance and improve care., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: The number of people living in high-rise buildings has recently been increasing in Japan, and delayed transport time by emergency-medical-service (EMS) personnel from higher floors could lead to lower survival after out-of-hospital cardiac arrest (OHCA). However, there are no clinical studies assessing the association between the floor where patients reside and neurologically favorable outcome after OHCA., Methods: This was a prospective, population-based study conducted in Osaka City, Japan that enrolled adults aged >=18years suffering an OHCA of cardiac origin before EMS arrival between 2013 and 2014. The primary outcome measure was one-month survival with neurologically favorable outcome. We divided OHCA patients into the following groups: those residing on >=3 floors (the high floor group) and <3 floors (the low floor group). Multiple logistic regression analysis was used to assess factors associated with neurologically favorable outcome., Results: A total of 2979 patients were eligible for analysis. Of them, 1885 (62.3%) occurred below the third floor and 1094 (37.4%) occurred at or above the third floor. The proportion of neurologically favorable outcome after OHCA was significantly lower in the high floor group than in the low floor group (2.7% [30/1094] versus 4.8% [91/1885], P=0.005). In a multivariate analysis, neurologically favorable outcome after OHCA was significantly lower in the high floor group than in the low floor group (adjusted odds ratio, 0.59 [95% confidence interval, 0.37-0.96])., Conclusions: In this population, one-month survival with neurologically favorable outcome from OHCA was lower in the high floor group than in the low floor group., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

It is widely accepted that the cerebellum acquires and maintain internal models for motor control. An internal model simulates mapping between a set of causes and effects. There are two candidates of cerebellar internal models, forward models and inverse models. A forward model transforms a motor command into a prediction of the sensory consequences of a movement. In contrast, an inverse model inverts the information flow of the forward model. Despite the clearly different formulations of the two internal models, it is still controversial whether the cerebro-cerebellum, the phylogenetically newer part of the cerebellum, provides inverse models or forward models for voluntary limb movements or other higher brain functions. In this article, we review physiological and morphological evidence that suggests the existence in the cerebro-cerebellum of a forward model for limb movement. We will also discuss how the characteristic input-output organization of the cerebro-cerebellum may contribute to forward models for non-motor higher brain functions., (Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

In addition to mental disorders such as attention, emotion, delusions, hallucinations, and difficulties in social skills, the patients with schizophrenia exhibits significant abnormality in sensorimotor perception and control. To seek a neurobiological cause of the heterogeneous symptoms in schizophrenia, we focused on the impaired inference mechanism of the self-agency of the schizophrenia's brain where the sensory outcome generated by the self-initiated action was misattributed to the other agent's action. By developing a novel computational model of agency experience using a Bayesian decision making framework, we united the computational mechanisms of agency and motor control via internal model: a model for one to predict the sensory consequence of action. Our theory based on optimal feedback control with Kalman filtering successfully predicted a variety of schizophrenia's motor abnormalities assuming a deformed internal model. To discuss the plausibility of these model predictions, we reviewed literature that might support these predictions. We further proposed some experiments that potentially examine the proposed model of schizophrenia. Our approach in investigating a problem of mind by projecting it on the coordinates system of the embodiment effectively shed light on a central neuropathology of this disease that had been latent behind the observed behaviors., (Copyright © 2015 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.)

Objective: To evaluate risk factors for bladder cancer recurrence in a cohort of patients treated with radical nephroureterectomy (RNU)., Patients and Methods: At 10 Canadian University Centers, we retrospectively evaluated data, between 1990 and 2010, from 743 patients who were free from bladder cancer and were previously treated with RNU for upper tract urothelial cancer., Results: Of 743 patients, 167 (22.5%) developed bladder tumors after a median time of 17.2 months after RNU. Multivariable analysis detected age (hazard ratio [HR] = 1.028; 95% CI: 1.010-1.046; P = 0.0018), tumor location in both the renal pelvis and the ureter (HR = 2.205; 95% CI: 1.355-3.589; P = 0.0015), the use of adjuvant systemic chemotherapy (HR = 2.309; 95% CI: 1.439-3.705; P = 0.0005), and laparoscopic surgery (HR = 1.876; 95% CI: 1.226-2.87; P = 0.0037) as risk factors for bladder cancer recurrence. Open excision of a bladder cuff (HR = 0.661; 95% CI: 0.453-0.965; P = 0.0319) and transurethral resection of the intramural ureter (HR = 0.548; 95% CI: 0.306-0.981; P = 0.0429) on comparison with extravesical resection decreased the risk of bladder cancer recurrence significantly. Major limitations were the retrospective design and partially missing data, although the significance of variables did not change in the imputation analysis., Conclusion: Older patients, those with tumor location in both the renal pelvis and the ureter, and those treated with adjuvant systemic chemotherapy were found at higher risk for intravesical recurrence, as were those having undergone extravesical ureterectomy or laparoscopic RNU., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: Upper-tract urothelial carcinoma (UTUC) is associated with poor outcomes. Our aim was to assess adequacy of renal function and evaluate the role of adjuvant chemotherapy (AC) in patients with UTUC treated by radical nephroureterectomy (RNU) in a universal health care system., Materials and Methods: Retrospective data from 1,029 patients treated with RNU across 10 Canadian academic centers were collected. Tested variables included various clinico-pathological parameters, the use of perioperative chemotherapy, preoperative and postoperative creatinine values, and estimated glomerular filtration rates (eGFR). Univariable and multivariable Cox regression models addressed overall survival and disease-specific survival after surgery. Kaplan-Meier survival curves were used to compare outcomes in patients who received or did not receive AC., Results: Median age of patients was 70 years with a median follow-up of patients who were alive of 26 months. The median preoperative and postoperative eGFR rates were 59 mL/min/1.73 m(2) and 47 mL/min/1.73 m(2), respectively. Using a cutoff eGFR of 60, 49% of all the patients and 48% of the patients with ≥ pT3 or pTxN+ or both diseases would have been eligible for cisplatin-based chemotherapy preoperatively and only 18% and 21% of the patients, respectively remained eligible postoperatively. Of the patients who received AC, 75% had an eGFR<60. On multivariate analysis, AC was not prognostic for improved overall survival or disease-specific survival., Conclusions: Chronic kidney disease is common in patients with UTUC. Following RNU, 57% of the high-risk patients with good preoperative renal function became ineligible for cisplatin-based chemotherapy. Use of AC did not translate into improved survival. Whether this is due to inherent biases of retrospective analysis, limited efficacy of AC in patients with UTUC, or use of suboptimal regimen or dose because of poor postoperative renal function requires further evaluation., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Biopsy of the prostate using 2D transrectal ultrasound (TRUS) guidance is the current gold standard for diagnosis of prostate cancer; however, the current procedure is limited by using 2D biopsy tools to target 3D biopsy locations. We propose a technique for patient-specific 3D prostate model reconstruction from a sparse collection of non-parallel 2D TRUS biopsy images. Our method conforms to the restrictions of current TRUS biopsy equipment and could be efficiently incorporated into current clinical biopsy procedures for needle guidance without the need for expensive hardware additions. In this paper, the model reconstruction technique is evaluated using simulated biopsy images from 3D TRUS prostate images of 10 biopsy patients. All reconstructed models are compared to their corresponding 3D manually segmented prostate models for evaluation of prostate volume accuracy and surface errors (both regional and global). The number of 2D TRUS biopsy images used for prostate modeling was varied to determine the optimal number of images necessary for accurate prostate surface estimation.

The study of genes, drugs, and behavior in three male adolescents with Prader-Willi syndrome (PWS) revealed a clinical profile that raises questions about the indications for neuroleptic and appetite-suppressing medications in this condition. Evidence of the inadvisability of neuroleptic medication and of the pathophysiology of PWS has led to a remarkable control of violent outbursts and hyperphagia by carbamazepine in one patient afflicted with both PWS and Klinefelter's syndrome. Testosterone and behavioral therapy proved to be useful in the management of two patients. The present observations, which are supported by recent advances in the pathophysiology of satiety, suggest that PWS should be understood as a metabolic disorder and subjected to psychopharmacogenetic study.