Trans-aortic mitral isthmus ablation after surgical patch closure for an atrial septal defect.

INTRODUCTION: In patients with prior atrial septal defect (ASD) closure and atrial tachyarrhythmias, transseptal puncture can be challenging. METHODS AND RESULTS: This case report discusses a 65-year-old man who had previously undergone pulmonary vein isolation (PVI) and cavo-tricuspid isthmus ablation for atrial fibrillation before ASD closure, respectively. He developed atrial tachycardia (AT) and underwent catheter ablation. AT was diagnosed as peri-mitral flutter and the mitral isthmus (MI) linear ablation via a trans-aortic approach successfully terminated it. CONCLUSION: This case demonstrates the feasibility and safety of transaortic MI linear ablation in patients with ASD closure devices or anatomical challenges when transseptal puncture is difficult.

T-wave oversensing after implantation of pacemakers with automatic sensitivity adjustment in patients with atrioventricular block.

T-wave oversensing in pacemakers is rare because the set sensitivity is generally fixed. However, several models of pacemaker employ automatic sensitivity adjustment. Here, we present two cases of atrioventricular block treated by implantation of the pacemaker with automatic sensitivity adjustment. After implanting the pacemaker with automatic sensitivity adjustment, ventricular pacing suppression due to T-wave oversensing occurred. In both cases, T-wave oversensing disappeared after adjusting the setting sensitivity from 0.9 to 2.0 mV.

Association between residual unipolar voltage and arrhythmia recurrence after left atrial posterior wall isolation for persistent atrial fibrillation.

INTRODUCTION: Posterior wall isolation (PWI) combined with pulmonary vein isolation (PVI) has proven effective for persistent atrial fibrillation (AF). However, when performing PWI, creating transmural lesions with subendocardial ablation is sometimes difficult. Endocardial unipolar voltage amplitude had a higher sensitivity than bipolar voltage mapping for identifying intramural viable myocardium in the atria. In this study, we aimed to retrospectively investigate the correlation between the residual potential in the posterior wall (PW) following PWI for persistent AF and atrial arrhythmia recurrence using endocardial unipolar voltage. METHODS: This was a single-center observational study. Patients who underwent PVI and PWI for persistent AF in the first procedure between March 2018 and December 2021 at the Tokyo Metropolitan Hiroo Hospital were included in this study. The patients were divided into two groups based on the presence of residual unipolar PW potentials after PWI with a cutoff of 1.08 mV and the recurrence of atrial arrhythmias was compared. RESULTS: In total, 109 patients were included in the analysis. Forty-three patients had residual unipolar potentials after PWI and 66 patients had no residual unipolar potentials. The atrial arrhythmia recurrence rate was significantly higher in the group with residual unipolar potential (41.8% vs. 17.9%, p = 0.003). The residual unipolar potential was an independent predictor of recurrence (odds ratio: 4.53; confidence interval: 1.67-12.3, p = 0.003). CONCLUSION: Residual unipolar potential after PWI for persistent AF is associated with recurrent atrial arrhythmias.

Loss of height predicts fall risk in elderly Japanese: a prospective cohort study.

INTRODUCTION: The purpose of this study was to explore whether height loss is associated with future falls and whether the combination of height loss and fall experience is associated with future falls. MATERIALS AND METHODS: In this prospective observational study, a total of 765 individuals (354 men, 411 women) agreed to join the study. Baseline data on demographics, comorbidities, physical performance, and previous falls were assessed. Height loss was calculated as the difference between the self-reported height at a younger age and the current height and was divided into two groups: < 2 cm and ≥ 2 cm. Approximately 15 months after the baseline evaluation, follow-up questionnaires were used to assess the fall history. Participants were classified as either "non-fallers" or "fallers." Multiple logistic regression was used to evaluate the association between falls and each factor and to obtain adjusted odds ratio estimates. RESULTS: The follow-up questionnaire was returned by 668 participants, 74 of whom (11.1%) fell at least once during the observation period. Multiple logistic regression analysis found that height loss of > 2 cm was a significant predictor of future falls, even after adjusting for other factors. Additionally, the combination of height loss and previous falls was a risk factor for falls. CONCLUSIONS: We suggest that height loss of ≥ 2 cm is a predictor of future falls in older adults, and the combination of height loss and fall experiences may be a useful screening tool for determining fall risk.

Single-cell immunoprofiling after immunotherapy for allergic rhinitis reveals functional suppression of pathogenic TH2 cells and clonal conversion.

BACKGROUND: Allergic rhinitis is a growing problem worldwide. Currently the only treatment that can modify the disease is antigen-specific immunotherapy, but its mechanism of action is not fully understood. OBJECTIVE: We comprehensively investigated the role and changes of antigen-specific T cells before and after sublingual immunotherapy (SLIT) for Japanese cedar pollinosis. METHODS: We cultured peripheral blood mononuclear cells obtained both before and 1 year after initiating SLIT and used a combination of single-cell RNA sequencing and repertoire sequencing. To investigate biomarkers, we used cells from patients participating a phase 2/3 trial of SLIT tablets for Japanese cedar pollinosis and cells from outpatients with good and poor response. RESULTS: Antigen-stimulated culturing after SLIT led to clonal expansion of TH2 and regulatory T cells, and most of these CD4+ T cells retained their CDR3 regions before and after treatment, indicating antigen-specific clonal responses and differentiation resulting from SLIT. However, SLIT reduced the number of clonal functional TH2 cells but increased the trans-type TH2 cell population that expresses musculin (MSC), TGF-ß, and IL-2. Trajectory analysis suggested that SLIT induced clonal differentiation of the trans-type TH2 cells differentiated into regulatory T cells. Using real-time PCR, we found that the MSC levels increased in the active SLIT group and those with good response after 1 year of treatment. CONCLUSION: The combination of single-cell RNA sequencing and repertoire analysis helped reveal part of the underlying mechanism: SLIT promotes the expression of MSC on pathogenic TH2 cells and suppresses their function. MSC may be a potential biomarker of SLIT for allergic rhinitis.

Differences in the expression of multidrug resistance proteins in chronic rhinosinusitis according to endotype.

BACKGROUND: Chronic rhinosinusitis is a common disease of the nasal cavity and is classified into two major endotypes, which are neutrophilic and eosinophilic. Some patients with neutrophilic and eosinophilic chronic rhinosinusitis are refractory to treatment, and the mechanism of drug resistance is not completely understood. METHODS: Nasal polyp samples were collected from patients with non-eosinophilic chronic rhinosinusitis (nECRS) and eosinophilic chronic rhinosinusitis (ECRS). Transcriptomic and proteomic analyses were performed simultaneously. Gene Ontology (GO) analysis was conducted to extract genes involved in drug resistance. Then, GO analysis results were validated via real-time polymerase chain reaction and immunohistochemistry analysis. RESULTS: The nasal polyps of patients with ECRS were enriched with 110 factors in the genes and 112 in the proteins, unlike in those of patients with nECRS. GO analysis on the combined results of both showed that the factors involved in extracellular transportation were enriched. Our analysis focused on multidrug resistance protein 1-5 (MRP1-5). Real-time polymerase chain reaction revealed that the MRP4 expression was significantly upregulated in ECRS polyps. Immunohistochemical staining showed that the MRP3 and MRP4 expressions significantly increased in nECRS and ECRS, respectively. MRP3 and MRP4 expressions were positively correlated with the number of neutrophil and eosinophil infiltrates in polyps and associated with the tendency to relapse in patients with ECRS. CONCLUSIONS: MRP is associated with treatment resistance and is expressed in nasal polyps. The expression pattern had different features based on chronic rhinosinusitis endotype. Therefore, drug resistance factors can be associated with therapeutic outcomes.

Left atrial macroreentrant tachycardia via Bachmann bundle revealed by epicardial mapping.

Although it is common for bi-atrial tachycardia (AT) circuits to include the Bachmann bundle, there are few reports of its role in left AT circuits. A 77-year-old man was admitted for recurrent AT with a cycle length of 425 ms. The endocardial and epicardial activation map revealed an AT circuit located in the left atrial anterior wall and transverse pericardial sinus, showing a centrifugal pattern stemming from the left atrial appendage. After radiofrequency ablation, AT was no longer induced. This case suggests that the Bachmann bundle may be part of the left AT circuit.

Benefits of excimer laser coronary angioplasty over thrombus aspiration therapy for patients with acute coronary syndrome and thrombolysis in myocardial infarction flow grade 0.

In primary percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS), the presence of a thrombus or unstable plaque can cause microvascular obstructions, which may increase infarct size and reduce survival. Excimer laser coronary angioplasty (ELCA) is a unique revascularization technique that can vaporize plaques and thrombi. However, to date, only few reports indicate the efficacy of ELCA for ACS. We retrospectively analyzed 113 consecutive ACS patients who underwent PCI with either ELCA or manual thrombus aspiration therapy (TA) before balloon angioplasty or stenting and who had a Thrombolysis in Myocardial Infarction flow (TIMI) grade 0 on the first contrast injection within 24 h of onset at our hospital from March 2011 to March 2020. Patients were divided into two groups by the procedure used: ELCA (N = 48) and TA (N = 50). Door-to-reperfusion time was significantly shorter in the ELCA group than TA group (89.2 ± 6.7 vs. 137.9 ± 12.3 min, respectively; P < 0.01). There was also a significant difference in peak creatine kinase-myocardial band between the ELCA and TA groups (242 ± 25 vs. 384 ± 63 IU/L, respectively; P = 0.04). Although there was no difference in myocardial blush grade (MBG) before treatment, the MBG after treatment was higher in the ELCA group (P < 0.01). In-hospital major adverse cardiac events (MACE) were also significantly fewer in the ELCA group than in the TA group (8% vs. 20%, P = 0.045). ELCA for TIMI grade 0 ACS may shorten reperfusion time, improve the MBG score, and reduce MACE when compared to TA.

Impact of small diameter and low level of emission laser coronary atherectomy in patients with acute myocardial infarction.

Excimer laser coronary atherectomy (ELCA) is an effective treatment to remove intracoronary thrombi. In the present study, we compared in-hospital mortality in patients with acute myocardial infarction (AMI) who underwent conventional treatment and conventional treatment plus ELCA. Among 656 patients who were admitted to our hospital through the Tokyo CCU Network, 104 patients with AMI who were treated by percutaneous coronary intervention between January 2013 and December 2016 met inclusions criteria and underwent conventional treatment with ELCA (ELCA group) and 89 underwent conventional treatment alone (conventional group). We retrospectively evaluated in-hospital mortality within 30 days and used propensity score (PS) matching to reduce assignment bias and multivariate analysis to detect the predictors of in-hospital mortality. In-hospital mortality rate was significantly lower in the ELCA group before and after PS matching (2.9% vs. 13.5%, p = 0.006 before PS matching, and 2.8% vs. 14.1%, p = 0.016 after PS matching). After PS matching, ß-blocker or statins use, incidence of shock, Killip classification, and door-to-balloon time were not significantly different. A multivariate logistic regression analysis identified ELCA, dyslipidemia, shock, and left ventricular ejection fraction as independent predictors of in-hospital mortality (odds ratio (OR), 0.147, 95% confidence interval [CI], 0.022-0.959, p = 0.045; OR, 0.077, 95% CI, 0.007-0.805, p = 0.032; OR, 6.494, 95% CI, 1.228-34.34, p = 0.028; OR, 0.890, 95% CI, 0.828-0.957, p = 0.002, respectively). Our data indicate that ELCA with the small diameter and low level emission may reduce the in-hospital mortality compared to conventional methods in patients with AMI in drug-eluting stent era.

The one-leg portion of the Stand-Up Test predicts fall risk in aged individuals: A prospective cohort study.

BACKGROUND: Falls are a primary cause of physical disability in older adults, making them a major public health problem. Locomotive syndrome risk assessments have proven to be simple to administer, practical, and useful as screening tools in detecting decreased mobility in middle-aged and elderly adults. The current prospective study investigated whether these tests were associated with future falls among elderly Japanese. METHODS: This study was a two-year prospective observational study. A total of 1800 individuals (aged 65-79 years) who were without certification of long-term care or physical disability were initially invited through letters to participate in the study. Of these, 499 individuals (225 men, 274 women) agreed to participate and underwent baseline assessments. Demographic information, body function physical performance measurements, and locomotive syndrome risk tests [Stand-Up Test (SUT), Two-Step Test (TST), and the 25-question Geriatric Locomotive Function Scale (GLFS-25)] were assessed. Following baseline evaluation, we sent a follow-up questionnaire to assess fall history in the past two years. Participants were classified as either "non-fallers" or "fallers" (denoted by one or more falls). Multiple logistic regression was used to evaluate the association between falls and each factor by providing adjusted odds ratio estimates. RESULTS: The follow-up questionnaire was returned by 399 participants, 54 of whom (13.5%) fell at least once during the two-year observation period. The multiple logistic regression analysis revealed that difficulty with standing on one leg from a 40-cm-high seat (a portion of the SUT) was a significant predictor of future falls (odds ratio = 2.20, 95%CI = 1.04-4.69, p = 0.04). A history of falling was also a risk factor of falls. CONCLUSION: Our results suggest that standing on one leg from a 40-cm-high seat is predictive of falling in older adults, even after adjustment for previous falls and other confounding variables.

Association of Built Environments With Frequency of Going Outdoors Among Older Community-Dwelling Adults in Japan.

Built environmental factors are important for encouraging outdoor activity among community-dwelling older adults. A total of 214 participants aged 59-94 years were recruited from local cities in Japan. A mixed-effects multivariate linear regression model was conducted for the analysis. Parks that are easy to get to and car availability were positively associated with the number of days per week with any outdoor exposure. Further, the ability to conduct activities of daily living had a significant effect on the use of safe parks and walking areas and the number of days per week with outdoor time. The findings suggest that subjectively assessed neighborhood-built environments, such as readily available safe parks, walking areas, and car availability, are important for encouraging outdoor activity among older community-dwelling adults in Japan. For those with a limited ability to conduct daily activities, the safeness of parks and walking areas are most important.

Sublingual administration of liposomes enclosing alpha-galactosylceramide as an effective adjuvant of allergen immunotherapy in a murine model of allergic rhinitis.

BACKGROUND: Sublingual immunotherapy (SLIT) is an established efficacious approach for the treatment of allergic rhinitis (AR). However, SLIT requires a long administration period to establish stable and adequate responses. This study investigated the efficacy of the sublingual administration of an allergen with liposomes enclosing α-GalCer (α-GC-liposome) as a potential adjuvant in mice with AR. METHODS: Mice with AR induced by OVA received the sublingual administration of OVA, α-GC-liposomes, or OVA plus α-GC-liposomes for 7 days. After nasal re-challenge with OVA, nasal symptoms were evaluated. The serum levels of OVA-specific Ig, the cytokine production of CD4+ T cells in the cultures of cervical lymph node (CLN) cells, and the gene expression of CLNs were analyzed. RESULTS: Although IL-4, IL-5 and IL-13 production from CD4+ T cells in CLN cells was significantly inhibited by the sublingual administration of OVA alone in mice with AR induced by OVA, their nasal symptoms were not significantly diminished. However, the combined sublingual administration of α-GC-liposomes and OVA completely suppressed nasal symptoms, downregulated Th2 and Th17 type cytokine production in CD4+ T cells as well as Th2 and Th17 gene expressions, and upregulated Th1 type cytokine production as well as Th1 gene expressions in CLN cells. Additionally, the serum levels of specific IgG2a were promoted, and specific IgE and IgG1 were inhibited. CONCLUSIONS: Our findings suggest that the sublingual administration of an allergen with α-GC-liposomes as an adjuvant might increase the therapeutic efficacy and effectiveness of this treatment method.

Basophils from allergic rhinitis patients show allergen-specific upregulation of thymic stromal lymphopoietin receptor.

BACKGROUND: An allergic rhinitis (AR) diagnosis is based on typical nasal symptoms and allergen sensitization testing. However, it is sometimes difficult to distinguish AR from non-AR, and it is especially difficult to identify the causal allergen for immunotherapy of patients with AR. OBJECTIVE: To identify differences among patients with AR, subjects with asymptomatic sensitization (AS), and subjects without sensitization (NS) that could facilitate the diagnosis of AR. METHODS: We used RNA sequencing to examine differential gene expression in unstimulated and allergen-stimulated peripheral basophils from participants with NS, AS, and AR. We selected genes that were upregulated after allergen stimulation and showed differences in expression in patients with AR compared with subjects with AS and NS. Basophil surface expression of 1 gene product was examined by flow cytometry. The usefulness of gene expression in the diagnosis of AR was examined with receiver operating characteristic curves. RESULTS: Expression of cytokine receptor-like factor 2 and its product, thymic stromal lymphopoietin receptor (TSLPR), was significantly increased in basophils of patients with AR after allergen stimulation. A significantly larger percentage of TSLPR-positive cells was observed after allergen-specific stimulation of basophils from patients with AR compared with subjects with AS. Basophil TSLPR expression was as good as or better than CD203c expression in discriminating between patients with AR and subjects with AS, as judged by receiver operating characteristic curves. CONCLUSION: Our data suggest that TSLPR expression on basophils was specifically upregulated by allergen stimulation and might be useful for the identification of the causative allergen in patients with AR.

Identifying elderly people at risk for cognitive decline by using the 2-step test.

[Purpose] The purpose is to verify the effectiveness of the 2-step test in predicting cognitive decline in elderly individuals. [Subjects and Methods] One hundred eighty-two participants aged over 65 years underwent the 2-step test, cognitive function tests and higher level competence testing. Participants were classified as Robust, <1.3, and <1.1 using criteria regarding the locomotive syndrome risk stage for the 2-step test, variables were compared between groups. In addition, ordered logistic analysis was used to analyze cognitive functions as independent variables in the three groups, using the 2-step test results as the dependent variable, with age, gender, etc. as adjustment factors. [Results] In the crude data, the <1.3 and <1.1 groups were older and displayed lower motor and cognitive functions than did the Robust group. Furthermore, the <1.3 group exhibited significantly lower memory retention than did the Robust group. The 2-step test was related to the Stroop test (ß: 0.06, 95% confidence interval: 0.01-0.12). [Conclusion] The finding is that the risk stage of the 2-step test is related to cognitive functions, even at an initial risk stage. The 2-step test may help with earlier detection and implementation of prevention measures for locomotive syndrome and mild cognitive impairment.

Effect of a simple and adherent home exercise program on the physical function of community dwelling adults sixty years of age and older with pre-sarcopenia or sarcopenia.

[Purpose] To evaluate the effect of a home exercise program on physical function in community dwelling elderly with pre-sarcopenia or sarcopenia. [Subjects and Methods] Fifty-two community-dwelling individuals, over 60 years and meeting the diagnostic criteria for pre-sarcopenia or sarcopenia, were randomly assigned to intervention group (n=34) and control group (n=18). The intervention group completed 6-months home exercise programs, combining walking with lower limb resistance exercises. Body mass index, skeletal mass index, body fat percentage, handgrip strength, single-leg standing, walking speed (comfortable and maximal), and knee extension strength were evaluated at baseline and post-intervention. Activity was assessed using the 25-question Geriatric Locomotive Functional Scale (GLFS-25) and quality of life using the Euro QOL questionnaire. [Results] Pre- and post-training assessments were completed by 76.5% and 77.8% of participants in the intervention and control groups, respectively. The intervention improved single-leg standing (60.5 s to 77.2 s) and knee extension strength (1.38 Nm/kg to 1.69 Nm/kg). In the control group, maximum walking speed (2.02 m/s to 1.86 m/s) and GLFS-25 score (2.9 to 5.1) worsened. Change of pre-sarcopenia/sarcopenia status was comparable for the intervention (15.4%) and control (14.3%) groups. [Conclusion] A 6-month home exercise program improved physical function in community-dwelling individuals with pre-sarcopenia or sarcopenia.

New-onset atrial high-rate episodes between his bundle pacing and conventional right ventricular septum pacing in patients with atrioventricular conduction disturbance.

BACKGROUND: The effect of His bundle pacing (HBP) on the incidence of new-onset atrial fibrillation (AF) after pacemaker implantation (PMI) for atrioventricular conduction disturbance (AVCD) remains unknown. We compared the incidence of new-onset atrial high-rate episode (AHRE) in conventional right ventricular (RV) septum pacing (RVSP) and His bundle pacing (HBP) after PMI for AVCD. METHODS: One hundred and four consecutive patients who underwent dual chamber PMI for AVCD in our hospital were screened. Thirty-five patients with mitral or aortic valve disease, history of open-heart surgery, prior AF, subclinical AF, cumulative ventricular pacing percentage < 90%, and RV lead revision were excluded, and 69 patients were effectively enrolled in this study. The primary endpoint was new-onset AHRE within the follow-up period. New-onset AHRE was defined as an atrial high-rate episode that occurred 3 months after PMI and lasted for > 6 min at an atrial heart rate > 190 bpm. RV leads were placed in the His bundle region and RV septum region in 22 and 47 patients, respectively. The mean follow-up period was 539 ± 218 days. The follow-up period was 2 years after PMI or until the new-onset AHRE occurred. RESULTS: The incidence of new-onset AHRE was lower in the HBP group than in the RVSP group (11% vs. 43%, p = 0.01). Multivariate analysis in the Cox regression hazard model showed that HBP had a significantly lower risk of new-onset AHRE compared with RVSP (HR = 0.21; 95% confidence interval 0.04-0.78, p = 0.02). CONCLUSION: The incidence of new-onset AHRE was significantly less in HBP compared to RVSP during the 2-year follow-up period after pacemaker implantation in AVCD patients with RV pacing dependence.

Cryoballoon ablation of peri-mitral atrial flutter refractory to radiofrequency ablation: a case report.

Background: The radiofrequency catheter ablation of peri-mitral atrial flutter is occasionally difficult, mostly due to epicardial or intramural conduction on the mitral isthmus (MI). However, cryoballoon ablation (CBA) of peri-mitral atrial flutter refractory to radiofrequency ablation has not been reported. Case summary: We report a case of a 66-year-old male patient who experienced a recurrence of atypical atrial flutter and underwent the sixth catheter ablation. The activation and entrainment maps showed that this atypical atrial flutter (AFL) was peri-mitral AFL via pathways other than endocardial conduction in the MI. Previous radiofrequency catheter ablation attempts on the MI line, including endocardial, coronary sinus, and epicardial ablations, failed to achieve a bidirectional block of the MI. In this case, we selected CBA for the MI area and successfully achieved a bidirectional block of the MI. Discussion: Although using CBA in the MI is off-label, it could be safely implemented using CARTOUNIVU™. We attributed the success of the bidirectional block of the MI in this case to the crimping of the northern hemisphere of the CBA to the mitral isthmus area, which resulted in the formation of a broad, uniform, and deep ablation lesion site.

Peak frequency annotation algorithm-guided slow pathway ablation in typical atrioventricular nodal reentrant tachycardia.

BACKGROUND: The slow pathway potential is difficult to annotate because it is buried within the atrial potential. Omnipolar technology near field can automatically annotate the peak frequency potential associated with acquired intracardiac electrograms. OBJECTIVES: This study aimed to visualize the junction between the transitional cells and the slow pathway using a peak frequency map with omnipolar technology near field and evaluate whether the high-frequency site around the tricuspid annulus (TA) is an effective target for slow pathway ablation. METHODS: This prospective observational study enrolled 37 patients with typical atrioventricular nodal reentrant tachycardia. Patients underwent slow pathway ablation using a peak frequency map (n = 17) and the conventional approach based on anatomical and electrophysiological findings (n = 20). RESULTS: High-frequency sites were distributed at the TA side of the 4-5 o'clock position in all patients mapped using the peak frequency map of OTNF. The distance to the His bundle from the successful ablation site was farther (24.0 ± 4.8 mm vs 12.7 ± 4.0 mm; P < .0001), junctional rhythm was slower (88 ± 17 beats/min vs 115 ± 12 beats/min; P < .0001), the time to junctional rhythm after radiofrequency application was shorter (3.4 ± 1.4 seconds vs 8.2 ± 4.6 seconds; P < .0001), and the elimination rate of jump ups (71% vs 30%; P = .02) was higher in the peak frequency map-guided group. CONCLUSION: The high-frequency site of the TA at 4-5 o'clock in the peak frequency map could be a novel target of slow pathway ablation with high safety, efficiency, and efficacy.

The clinicopathological and prognostic significance of autonomic nerves in salivary duct carcinoma.

Many researchers have focused on the role of the autonomic nervous system in the tumor microenvironment. Autonomic nerves include the sympathetic and parasympathetic nerves, which are known to induce cancer growth and metastasis. However, in salivary duct carcinoma (SDC), a rare and highly malignant tumor, the issue should be investigated from both biological and therapeutic perspectives. We explored the clinicopathological and prognostic implications of the autonomic nerves in 129 SDCs. Immunohistochemistry was performed to determine the nature of each nerve using antibodies against S100, tyrosine hydroxylase (TH) as a sympathetic marker, and vesicular acetylcholine transporter (VAChT) as a parasympathetic marker. The area of each marker-positive nerve was digitized and evaluated quantitatively. Double immunofluorescence for TH and VAChT was performed in selected cases. The expression of the secreted neurotrophins was also examined. S100-positive nerves were present in the cancer tissue in 94 of 129 cases (72.9%). Among them, TH-positive sympathetic nerves and/or VAChT-positive parasympathetic nerves were identified in 92 cases (97.9%), and 59 cases (62.8%) had TH/VAChT-co-expressing nerves. Double immunofluorescence revealed a mosaic pattern of sympathetic and parasympathetic fibers in co-expressing nerve bundles. The presence of autonomic nerves, regardless of their area, was significantly associated with aggressive histological features, advanced T/N classification, and a poor prognosis, with shorter disease-free and overall survival. There was an association between some tumor immune microenvironment-related markers and the autonomic nerve status, but not the latter and the secreted neurotrophin expression. This study suggests that autonomic nerves might play a role in the progression of SDC.