Utility of Contrast-Enhanced Harmonic Endoscopic Ultrasonography to Diagnose Pancreaticobiliary Maljunction.

BACKGROUND: Detection of a common channel outside the duodenal wall is important in diagnosing pancreaticobiliary maljunction (PBM). The present study evaluated the utility of contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) in diagnosing PBM. METHODS: This single-center retrospective study enrolled 45 patients who were diagnosed with PBM or high confluence of pancreatobiliary ducts (HCPBD) between January 2007 and December 2021. The diagnostic sensitivities of contrast-enhanced computed tomography (CE-CT), magnetic resonance imaging (MRI), and CH-EUS for diagnosing PBM were analyzed. Imaging findings were evaluated by two reviewers blinded to the clinicopathological results. RESULTS: Based on diagnostic criteria, 33 patients were diagnosed with PBM and 12 with HCPBD. Compared with the patients with HCPBD, those with PBM had significantly longer common channel (12.5 mm vs. 8.1 mm, P = 0.018) and common bile duct (13.0 mm vs. 8.6 mm, P = 0.049) lengths. The κ-coefficients for differentiating PBM and HCPBD were 0.871 between CE-CT and MRI, 0.330 between CE-CT and CH-EUS, and 0.611 between MRI and CH-EUS. The diagnostic sensitivity of CH-EUS (95.2%) was higher than that of CE-CT (83.3%) and MRI (82.8%), although the differences were not statistically significant. CONCLUSION: CH-EUS may be useful for the diagnosis of PBM.

The safety of perioperative antiplatelet continuation without selection biases in microsurgical decompression surgery for single level lumbar spinal stenosis and lumbar disc herniotomy.

PURPOSE: Each institution or physician has to decide on an individual basis whether to continue or discontinue antiplatelet (AP) therapy before spinal surgery. The purpose of this study was to determine if perioperative AP continuation is safe during single-level microsurgical decompression (MSD) for treating lumbar spinal stenosis (LSS) and lumbar disc hernia (LDH) without selection bias. METHODS: Patients who underwent single-level MSD for LSS and LDH between April 2018 to December 2022 at our institute were included in this retrospective study. We collected data regarding baseline characteristics, medical history/comorbidities, epidural hematoma (EDH) volume, reoperation for EDH, differences between preoperative and one-day postoperative blood cell counts (ΔRBC), hemoglobin (ΔHGB), and hematocrits (ΔHCT), and perioperative thromboembolic complications. Patients were divided into two groups: the AP continuation group received AP treatment before surgery and the control group did not receive antiplatelet medication before surgery. Propensity scores for receiving AP agents were calculated, with one-to-one matching of estimated propensity scores to adjust for patient baseline characteristics and past histories. Reoperation for EDH, EDH volume, ΔRBC, ΔHGB, ΔHCT, and perioperative thromboembolic complications were compared between the groups. RESULTS: The 303 enrolled patients included 41 patients in the AP continuation group. After propensity score matching, the rate of reoperation for EDH, the EDH volume, ΔRBC, ΔHGB, ΔHCT, and perioperative thromboembolic complication rates were not significantly different between the groups. CONCLUSION: Perioperative AP continuation is safe for single-level lumbar MSD, even without biases.

Solid-State Electrochemical Thermal Switches with Large Thermal Conductivity Switching Widths.

Thermal switches that switch the thermal conductivity (κ) of the active layers are attracting increasing attention as thermal management devices. For electrochemical thermal switches, several transition metal oxides (TMOs) are proposed as active layers. After electrochemical redox treatment, the crystal structure of the TMO is modulated, which results in the κ switching. However, the κ switching width is still small (<4 W m-1 K-1). In this study, it demonstrates that LaNiOx-based solid-state electrochemical thermal switches have a κ switching width of 4.3 W m-1 K-1. Fully oxidized LaNiO3 (on state) has a κ of 6.0 W m-1 K-1 due to the large contribution of electron thermal conductivity (κele, 3.1 W m-1 K-1). In contrast, reduced LaNiO2.72 (off state) has a κ of 1.7 W m-1 K-1 because the phonons are scattered by the oxygen vacancies. The LaNiOx-based electrochemical thermal switch is cyclable of κ and the crystalline lattice of LaNiOx. This electrochemical thermal switch may be a promising platform for next-generation devices such as thermal displays.

Left Ventricular Longitudinal Myocardial Function of Heart Failure Patients With Transition From Reduced to Preserved Ejection Fraction and of Those With Preserved Ejection Fraction.

Background: Left ventricular (LV) longitudinal myocardial function is associated with the outcomes of heart failure (HF) patients. HF with improved ejection fraction (EF), known as HFimpEF, which is defined as current LVEF >40% but any previously documented LVEF ≤40%, has favorable outcomes compared with HF with preserved EF (HFpEF). However, LV longitudinal myocardial function in patients with previously reduced LVEF (<50%) but improved LVEF to within the normal range (≥50%) (HFnorEF) and its association with cardiovascular events remain unclear. Methods and Results: We studied 70 patients with HFpEF and 65 with HFnorEF. LV longitudinal myocardial function was assessed as global longitudinal strain (GLS). The primary endpoint was defined as cardiovascular death or HF hospitalization during follow-up of 5.6±3.1 years. The GLS of HFpEF patients was significantly lower than that of HFnorEF patients (13.6±3.5% vs. 14.8±2.2%, P=0.02) even when the LVEF was similar. Multivariate Cox proportional hazards analysis showed that GLS was independently associated with cardiovascular events. Furthermore, of the entire study population, patients with GLS >15.0% had fewer cardiovascular events than those without (log-rank P=0.014) among all the patients. Conclusions: LV longitudinal myocardial dysfunction was more frequently observed in patients with HFpEF than in those with HFnorEF, even when LVEF was similar, and was independently associated with cardiovascular events for HF patients with current LVEF ≥50%.

Effect of Ivabradine on Left Ventricular Reverse Remodeling in Relatively Stable Heart Failure Outpatients With Reduced Ejection Fraction.

Background: Elevations of resting heart rate (HR) in patients with heart failure (HF) with reduced ejection fraction (HFrEF) are often missed, resulting in some patients with an indication for ivabradine reportedly being missed. Methods and Results: We studied 30 relatively stable HFrEF outpatients, and ivabradine was administered when regular follow-up echocardiography showed a resting HR ≥75 beats/min. Significant left ventricular reverse remodeling was observed 10.1±3.9 months after administration of ivabradine. Conclusions: This finding may well make this procedure a potential new approach for preventing worsening of HF for relatively stable patients with HFrEF.

Effect of tafamidis on left atrial function of patients with transthyretin amyloid cardiomyopathy.

Transthyretin amyloid cardiomyopathy (ATTR-CM) is characterized by the functional and structural effects of amyloid infiltration, predominantly within the ventricles, causing biventricular wall thickening. Amyloid infiltration can be observed in the left atrium in ATTR-CM patients, but the association of left atrial (LA) myocardial function with cardiovascular events and of changes in LA myocardial function with tafamidis administration have not yet been clarified. Our aim was, therefore, to use speckle-tracking strain for investigating LA myocardial function in patients with ATTR-CM treated with tafamidis. We studied 55 patients with biopsy-proven ATTR-CM who had been treated with tafamidis (age: 76 ± 2 years, male: 93%). For speckle-tracking analysis of LA myocardial function, the systolic LA strain (LA reservoir function) was defined for this study as LA myocardial function from the apical 4-chamber view. The primary endpoint was defined as a composite comprising cardiovascular death and/or heart failure hospitalization after tafamidis administration over a median follow-up period of 28 ± 4 months. Patients with baseline LA strain < 8.6% (median value) experienced significantly more cardiovascular events than those without (log-rank P = 0.002). Moreover, LA strain in 26 patients worsened after tafamidis administration, and multivariate logistic regression analysis showed age, global longitudinal strain and relative apical longitudinal strain index were identified as independent determinants of deterioration of LA strain after tafamidis administration. In conclusion, baseline LA reservoir function is closely associated with cardiovascular events after tafamidis administration, and could be an additional parameter for the management of patients with ATTR-CM.

Development and web deployment of prediction model for pulmonary arterial pressure in chronic thromboembolic pulmonary hypertension using machine learning.

BACKGROUND AND PURPOSE: Mean pulmonary artery pressure (mPAP) is a key index for chronic thromboembolic pulmonary hypertension (CTEPH). Using machine learning, we attempted to construct an accurate prediction model for mPAP in patients with CTEPH. METHODS: A total of 136 patients diagnosed with CTEPH were included, for whom mPAP was measured. The following patient data were used as explanatory variables in the model: basic patient information (age and sex), blood tests (brain natriuretic peptide (BNP)), echocardiography (tricuspid valve pressure gradient (TRPG)), and chest radiography (cardiothoracic ratio (CTR), right second arc ratio, and presence of avascular area). Seven machine learning methods including linear regression were used for the multivariable prediction models. Additionally, prediction models were constructed using the AutoML software. Among the 136 patients, 2/3 and 1/3 were used as training and validation sets, respectively. The average of R squared was obtained from 10 different data splittings of the training and validation sets. RESULTS: The optimal machine learning model was linear regression (averaged R squared, 0.360). The optimal combination of explanatory variables with linear regression was age, BNP level, TRPG level, and CTR (averaged R squared, 0.388). The R squared of the optimal multivariable linear regression model was higher than that of the univariable linear regression model with only TRPG. CONCLUSION: We constructed a more accurate prediction model for mPAP in patients with CTEPH than a model of TRPG only. The prediction performance of our model was improved by selecting the optimal machine learning method and combination of explanatory variables.

Nitrergic inhibition of sympathetic arteriolar constrictions in the female rodent urethra.

During the urine storage phase, tonically contracting urethral musculature would have a higher energy consumption than bladder muscle that develops phasic contractions. However, ischaemic dysfunction is less prevalent in the urethra than in the bladder, suggesting that urethral vasculature has intrinsic properties ensuring an adequate blood supply. Diameter changes in rat or mouse urethral arterioles were measured using a video-tracking system. Intercellular Ca2+ dynamics in arteriolar smooth muscle (SMCs) and endothelial cells were visualised using NG2- and parvalbumin-GCaMP6 mice, respectively. Fluorescence immunohistochemistry was used to visualise the perivascular innervation. In rat urethral arterioles, sympathetic vasoconstrictions were predominantly suppressed by α,ß-methylene ATP (10 µM) but not prazosin (1 µM). Tadalafil (100 nM), a PDE5 inhibitor, diminished the vasoconstrictions in a manner reversed by N-ω-propyl-l-arginine hydrochloride (l-NPA, 1 µM), a neuronal NO synthesis (nNOS) inhibitor. Vesicular acetylcholine transporter immunoreactive perivascular nerve fibres co-expressing nNOS were intertwined with tyrosine hydroxylase immunoreactive sympathetic nerve fibres. In phenylephrine (1 µM) pre-constricted rat or mouse urethral arterioles, nerve-evoked vasodilatations or transient SMC Ca2+ reductions were largely diminished by l-nitroarginine (l-NA, 10 µM), a broad-spectrum NOS inhibitor, but not by l-NPA. The CGRP receptor antagonist BIBN-4096 (1 µM) shortened the vasodilatory responses, while atropine (1 µM) abolished the l-NA-resistant transient vasodilatory responses. Nerve-evoked endothelial Ca2+ transients were abolished by atropine plus guanethidine (10 µM), indicating its neurotransmitter origin and absence of non-adrenergic non-cholinergic endothelial NO release. In urethral arterioles, NO released from parasympathetic nerves counteracts sympathetic vasoconstrictions pre- and post-synaptically to restrict arteriolar contractility. KEY POINTS: Despite a higher energy consumption of the urethral musculature than the bladder detrusor muscle, ischaemic dysfunction of the urethra is less prevalent than that of the bladder. In the urethral arterioles, sympathetic vasoconstrictions are predominately mediated by ATP, not noradrenaline. NO released from parasympathetic nerves counteracts sympathetic vasoconstrictions by its pre-synaptic inhibition of sympathetic transmission as well as post-synaptic arteriolar smooth muscle relaxation. Acetylcholine released from parasympathetic nerves contributes to endothelium-dependent, transient vasodilatations, while CGRP released from sensory nerves prolongs NO-mediated vasodilatations. PDE5 inhibitors could be beneficial to maintain and/or improve urethral blood supply and in turn the volume and contractility of urethral musculature.

Plasma D-Dimer Levels Can Provide Useful Diagnostic Information on Acute Vertebral Compression Fractures in Patients with Low Back Pain in the Emergency Room.

BACKGROUND: Patients with acute vertebral compression fractures (aVCFs) are frequently transferred to an emergency department by ambulance. The most useful imaging modality is magnetic resonance imaging (MRI); however, which patients should be prioritized for MRI evaluation may be unclear. The aim of this study was to evaluate plasma D-dimer levels as a biomarker for aVCFs. METHODS: This retrospective cohort study included patients with low back pain in the emergency department between November 2017 and October 2020. Patients with infections, patients with coagulation disorders, and patients without D-dimer level measurements were excluded. The presence of an aVCF was detected with MRI. Blood samples were collected for routine blood tests. The predictive factors for aVCFs were evaluated with univariate and multivariable logistic regression analyses. RESULTS: Overall, 191 consecutive MRI evaluations were ordered. After exclusions, 101 patients were reviewed. Based on MRI, 65 (64.4%) patients were diagnosed with aVCF. The presence of aVCF was significantly correlated with age (odds ratio [OR] = 1.052, 95% confidence interval [CI] 1.018-1.191), an old vertebral compression fracture (OR = 3.290, 95% CI 1.342-8.075), hemoglobin (OR = 0.699, 95% CI 0.535-0.912), and D-dimer levels (OR = 1.829, 95% CI 1.260-2.656). Results from a multivariable logistic regression analysis showed that D-dimer levels (OR = 1.642, 95% CI 1.188-2.228) remained a significant risk factor for the presence of aVCFs after adjustment for potential confounders. CONCLUSIONS: Plasma D-dimer levels can provide useful diagnostic information about whether an aVCF is present.

Microvascular Decompression for Trigeminal Neuralgia with Complicated Offending Vessel Involving Trigeminocerebellar Artery: 2-Dimensional Operative Video.

Microvascular decompression (MVD) is a well-established and definitive treatment option for trigeminal neuralgia (TN).1 However, complex vascular geometry and numerous offending vessels make it difficult to perform nerve decompression in certain cases.2 The trigeminocerebellar artery (TCA) is a unique branch of the basilar artery. The vessel is named the TCA because it supplies both the trigeminal nerve root and the cerebellar hemisphere.3 This anatomical variant may increase the risk of neurovascular compression in the trigeminal nerve. We present the case of a 74-year-old man with left TN in whom a TCA was one of the responsible compression vessels. Preoperative images revealed the ipsilateral anterior inferior cerebellar artery, well-developed TCA, and superior cerebellar artery, wherein these branches were all suspected to be involved in trigeminal nerve compression. In MVD, 3 arteries were suspected to compress the trigeminal nerve in 5 sites, and all of them needed to be meticulously dissected from the nerve root and decompressed. Moreover, 2 of them branched many short perforators to the brainstem. Three decompression procedures (transposition to the dura, transposition to the brain, and interposition) were performed to decompress the trigeminal nerve. Postoperatively, TN was completely resolved immediately. MVD for TN could be difficult to perform in cases with TCA, as in the present case, and rigorous procedures were required intraoperatively.

Multicenter Prospective Cohort Study of Neoadjuvant Chemotherapy for Borderline Resectable Pancreatic Cancer (YPB-001).

OBJECTIVES: The present multicenter prospective observational study investigated the effectiveness and safety of neoadjuvant chemotherapy (NAC) for patients with borderline resectable pancreatic cancer (BRPC) and those with RPC contacting major vessels, with respect to a historical control of upfront surgery. MATERIALS AND METHODS: Patients with BRPC and RPC contacting major vessels were prospectively registered and administered NAC with durations and regimens determined by the corresponding treating physician. Our primary aim was to assess the R0 resection rate, and secondary aim was to evaluate safety, resection rate, time to treatment failure, overall survival, and response rate. RESULTS: Fifty of 52 enrolled patients were analyzed; 2 with serious comorbidities died during treatment. Thirty-one patients underwent resection, with R0 resection being achieved in 26 (52% of total and 84% of all resected cases). Univariate and multivariate analyses indicated age (≥75 years) as the only independent predictor of nonresection. Median progression-free survival and median survival time were longer in the prospective cohort than in the historical cohort. CONCLUSIONS: Overall, NAC for BRPC in real-world setting might yield R0 resection rates similar to those reported in previous clinical studies. Development of safe regimens and management strategies that can maintain treatment intensity in geriatric patients is warranted.

Interparticle normal force in highly porous granular matter during compression.

We perform a numerical simulation of compression of a highly porous dust aggregate of monodisperse spheres. We find that the average interparticle normal force within the aggregate is inversely proportional to both the filling factor and the average coordination number and we also derive this relation theoretically. Our findings would be applicable for granular matter of arbitrary structures, as long as the constituent particles are monodisperse spheres.

Majorana-fermion origin of the planar thermal Hall effect in the Kitaev magnet α-RuCl3.

The field-induced quantum-disordered state of layered honeycomb magnet α-RuCl3 is a prime candidate for Kitaev spin liquids hosting Majorana fermions and non-Abelian anyons. Recent observations of anomalous planar thermal Hall effect demonstrate a topological edge mode, but whether it originates from Majorana fermions or bosonic magnons remains controversial. Here, we distinguish these origins from combined low-temperature measurements of high-resolution specific heat and thermal Hall conductivity with rotating magnetic fields within the honeycomb plane. A distinct closure of the low-energy bulk gap is observed for the fields in the Ru-Ru bond direction, and the gap opens rapidly when the field is tilted. Notably, this change occurs concomitantly with the sign reversal of the Hall effect. General discussions of topological bands show that this is the hallmark of an angle rotation-induced topological transition of fermions, providing conclusive evidence for the Majorana-fermion origin of the thermal Hall effect in α-RuCl3.

Relationship of Mild to Moderate Impairment of Left Ventricular Ejection Fraction With Fatal Ventricular Arrhythmic Events in Cardiac Sarcoidosis.

BACKGROUND: Current guidelines recommend placing an implantable cardiac defibrillator for patients with cardiac sarcoidosis and a severely impaired left ventricular ejection fraction (LVEF) of ≤35%. In this study, we determined the association between mild or moderate LVEF impairment and fatal ventricular arrhythmic event (FVAE). METHODS AND RESULTS: We retrospectively analyzed 401 patients with cardiac sarcoidosis without sustained ventricular arrhythmia at diagnosis. The primary end point was an FVAE, defined as the combined endpoint of documented ventricular tachycardia or ventricular fibrillation and sudden cardiac death. Two cutoff points for LVEF were used: a sex-specific lower threshold of normal range of LVEF (52% for men and 54% for women) and an LVEF of 35%, which is used in the current guidelines. During a median follow-up of 3.2 years, 58 FVAEs were observed, and the 5- and 10-year estimated incidences of FVAEs were 16.8% and 23.0%, respectively. All patients were classified into 3 groups according to LVEF: impaired LVEF group, mild to moderate impairment of LVEF group, and maintained LVEF group. Multivariable competing risk analysis showed that both the impaired LVEF group (hazard ratio [HR], 3.24 [95% CI, 1.49-7.04]) and the mild to moderate impairment of LVEF group (HR, 2.16 [95% CI, 1.04-4.46]) were associated with a higher incidence of FVAEs than the maintained LVEF group after adjustment for covariates. CONCLUSIONS: Patients with cardiac sarcoidosis are at a high risk of FVAEs, regardless of documented ventricular arrhythmia at the time of diagnosis. In patients with cardiac sarcoidosis, mild to moderate impairment of LVEF is associated with FVAEs.

Biomechanical imaging biomarker during chemoradiotherapy predicts treatment response in head and neck squamous cell carcinoma.

Objective. For response-adapted adaptive radiotherapy (R-ART), promising biomarkers are needed to predict post-radiotherapy (post-RT) responses using routine clinical information obtained during RT. In this study, a patient-specific biomechanical model (BM) of the head and neck squamous cell carcinoma (HNSCC) was proposed using the pre-RT maximum standardized uptake value (SUVmax) of18F-fluorodeoxyglucose (FDG) and tumor structural changes during RT as evaluated using computed tomography (CT). In addition, we evaluated the predictive performance of BM-driven imaging biomarkers for the treatment response of patients with HNSCC who underwent concurrent chemoradiotherapy (CCRT).Approach. Patients with histologically confirmed HNSCC treated with definitive CCRT were enrolled in this study. All patients underwent CT two times as follows: before the start of RT (pre-RT) and 3 weeks after the start of RT (mid-RT). Among these patients, 67 patients who underwent positron emission tomography/CT during the pre-RT period were included in the final analysis. The locoregional control (LC), progression-free survival (PFS), and overall survival (OS) prediction performances of whole tumor stress change (TS) between pre- and mid-RT computed using BM were assessed using univariate, multivariate, and Kaplan-Meier survival curve analyses, respectively. Furthermore, performance was compared with the pre and post-RT SUVmax, tumor volume reduction rate (TVRR) during RT, and other clinical prognostic factors.Main results. For both univariate, multivariate, and survival curve analyses, the significant prognostic factors were as follows (p< 0.05): TS and TVRR for LC; TS and pre-RT FDG-SUVmaxfor PFS; and TS only for OS. In addition, for 2 year LC, PFS, and OS prediction, TS showed a comparable predictive performance to post-RT FDG-SUVmax.Significance. BM-driven TS is an effective prognostic factor for tumor treatment response after CCRT. The proposed method can be a feasible functional imaging biomarker that can be acquired during RT using only routine clinical data and may provide useful information for decision-making during R-ART.

A Case of Symptomatic Multiple Tarlov Cysts Treated with Microsurgical Wrapping Technique -Efficacy and Limitation of Surgical Procedure.

Tarlov cysts (TCs) rarely cause clinical symptoms, such as leg pain, buttock pain, and bladder/bowel dysfunction. Surgery is considered when these symptoms persist despite medical treatments. Among several surgical procedures, microsurgical wrapping (MSW) is a relatively novel, simple technique with few complications, including cerebrospinal fluid leakage. Herein, we report a case of multiple TCs treated with MSW and present the mechanism of symptoms generated by TC and the procedure's limitations. A 58-year-old man complained of severe right leg and buttock pain for 3 months and was admitted to our hospital. His symptoms aggravated with sitting and standing and improved with the prone position. Spinal magnetic resonance imaging (MRI) demonstrated multiple sacral cysts containing intense cerebrospinal fluid. The cysts connect to the right S3 and S4 nerve roots. He was treated conservatively with medications; however, his symptoms were not improved. Therefore, MSW was performed for TCs connected to the S3 and S4 roots. The postoperative course was uneventful, and cerebrospinal fluid leakage did not occur. MRI performed 1 year after the operation demonstrated no recurrence of the TCs, and his leg pain was completely relieved; however, the buttock pain remained. MSW for TCs is effective for symptoms of adjacent nerve root compression; however, repairing the damaged nerve root in TCs is sometimes difficult. This may be a limitation of present surgical interventions because these symptoms may be difficult to treat even with other interventions.

Efficacy of Native T1 Mapping for Patients With Non-Ischemic Cardiomyopathy and Ventricular Functional Mitral Regurgitation Undergoing Transcatheter Edge-to-Edge Repair.

BACKGROUND: We investigated the efficacy of left ventricular (LV) myocardial damage by native T1mapping obtained with cardiac magnetic resonance (CMR) for patients undergoing transcatheter edge-to-edge repair (TEER).Methods and Results: We studied 40 symptomatic non-ischemic heart failure (HF) patients and ventricular functional mitral regurgitation (VFMR) undergoing TEER. LV myocardial damage was defined as the native T1Z-score, which was converted from native T1values obtained with CMR. The primary endpoint was defined as HF rehospitalization or cardiovascular death over 12 months after TEER. Multivariable Cox proportional hazards analysis showed that the native T1Z-score was the only independent parameter associated with cardiovascular events (hazard ratio 3.40; 95% confidential interval 1.51-7.67), and that patients with native T1Z-scores <2.41 experienced significantly fewer cardiovascular events than those with native T1Z-scores ≥2.41 (P=0.001). Moreover, the combination of a native T1Z-score <2.41 and more severe VFMR (effective regurgitant orifice area [EROA] ≥0.30 cm2) was associated with fewer cardiovascular events than a native T1Z-score ≥2.41 and less severe VFMR (EROA <0.30 cm2; P=0.002). CONCLUSIONS: Assessment of baseline LV myocardial damage based on native T1Z-scores obtained with CMR without gadolinium-based contrast media is a valuable additional parameter for better management of HF patients and VFMR following TEER.

Anti-Vα24Jα18 TCR Antibody Tunes iNKT Cell Responses to Target and Kill CD1d-negative Tumors in an FcγRII (CD32)-dependent Manner.

Invariant natural killer T (iNKT) cells play an essential role in antitumor immunity by exerting cytotoxicity and producing massive amounts of cytokines. iNKT cells express invariant T-cell receptors (TCR) to recognize their cognate glycolipid antigens such as α-galactosylceramide (α-GalCer) presented on CD1d. We recently reported that iNKT cells recognize CD1d-negative leukemia cell line K562 in a TCR-dependent manner. However, it remains controversial how iNKT cells use TCRs to recognize and exhibit cytotoxic activity toward CD1d-negative tumors cells without CD1d restriction. Here, we report that iNKT cells exerted cytotoxicity toward K562 cells via a carried over anti-Vα24 TCR mAb from positive selection by magnetic bead sorting. We found that addition of the anti-Vα24Jα18 TCR mAb (6B11 mAb) rendered iNKT cells cytotoxic to K562 cells in an FcγRII (CD32)-dependent manner. Moreover, iNKT cells treated with 6B11 mAb became cytotoxic to other CD32+ cell lines (U937 and Daudi). In addition, iNKT cells treated with 6B11 mAb suppressed K562 cell growth in a murine xenograft model in vivo. These data suggest that anti-iNKT TCR mAb treatment of iNKT cells can be applied as a therapeutic strategy to treat CD32+ cancers such as leukemia, lymphoma, and lung cancer. SIGNIFICANCE: Our findings unveiled that iNKT cells recognize and kill CD1d-negative target tumors via the anti-iNKT TCR mAb bound to CD32 at the tumor site, thereby bridging iNKT cells and CD1d-negative tumors. These findings shed light on the therapeutic potential of anti-iNKT TCR mAbs in NKT cell-based immunotherapy to treat CD1d-negative CD32+ cancers.

Importance of B-Type Natriuretic Peptide in the Detection of Patients With Structural Heart Disease in a Primary Care Setting.

BACKGROUND: Early detection and intervention for preclinical heart failure (HF) are crucial for restraining the potential increase in patients with HF. Thus, we designed and conducted a single-center retrospective cohort study to confirm the efficacy of B-type natriuretic peptide (BNP) for the early detection of preclinical HF in a primary care setting.Methods and Results: We investigated 477 patients with no prior diagnosis of HF who were under the care of general practitioners. These patients were categorized into 4 groups based on BNP concentrations: Category 1, 0 pg/mL≤BNP≤35 pg/mL; Category 2, 35 pg/mL200 pg/mL. There was a marked and statistically significant increase in the prevalence of preclinical HF with increasing BNP categories: 19.9%, 57.9%, 87.5%, and 96.0% in Categories 1, 2, 3, and 4, respectively. Compared with Category 1, the odds ratio of preclinical HF in Categories 2, 3, and 4 was determined to be 5.56 (95% confidence interval [CI] 3.57-8.67), 23.70 (95% CI 8.91-63.11), and 171.77 (95% CI 10.31-2,861.93), respectively. CONCLUSIONS: Measuring BNP is a valuable tool for the early detection of preclinical HF in primary care settings. Proactive testing in patients at high risk of HF could play a crucial role in addressing the impending HF pandemic.