Control of Diabetes Mellitus and Long-Term Prognosis in Stroke Patients: The Shiga Stroke and Heart Attack Registry.

BACKGROUND: The relationship between diabetes control status and long-term prognosis after stroke incidence remains unclear. This study aimed to investigate the effect of diabetes status at admission on long-term survival in patients with first-ever stroke. METHODS: A retrospective cohort study was conducted based on the Shiga Stroke and Heart Attack Registry in Japan. Patients were classified according to their diabetes status and glycated hemoglobin (HbA1c) value at hospital admission into the following: (1) free of diabetes (no history of diabetes and HbA1c <6.5%); (2) good control (history of diabetes and HbA1c <7%; free of history and 6.5% ≤HbA1c <7%); and (3) poor control (with or without a history of diabetes and HbA1c ≥7%). Multivariable Cox regression models were used to evaluate the association between diabetes status and long-term survival from stroke onset. Additionally, we also evaluated the association between diabetes status and conditional survival, beginning 29 days after stroke onset. RESULTS: A total of 6,331 first-ever stroke patients were eligible for this study. Among study patients, the mean (±SD) age was 72.85 ± 13.19 years, and the mean (±SD) follow-up year was 2.76 ± 1.66 years; additionally, 42.09% of patients were women. Among patients with all strokes, considering the free-of-diabetes group as the reference group, the adjusted hazard ratio (95% confidence interval) for mortality was 1.26 (1.10, 1.44) in the good control group and 1.22 (1.05, 1.41) in the poor control group. Among patients with ischemic stroke, the adjusted hazard ratio was 1.24 (1.06, 1.46) in good control group and 1.27 (1.08, 1.50) in poor control group. After excluding patients who died within 28 days, the adjusted hazard ratio for conditional mortality in the poor control group was 1.31 (1.12, 1.54) among all stroke patients and 1.29 (1.08, 1.54) among ischemic stroke patients. No significant associations were observed between diabetic status and long-term mortality in intracerebral hemorrhage patients. CONCLUSIONS: The findings suggest that first-ever stroke patients with diabetes exhibited a higher risk of all-cause mortality than those without diabetes, particularly in the overall stroke and ischemic stroke populations. Additionally, in stroke populations after 28 days of onset, high risk of long-term mortality was stated in stroke patients with poor HbA1c control.

Factors Affecting Energy Metabolism and Prognosis in Patients with Amyotrophic Lateral Sclerosis.

BACKGROUND/AIMS: Nutritional status is a factor affecting prognosis in patients with amyotrophic lateral sclerosis (ALS). Here, we aimed to clarify the factors associated with hypermetabolism and the prognosticators of ALS. METHODS: Forty-two inpatients (22 men, 20 women) diagnosed with ALS according to the revised El-Escorial criteria were investigated. The following data were retrospectively analyzed: anthropometric measurements, blood biochemistry, disease severity, basal energy expenditure (BEE), resting energy expenditure (REE) measured by indirect calorimetry, spirometry, and bioelectrical impedance analysis. Single and multiple regression analysis was performed to examine factors affecting REE and metabolic changes (defined as the ratio of REE to fat-free mass [FFM]). The Kaplan-Meier method was used to examine factors associated with the occurrence of cumulative events (death or tracheostomy). RESULTS: Among the 42 inpatients, REE was significantly higher than BEE, indicating hypermetabolism in ALS. Multiple regression analysis revealed that REE/FFM is strongly associated with the skeletal muscle index (-3.746 to -1.532, p < 0.0001) and percent forced vital capacity (%FVC) (-0.172 to -0.021, p = 0.013). Moreover, both the skeletal muscle index and %FVC were significant prognosticators associated with the occurrence of cumulative events. CONCLUSIONS: Energy metabolism was elevated in ALS, and respiratory status and muscle mass were associated with the hypermetabolism and poor prognosis. Adequate nutritional support may improve outcomes in ALS by preventing deterioration of respiratory status and reduction in muscle mass.

Two-Year Recurrence After First-Ever Stroke in a General Population of 1.4 Million Japanese Patients　- The Shiga Stroke and Heart Attack Registry Study.

BACKGROUND: Despite many effective strategies for the prevention of recurrent stroke, individuals who survive an initial stroke have been shown to be at high risk of recurrent stroke. The aim of this study was to investigate the current status of stroke recurrence after first-ever stroke using a population-based stroke registry in Japan.Methods and Results:As part of the Shiga Stroke and Heart Attack Registry, the Shiga Stroke Registry is an ongoing population-based stroke registry study that covers approximately 1.4 million residents of Shiga Prefecture, Japan. A total of 1,883 first-ever stroke survivors at 28 days was registered in 2011 and followed-up until the end of 2013. Recurrence was defined as any type of stroke after 28 days from the onset of an index event. Two-year cumulative recurrence rates were estimated using cumulative incidence function methods. Over a mean 2.1-year follow-up period, 120 patients experienced recurrent stroke and 389 patients died without recurrence. The 2-year cumulative recurrence rate was higher in patients with index ischemic stroke (6.8%) than in those with index hemorrhagic stroke (3.8%). CONCLUSIONS: Two-year cumulative recurrence rate after first-ever stroke remained high, particularly among patients with ischemic stroke, in the present population-based registry study in a real-world setting in Japan. Further intensive secondary prevention strategies are required for these high-risk individuals.

Minocycline reduces microgliosis and improves subcortical white matter function in a model of cerebral vascular disease.

Chronic cerebral hypoperfusion is a key mechanism associated with white matter disruption in cerebral vascular disease and dementia. In a mouse model relevant to studying cerebral vascular disease, we have previously shown that cerebral hypoperfusion disrupts axon-glial integrity and the distribution of key paranodal and internodal proteins in subcortical myelinated axons. This disruption of myelinated axons is accompanied by increased microglia and cognitive decline. The aim of the present study was to investigate whether hypoperfusion impairs the functional integrity of white matter, its relation with axon-glial integrity and microglial number, and whether by targeting microglia these effects can be improved. We show that in response to increasing durations of hypoperfusion, the conduction velocity of myelinated fibres in the corpus callosum is progressively reduced and that paranodal and internodal axon-glial integrity is disrupted. The number of microglial cells increases in response to hypoperfusion and correlates with disrupted paranodal and internodal integrity and reduced conduction velocities. Further minocycline, a proposed anti-inflammatory and microglia inhibitor, restores white matter function related to a reduction in the number of microglia. The study suggests that microglial activation contributes to the structural and functional alterations of myelinated axons induced by cerebral hypoperfusion and that dampening microglia numbers/proliferation should be further investigated as potential therapeutic benefit in cerebral vascular disease.

Chronic cerebral hypoperfusion: a key mechanism leading to vascular cognitive impairment and dementia. Closing the translational gap between rodent models and human vascular cognitive impairment and dementia.

Increasing evidence suggests that vascular risk factors contribute to neurodegeneration, cognitive impairment and dementia. While there is considerable overlap between features of vascular cognitive impairment and dementia (VCID) and Alzheimer's disease (AD), it appears that cerebral hypoperfusion is the common underlying pathophysiological mechanism which is a major contributor to cognitive decline and degenerative processes leading to dementia. Sustained cerebral hypoperfusion is suggested to be the cause of white matter attenuation, a key feature common to both AD and dementia associated with cerebral small vessel disease (SVD). White matter changes increase the risk for stroke, dementia and disability. A major gap has been the lack of mechanistic insights into the evolution and progress of VCID. However, this gap is closing with the recent refinement of rodent models which replicate chronic cerebral hypoperfusion. In this review, we discuss the relevance and advantages of these models in elucidating the pathogenesis of VCID and explore the interplay between hypoperfusion and the deposition of amyloid ß (Aß) protein, as it relates to AD. We use examples of our recent investigations to illustrate the utility of the model in preclinical testing of candidate drugs and lifestyle factors. We propose that the use of such models is necessary for tackling the urgently needed translational gap from preclinical models to clinical treatments.

A novel mouse model of subcortical infarcts with dementia.

Subcortical white matter (WM) is a frequent target of ischemic injury and extensive WM lesions are important substrates of vascular cognitive impairment (VCI) in humans. However, ischemic stroke rodent models have been shown to mainly induce cerebral infarcts in the gray matter, while cerebral hypoperfusion models show only WM rarefaction without infarcts. The lack of animal models consistently replicating WM infarct damage may partially explain why many neuroprotective drugs for ischemic stroke or VCI have failed clinically, despite earlier success in preclinical experiments. Here, we report a novel animal model of WM infarct damage with cognitive impairment can be generated by surgical implantation of different devices to the right and left common carotid artery (CCA) in C57BL/6J mice. Implantation of an ameroid constrictor to the right CCA resulted in gradual occlusion of the vessel over 28 d, whereas placement of a microcoil to the left CCA induced ∼50% arterial stenosis. Arterial spin labeling showed a gradual reduction of cerebral blood flow over 28 d post operation. Such reductions were more marked in the right, compared with the left, hemisphere and in subcortical, rather than the cortical, areas. Histopathological analysis showed multiple infarct damage in right subcortical regions, including the corpus callosum, internal capsule, hippocampal fimbria, and caudoputamen, in 81% of mice. Mice displaying such damage performed significantly poorer in locomotor and cognitive tests. The current mouse model replicates the phenotypes of human subcortical VCI, including multiple WM infarcts with motor and cognitive impairment.

[A case of Neuropsychiatric systemic lupus erythematosus with varying stenotic lesions in several cerebral major arteries and a vertebral artery aneurysm].

A 42 years old female suffered from systemic lupus erythematosus (SLE) about 20 years ago. While steroid was tapered for a steroid-induced psychiatric disorder, she presented with an acute confusional state and was diagnosed with neuropsychiatric SLE (NPSLE). MRI showed acute infarction mainly in the cortex of the right temporal lobe and MRA demonstrated dynamic subacute morphological changes such as stenosis and dilation in several major intracrainal arteries. The right vertebral artery diffusely dilated and subsequently formed an aneurysm in a week. Contrast-enhanced MRI vessel-wall imaging showed a remarkable enhancement of the aneurysm wall, which might indicate an unstable unruptured aneurysm. The prompt introduction of intravenous cyclophosphamide improved both clinical and radiological signs. Our case indicates that intensive immunosuppressive treatments should be considered in NPSLE patients with varying vasospasm and aneurysm, indicating exacerbated disease activity.

Ideal body weight-based determination of minimum oral calories beneficial to function and survival in ALS.

Introduction: This study sought to identify the optimal caloric intake to improve function and survival in ALS patients by comparing oral intake per ideal body weight (IBW) and its discrepancy with total energy expenditure (TEE) using the Shimizu formula. Methods: A retrospective analysis of 104 ALS patients was conducted, categorizing them based on their average intake during the first week after admission using two primary intake cutoffs: 25 kcal/kgIBW and 30 kcal/kgIBW. The variance between oral intake and TEE was also evaluated using -300 kcal and 0 kcal as reference points. Results: Oral caloric intake per IBW and functional decline rate (rs = -0.35, p < 0.001), but the variance from TEE was not significantly correlated (-0.11, p = 0.27). Survival data showed that patients consuming less than 25 kcal/kgIBW had a median survival of 24 months, increasing to 38 months for those consuming between 25-30 kcal/kgIBW and 63 months for those consuming 30 kcal/kgIBW or more. Deviations from the TEE did not significantly affect survival (p = 0.36). Among patients consuming less than their TEE, those consuming less than 25 kcal/kgIBW had a shorter median survival (24 months) compared to their counterparts (46 months) (p = 0.022). Consumption of less than 25 kcal/kgBW emerged as a significant negative predictor of patient outcome, independent of factors such as age, gender or disease progression. Discussion: Intakes of 25 kcal/kgIBW or more are correlated with improved ALS outcomes, and larger, multi-regional studies are recommended for deeper insights.

Occupational therapy using a robotic-assisted glove ameliorates finger dexterity and modulates functional connectivity in amyotrophic lateral sclerosis.

INTRODUCTION: Although rehabilitation is recommended for amyotrophic lateral sclerosis (ALS), improvement of functional decline has hardly been achieved. We investigated the effect of occupational therapy that uses a robotic-assisted glove (RAG) on hand dexterity and the functional connectivities found in the brain of ALS patients. METHOD: Ten patients diagnosed with ALS and admitted to the Shiga University of Medical Science (SUMS) Hospital from December 2018 to December 2021 participated in the study. These participants chose the hand side to wear RAG and exercised for two weeks. A sham movement was performed on the other side. We administered several functional assessments, including the Simple Test for Evaluating Hand Function (STEF), grip strength, pinch meter for grip strength, Canadian occupational performance measure (COPM), as well as nerve conduction study (NCS) before and after the exercise, and evaluated the results. We also analyzed six patients' resting-state functional magnetic resonance imaging (rs-fMRI). RESULTS: Two-week robotic rehabilitation improved the STEF, grip strength, and COPM scores when compared with those of the other side. However, no significant effect was observed in the pinch meter and the NCS results. The rs-fMRI data analysis revealed that the robotic rehabilitation augmented two functional connectivities between the left pallidum-right supplementary motor cortex and right insular cortex-right sensorimotor network among the patients, which had beneficial effects. CONCLUSION: The occupational therapy using RAG displayed improved hand dexterity. The enhanced functional connectivities around the sensorimotor network might be associated with the improvement in hand dexterity because of the RAG.

Plasma mid-regional pro-adrenomedullin: A biomarker of the ischemic penumbra in hyperacute stroke.

Reperfusion therapy has improved the outcomes of ischemic stroke but also emphasized the importance of ischemic penumbra. However, blood biomarkers are currently unavailable for this region. Adrenomedullin (ADM) is a neuroprotective peptide, secreted in a compensatory response to brain ischemia. We thus investigated whether an increase in mid-regional pro-ADM (MR-proADM), a stable peptide fragment of the ADM precursor, could act as a biomarker by predicting the ischemic penumbra in hyperacute ischemic stroke (HAIS). We prospectively enrolled consecutive HAIS patients (n = 119; median age, 77 years; male, 59.7%) admitted to our institutes from July 2017 to March 2019 and evaluated plasma MR-proADM levels within 4.5 h of onset. MR-proADM levels in HAIS were compared to healthy controls (n = 1298; median age, 58 years; male, 33.2%) in the Japan Multi-Institutional Collaborative Cohort Study from 2013 to 2017. Furthermore, we evaluated whether MR-proADM levels were associated with the penumbra estimated by clinical-diffusion mismatch (CDM) (National Institute of Health Stroke Scale [NIHSS] ≥8, diffusion ischemic core volume ≤25 ml), or magnetic resonance angiography-diffusion-weighted imaging mismatch (MDM) (NIHSS ≥5, a proximal vessel occlusion with core volume ≤25 ml, or a proximal vessel stenosis/distal vessel occlusion with core volume ≤15 ml). In a case-control study, multivariate logistic analysis showed a significant association between HAIS and MR-proADM ≥0.54 nmol/L (adjusted odds ratio, 7.92 [95% CI, 4.17-15.02], p < 0.001). Though MR-proADM levels in HAIS did not correlate with the ischemic core volume (rs  = 0.09, p = 0.348), they were higher in HAIS with CDM (n = 34; 0.81 vs. 0.61 nmol/L, p < 0.001) or MDM (n = 26; 0.83 vs. 0.62 nmol/L, p = 0.002). These differences remained significant after adjusting baseline factors (adjusted odds ratio, 4.06 [95% CI, 1.31-12.55], p = 0.015 and 4.65 [1.35-16.11], p = 0.015, respectively). Plasma MR-proADM is elevated in HAIS, especially in those with a substantial penumbra, suggesting potential as a blood biomarker in this region.

Cerebral hypoperfusion accelerates cerebral amyloid angiopathy and promotes cortical microinfarcts.

Cortical microinfarcts (CMIs) observed in brains of patients with Alzheimer's disease tend to be located close to vessels afflicted with cerebral amyloid angiopathy (CAA). CMIs in Alzheimer's disease are preferentially distributed in the arterial borderzone, an area most vulnerable to hypoperfusion. However, the causal association between CAA and CMIs remains to be elucidated. This study consists of two parts: (1) an observational study using postmortem human brains (n = 31) to determine the association between CAA and CMIs, and (2) an experimental study to determine whether hypoperfusion worsens CAA and induces CMIs in a CAA mouse model. In postmortem human brains, the density of CMIs was 0.113/cm(2) in mild, 0.584/cm(2) in moderate, and 4.370/cm(2) in severe CAA groups with a positive linear correlation (r = 0.6736, p < 0.0001). Multivariate analysis revealed that, among seven variables (age, disease, senile plaques, neurofibrillary tangles, CAA, atherosclerosis and white matter damage), only the severity of CAA was a significant multivariate predictor of CMIs (p = 0.0022). Consistent with the data from human brains, CAA model mice following chronic cerebral hypoperfusion due to bilateral common carotid artery stenosis induced with 0.18-mm diameter microcoils showed accelerated deposition of leptomeningeal amyloid ß (Aß) with a subset of them developing microinfarcts. In contrast, the CAA mice without hypoperfusion exhibited very few leptomeningeal Aß depositions and no microinfarcts by 32 weeks of age. Following 12 weeks of hypoperfusion, cerebral blood flow decreased by 26% in CAA mice and by 15% in wild-type mice, suggesting impaired microvascular function due to perivascular Aß accumulation after hypoperfusion. Our results suggest that cerebral hypoperfusion accelerates CAA, and thus promotes CMIs.

Assessment of liver function in thioacetamide-induced rat acute liver injury using an empirical mathematical model and dynamic contrast-enhanced MRI with Gd-EOB-DTPA.

PURPOSE: To evaluate thioacetamide (TAA)-induced acute liver injury in rats using an empirical mathematical model (EMM) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA). MATERIALS AND METHODS: Eighteen rats were divided into three groups (normal control [n = 6], TAA [140] [n = 6], and TAA [280] groups [n = 6]). The rats of the TAA (140) and TAA (280) groups were intravenously injected with 140 and 280 mg/kg body weight (BW) of TAA, respectively, while those of the normal control group were intravenously injected with the same volume of saline. DCE-MRI studies were performed using Gd-EOB-DTPA (0.025 mmol Gd/kg; 0.1 mL/kg BW) as the contrast agent 48 hours after TAA or saline injection. After the DCE-MRI study, blood was sampled and serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured. We calculated the rate of contrast uptake (α), the rate of contrast washout (ß), the elimination half-life of relative enhancement (RE) (T(1/2)), the maximum RE (RE(max)), and the time to (RE(max)) (T(max)) from time-signal intensity curves using EMM. RESULTS: The RE(max) values in the TAA (140) groups and TAA (280) groups were significantly smaller than that in the normal control group. The T(max) value in the TAA (280) group was significantly greater than that in the normal control group. The ß value in the TAA (280) group was significantly smaller than those in the normal control and TAA (140) groups, whereas there were no significant differences in ß among groups. The T(1/2) value in the TAA (280) group was significantly greater than those in the normal control and TAA (140) groups. The RE(max), T(max), ß, and T(1/2) values significantly correlated with AST and ALT. CONCLUSION: The EMM is useful for evaluating TAA-induced acute liver injury using DCE-MRI with Gd-EOB-DTPA.

Investigation of the prognostic predictive value of serum lipid profiles in amyotrophic lateral sclerosis: roles of sex and hypermetabolism.

The prognostic predictive value of lipid profiling in amyotrophic lateral sclerosis (ALS) remains unclear. Here, we aimed to clarify the value of the levels of serum lipids, including high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), and triglycerides (TG), for predicting the prognosis in ALS. This was a single-center retrospective study of 78 patients with ALS. The serum lipid profiles at the first hospital visit after symptom onset were analyzed to determine the correlations of lipids with survival and physical parameters, including nutritional, respiratory, and metabolic conditions. The cutoff level for high HDL was defined as the third quartile, while that of low LDL and TG, as the first quartile. Hypermetabolism was defined as the ratio of resting energy expenditure to lean soft tissue mass ≥ 38 kcal/kg. High HDL was an independent factor for poor prognosis in all patients (hazards ratio [HR]: 9.87, p < 0.001) in the Cox proportional hazard model, including %vital capacity and the monthly decline rate in body mass index and the Revised Amyotrophic Lateral Functional Rating Scale score from symptom onset to diagnosis. Low LDL was a factor for poor prognosis (HR: 6.59, p = 0.017) only in women. Moreover, subgroup analyses with log-rank tests revealed that the prognostic predictive value of high HDL was evident only in the presence of hypermetabolism (p = 0.005). High HDL predicts poor prognosis in all patients, whereas low LDL, only in women. Hypermetabolism and high HDL synergistically augment the negative effect on prognosis.

[A case of neuro-Behçet's disease triggered by herpes zoster-associated uveitis].

A 69-year-old man was admitted for persistent fever, arthralgia, and visual impairment. Physical examination demonstrated bilateral uveitis and recurrent aphthous stomatitis. The PCR analysis of the aqueous humor of the anterior chamber was positive for the Varicella-zoster virus (VZV). Although no neurological defect was evident, the cerebrospinal fluid contained elevated monocytes but was negative for VZV-PCR. Brain MRI revealed Gd-enhanced lesions in the subcortical white matter, basal ganglia, and cerebellum. With his positive HLAB51, he was diagnosed with neuro-Behcet's disease (NBD) and was successfully treated with high-dose prednisolone. Although the pathogenesis of Behcet's disease is still unknown, the involvement of viral infection is reported. The present case implies that NBD could be triggered by herpes zoster virus associate-uveitis; the accumulation of such cases would help clarify the pathogenesis of Behcet's disease.

Short-Term Effect of Intensive Speech Therapy on Dysarthria in Patients With Sporadic Spinocerebellar Degeneration.

Purpose The aim of this study was to investigate a structured approach for effective speech therapy (ST) for dysarthria and speech-related quality of life in patients with sporadic spinocerebellar degeneration (SCD), including cerebellar-type multiple-system atrophy and cerebellar cortical atrophy. Method Twenty-two patients with SCD (cerebellar-type multiple system atrophy, 15 patients; cerebellar cortical atrophy, seven patients) who underwent intensive ST were examined. Dysarthria was evaluated using the Scale for Assessment and Rating of Ataxia Speech Dysfunction, Assessment of Motor Speech for Dysarthria Articulation, oral diadochokinesis (OD), and Voice Handicap Index-10 (VHI-10). Respiratory muscle strength (inspiratory and expiratory pressure) and respiratory-phonatory coordination (maximum phonation time) were measured. Cognitive function was evaluated using the Montréal Cognitive Assessment and the word fluency test. Mood was evaluated using the Hospital Anxiety and Depression Scale. The relationships between dysarthria scales (particularly, VHI-10) and clinical data were analyzed using stepwise regression. The differences in outcomes after intensive ST were analyzed using the Wilcoxon signed-rank test. The alpha level (p) for statistical significance was set at .0125 by Bonferroni correction. Results For both pre- and post-ST, the patient's OD (p = .002) and maximum phonation time (p = .002) significantly improved, except for Speech Dysfunction scores of the Scale for Assessment and Rating of Ataxia (p = .705) and the VHI-10 (p = .018). The Assessment of Motor Speech for Dysarthria Articulation, OD, and inspiratory pressure were identified as independent variables of VHI-10 (adjusted R 2 = .820) for speech-related quality of life; no correlations among the Montréal Cognitive Assessment, word fluency test, and Hospital Anxiety and Depression Scale scores were observed. Conclusion OD and VHI-10 showed improvements due to changes in speech function and respiratory-phonatory coordination, justifying intensive ST treatment for dysarthria in patients with SCD.

Spinal Muscular Atrophy Type 3 Showing a Specific Pattern of Selective Vulnerability on Muscle Ultrasound.

A 23-year-old woman was admitted for slowly progressive proximal limb muscle weakness from childhood with elevated muscle enzyme levels. Although muscular diseases were suspected, an electromyogram showed remarkable neurogenic changes, and a muscle echogram indicated selective muscle involvement, including dissociation between the soleus and gastrocnemius, which was consistent with previous reports using magnetic resonance imaging (MRI). She was diagnosed with SMA type 3 following genetic testing, and nusinersen was soon initiated. An early diagnosis is mandatory to maximize the benefit of treatment. A muscle echogram may facilitate an early diagnosis in a non-invasive and time-saving manner compared to MRI.

Online Solid-Phase Extraction-Inductively Coupled Plasma-Quadrupole Mass Spectrometry with Oxygen Dynamic Reaction for Quantification of Technetium-99.

Quantification of pg/L levels (i.e., 0.6 mBq/L) of radioactive technetium-99 (99Tc) was achieved within 15 min in the presence of isobaric and polyatomic interference sources such as ruthenium-99 (99Ru) and molybdenum hydride (98Mo1H) at 3-11 orders of magnitude higher concentrations. Online solid-phase extraction-inductively coupled plasma-quadrupole mass spectrometry (ICP-QMS) with oxygen (O2) dynamic reaction cell (online SPE-ICP-MS-DRC) was shown to be a thorough automatic analytical system, circumventing the need for human handling. At three stepwise separations (SPE-DRC-Q mass filters), we showed that interference materials allowed the coexistence of abundance ratios of 1.5 × 10-13 and 1.1 × 10-5 for 99Tc/Mo and 99Tc/Ru, respectively. A classical mathematical correction using the natural isotope ratio of 99Ru/102Ru was used to calculate the residues of 99Ru. Using this optimized system, a detection limit (DL; 3σ) of 99Tc was 9.3 pg/L (= 5.9 mBq/L) for a 50 mL injection and sequential measurements were undertaken at a cycle of 24 min/sample. For the measurement of a lower concentration of 99Tc, an AG1-X8 anion-exchange column was used to study 20 L of seawater. Its DL was approximately 1000 times greater than that of previous methods (70.0 fg/L). Thus, this method withstands coexistences of 5.8 × 10-18 and 3.5 × 10-9 for 99Tc/Mo and 99Tc/Ru, respectively. Spike and recovery tests were conducted for environmental samples; the resulting values showed good agreement with the spike applied.

Prognostic prediction by hypermetabolism varies depending on the nutritional status in early amyotrophic lateral sclerosis.

To examine whether hypermetabolism could predict the prognosis of early amyotrophic lateral sclerosis (ALS) patients with differing nutritional profiles. This single-center, retrospective study examined the prognosis of ALS patients with hypermetabolism in relation to their nutritional status at hospitalization. The metabolic state was estimated by the ratio of measured resting energy expenditure (mREE) to lean soft tissue mass (LSTM) (mREE/LSTM), wherein patients with ratios ≥ 38 were defined as hypermetabolic. Malnutrition was defined as %ideal body weight < 0.9. Forty-eight patients were enrolled in this study. The hypermetabolic group had shorter survival in the normal-weight group but more prolonged survival in the malnutrition group. Multiplication of nutritional and metabolic factors, such as [(body mass index (BMI) - 19.8) × (mREE/LSTM - 38)], designated as BMI-muscle metabolism index (BMM index), successfully predicted the prognosis in the group with a high BMM index (≥ 1), which showed shorter survival and a faster rate of weight loss and functional decline. Multivariate analysis using the Cox model showed high BMM index was an independent poor prognostic factor (hazard ratio: 4.05; p = 0.025). Prognostic prediction by hypermetabolism varies depending on the nutritional status in ALS, and the BMM index is a consistent prognostic factor.