Hemodiafiltration Improves Low Levels of Health-Related Quality Of Life (Qol) and Nutritional Conditions of Hemodialysis Patients.

We compared the effects on the nutritional condition and health-related quality of life (HR-QoL) of the treatment of patients with on-line hemodiafiltration (OL-HDF) and conventional hemodialysis (CHD) using a superflux dialyzer. In total, 47 maintenance (M) HD patients were treated by CHD with a high-flux dialyzer for the first 4 months (1st CHD) and were then switched to predilution OL-HDF for the next 4 months (OL-HDF), after which CHD was resumed for the last 4 months (2nd CHD). We assessed the clinical parameters, fat mass value, muscle mass value, and HR-QoL. In patients with low serum albumin levels, these levels significantly (p < 0.05) increased in the OL-HDF period. Moreover, the fat mass values significantly (p < 0.05) increased in patients with decreased fat mass values in the OL-HDF period. Although there was no significant difference in the patients with higher scores of physical functioning, role physical, vitality, and social functioning, patients with lower scores in the 1st CHD period had significantly increased (p < 0.05) in the OL-HDF period. In this crossover study, we revealed that OL-HDF treatment significantly improved the nutritional conditions and HR-QoL scores compared with the improvement observed after CHD with a superflux dialyzer, especially for maintenance hemodialysis patients with malnutrition and a low QoL.

Long-acting erythropoiesis-stimulating agent (ESA) induces physiological erythropoiesis via improvement of iron availability.

PURPOSE: Previous studies reported that the long-acting erythropoiesis-stimulating agent (ESA) significantly suppresses the expression of hepcidin, which regulates iron availability. In this study, we compared the iron availability for erythropoiesis between short and long-acting ESA over a long period. METHODS: We enrolled 69 hemodialysis patients in this study. All patients were treated with short-acting ESA (epoetin-α or epoetin-ß) for the first 30 months. Then, all patients switched to long-acting ESA (continuous erythropoietin receptor activator-methoxy polyethylene glycol-epoetin beta) for the next 30 months. We measured their blood levels of Hb, ferritin, iron, total iron-binding capacity, intact-parathyroid hormone, calcium, phosphate, albumin, and highly sensitive CRP level. RESULTS: There was no significant change in the dose of short or long-acting ESA during the study period. Compared with the short-acting ESA period, the mean hemoglobin (Hb) and transferrin saturation levels were significantly increased in the long-acting ESA period (from 10.3 ± 0.2 to 10.6 ± 0.3 g/dL). On the other hand, the mean serum ferritin level (from 72 ± 22.2 to 56.3 ± 14 ng/mL) and the dose of IV iron (from 108 ± 63 to 53 ± 27 mg/month) were significantly decreased in the long-acting ESA period. CONCLUSION: In this study, we found that anemia treatment with long-acting ESA attenuated the iron utilization for erythropoiesis and maintained target Hb levels without requiring a higher dose of IV iron or ESA.

Pitfalls of Commonly Used Ischemic and Dementia Models Due to Early Seizure by Carotid Ligation.

While the bilateral common carotid artery (CCA) ligation model is widely used in cerebrovascular disease and dementia studies, it can frequently cause seizures. We examined the validity of seizure as an experimental model of ischemia. Eight-week-old male Wistar and Sprague-Dawley (SD) rats were implanted with electrocorticography (ECoG) electrodes and bilateral CCA ligation was performed and compared to the sham groups. ECoG monitoring was used to confirm the seizure discharge and count the number of spikes in the interictal phase 2 h after ligation, followed by power spectral analysis. Magnetic resonance imaging (MRI) was performed 6 h after bilateral CCA ligation to assess fractional anisotropy (FA), apparent diffusion coefficient (ADC), and cerebral blood flow (CBF) values. Magnetic resonance spectroscopy (MRS) was also performed and the ischemic parameters and electrophysiological changes were compared. The Wistar rat group had significantly higher mortality, frequency of seizures, incidence of non-convulsive seizures, and number of spikes in the interictal period compared to those in the SD rat group. Power spectral analysis showed increased power in the delta band in both Wistar and SD rat groups. MRI, after CCA ligation, showed significantly lower ADC values, lower glutamine and glutamate levels, and higher lactate values in Wistar rats, although there was no difference in FA values. Metabolic and electrophysiological changes after CCA ligation differed according to the rat strain. Wistar rats were prone to increased lactate and decreased glutamine and glutamate levels and the development of status epilepticus. Seizures can affect the results of ischemic experiments.

Interhemispheric Asymmetry of Network Connecting Between Frontal and Temporoparietal Cortices: A Corticocortical-Evoked Potential Study.

BACKGROUND: The connection between the ventrolateral frontal and temporoparietal cortices has an important role in language function on the language-dominant side and spatial awareness on the nondominant side. However, the laterality of these pathways remains controversial. We investigated the laterality of this connection using corticocortical-evoked potentials (CCEPs). METHODS: From April 2014 to March 2016, 27 patients who had undergone frontotemporal craniotomy were enrolled. With the patients under general anesthesia, subdural electrodes were placed on both frontal and temporoparietal areas intraoperatively. Alternating 1-Hz electrical stimuli were delivered to the pars opercularis and pars triangularis with a stimulus intensity of 10 mA. CCEPs were obtained from temporoparietal areas by averaging the electrocorticogram time-locked to the stimulus onset. The amplitudes and latencies of the CCEP N1 components were compared between the dominant and nondominant sides. RESULTS: The median amplitudes of the CCEPs were 335.1 µV (range, 60.2-750) and 125.65 µV (range, 55.1-634) on the dominant and nondominant sides, respectively. The CCEP amplitudes were significantly larger on the dominant side than on the nondominant side (P = 0.013). In contrast, the median latency was 27.8 ms (range, 19.3-36.6) on the language-dominant side and 28.9 ms (range, 8.9-38.5) on the nondominant side. The latencies were not significantly different between the 2 sides (P = 0.604). CONCLUSIONS: The CCEP amplitudes were significantly larger in the dominant hemisphere. These findings can lead to better hypotheses regarding the relationship between language functions and the development of the network connecting the frontal and temporoparietal cortices.

Threshold and distribution of afterdischarges with electrical cortical stimulation.

OBJECTIVE: The present study aimed to investigate the threshold and distribution of afterdischarges (ADs) with cortical electrical stimulation for functional brain mapping. METHOD: We retrospectively analyzed data from 11 patients with medically intractable epilepsy who underwent 50-Hz cortical electrical stimulation for functional mapping followed by resection. These patients became seizure free for more than six months. The threshold and distribution of ADs induced by the stimulation were evaluated. RESULTS: The median threshold was 6 mA (range: 2-15 mA) for the frontal lobe, 8 mA (3-15 mA) for the temporal lobe, 6 mA (2-15 mA) for the parietal lobe, and 6 mA (4-12 mA) for the occipital lobe. No significant interlobar differences were observed in AD thresholds. No significant differences were noted between within and outside epileptogenic zones. The distribution of ADs, remote spread was observed in all patients, reflecting fronto-parieto-temporal connections, as well as contiguous spread. The stimulation of premotor areas, the inferior parietal lobule, supplementary motor area, and basal temporal areas appeared to induce ADs in remote cortices. CONCLUSION: While no locational differences were observed in AD thresholds, each brain region showed a characteristic pattern for AD spread. Remote AD spread needs to be considered for safe functional mapping.

Location and Threshold of Electrical Cortical Stimulation for Functional Brain Mapping.

BACKGROUND AND OBJECTIVE: Although many studies have investigated functional localization by electrical stimulation, the threshold to identify each area remains controversial. The present study aimed to elucidate the threshold of a cortical stimulation for functional mapping. METHODS: We analyzed data from 17 patients with medically intractable epilepsy who underwent a 50-Hz electrical cortical stimulation for functional mapping between October 2013 and May 2017. The symptoms induced by the stimulation and the thresholds of the stimulation for these responses were evaluated. RESULTS: Motor responses were observed after the stimulation of the primary motor cortex, supplementary motor area, and frontal eye field, and sensory responses after the stimulation of the primary and secondary sensory cortex. Regarding negative responses, language impairment was observed after the stimulation of the anterior, posterior, and basal temporal language areas, negative motor responses after the stimulation of the premotor cortex, posterior parietal cortex, and the pre- supplementary motor area, and an impairment in spatial recognition after the stimulation of the right posterior parietal cortex. Negative or positive auditory symptoms were observed with the stimulation of the posterior superior temporal gyrus. The thresholds for positive phenomena were significantly lower than those for negative phenomena (Mann-Whitney U test, P < 0.01), and sensory responses were induced at significantly lower intensities than motor responses (P < 0.01). CONCLUSIONS: Positive and sensory effects are induced by lower intensities than negative and motor responses, respectively. The present results provide not only a practical guide for functional mapping, but also a hierarchal concept of processing in the brain.

Actin, alpha, cardiac muscle 1 (ACTC1) knockdown inhibits the migration of glioblastoma cells in vitro.

BACKGROUND: Recurrence is inevitable in glioblastomas (GBMs) and requires multifactorial processes. One of the factors that cause recurrence is the strong migratory capacity of GBM cells. We recently reported that actin, alpha, cardiac muscle 1 (ACTC1) could serve as a marker to detect GBM migration in clinical cases. OBJECTIVE: This study aimed to clarify whether the knockdown of highly expressed ACTC1 can inhibit the migratory capacity of cells in the GBM cell line. METHODS: ACTC1 expression was examined using immunocytochemistry and droplet digital polymerase chain reaction. The motility of GBM cells that were either treated with siRNA to knock down ACTC1 or untreated were investigated using a time-lapse study in vitro. RESULTS: The relatively high ACTC1 expression was confirmed in a GBM cell line, i.e., U87MG. The ACTC1 expression in U87MG cells was significantly inhibited by ACTC1-siRNA (p < 0.05). A cell movement tracking assay using time-lapse imaging demonstrated the inhibition of U87MG cell migration by ACTC1 knockdown. The quantitative cell migration analysis demonstrated that the distance traversed during 72 h was 3607 ±â€¯458 (median ±â€¯SD) µm by untreated U87MG cells and 3570 ±â€¯748 µm by negative control siRNA-treated cells. However, the distance migrated by ACTC1-siRNA-treated cells during 72 h was significantly shorter (1265 ±â€¯457 µm, p < 0.01) than the controls. CONCLUSION: ACTC1 knockdown inhibits U87MG cell migration.

Digital Polymerase Chain Reaction Quantification of SERPINA1 Predicts Prognosis in High-Grade Glioma.

BACKGROUND: SERPINA1 plays an anti-inflammatory role in protecting tissues from proteolytic mechanisms. SERPINA1 is positive in gliomas by immunohistochemical analysis; however, the role of SERPINA1, including the relationship with prognosis, has been uncertain. In recent years, digital polymerase chain reaction (PCR) has provided ultra-sensitive assessment of messenger RNA expression from formalin-fixed paraffin-embedded (FFPE) tissues. OBJECTIVE: In this study, we quantitatively determined the expression of SERPINA1 in high-grade gliomas (HGGs) using digital PCR, and we analyzed its relationship with prognosis. METHODS: Twenty-nine FFPE surgical samples from patients with HGGs (7 of World Health Organization [WHO] grade III and 22 of WHO grade IV), and human glioblastoma cell lines, U87 and U118, were used for analysis. A qualitative assessment using immunostaining and quantitative assessment using digital PCR were performed to assess the expression of SERPINA1. RESULTS: The expression of SERPINA1 was demonstrated in glioma tissues and glioblastoma multiforme cell lines by immunostaining. Digital PCR analysis showed that SERPINA1 was expressed in 14.3% and 63.6% of the tissues from patients with grade III and grade IV HGG, respectively (P = 0.035). The median overall survival of 38.8 months in the low SERPINA1 expression group was longer than that of 15.3 months in the high expression group (P = 0.030). CONCLUSIONS: The frequency and the amount of SERPINA1 expression were higher in grade IV than in grade III HGGs. The high expression of SERPINA1 indicates a poor prognosis of HGGs.

Interleukin-13 receptor alpha 2 as a marker of poorer prognosis in high-grade astrocytomas.

BACKGROUND: Interleukin-13 receptor alpha 2 (IL13Rα2) is considered a prognostic marker for gliomas according to the World Health Organization (WHO) grade. However, the expression levels of the marker vary from case to case, even within the same grade. We investigated whether IL13Rα2 could serve as a predictor of poorer prognosis in gliomas. METHODS: mRNA expression of IL13Rα2 was measured using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) in 52 formalin-fixed paraffin-embedded glioma samples (4 pilocytic astrocytomas, 9 diffuse astrocytomas, 12 anaplastic astrocytomas, and 27 glioblastomas, grade IV). The expression levels were compared with regard to WHO grade, MIB-1 index, patient's age, and overall survival. RESULTS: Real time qRT-PCR showed that IL13Rα2 is expressed in a subset of cases with a progressive increase from low- to high-grade astrocytomas (HGAs). The expression had a significant positive correlation with the MIB-1 index and advanced patient age at diagnosis. The overall survival (OS) of patients who had HGAs with higher levels of IL13Rα2 expression was significantly lower than the OS of those with HGAs with lower levels of IL13Rα2. In the 39 HGA cases studied, the median survival benefit in the lower expression group was 167.4 months. The median OS (mOS) in HGA group with lower IL13Rα2 expression was 186.4 months, while the mOS in the group with higher IL13Rα2 expression was 18.6 months (P=0.033). The hazard ratio, adjusted by fitting the Cox proportional hazard models for the mOS in the HGAs with higher IL13Rα2 levels and the HGGs with lower IL13Rα2 levels, was 5.97 (95% CI: 1.76 to 20.32). CONCLUSIONS: The results showed that IL13Rα2 may be used as a marker of poorer prognosis in HGAs, even among tumors of the same grade.

Frontal Fibers Connecting the Superior Frontal Gyrus to Broca Area: A Corticocortical Evoked Potential Study.

BACKGROUND: The frontal aslant tract is a deep frontal pathway connecting the superior frontal gyrus (SFG) to Broca area. This fiber is assumed to be associated with language functions, especially speech initiation and spontaneity. The aim of this study was to electrophysiologically investigate this network using corticocortical evoked potentials (CCEPs). METHODS: This study enrolled 8 patients with brain tumors or medically intractable focal epilepsies who underwent frontal craniotomy over the language-dominant side. All patients underwent CCEP recordings during tumor resection or during invasive evaluation for epilepsy surgery. Alternating 1-Hz electrical stimuli were delivered to pars opercularis (pO) and pars triangularis (pT), corresponding to Broca area, and SFG via the subdural grid electrodes with intensity of 10 mA. Electrocorticograms from SFG and pO/pT time-locked to 50 stimuli were averaged in each trial to obtain CCEP responses. RESULTS: In all patients, stimulation of pO/pT induced CCEP responses in SFG. CCEP responses were recorded in lateral SFG in 5 patients and in supplementary motor areas in 4 patients. Reciprocality was observed in 7 patients in the stimulation of SFG. CCEP responses were significantly faster at SFG from pO/pT than at pO/pT from SFG (Wilcoxon signed rank test, P = 0.028). CONCLUSIONS: The present study demonstrated a corticocortical network connecting Broca areas and SFG in a reciprocal manner. Our findings might provide new insight into language and motor integration.

Distribution and Network of Basal Temporal Language Areas: A Study of the Combination of Electric Cortical Stimulation and Diffusion Tensor Imaging.

OBJECTIVE: The basal temporal language area (BTLA) is considered to have several functions in language processing; however, its brain network is still unknown. This study investigated the distribution and networks of the BTLA using a combination of electric cortical stimulation and diffusion tensor imaging (DTI). METHOD: 10 patients with intractable focal epilepsy who underwent presurgical evaluation with subdural electrodes were enrolled in this study (language dominant side: 6 patients, language nondominant side: 4 patients). Electric stimulation at 50 Hz was applied to the electrodes during Japanese sentence reading, morphograms (kanji) reading, and syllabograms (kana) reading tasks to identify the BTLA. DTI was used to identify the subcortical fibers originating from the BTLA found by electric stimulation. RESULTS: The BTLA was found in 6 patients who underwent implantation of the subdural electrodes in the dominant hemisphere. The BTLA was located anywhere between 20 mm and 56 mm posterior to the temporal tips. In 3 patients, electric stimulation of some or all areas within the BTLA induced disturbance in reading of kanji words only. DTI detected the inferior longitudinal fasciculus (ILF) in all patients and the uncinate fasciculus (UF) in 1 patient, originating from the BTLA. ILF was detected from both kanji-specific areas and kanji-nonspecific areas. CONCLUSION: This study indicates that the network of the BTLA is a part of a ventral stream and is mainly composed of the ILF, which acts as a critical structure for lexical retrieval. ILF is also associated with the specific processing of kanji words.