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The survival energy model (SEM) is a recently introduced novel approach to mortality prediction, which offers a cohort-wise distribution function of the time of death as the first hitting time of a “survival energy” diffusion process to zero. In this study, we propose a novel SEM that can serve as a suitable candidate in the family of prediction models. We also proposed a method to improve the prediction in an earlier work. We further examine the practical advantages of SEM over existing mortality models.

BackgroundPrevious studies have shown that patients with amyotrophic lateral sclerosis (ALS) have hyperexcitability in both the motor cortex and peripheral motor axons, but the relationship between central and peripheral excitability has not been fully disclosed.MethodsThreshold tracking transcranial magnetic stimulation (TMS) and motor nerve excitability testing were prospectively performed in 53 patients with ALS and 50 healthy subjects, and their relations to compound muscle action potential (CMAP) amplitude and revised ALS Functional Rating Scale were cross-sectionally analysed.ResultsCompared with controls, patients with ALS showed both cortical and peripheral hyperexcitability; TMS showed reduced short-interval intracortical inhibition (interstimulus interval 1–7 ms) (pConclusionsOur results suggest that in ALS, cortical excitability is continuously high regardless of the extent of the peripheral burden, but peripheral hyperexcitability is associated with the extent of the peripheral burden and disease evolution speed. Alterations of ion channel function may play an important role in ALS pathophysiology.

Among subtypes of chronic inflammatory demyelinating polyneuropathy (CIDP), different immune pathophysiologies have been proposed. In this study, sensory nerve conduction studies were compared among clinical subtypes to attempt to better understand the underlying pathophysiology.A total of 138 patients with CIDP was classified into clinical subtypes: typical CIDP (N = 68), multifocal CIDP (N = 27), or other (N = 2). Patients with immunoglobulin M (IgM) neuropathy anti-myelin-associated glycoprotein neuropathy (MAG; N = 19) were also included as disease controls. Sensory nerve action potentials (SNAPs) were recorded in the median, ulnar, and superficial radial and sural nerves.SNAP amplitudes (P .05) and conduction velocities (P .01) in the median nerve and conduction velocities (P .05) in the ulnar nerve were lower in typical CIDP than in multifocal CIDP, whereas those in the radial and sural nerves were comparable in each group. Low median and normal sural SNAP amplitudes were more common in typical CIDP (P .005) than in multifocal CIDP, suggesting predominant involvement at terminal portions of the nerves.Terminal portions of sensory nerves are preferentially affected in typical CIDP compared with multifocal CIDP. These findings might be partially explained by the hypothesis of antibody-mediated demyelination in typical CIDP at the regions where the blood-nerve barrier is anatomically deficient, whereas multifocal CIDP predominantly affects the nerve trunks, largely due to cell-mediated demyelination, with disruption of the blood-nerve barrier.

Objective To evaluate the effect of postoperative pathological findings related to the eligibility of adjuvant immunotherapy on oncologic outcomes in patients with localized and locally advanced muscle‐invasive bladder carcinoma (MIBC) and upper tract urothelial carcinoma (UTUC). Patients and methods We retrospectively evaluated 1082 patients treated with radical cystectomy (n = 597) and nephroureterectomy (n = 485) between January 2000 and April 2021. Patients were divided into two groups: pT3‐4 or pN+ without neoadjuvant chemotherapy and ypT2‐4 or pN+ treated with neoadjuvant chemotherapy (trial‐eligible group) or others (trial‐ineligible group). The primary outcome was the effect of trial eligibility for adjuvant immunotherapy on disease‐free survival (DFS) and overall survival (OS). Secondary outcomes included the additional effect of lymphovascular invasion (LVI) status to the clinical trial criteria on prognosis and a risk model development. Results The median ages of the patients were 69 and 72 years in the MIBC and UTUC groups, respectively. Fifty‐two percent of patients met the trial inclusion criteria. Trial eligibility was significantly associated with poor DFS and OS among patients with MIBC and UTUC. LVI‐positive status was significantly associated with poor prognosis among patients in the trial‐eligible group. A very high risk (LVI+ or pN+ among the pT3‐4 or ypT2‐4) was significantly associated with poor prognosis. Conclusion A total of 52% of patients were eligible for adjuvant immunotherapy. Trial eligibility was significantly associated with a poor prognosis. LVI+ and pN+ may play a key role in candidate selection for adjuvant immunotherapy.

To elucidate the utility of the proximal to distal compound muscle action potential (CMAP) duration ratio to distinguish between demyelinating Charcot-Marie-Tooth disease (CMT) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) compared with nerve ultrasound.Thirty-nine demyelinating CMT patients and 19 CIDP patients underwent nerve conduction studies (NCS) and nerve ultrasound. NCS parameters including CMAP duration ratio calculated by dividing the value at the proximal site by that at the distal site and nerve cross-sectional area (CSA) measured by ultrasound were compared between the two groups. The diagnostic sensitivity and specificity of each parameter were analysed.CMT patients showed a significantly lower CMAP duration ratio than CIDP patients (p 0.05). The area under the curve (AUC) value of the CMAP duration ratio exceeded 0.95 when CMT was considered "positive", and a cut-off value of 1.13 resulted in high diagnostic sensitivity and specificity (84.6 and 100 % for median nerve, 97.4 and 85.7 % for ulnar nerve, respectively), whereas the AUC value of nerve CSA ranged from 0.70 to 0.81.The CMAP duration ratio could effectively distinguish between demyelinating CMT and CIDP.Adding the CMAP duration ratio to a routine NCS may improve the accuracy of the diagnosis of demyelinating CMT.

This study examined the role of Tfh and Treg associated molecules also known as checkpoint molecules, their ligands, and IL-21 in myasthenia gravis (MG) pathogenesis. Serum levels of sPD-1, sPD-L1, sICOS, sICOSLG, sCTLA4, and IL-21 were measured in 39 patients with acetylcholine receptor (AChR) antibody-positive generalized MG and 27 controls. sPD-1 and IL-21 levels were higher in MG patients than in controls. Additionally, sPD-1 levels correlated positively with the levels of IL-21, sICOSLG, sCTLA4, and AChR antibody titers. sICOS are correlated with MGADL and AChR antibody titers. These Tfh associated molecules could be used as biomarkers of MG disease activity.

Myasthenia gravis (MG) is an autoimmune disease with autoantibodies against the mainly nicotinic acetylcholine receptor (AChR). High mobility group box1 (HMGB1) acts as a danger signal and drives the pathogenesis of autoimmune-mediated diseases. However, the role of HMGB1 in the pathogenesis of MG is not fully understood. Therefore, in this study, we analyzed serum levels of HMGB1 and immunohistochemical HMGB1 staining of muscle tissues in the passive transfer MG model to investigate the role of HMGB1 in MG. As a result, serum HMGB1 levels tended to be higher and the quantitative score of muscle pathology showed greater HMGB1 deposition (P = 0.02) along with sparser AChR staining and more severe inflammation in the passive transfer MG rats (n = 6) than those in control rats (n = 6). These findings indicate that HMGB1 is an important mediator and biomarker for inflammation in the pathogenesis of MG and can be a therapeutic target in MG.

INTRODUCTION In this study we aimed to investigate the dispersion of mean consecutive difference (MCD) of concentric needle jitter studies of patients with myasthenia gravis (MG) and its effect on diagnostic sensitivity for MG. METHODS One hundred fifty-three patients, including 76 patients with MG and 77 controls with possible MG who later received another diagnosis, underwent stimulated concentric needle jitter studies of the frontalis muscle. MCD mean, standard deviation (SD), and coefficient of variation (CV) were calculated. Diagnostic sensitivity and specificity were determined using receiver operating characteristic (ROC) analyses. RESULTS MG patients showed a significantly greater MCD mean (MG: control, 26.3 μs; 13.5 μs [median]; P

This study aimed to investigate the timing of meeting the criteria for a status of “minimal manifestation (MM) or better” and the factors that influenced whether “MM or better status” or “MM or better status with an oral prednisolone (PSL) dose of 5 mg/day or less (5-mg MM)” was met in patients with acetylcholine receptor (AChR) antibody-positive generalized myasthenia gravis (MG). We performed a retrospective study in 93 patients with AChR antibody-positive generalized MG who were followed for 3 years after the start of immunotherapy. We reviewed clinical data, such as MG-related symptoms, the MG activities of daily living profile (MGADL) score, immunotherapy including the dose of PSL, and achievement of the status of MM or better at baseline and 3, 6, 12, 24, and 36 months after treatment. An MM or better status was achieved in 60% of the patients 3 months and in 90% of the patients 2 years after initiating immunotherapy. At 2 years, 60% of the patients had achieved the treatment goal, which was an “5-mg MM”. More frequent plasmapheresis and higher dose of PSL within 3 months after immunotherapy initiation were associated with difficulty in achieving the 5-mg MM status at 2 years. Approximately 60% of the MG patients achieved the treatment goal within 2 years after treatment. PSL dose and the cumulative number of plasmapheresis procedures at 3 months after immunotherapy initiation may help identify treatment-resistant patients with MG.

ObjectiveTo investigate the association between changes in anti-acetylcholine receptor antibody (AChR Ab) levels induced by immunosuppressive treatment and myasthenia gravis (MG) prognosis at 1-year post-treatment in patients with MG.MethodsWe included 53 consecutive AChR Ab-positive patients with MG whose AChR Ab levels were remeasured within 100 days of initiating immunosuppressive treatment (median remeasuring time post-treatment: 71 (55–84) days). The AChR Ab level reduction rate (RR-AChRAb, %/day) adjusted for the time between treatment initiation, and AChR Ab level remeasurement was calculated as follows: (pretreatment–post-treatment AChR Ab level)/pretreatment AChR Ab level/days between therapy initiation and AChR Ab level remeasurement ×100. Participants were divided into two groups based on the cut-off value of RR-AChR Ab, determined using receiver operating characteristic analyses for achieving minimal manifestation (MM) or better status at 1-year postimmunosuppressive treatment. The Myasthenia Gravis Foundation of America postintervention status and MG activity of daily living (MG-ADL) score at 1-year post-treatment were compared between the two groups.ResultsThe RR-AChRAb cut-off value was 0.64%/day. The high RR-AChRAb group had a higher ratio of MM or better status (90% vs 65%, p=0.03) and lower MG-ADL score (median; 1 vs 2, p=0.04) than the low RR-AChRAb group. Kaplan-Meier analyses showed the early MM achievement in the high RR-AChRAb group (p=0.002, log-rank test).ConclusionsHigh RR-AChRAb is associated with a favourable outcome at 1-year post-treatment. AChR Ab remeasurement within 100 days of therapy may be useful for predicting AChR Ab-positive MG outcomes at 1-year post-treatment.

Introduction: The causal relationship between sleep disorder and frequency of nocturia remains unclear. Methods: We longitudinally evaluated sleep disorder and frequency of nocturia in 547 community-dwelling adults between baseline and 5-year follow-up. We included participants ≥50 years old who have no sleep disorder (the Pittsburgh Sleep Quality Index [PSQI] ≥ 5) nor nocturia (≥1). For 5 years, we evaluated the temporal changes in sleep disorder and nocturia and the bidirectional relationships between sleep disorder and nocturia. Results: Of the 547 participants, we included 268 adults with a median age of 61 years in this study. Median PSQI and nocturia were significantly increased for 5 years from 2 to 3 and from 1 to 2, respectively. New onset of sleep disorder (PSQI > 5) and nocturia >1 was observed in 42 (16%) and 137 (51%) participants, respectively. The cross-lagged panel analysis showed that the path coefficient from PSQI to nocturia (β = 0.22, p = 0.031) was significantly higher than that from nocturia to PSQI (β = 0.02, p = 0.941). Conclusions: Our longitudinal study showed the effect of sleep disorder on nocturia was significant, although nocturia may not significantly worsen sleep disorder in community-dwelling adults.

OBJECTIVE To investigate changes in serum complements and their regulators in the pathogenesis of myasthenia gravis (MG). METHODS Forty-four patients with acetylcholine receptor antibody-positive MG, as well as 20 patients with non-inflammatory neurological disorders were enrolled. Serum complements (C3, C4 and soluble C5b-9) and complement regulators (vitronectin, clusterin and properdin) were extensively analysed by enzyme-linked immunosorbent assay and their associations with clinical profiles of MG were examined. RESULTS Serum C3, C4 and clusterin levels were not significantly different between patients with MG and controls. The patients with MG had higher soluble C5b-9 (P = 0.09) and vitronectin (P = 0.001) levels than the controls; moreover, vitronectin levels decreased after treatment (P = 0.09). Serum properdin (P = 0.03) levels were lower in the patients with MG than in the controls, and negatively correlated with the MG Activities of Daily Living score (rs = -0.26, P = 0.09) and with the presence of bulbar palsy (P = 0.04). CONCLUSION Our results show that activation of complements and an altered complement network could contribute to the inflammatory pathogenesis of MG.

Summary Myasthenia gravis (MG) is an autoantibody-mediated inflammatory disease of the neuromuscular junction. Biomarkers indicating disease activity in MG are warranted. Recently, the soluble urokinase plasminogen activator receptor (suPAR) has been reported to be associated with inflammation, tissue damage, disease activity and prognosis in various diseases, including autoimmune diseases. In this study, serum suPAR levels were measured in 40 patients with anti-acetylcholine receptor antibody-positive MG and 30 controls, and their correlations with clinical variables and severity scale scores were investigated. We identified that serum suPAR levels significantly correlated with MG activities of daily living scale (Spearman's ρ = 0·45; P = 0·004) and MG Foundation of America classification (Spearman's ρ = 0·37; P = 0·02) at serum sampling, but not with anti-acetylcholine receptor antibody titers. In conclusion, serum suPAR levels can be a candidate for a novel biomarker of disease activity in anti-acetylcholine receptor antibody-positive MG.

Background: Antiplatelet agents are effective in secondary prevention of ischemic stroke and can reduce the severity of first-ever ischemic stroke. However, it remains controversial whether prophylactic administration of antiplatelet agents can reduce the severity of recurrent ischemic stroke. This study aimed to determine the effect of preceding antiplatelet treatment on ischemic stroke severity in patients with a prior history of stroke.Methods: From the prospective hospital registry of 1338 consecutive patients with ischemic stroke within 7 days of symptom onset, we identified patients with a prior history of stroke who were admitted due to cerebral thrombosis, which included large-artery atherosclerosis, small vessel occlusion, and branch atheromatous disease. Patients were categorized into 2 groups according to preceding medication: antiplatelet (AP) group and none (N) group. Those with preceding anticoagulant agents or unknown prior medication were excluded. Stroke severity (National Institutes of Health Stroke Scale: NIHSS) on admission was compared between the 2 groups.Results: A total of 88 patients were analyzed. Out of these, 66 were identified in the AP group (median age 78, male 71%), and 22 in the N group (median age 71, male 73%). The median NIHSS on admission was lower in the AP group than in the N group (3 vs 5, p=0.043). In multivariate analysis, preceding antiplatelet treatment was independently associated with mild stroke (NIHSS ≤4) on admission (odds ratio 5.77, 95% confidence interval 1.73-21.6, p=0.004).Conclusion: Preceding antiplatelet treatment in patients with a prior history of stroke may reduce the severity of subsequent cerebral thrombosis.

BackgroundWe aimed to determine the prognostic and staging benefit of limited pelvic lymph node dissection (PLND) during radical prostatectomy (RP) in high-risk prostate cancer (PC) patients treated with neoadjuvant chemohormonal therapy.MethodsWe retrospectively analyzed 516 patients with high-risk localized PC (

Background and purpose Muscle ultrasonography has been increasingly recognized as a useful tool for detection of fasciculations. Separately, concordance between dominant hand and onset side has been reported in amyotrophic lateral sclerosis (ALS). The aim of this study was to reveal the distribution of fasciculations in the whole body, focusing on handedness. Methods In 106 consecutive patients with ALS, muscle ultrasonography was systematically performed in 11 muscles (the tongue, and bilateral biceps brachii, 1st dorsal interosseous [FDI], T10-paraspinalis, vastus lateralis and tibialis anterior muscles). The fasciculation intensity was scored from 0 to 3 for each muscle. Results Fasciculations were more frequently found in the limb muscles than the tongue and paraspinalis. Side and handedness analyses revealed that fasciculation intensity in FDI was significantly more prominent on the right (median [inter-quartile range] 2 [0 - 3]) than left (1.5 [0 - 3]; p = 0.016), and in the dominant hand (2 [1 - 3]) than non-dominant side (1.5 [0 - 3]; p = 0.025). The differences were greater in patients with upper limb onset. There were no side differences in the lower limb muscles. Multivariate analyses showed that male patients had more frequent fasciculations in the dominant FDI (β = 0.22, p < 0.05). Conclusion More intensive fasciculations are present in the FDI in the dominant hand and gender might be associated with fasciculation intensities. This distribution pattern of fasciculations might be associated with pathogenesis of ALS.

Immunoadsorption apheresis (IA) or intravenous immunoglobulin (IVIg) is used to treat exacerbation of myasthenia gravis (MG). This study aimed to compare the efficacy and safety between IA and IVIg for MG patients with anti-acetylcholine receptor (AChR) antibodies. We retrospectively studied 19 AChR antibody-positive generalized MG patients who underwent IA (n = 9) or IVIg treatment (n = 10). We reviewed the MG activities of daily living profile (MG-ADL) scores at baseline, 1 and 3 months after the treatment. Adverse events during the treatment period were also reviewed. The MG-ADL scores showed significantly greater improvement from the baseline in the IA group than in the IVIg group (1 month: -7 vs -3, P = .035; 3 months -9 vs -2.5, P = .016). An adverse event that led to the discontinuation of the treatment was observed in only one patient in the IVIg group (anaphylactic reaction). Our data suggest that the IA treatment is safe and more efficacious than the IVIg treatment for aggravation of anti-AChR-positive MG. Larger prospective studies are required to confirm the finding.

INTRODUCTION AND OBJECTIVE:Although exact etiologies of overactive bladder (OAB) remains unclear, one of the believed theories to describe the disease process involves ischemia, vascular damage, an...

INTRODUCTION AND OBJECTIVE:Discriminating between urothelial carcinoma (UC) including bladder cancer (BCa) and upper urinary tract UC (UTUC) is often challenging.METHODS:We evaluated the diagnostic...

INTRODUCTION AND OBJECTIVE:To determine how frailty and comorbidities affect surgical contraindication in patients with localized prostate cancer (CaP).METHODS:We evaluated the effects of frailty i...

A small centrum ovale infarct in the territory of the white matter medullary artery can be caused not only by embolism but also small-vessel disease. In our study, thorough screening for emboligenic diseases was performed, including the modality of transesophageal echocardiography (TEE), in patients with an acute, isolated, small (less than 1.5 cm) infarct in the centrum ovale. Of 79 patients enrolled in this study, 45 had emboligenic diseases, in whom a patent foramen ovale was detected in 29 patients, complicated aortic arch lesion in 15, atrial fibrillation in 6, occlusive carotid disease in 2, and others in 2. The majority (80%) of the emboligenic diseases were diagnosed by TEE. Therefore, TEE may be mandatory for the etiologic diagnosis of centrum ovale infarcts.

Objective To determine the diagnostic and prognostic significance of neurofilament light chain (NfL), TAR DNA‐binding protein 43 (TDP‐43), and total tau (t‐tau) in cerebrospinal fluid (CSF) and plasma of patients with amyotrophic lateral sclerosis (ALS) and to investigate whether the combined use of those biomarker candidates can improve their diagnostic performance. Methods This was a single–center, prospective, longitudinal study. CSF and plasma samples were collected at the time of enrollment from a discovery cohort of 29 patients with ALS and 29 age–matched controls without neurodegenerative disease. In a validation cohort, there were 46 patients with ALS, and 46 control (not age‐matched) patients with motor weakness resulting from neuromuscular diseases. NfL, TDP‐43, and t‐tau levels in CSF and plasma were measured using ultrasensitive single molecule assay (Simoa) technology. Results The following findings were reproducibly observed among the discovery and validation cohorts: increased levels of CSF NfL, plasma NfL, and CSF TDP‐43 in ALS compared with control groups; shorter survival associated with higher levels of CSF and plasma NfL. When the CSF NfL and CSF TDP‐43 levels were combined, the areas under the ROC curves (AUC) were slightly improved relative to AUCs for each biomarker alone. Interpretation CSF and plasma NfL may not only serve as diagnostic biomarkers but also provide a measure of disease progression. CSF TDP‐43 is also useful as a diagnostic biomarker of ALS, but has no prognostic value. The combined use of CSF NfL and CSF TDP‐43 may be a useful biomarker for the diagnosis of ALS.

To investigate the utility of automatic thresholding methods for quantitative muscle echogenicity assessment as a marker of disease severity in Charcot-Marie-Tooth disease type 1A (CMT1A).Muscle ultrasound was performed in 15 CMT1A patients and 7 healthy controls. Muscle echogenicity of six limb muscles in each subject was assessed by 16 automatic thresholding methods and conventional grey-scale analysis. Echogenicity of each method in CMT1A patients was compared with that in controls. A correlation between the echogenicity and CMT neuropathy score (CMTNS) was also analysed in CMT1A patients.Significant differences in mean echogenicity of the 6 muscles between CMT1A patients and controls were found both in grey-scale analysis (p 0.01) and 11 of the 16 automatic thresholding methods (p 0.05 in each method). In CMT1A patients, mean echogenicity of the 6 muscles was positively correlated with CMTNS in 8 of the 16 automatic thresholding methods, but not in grey-scale analysis.Automatic thresholding methods can be used to detect the difference in muscle echogenicity between CMT1A patients and controls. Echogenicity parameters correlate with the disease severity.Quantitative muscle echogenicity assessment by automatic thresholding methods shows potential as a surrogate marker of disease progression in CMT1A.

This study aimed to investigate the timing of meeting the criteria for a status of "minimal manifestation (MM) or better" and the factors that influenced whether "MM or better status" or "MM or better status with an oral prednisolone (PSL) dose of 5 mg/day or less (5-mg MM)" was met in patients with acetylcholine receptor (AChR) antibody-positive generalized myasthenia gravis (MG).We performed a retrospective study in 93 patients with AChR antibody-positive generalized MG who were followed for 3 years after the start of immunotherapy. We reviewed clinical data, such as MG-related symptoms, the MG activities of daily living profile (MGADL) score, immunotherapy including the dose of PSL, and achievement of the status of MM or better at baseline and 3, 6, 12, 24, and 36 months after treatment.An MM or better status was achieved in 60% of the patients 3 months and in 90% of the patients 2 years after initiating immunotherapy. At 2 years, 60% of the patients had achieved the treatment goal, which was an "5-mg MM". More frequent plasmapheresis and higher dose of PSL within 3 months after immunotherapy initiation were associated with difficulty in achieving the 5-mg MM status at 2 years.Approximately 60% of the MG patients achieved the treatment goal within 2 years after treatment. PSL dose and the cumulative number of plasmapheresis procedures at 3 months after immunotherapy initiation may help identify treatment-resistant patients with MG.

The present study aimed to evaluate oncologic outcomes, patient-reported outcomes (PROs), and frailty in older adult patients aged ≥75 years who underwent robot-assisted radical prostatectomy (RARP).This retrospective study reviewed the medical records of 752 patients who underwent RARP from July 2011 to May 2020. The PROs were evaluated by Expanded Prostate Cancer Index Composite questionnaire at baseline and 1 year after RARP. Patients were divided into 3 groups according to age at RARP:70, 70-74, and ≥75 years. Oncologic outcomes and PROs were compared between the ≥75 and 70-74 years groups and between the ≥75 and70 years groups.Median follow up was 47 months. Of the 752 patients, 469, 216, and 74 were classified into the70, 70-74, and ≥75 years groups, respectively. No significant differences were observed in the biochemical recurrence-free survival, cancer-specific survival, and overall survival among the groups. No significant differences were observed in the PROs and pad-free rates at baseline and 1 year after RARP among the groups. The full satisfaction (Expanded Prostate Cancer Index Composite score = 100) at 12 months after RARP was significantly higher in the ≥75 years group (27%) than in the70 years group (15%, P = 0.045).The oncologic outcomes and PROs in select patients with prostate cancer aged ≥75 years were feasible and acceptable with RARP.