ABSTRACT In this study, we examined clinical and cohort data to explore the potential renoprotective effects of natto (fermented soybeans) consumption and its relationship with D‐amino acids. In a clinical study, ten healthy adults consumed one 40‐g pack of natto three times in a single day, and plasma and urine samples were collected 1 h and 24 h after intake. In a 5‐year cohort of 295 adults, natto intake was categorized as none (0 g/day), low (1–10 g/day), middle (11–25 g/day), or high (> 25 g/day). The plasma and urinary D‐alanine levels increased significantly after natto consumption. In the cohort, the adjusted mean annual changes in estimated glomerular filtration rate (eGFR, mL/min/1.73 m2) were −1.41, −0.78, −1.01, and −1.01 for the none, low, middle, and high groups, respectively. Low natto intake was significantly associated with a slower decline in eGFR, although no dose‐dependent trend was observed. No significant differences in gut microbiota diversity or composition were found across intake groups. Natto consumption was associated with increased plasma D‐alanine levels and a slower decline in renal function. Further studies are warranted to clarify the mechanisms underlying these associations.

Novel therapeutic targets for renal protection are imperative due to the escalating prevalence of end-stage kidney disease despite existing treatments for chronic kidney disease (CKD). We explored the reno-protective effects of D-serine and D-alanine, which have previously demonstrated efficacy in acute kidney injury against CKD. Female and male 5/6-nephrectomy mice were used as CKD models, receiving 20 mM D-serine or D-alanine supplementation, and their survival rates, renal function, and transcriptomic changes were examined. The proliferation of human tubular epithelial cells supplemented with D-serine or D-alanine was evaluated in vitro. A prospective cohort study involving 14 patients was conducted to examine the association between increased blood D-serine or D-alanine levels and long-term renal function decline. D-serine or D-alanine supplementation improved survival rates and renal function in female 5/6-nephrectomy mice. D-alanine supplementation was associated with the upregulation of mitochondrial pathway-related genes. Long-term supplementation (500 days) in normal mice did not induce nephrotoxicity, and promoted tubular epithelial cell proliferation. Although a trend toward a slower decline in eGFR was observed in patients with higher D-alanine levels, this association was limited and does not indicate a causal relationship. Further studies involving D-Ala interventions in patients with CKD are needed to confirm these findings.

Background:Nasal nitric oxide (nNO) is an effective screening indicator for primary ciliary dyskinesia (PCD) and a potential biomarker for nasal diseases; however, Measurement of nNO using standard methods is not available everywhere. Therefore, we aimed to estimate nNO values from measured fractional exhaled NO (FeNO) and nasal FeNO (nFeNO) levels using a widely used FeNO analyzer. Methods:In this single-center cross-sectional study, the proportion of NO from the lower airway mixed with nFeNO was calculated by simultaneously measuring nFeNO and nNO in 15 healthy participants. Additionally, nNO values were estimated from the measured FeNO and nFeNO in healthy controls and patients with asthma or PCD. Results:The average rate of mixed NO from the lower airway tract was 0.86±0.04. Assuming NO to be 0.86, nNO estimated from the measured FeNO and nFeNO was 329.1±127.8 and 313.4±203.7 parts per billion (ppb) in healthy participants (n=53) and patients with asthma (n=19), respectively. Among patients with asthma, no significant difference was observed in the estimated nNO values between patients with and without peripheral blood eosinophilia; however, the nNO-FeNO ratio was significantly lower in those with eosinophilia. The estimated nNO value in four of eight patients with PCD was <77 nL/min and was used as a cutoff used to identify patients with PCD. Conclusions:The estimated nNO value, which is derived from the average rate of NO contamination from the lower respiratory tract, may be a possible substitute for nNO and can be measured with instruments that are widely used.

Patients with chronic kidney disease (CKD) are at high risk for kidney failure and cardiovascular events. d-alanine administration prevented kidney damage in a murine acute kidney injury model. This pilot trial aims to assist the design of a larger trial on the efficacy and safety of d-alanine intake on kidney function in patients with CKD. This pilot, open-label, randomized controlled trial will enroll 24 patients with sustained albuminuria or proteinuria. Participants will be randomized in a 1:1 ratio to receive 3 g of d-alanine supplementation per day for 12 weeks or standard care alone. The primary endpoint will be change in albuminuria from baseline to 12 weeks. The secondary endpoints include changes in estimated glomerular filtration rate and other clinical parameters. Safety will be evaluated according to adverse events and laboratory parameters. The findings of this trial are expected to help design a larger-scale trial of d-alanine and support further development of d-alanine as a novel nutrition management for CKD.

d-serine administration prevents kidney damage in murine models of acute kidney injury, and risperidone inhibits the activity of d-amino acid oxidase, which regulate plasma d-amino acid levels. This pilot randomized controlled trial investigated the effects of risperidone on glucose, amino acid metabolism, and kidney function in healthy adults. Healthy adults with a homeostasis model assessment of insulin resistance (HOMA-IR) of ≥ 1.6 and estimated glomerular filtration rate (eGFR) of ≥ 60 mL/min/1.73m 2 were randomly assigned to the risperidone and control groups. The risperidone group received 0.5 mg/day risperidone for 4 days. The primary outcome was mean change in HOMA-IR on day 5, and the secondary outcomes were changes in d-amino acid levels, eGFR, and urinary albumin. Seven participants were randomized to the risperidone and control groups. The changes in HOMA-IR, eGFR, and urinary albumin on day 5 were not significantly different between the two groups (all p > 0.05). Mean changes in plasma d-serine level and urinary d-serine/creatinine ratio were significantly higher in the risperidone group than in the control group (0.2 vs. −0.3 nmol/mL, p = 0.03 and 38.2 vs. −25.8 nmol/mL, p = 0.01, respectively). Short-term risperidone affects d-serine metabolism without instigating acute adverse effects on kidney or glucose homeostasis in healthy individuals. Clinical Trial Registry number: This study was registered with the Japan Registry for Clinical Trials (jRCTs041210165).

This study aimed to evaluate the utility of ultrasound elastography for assessing postoperative recovery of the masseter muscle, and its potential role in predicting functional outcomes in patients undergoing orthognathic surgery. Fifteen patients with dentofacial deformities (30 masseter muscles) underwent ultrasound strain elastography at rest, during mouth opening, and during clenching, at four time points: preoperatively, and at seven days, one month, and three months postoperatively. Strain values (SVs), cross-sectional muscle area, and maximal mouth opening (MMO) were measured. Statistical analyses included Friedman and Wilcoxon signed-rank tests, with correlations assessed using Pearson's or Spearman's coefficients, as appropriate. SVs significantly decreased at seven days postoperatively and recovered to baseline by one month, remaining stable at three months. The cross-sectional area increased significantly at seven days and one month in the rest and mouth opening conditions, returning to baseline at three months, while no significant changes were observed during clenching. Significant positive correlations were observed between SVs and muscle area at rest and during mouth opening. In addition, higher preoperative SVs were associated with greater postoperative improvement in MMO. Ultrasound elastography provides objective, non-invasive information on postoperative changes in the masseter muscle. This modality may serve as a useful tool for predicting functional recovery after orthognathic surgery in patients with dentofacial deformities.

BACKGROUND:Sake lees consumption has the potential to reduce uremic toxins by influencing the gut microbiome. To lay the groundwork for a clinical trial targeting chronic kidney disease (CKD) patients, we conducted a pilot study to explore the relationship between sake lees intake and changes in fecal uremic toxin levels among individuals with constipation. D-alanine, a renoprotective component of sake lees, was also evaluated. METHODS:This single-arm, before and after study lacked a control group. Participants met the diagnostic criteria for chronic constipation. They consumed 25 or 50 g of sake lees daily for 6 weeks. The primary endpoint was the change in fecal indole levels from baseline. Secondary endpoints included changes in plasma D-alanine, Constipation Scoring System (CSS) scores, and the composition of the fecal microbiome. RESULTS:Eight participants, with a mean age of 46 years, completed the study. Percentage changes in fecal indole levels were +42%, + 52%, and -6% at weeks 2, 4, and 6, respectively. Plasma D-alanine levels showed percentage changes of +39%, + 24%, and +38% at the same time points. CSS scores improved from 9.2 to 6.8 by week 2 and remained stable after week 4. The proportion of the phylum Firmicutes in the gut microbiome increased slightly from 53% at baseline to 57% by week 6. CONCLUSION:Sake lees intake may reduce fecal uremic toxins, elevate plasma D-alanine levels, alleviate constipation, and modify the gut microbiome. However, future studies are needed to confirm these effects in patients with CKD.

Background/Objectives: Non-functional oral habits, such as unilateral chewing, bruxism, and clenching, may exacerbate temporomandibular disorder (TMD) symptoms and affect skeletal morphology in patients with dentofacial deformities. This study aimed to elucidate the relationships among these habits, TMD symptoms, and mandibular morphology, and to examine the association between non-functional habits and TMD symptom severity. Methods: A cross-sectional study was conducted in 141 patients with dentofacial deformities. At the initial consultation, participants completed a questionnaire assessing non-functional oral habits (unilateral chewing, bruxism, and clenching) and TMD symptoms, scored as follows: limited mouth opening (2 points), pain on opening (2 points), and joint sounds (1 point). Patients were stratified into three groups according to the number of habits (≥2, 1, none). Total TMD scores were compared among groups, and the relationship between unilateral chewing and mandibular asymmetry was analyzed. Results: Unilateral chewing was reported by 82 patients (58%), bruxism by 28 (20%), and clenching by 29 (21%). Mean TMD scores were 1.94 (range: 0–5) in patients with ≥2 habits, 1.50 (0–5) in those with one habit, and 0.86 (0–3) in those without habits. TMD symptoms were significantly more severe in patients with multiple habits (p < 0.05). Among patients with mandibular asymmetry, 41 of 56 (73%) reported unilateral chewing, which was significantly higher than in those without asymmetry (42 of 85; 49%) (p < 0.05). Conclusions: In patients with dentofacial deformities, multiple non-functional oral habits were associated with greater TMD symptom severity, and unilateral chewing was significantly associated with mandibular asymmetry.

Chronic kidney disease (CKD) is increasingly prevalent worldwide, and its management is an urgent issue. Understanding of its pathophysiology and the development of new treatment methods are critical. In recent years, gut microbiota reportedly contributes to the homeostasis of systemic organs and the pathogenesis of diseases. Also, in kidney disease, alterations in the gut microbiota (dysbiosis) have been observed and are deeply involved in pathophysiology. d-Amino acids derived from gut microbiota change in concentration in the body concomitant with dysbiosis. d-Serine and d-alanine have been shown to have renal tubular protective effects in acute tubular necrosis, suggesting their potential as renal therapeutic agents. We have been evaluating the therapeutic effects of d-alanine, metabolic enzyme inhibitors, and food products containing d-amino acids in human CKD. The recent association between gut and systemic organ dysfunction not only reveals new mechanisms of disease but also indicates the possibility of new therapeutic strategies. This article provides an overview of new insights into kidney disease, gut microbiota, and its metabolites.

Acute kidney injury (AKI) remains a significant clinical challenge with limited therapeutic options. While d-alanine shows promise in AKI treatment, its formulation requires l-alanine co-inclusion for pharmaceutical stabilization through racemization. This study investigated the biological activity of synthetic d-alanine compounds in the human proximal tubular epithelial cell line (HK-2). We synthesized d-alanine hydrochloride, a dipeptide, and a tripeptide and evaluated their effects on cell viability under normal and hypoxic conditions. d-Alanine hydrochloride (10 µM) and dipeptide (10 µM) significantly enhanced cell viability compared with the controls, with d-alanine hydrochloride demonstrating superior efficacy under hypoxic conditions. Gene expression analysis revealed that these compounds promoted cell cycle progression and increased cyclin B1 expression under hypoxic conditions. Notably, these synthetic forms maintained therapeutic efficacy without requiring l-alanine co-inclusion. Although limited to in vitro experiments, our findings suggest that d-alanine hydrochloride and dipeptide forms are promising therapeutic candidates for AKI treatment.

Despite extensive research efforts, clinically applicable liquid biomarkers for glioblastoma (GBM) have yet to be established. This study aimed to identify novel blood and urinary biomarkers for GBM, with a particular focus on chiral amino acids. A total of 33 patients with glioma (WHO grade 2: n=10, grade 3: n=6, grade 4: n=17) and 24 healthy volunteers were enrolled. Chiral amino acid analysis was conducted on resected tissue samples (both tumor and non-tumor), as well as corresponding blood and urine samples, to quantify L- and D-isomers of amino acids. To validate these findings, we also evaluated chiral amino acid profiles in a GBM mouse model. Among the findings, D-asparagine (D-Asn) and several L-amino acids were present at significantly higher concentrations in tumor tissues than in non-tumor brain tissues. Notably, both blood and urinary D-Asn levels were significantly lower in GBM patients compared to healthy individuals (p<0.05 and p<0.001, respectively). Furthermore, urinary D-Asn levels increased significantly after initial GBM treatment (p<0.05), suggesting its potential utility in disease monitoring. Urinary D-Asn also showed excellent diagnostic performance in distinguishing GBM patients from healthy controls, with an area under the curve (AUC) of 0.93, sensitivity of 0.88, and specificity of 0.92. Similar trends in amino acid profiles were observed in the GBM mouse model, supporting translational relevance. In conclusion, urinary D-Asn appears to be a promising, non-invasive biomarker for the detection and monitoring of GBM, with potential for clinical application.

ABSTRACT Background Atrial fibrillation (AF), the most frequently occurring sustained arrhythmia in patients with hypertrophic cardiomyopathy (HCM), is linked to poor quality of life and increased thromboembolic risk. Chronic kidney disease (CKD) and reduced kidney function are known cardiovascular risk factors; however, their contributions to new‐onset AF in patients with HCM remain unclear. Estimated glomerular filtration rate (eGFR) is a key marker for CKD management. This study aimed to elucidate the incidence of new‐onset AF and to identify predictive factors in patients with HCM. Methods We analyzed 198 patients with HCM (121 men; mean age, 58 ± 17 years) without prior AF. The incidence and predictors of new‐onset AF were evaluated with a focus on kidney function and left atrial (LA) size. Cox proportional hazards modeling was used to assess the associations. Results Impaired kidney function (eGFR < 60 mL/min/1.73 m2) was present in 35 patients (17.7%). Over a median follow‐up of 7.52 years, 43 patients (21.7%) developed new‐onset AF for an incidence rate of 2.8 per 100 person‐years. The multivariate analysis identified reduced eGFR and increased LA diameter (LAD) as independent predictors of AF. Kaplan–Meier curves showed a significantly higher cumulative AF incidence among patients with an eGFR ≤ 76.1 mL/min/1.73 m2 or an LAD ≥ 48.0 mm. Conclusions Decreased kidney function and LA dilatation were significantly associated with new‐onset AF among patients with HCM. These findings suggest that this patient population requires closer monitoring for the early detection of AF.

Background Motor evoked potential (MEP) monitoring is a commonly employed method in neurosurgery to prevent postoperative motor dysfunction. However, it has low prediction accuracy for postoperative paralysis. This study aimed to develop a decision tree (DT) model for predicting postoperative motor function using MEP monitoring data. Methodology In this retrospective cohort study, we used datasets, comprising 14 variables including MEP amplitudes, obtained from 125 patients who underwent brain tumor resection with intraoperative MEP monitoring at our hospital. Prediction models were developed using DT and receiver operating characteristic (ROC) curve analyses. Model performance was assessed for accuracy, sensitivity, specificity, kappa (κ) coefficient, and area under the ROC curve (AUC) for internal and external validation. For the external validation of the classification model, we retrospectively collected data from an additional 28 patients who underwent brain tumor surgery with MEP monitoring. Results The amplitude of the last measured MEP and amplitude ratio were independent predictors of outcomes. The DT model achieved an accuracy of 0.921, sensitivity of 0.917, specificity of 0.923, and AUC of 0.931 using the internal test. In comparison, the ROC curve based on the amplitude of the last measured MEP achieved a sensitivity of 0.875, specificity of 0.906, and AUC of 0.941. External validation was performed and the DT model was superior to prediction by cutoff values from ROC curves in terms of accuracy, sensitivity, specificity, and κ coefficient. Conclusions Our study suggested the usefulness of DT modeling for predicting postoperative paralysis. However, this study has several limitations, such as the retrospective design and small sample size of the validation dataset. Nonetheless, the DT modeling presented in this study might be applicable to surgeries using MEP monitoring and is expected to contribute to devising treatment strategies by predicting postoperative motor function in various patients.

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.

Diabetic kidney disease (DKD) is a major complication of diabetes mellitus (DM), and stands out as the leading cause of end-stage renal disease (ESRD) worldwide. There is increasing evidence that mitochondrial dysfunction, including impaired mitochondrial biogenesis, dynamics, and oxidative stress, contributes to the development and progression of DKD. D-amino acids (D-AAs), which are enantiomers of L-amino acids (L-AAs), have recently been detected in various living organisms and are acknowledged to play important roles in numerous physiological processes in the human body. Accumulating evidence demonstrates that D-AA levels in blood or urine could serve as useful biomarkers for reflecting renal function. The physiological roles of D-AAs are implicated in the regulation of cellular proliferation, oxidative stress, generation of reactive oxygen species (ROS), and innate immunity. This article reviews current evidence relating to D-AAs and mitochondrial dysfunction and proposes a potential interaction and contribution of the D-AAs - mitochondria axis in DKD pathophysiology and progression. This insight could provide novel therapeutic approaches for preventing or ameliorating DKD based on this biological axis.

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. 2 . 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; - 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 f 8.8 mL/min/1.73 m(2) 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.

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 [degrees 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 (degrees 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 (degrees C) of -37 -30, -27, -8, 0, and 1. CONCLUSIONS: This study showed that 10-minute spinal cryoablation with LETs (degrees 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 degrees C. The epidural temperature threshold for cryogenic spinal cord injury is between 1 and 4 degrees C, suggesting that the epidural temperature should be maintained above at least 4 degrees C to prevent cryogenic spinal cord injury.

AbstractThe relationship between D-AA metabolic enzymes and cancer development remains unclear. We aimed to investigate this relationship using mice deficient in D-AA-related metabolic enzymes. We examined mice lacking these enzymes for approximately 900 days and the effects of altered D-AA metabolism on cancer development based on lifespan, pathological findings, and gene expression. The lifespan of female DASPO -knockout (DASPO−/−) mice was shorter than that of the other group mice; furthermore, these mice showed tumor-like masses in the liver, spleen, and small intestine. A pathological diagnosis of diffuse large B-cell lymphoma (DLBCL) was made. RNA sequencing of the liver samples showed specific alterations in the expression of 71 genes in DASPO−/− mice compared with that in wild-type B6 mice; RGS 1, MTSS1, and SMARCD 1 were identified as DLBCL-related genes. Patients with DLBCL exhibiting low DASPO expression demonstrated a shorter survival period than those showing high expression. However, the role of DASPO in DLBCL development is unclear. Therefore, future research should focus on B cells. DASPO may serve as novel biomarkers and therapeutic targets in cancer. Graphical abstract

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 degrees 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.