Urinary D-asparagine level is decreased by the presence of glioblastoma.

Gliomas, particularly glioblastomas (GBMs), pose significant challenges due to their aggressiveness and poor prognosis. Early detection through biomarkers is critical for improving outcomes. This study aimed to identify novel biomarkers for gliomas, particularly GBMs, using chiral amino acid profiling. We used chiral amino acid analysis to measure amino acid L- and D-isomer levels in resected tissues (tumor and non-tumor), blood, and urine from 33 patients with primary gliomas and 24 healthy volunteers. The levels of D-amino acid oxidase (DAO), a D-amino acid-degrading enzyme, were evaluated to investigate the D-amino acid metabolism in brain tissue. The GBM mouse model was created by transplanting GBM cells into the brain to confirm whether gliomas affect blood and urine chiral amino acid profiles. We also assessed whether D-amino acids produced by GBM cells are involved in cell proliferation. D-asparagine (D-Asn) levels were higher and DAO expression was lower in glioma than in non-glioma tissues. Blood and urinary D-Asn levels were lower in patients with GBM than in healthy volunteers (p < 0.001), increasing after GBM removal (p < 0.05). Urinary D-Asn levels differentiated between healthy volunteers and patients with GBM (area under the curve: 0.93, sensitivity: 0.88, specificity: 0.92). GBM mouse model validated the decrease of urinary D-Asn in GBM. GBM cells used D-Asn for cell proliferation. Gliomas induce alterations in chiral amino acid profiles, affecting blood and urine levels. Urinary D-Asn emerges as a promising diagnostic biomarker for gliomas, reflecting tumor presence and severity.

Effects of d-alanine Intake on Amino Acid Metabolism and Kidney Function in Healthy Adults: A Multicenter, Randomized Pilot Study.

Background: d-alanine administration prevented kidney damage in a murine acute kidney injury model. Further data are needed on the influence of d-alanine on kidney function in humans. Objective: This study investigated the effects of d-alanine intake on amino acid metabolism and kidney function in healthy volunteers. Methods: This multicenter pilot study randomly assigned individuals from the general Japanese population to receive 3 g or 6 g of d-alanine intake per day for 7 d in a 1:1 ratio. The primary endpoint was the mean change in plasma and urine d-alanine levels from baseline to 7 d after intake. The secondary endpoints were mean changes in kidney function and other clinical factors. Safety was assessed by evaluating adverse events and clinical parameters. Results: We randomly assigned 24 participants to the 3-g (n = 12) and 6-g d-alanine (n = 12) groups. The mean baseline estimated glomerular filtration rate (eGFR) was 73 mL/min/1.73 m2. The mean plasma d-alanine concentration increased from baseline by 77.5 ± 34.3 and 192.1 ± 80.9 nmol/mL in the 3-g and 6-g d-alanine groups (both p < 0.0001), respectively, in a dose-dependent manner (between-group difference: 114.6 nmol/mL; 95% CI: 62.1-167.2; P = 0.0002). A similar increase was observed for the urine d-alanine to creatinine ratio. The mean eGFR was elevated by 5.7 ± 8.8 mL/min/1.73 m2 in the 6-g d-alanine group (P = 0.045) but did not significantly change in the 3-g d-alanine group. Nonserious adverse events were reported in 11 participants. Conclusions: d-alanine intake increased plasma and urine d-alanine levels and was well tolerated in participants with normal kidney function. These results will be useful in future trials investigating the effects of d-alanine intake on kidney disease progression in patients with chronic kidney disease.This trial was registered at the UMIN Clinical Trials Registry as UMIN000051466.

Evaluation of Conditions for the Development of Cryogenic Spinal Cord Injury Using a Canine Model: An Experimental Study on the Safety of Cryoablation for Metastatic Spinal Tumors.

BACKGROUND AND PURPOSE: Although the application of cryoablation to metastatic spinal tumors has been attempted, spinal cryoablation has the unique complication of cryogenic spinal cord injury. This study aimed to elucidate the conditions for the development of cryogenic spinal cord injury. MATERIALS AND METHODS: Fifteen canines were used in this study. A metal probe was inserted into the 13th thoracic vertebral body. Cryoablation was performed for 10 minutes by freezing the probe in liquid nitrogen. The control canine underwent probe insertion only. Spinal cord monitoring, epidural temperature measurement, motor function assessment, and pathologic examination of the spinal cord were performed. RESULTS: During the 10 minutes of cryoablation, the epidural temperature decreased and reached the lowest epidural temperature (LET) at the end of cryoablation. The LETs (degrees celsius [°C]) of each canine were -37, -30, -27, -8, -3, -2, 0, 1, 4, 8, 16, 18, 20, and 25, respectively. As the epidural temperature decreased, waveform amplitudes also decreased. At the end of cryoablation (10 minutes after the start of cryoablation), abnormal waves were observed in 92.9% (13/14) of canines. With epidural rewarming, the amplitude of the waveforms tended to recover. After epidural rewarming (2 hours after the start of cryoablation), abnormal waves were observed in 28.6% (4/14) of canines. The LETs (°C) of the canines with abnormal waves after epidural rewarming were -37, -30, -27, and -8. None of the canines with normal waves after epidural rewarming had any motor impairment. In contrast, all canines with remaining abnormal waves after epidural rewarming had motor impairment. In the pathologic assessment, cryogenic changes were found in canines with LETs (°C) of -37 -30, -27, -8, 0, and 1. CONCLUSIONS: This study showed that 10-minute spinal cryoablation with LETs (°C) of -37, -30, -27, -8, 0, and 1 caused cryogenic spinal cord injury. There was no evidence of cryogenic spinal cord injury in canines with LET of ≥4°C. The epidural temperature threshold for cryogenic spinal cord injury is between 1 and 4°C, suggesting that the epidural temperature should be maintained above at least 4°C to prevent cryogenic spinal cord injury.

Motor-Evoked Potential Monitoring With Multi-train Electrical Stimulation During Thoracoabdominal Aortic Aneurysm Surgery: A Case Report.

Intraoperative motor-evoked potentials (MEPs) are measured for assessing motor function during surgery. MEP monitoring is often performed in thoracoabdominal aortic aneurysm (TAAA) surgery, but false positives are common and amplification methods are needed to obtain waveforms under severe conditions to assess proper spinal cord function. One method of amplitude amplification in transcranial-stimulated MEP monitoring is multitrain stimulation. There are few reports on multitrain-stimulated MEP monitoring for this surgery. A 57-year-old woman underwent open repair of the thoracoabdominal aorta due to a dissecting aortic aneurysm. After opening the chest, the aneurysm was incised proximally, and anastomosis with an artificial vessel was initiated. The lumbar artery leading to the Adam-Kiewicz artery was reconstructed at a body temperature of 25 °C. However, the single-train stimulation did not produce MEPs. When the measurement was switched to multitrain stimulation, MEPs were elicited in the lower extremity muscle groups and the waveforms were maintained until the end of the measurement. This case illustrates that MEP monitoring using multitrain stimulation during descending thoracic aortic aneurysm surgery can effectively elicit MEPs under challenging conditions, in which conventional single-train stimulation may be insufficient.

Design and rationale for an open-label, randomized, controlled pilot trial to evaluate the changes in blood uremic toxins in patients with chronic kidney disease by dietary therapy with sake lees.

BACKGROUND: Patients with chronic kidney disease (CKD) reportedly show dysbiosis, which is the imbalance of gut microbiome. Dysbiosis increases the uremic toxin level in the intestine, and uremic toxins transfer into the blood, causing CKD progression. Sake lees, a traditional Japanese fermented food, may help reduce uremic toxins by altering the gut microbiome. Additionally, D-alanine, which is present in sake lees, may have a renoprotective effect. The present pilot study aims to evaluate the effect of adding sake lees to the standard CKD dietary therapy in reducing blood uremic toxins. METHODS: This pilot study is a single-center, open-label, randomized controlled trial. Twenty-four patients with CKD will be enrolled and allocated 1:1 to the intervention and control groups. The intervention group will receive standard CKD dietary therapy with an additional intake of 50 g of sake lees per day for 8 weeks, whereas the control group will only receive standard CKD dietary therapy. The primary endpoint is the change in serum indoxyl sulfate after 8 weeks. The secondary endpoint is the plasma D-alanine and fecal microbiome changes. CONCLUSION: This pilot study provides insight into the development of a new diet focused on gut microbiome and D-amino acids in patients with CKD. CLINICAL TRIAL REGISTRATION: This protocol was approved by the Clinical Trial Review Board of Kanazawa University Hospital on October 27, 2022 (2022-001 [6139]) and available to the public on the website of the Japan Registry of Clinical Trials on November 22, 2022 (jRCT1040220095).

Association Between Risperidone Use and Kidney Function Decline in Patients with Schizophrenia: A Retrospective Cohort Study.

PURPOSE: Several D-amino acids have been shown to be protective against kidney injury in mice. Risperidone, a currently used atypical antipsychotic agent for schizophrenia, is also known to inhibit the activity of D-amino acid oxidase, which degrades certain D-amino acids. Based on the hypothesis that risperidone would prevent kidney disease progression, this study investigated the association between risperidone use and kidney function decline in patients with schizophrenia. METHODS: This retrospective cohort study included patients who were diagnosed with schizophrenia and had data available from two or more serum creatinine measurements between April 1, 2010, and March 31, 2020. Patients who used risperidone for at least 30 days were included in the risperidone group, whereas those who had no record of risperidone use were included in the control group. Cox regression models were used to evaluate the risk for 40% decline in estimated glomerular filtration rate (eGFR) in patients treated with risperidone compared to that in the control group. FINDINGS: Overall, 212 patients used risperidone and 1468 patients had no record of risperidone use. The mean age was 55 years, 759 (45%) of the patients were male, and the mean eGFR at baseline was 88 mL/min/1.73 m2. The mean age in the risperidone group was less than that in the control group (52 vs 56 years); other baseline characteristics were comparable between the two groups. During a mean follow-up of 1.6 years, 267 patients (16%) had a 40% eGFR decline. The incidence rate of 40% eGFR decline was lower in the risperidone group than in the control group (60 vs 104 per 1000 person-years). After adjustment for baseline age, sex, and eGFR, risperidone use was associated with a decreased risk for 40% eGFR decline (hazard ratio = 0.54; 95% CI, 0.33-0.87; P = 0.01). IMPLICATIONS: Risperidone use may be associated with decreased risk for kidney function decline in patients with schizophrenia. Further studies are warranted to validate these findings.

Intra-Brain and Plasma Levels of L-Serine Are Associated with Cognitive Status in Patients with Chronic Kidney Disease.

Introduction: The number of patients with chronic kidney disease (CKD) is increasing worldwide. Cognitive impairment is one of the comorbidities of CKD. With the increased number of aged population, novel biomarkers of impaired cognitive function are required. Intra-body profile of amino acid (AA) is reportedly altered in patients with CKD. Although some AAs act as neurotransmitters in the brain, it is not clear whether altered AA profile are associated with cognitive function in patients with CKD. Therefore, intra-brain and plasma levels of AAs are evaluated with respect to cognitive function in patients with CKD. Methods: Plasma levels of AAs were compared between 14 patients with CKD, including 8 patients with diabetic kidney disease, and 12 healthy controls to identify the alteration of specific AAs in CKD. Then, these AAs were evaluated in the brains of 42 patients with brain tumor using non-tumor lesion of the resected brain. Cognitive function is analyzed with respect to intra-brain levels of AAs and kidney function. Moreover, plasma AAs were analyzed in 32 hemodialyzed patients with/without dementia. Results: In patients with CKD, plasma levels of asparagine (Asn), serine (Ser), alanine (Ala), and proline (Pro) were increased as compared to patients without CKD. Among these AAs, L-Ser, L-Ala, and D-Ser show higher levels than the other AAs in the brain. Intra-brain levels of L-Ser was correlated with cognitive function and kidney function. The number of D-amino acid oxidase or serine racemase-positive cells was not correlated with kidney function. Moreover, the plasma levels of L-Ser are also decreased in patients with declined cognitive function who are treated with chronic hemodialysis. Conclusion: The decreased levels of L-Ser are associated with impaired cognitive function in CKD patients. Especially, plasma L-Ser levels may have a potential for novel biomarker of impaired cognitive function in patients with hemodialysis.

Increased levels of oral Streptococcus-derived D-alanine in patients with chronic kidney disease and diabetes mellitus.

The number of patients on hemodialysis is increasing globally; diabetes mellitus (DM) complications is the major cause of hemodialysis in patients with chronic kidney disease (CKD). The D-amino acid (AA) profile is altered in patients with CKD; however, it has not been studied in patients with CKD and DM. Furthermore, bacteria responsible for altering the D-AA profile are not well understood. Therefore, we examined the D-AA profiles and associated bacteria in patients with CKD, with and without DM. We enrolled 12 healthy controls and 54 patients with CKD, with and without DM, and determined their salivary, stool, plasma, and urine chiral AA levels using two-dimensional high-performance liquid chromatography. We performed 16S rRNA gene sequencing analysis of the oral and gut microbiota to determine the association between the abundance of bacterial species and D-AA levels. Plasma D-alanine and D-serine levels were higher in patients with CKD than in healthy adults (p < 0.01), and plasma D-alanine levels were higher in patients with CKD and DM than in those without DM. The abundance of salivary Streptococcus, which produced D-alanine, increased in patients with CKD and DM and was positively correlated with plasma D-alanine levels. Patients with CKD and DM had unique oral microbiota and D-alanine profiles. Plasma D-alanine is a potential biomarker for patients with CKD and DM.

Evaluation of factors related to morphological masseter muscle changes after preoperative orthodontic treatment in female patients with skeletal class III dentofacial deformities.

BACKGROUND: The purpose of the current study was to investigate factors related to morphological changes in the masseter muscle after preoperative orthodontic treatment in patients with skeletal class III dentofacial deformities for analysis of muscle changes and malocclusions. METHODS: Twenty female patients with dentofacial deformities were included in the study. Computed tomography was performed before and after preoperative orthodontic treatment, and the lengths, widths, and cross-sectional areas of the masseter muscles were measured. Changes in these parameters were evaluated, and factors related to changes in masseter muscle area after preoperative orthodontic treatment were analyzed. RESULTS: The lengths, widths, and areas of masseter muscles were significantly smaller after preoperative orthodontic treatment. Smaller masseter muscle area was significantly associated with changes in overbite and pretreatment values of SNA angle. CONCLUSIONS: Atrophy of the masseter muscle during preoperative orthodontic treatment was greater in patients with increased open bite due to improved dental compensation in patients with skeletal class III dentofacial deformities with maxillary retraction.

Evaluation of Rhythmic Masseter Muscle Activity during Sleep and Awake in Patients with Dentofacial Deformity.

Objectives: Investigate the activity of rhythmic masseter muscles activity (RMMA) during sleep in patients with dentofacial deformities. Materials and methods: Fifty patients with dentofacial deformities (16 male, 34 female) who required orthognathic surgery. An electrode was attached to the masseter muscle bilaterally, and preoperative polysomnography was performed. The frequency of RMMA onset per hour was measured on the left and the right sides. Values were classified as phasic (grinding: P-RMMA) and tonic (clenching: T-RMMA) to examine the onset of RMMA. Correlation between the RMMA index and various morphological and physical factors were determined including sleep or awake, rapid eye movement (REM), non-rapid eye movement (NREM) phases (NR1-NR4) in the sleep stage, phasic and tonic, gender, and mandibular asymmetry. Results: The RMMA index values at the time of sleep were significantly small than during awake. The values were significantly higher during the NREM sleep than during the REM sleep and were the highest in the NR1 phase. P-RMMA index was significantly higher than the T-RMMA index. The P-RMMA index was also significantly higher than the T-RMMA index for men. In patients with greater asymmetry in the RMMA index values between the left and the right side (more than 30% difference), deviation between the midpoint of the maxillary and the mandibular incisal edges (U1-L1 deviation) was significantly higher. Conclusion: RMMA in patients with dentofacial deformity was statistically higher in awake than sleep, higher in NREM sleep than REM sleep, higher in male than female on grinding, and higher in upper and lower incisor high deviation.

In Carpal Tunnel Syndrome, Sensory Nerve Conduction Velocities Are Worst in the Middle Finger Than in the Index Finger.

Although the index finger is generally used for sensory nerve conduction study in cases of carpal tunnel syndrome, there are reports that the middle finger should be used. The purpose of this study was to compare the results of sensory nerve conduction studies of the index finger and middle finger in patients with carpal tunnel syndrome. Among the 120 hands of 93 patients who were diagnosed with carpal tunnel syndrome and underwent carpal tunnel release surgery at our hospital, 54 hands of 48 patients who showed waveforms in sensory nerve conduction studies both index and middle fingers were included. 6 hands of 6 patients who showed no waveform in the index or middle finger, and 60 hands of 39 patients who showed no waveform in both index and middle finger were excluded. The subjects were 14 males and 34 females, and their ages were 66.2 years. The preoperative sensory nerve action potential (µV) and sensory nerve conduction velocity (m/s) of the index and middle fingers were tested using Wilcoxon's signed rank test. Spearman's rank correlation coefficient was also calculated for the results of the index and middle fingers. Sensory nerve action potentials were 2.0 in the index finger and 1.8 in the middle finger, with significantly lower in the middle finger. Sensory nerve conduction velocity was 30.1 in the index finger and 27.2 in the middle finger, with significantly lower in the middle finger. The correlation coefficients of sensory nerve action potentials and conduction velocities between the index finger and middle finger were 0.82 and 0.96, respectively, both of which showed a significant correlation. The results of the sensory nerve conduction studies of the middle finger were significantly worse than those of the index finger in cases of carpal tunnel syndrome. In addition, there was a strong correlation between the results of the index finger and the middle finger. The results of this study suggest that the nerve bundle to the middle finger may be more strongly affected than the nerve bundle to the index finger in cases of carpal tunnel syndrome.

Protective effect of d-alanine against acute kidney injury.

Recent studies have revealed the connection between amino acid chirality and diseases. We have previously reported that the gut microbiota produces various d-amino acids in a murine acute kidney injury (AKI) model. Here, we further explored the pathophysiological role of d-alanine (d-Ala) in AKI. Levels of d-Ala were evaluated in a murine AKI model. We analyzed transcripts of the N-methyl-d-aspartate (NMDA) receptor, a receptor for d-Ala, in tubular epithelial cells (TECs). The therapeutic effect of d-Ala was then assessed in vivo and in vitro. Finally, the plasma level of d-Ala was evaluated in patients with AKI. The Grin genes encoding NMDA receptor subtypes were expressed in TECs. Hypoxic conditions change the gene expression of Grin1, Grin2A, and Grin2B. d-Ala protected TECs from hypoxia-related cell injury and induced proliferation after hypoxia. These protective effects are associated with the chirality of d-Ala. d-Ala inhibits reactive oxygen species (ROS) production and improves mitochondrial membrane potential, through NMDA receptor signaling. The ratio of d-Ala to l-Ala was increased in feces, plasma, and urine after the induction of ischemia-reperfusion (I/R). Moreover, Enterobacteriaceae, such as Escherichia coli and Klebsiella oxytoca, produce d-Ala. Oral administration of d-Ala ameliorated kidney injury after the induction of I/R in mice. Deficiency of NMDA subunit NR1 in tubular cells worsened kidney damage in AKI. In addition, the plasma level of d-Ala was increased and reflected the level of renal function in patients with AKI. In conclusion, d-Ala has protective effects on I/R-induced kidney injury. Moreover, the plasma level of d-Ala reflects the estimated glomerular filtration rate in patients with AKI. d-Ala could be a promising therapeutic target and potential biomarker for AKI.NEW & NOTEWORTHY d-Alanine has protective effects on I/R-induced kidney injury. d-Ala inhibits ROS production and improves mitochondrial membrane potential, resulting in reduced TEC necrosis by hypoxic stimulation. The administration of d-Ala protects the tubules from I/R injury in mice. Moreover, the plasma level of d-Ala is conversely associated with eGFR in patients with AKI. Our data suggest that d-Ala is an appealing therapeutic target and a potential biomarker for AKI.

Intestinal Bacterial Translocation Contributes to Diabetic Kidney Disease.

BACKGROUND: In recent years, many studies have focused on the intestinal environment to elucidate pathogenesis of various diseases, including kidney diseases. Impairment of the intestinal barrier function, the "leaky gut," reportedly contributes to pathologic processes in some disorders. Mitochondrial antiviral signaling protein (MAVS), a component of innate immunity, maintains intestinal integrity. The effects of disrupted intestinal homeostasis associated with MAVS signaling in diabetic kidney disease remains unclear. METHODS: To evaluate the contribution of intestinal barrier impairment to kidney injury under diabetic conditions, we induced diabetic kidney disease in wild-type and MAVS knockout mice through unilateral nephrectomy and streptozotocin treatment. We then assessed effects on the kidney, intestinal injuries, and bacterial translocation. RESULTS: MAVS knockout diabetic mice showed more severe glomerular and tubular injuries compared with wild-type diabetic mice. Owing to impaired intestinal integrity, the presence of intestine-derived Klebsiella oxytoca and elevated IL-17 were detected in the circulation and kidneys of diabetic mice, especially in diabetic MAVS knockout mice. Stimulation of tubular epithelial cells with K. oxytoca activated MAVS pathways and the phosphorylation of Stat3 and ERK1/2, leading to the production of kidney injury molecule-1 (KIM-1). Nevertheless, MAVS inhibition induced inflammation in the intestinal epithelial cells and KIM-1 production in tubular epithelial cells under K. oxytoca supernatant or IL-17 stimulation. Treatment with neutralizing anti-IL-17 antibody treatment had renoprotective effects. In contrast, LPS administration accelerated kidney injury in the murine diabetic kidney disease model. CONCLUSIONS: Impaired MAVS signaling both in the kidney and intestine contributes to the disrupted homeostasis, leading to diabetic kidney disease progression. Controlling intestinal homeostasis may offer a novel therapeutic approach for this condition.

Significance of the Gut Microbiota in Acute Kidney Injury.

Recent studies have revealed that the gut microbiota plays a crucial role in maintaining a healthy, as well as diseased condition. Various organs and systems, including the kidney, are affected by the gut microbiota. While the impacts of the gut microbiota have been reported mainly on chronic kidney disease, acute kidney injury (AKI) is also affected by the intestinal environment. In this review, we discussed the pathogenesis of AKI, highlighting the relation to the gut microbiota. Since there is no established treatment for AKI, new treatments for AKI are highly desired. Some kinds of gut bacteria and their metabolites reportedly have protective effects against AKI. Current studies provide new insights into the role of the gut microbiota in the pathogenesis of AKI.

Chest Dynamic-Ventilatory Digital Radiography in Chronic Obstructive or Restrictive Lung Disease.

OBJECTIVE: The aim of this study was to identify the relationships between parameters obtained from dynamic-ventilatory digital radiography (DR) and ventilatory disorders. METHODS: This study comprised 273 participants with respiratory diseases who underwent spirometry and functional residual capacity measurements (104 with normal findings on spirometry as controls, 139 with an obstructive lung disorder, 30 with a restrictive lung disorder) were assessed by dynamic-ventilatory DR. Sequential chest radiography images of the patient's slow and maximum breathing were captured at 15 frames per second by a dynamic flat-panel imaging system. The system measured the following parameters: lung area at maximum inspiration divided by height (lung area_in/height), changes in tracheal diameter due to respiratory motions, rate of tracheal narrowing, diaphragmatic motion, and rate of change in lung area due to respiratory motion. Relationships between these parameters and ventilatory disorders were analyzed. RESULTS: Lung area_in/height in patients with restrictive disorders showed significant decreases. Tracheal diameter change and tracheal narrowing rate in patients with obstructive disorders were significantly increased compared to both the control participants and patients with restrictive disorders. Patients with obstructive disorders and patients with restrictive disorders showed decreased diaphragmatic motion and lung area change rate. With the restrictive disorders as references, the area under the curve (AUC), sensitivity and specificity of lung area_in/height were 0.88, 0.77, and 0.88, respectively. With the obstructive disorders as references, the AUC, sensitivity and specificity of tracheal narrowing rate were 0.67, 0.53 and 0.81, respectively. CONCLUSION: Dynamic-ventilatory DR shows potential as a method for the detection and evaluation of ventilatory disorders in patients with respiratory diseases.

Relationships between kidney dysfunction and left ventricular diastolic dysfunction: a hospital-based retrospective study.

BACKGROUND: Preclinical left ventricular diastolic dysfunction (LVDD) is a high-risk state for heart failure. Kidney dysfunction is a known risk factor for heart failure, but its association with asymptomatic LVDD is not well-known. METHODS: A hospital-based retrospective cohort study was conducted on patients who underwent echocardiogram between 2006 and 2016 to assess the association between baseline kidney function and LVDD on echocardiogram. E/e' ratio was defined as the ratio of peak velocity of early diastolic left ventricular inflow (E) to mitral annular velocity (e'). The primary outcome was time to development of LVDD, which was defined as E/e' ratio > 14. The changes in the E/e' ratio and other echocardiographic parameters were assessed using a mixed effects model. RESULTS: Among 1167 patients, the mean age was 61 years, and the mean baseline E/e' ratio and ejection fraction were 9.6 and 69%, respectively. During a median follow-up of 3.2 years, 231 (19.8%) people developed LVDD. According to eGFR (mL/min/1.73 m2), the risk for LVDD based on hazard ratio [95% confidence interval (95% CI)] was 1.20 (0.82, 1.75) for 60 to < 90, 1.42 (0.87, 2.31) for 45 to < 60, and 2.57 (1.61, 4.09) for < 45 (P trend < 0.001). The adjusted risks (95% CI) for annual change in E/e' ratio was 0.09 (0.03, 0.14) overall and 0.28 (0.11, 0.45) in the lowest eGFR group; the trend in changes in annual E/e' ratio by baseline eGFR was significant (P trend = 0.01). CONCLUSIONS: Relatively low kidney function was related with the risks for LVDD. Long-term cohort studies are warranted to confirm the association between LVDD and symptomatic heart failure in patients with kidney dysfunction.

Awake surgery for right frontal lobe glioma can preserve visuospatial cognition and spatial working memory.

PURPOSE: Awake surgery is the standard treatment to preserve motor and language functions. This longitudinal study aimed to evaluate the resection rate and preservation of neurocognitive functions in patients with right frontal lobe glioma who underwent awake surgery. METHODS: Thirty-three patients (mean age, 48.0 years) with right frontal lobe glioma who underwent awake surgery at our hospital between 2013 and 2019 were included. Fourteen, thirteen, and six cases had WHO classification grades of II, III, and IV, respectively. We evaluated visuospatial cognition (VSC) and spatial working memory (SWM) before and three months after surgery. Relevant brain areas for VSC and SWM were intraoperatively mapped, whenever the task was successfully accomplished. Therefore, patients were divided into an intraoperative evaluation group and a non-evaluation group for each function, and the resection rate and functional outcomes were compared. RESULTS: The removal rate in the evaluation group for VSC and SWM were similar to that in the non-evaluation group. Chronic impairment rate of VSC was significantly lower in the evaluation than in the non-evaluation group (5.6% vs. 33.3%, p = 0.034). No patient showed postoperative SWM impairment in the evaluation group as opposed to the non-evaluation group (16.7%, p = 0.049). The probability of resection of the deeper posterior part of the middle frontal gyrus, the relevant area of VSC, was higher in the non-evaluation group than in the evaluation group. CONCLUSIONS: We statistically verified that awake surgery for right frontal lobe glioma results in successful preservation of VSC and SWM with satisfying resection rates.

Methacholine-induced cough as an indicator of bronchodilator-responsive cough.

BACKGROUND: Cough variant asthma (CVA) is the most common cause of chronic cough and responds well to bronchodilator therapy. Previous studies on methacholine -induced cough have shown that heightened cough response due to bronchoconstriction is a feature of CVA. The aim of this study was to assess Mch-induced cough as an indicator of bronchodilator-responsive cough (BRC). METHODS: This was a single-center retrospective study of prolonged/chronic cough cases who underwent evaluation via spirometry, FeNO and bronchial challenge testing using Mch and capsaicin (C5). Resultant bronchoconstriction after Mch challenge was assessed by flow-volume curves measuring the expiratory flow of the partial flow-volume curve 40% above residual volume (PEF40) and FEV1. BRC was defined as a decrease in cough with bronchodilator therapy by 30% or more on a visual analog scoring scale. RESULTS: Of the 100 patients evaluated, 63 were diagnosed with BRC. Mch-induced cough at a decrease in PEF40 of 35% (PC35-PEF40) was predictive of BRC on AUROC analysis with an AUC of 0.82 (95% CI 0.73-0.90) and cut-off of 24. The AUC for C5, FeNO and PC20-FEV1 were 0.65, 0.47, and 0.58, respectively. CONCLUSION: Compared to C5, FeNO and PC20-FEV1, Mch-induced cough better supports a diagnosis of BRC.

Dynamic-Ventilatory Digital Radiography in Air Flow Limitation: A Change in Lung Area Reflects Air Trapping.

OBJECTIVE: The aim of this study was to determine the utility of dynamic-ventilatory digital radiography (DR) for pulmonary function assessment in patients with airflow limitation. METHODS: One hundred and eighteen patients with airflow limitation (72 patients with lung cancer before surgery, 35 patients with chronic obstructive pulmonary disease [COPD], 6 patients with asthma, and 5 patients with asthma-COPD overlap syndrome) were assessed with dynamic-ventilatory DR. The patients were instructed to inhale and exhale slowly and maximally. Sequential chest X-ray images were captured in 15 frames per second using a dynamic flat-panel imaging system. The relationship between the lung area and the rate of change in the lung area due to respiratory motion with respect to pulmonary function was analyzed. RESULTS: The rate of change in the lung area from maximum inspiration to maximum expiration (Rs ratio) was associated with the RV/TLC ratio (r = 0.48, p < 0.01) and the percentage of the predicted FEV1 (r = -0.33, p < 0.01) in patients with airflow limitations. The Rs ratio also decreased in an FEV1-dependent manner. CONCLUSION: The rate of change in the lung area due to respiratory motion evaluated with dynamic DR reflects air trapping. Dynamic DR is a potential tool for the comprehensive assessment of pulmonary function in patients with COPD.