Assessment of the renal angina index in patients hospitalized in a cardiac intensive care unit.

The renal angina index (RAI) is a validated scoring tool for predicting acute kidney injury (AKI). We investigated the efficacy of the RAI in 2436 heterogeneous patients (mean age, 70 years) treated in cardiac intensive care units (CICUs). The RAI was calculated from creatinine and patient condition scores. AKI was diagnosed by the Kidney Disease: Improving Global Outcome criteria. The primary and secondary endpoints were the development of severe AKI and all-cause mortality, respectively. Four hundred thirty-three patients developed AKI, 87 of them severe. In multivariate analyses, the RAI was a significant independent predictor of severe AKI. During the 12-month follow-up period, 210 patients suffered all-cause death. Elevated RAI was independently associated with all-cause mortality, as was NT-proBNP (p < 0.001). The RAI is a potent predictor not only of severe AKI but also of adverse outcomes and substantially improved the 12-month risk stratification of patients hospitalized in CICUs.

Multicentre, open-label, randomised, controlled trial to compare early intervention with calcimimetics and conventional therapy in preventing coronary artery calcification in patients with secondary hyperparathyroidism (UPCOMING): a study protocol.

INTRODUCTION: Coronary artery and heart valve calcification is a risk factor for cardiovascular death in haemodialysis patients, so calcification prevention should be started as early as possible. Treatment with concomitant calcimimetics and low-dose vitamin D receptor activators (VDRAs) is available, but not enough evidence has been obtained on the efficacy of this regimen, particularly in patients with short dialysis duration. Therefore, this study will evaluate the efficacy and safety of early intervention with upacicalcet, a calcimimetic used to prevent coronary artery calcification in this patient population. METHODS AND ANALYSIS: This multicentre, open-label, randomised, parallel-group controlled study will compare an early intervention group, which received upacicalcet and a low-dose VDRA, with a conventional therapy group, which received a VDRA. The primary endpoint is a change in log coronary artery calcium volume score from baseline to 52 weeks. The main inclusion criteria are as follows: (1) age 18 years or older; (2) dialysis is planned or dialysis duration is less than 60 months; (3) intact parathyroid hormone (PTH) >240 pg/mL or whole PTH level>140 pg/mL; (4) serum-corrected calcium≥8.4 mg/dL and (5) Agatston score >30. The main exclusion criteria are as follows: (1) history of parathyroid intervention or fracture in the past 12 weeks; (2) history of myocardial infarction, stroke or leg amputation in the past 12 weeks; (3) history of coronary angioplasty and (4) heart failure of New York Heart Association class III or worse. ETHICS AND DISSEMINATION: The study will comply with the Declaration of Helsinki and the Japanese Clinical Trials Act. The study protocol has been approved by the Fujita Health University Certified Review Board (file no. CR22-052). Written informed consent will be obtained from all participants. Study results will be presented in academic meetings and peer-reviewed academic journals. TRIAL REGISTRATION NUMBER: jRCTs041220126.

Clinical Outcomes Based on Coronary Computed Tomography-Derived Fractional Flow Reserve and Plaque Characterization.

BACKGROUND: Coronary computed tomography angiography (CTA) followed by computed tomography angiography-derived fractional flow reserve (FFRCT) is now commonly used for the management of chronic coronary syndrome (CCS). CTA-verified high-risk plaque (HRP) characteristics have also been reported to be associated with a greater likelihood of adverse cardiac events but have not been used for management decisions. OBJECTIVES: The aim of this study was to evaluate clinical outcomes based on a combination of point-of-care computed tomography angiography-derived fractional flow reserve (POC-FFRCT) and the presence of HRP in CCS patients initially treated medically or with revascularization based on invasive coronary angiography findings. METHODS: CTA was performed as the initial test in 5,483 patients presenting with CCS between September 2015 and December 2020 followed by invasive coronary angiography and revascularization as necessary. POC-FFRCT assessment and HRP characterization were obtained subsequently in 745 consecutive patients. We investigated how HRP and POC-FFRCT, which were not available during the original clinical decision making, correlated with the endpoint defined as a composite of cardiac death, acute coronary syndrome, and a need for unplanned revascularization. RESULTS: Cardiac events occurred in 20 patients (2.7%) during a median follow-up of 744 days. The event rate was significantly higher in patients with POC-FFRCT <0.80 compared with POC-FFRCT ≥0.8 (5.4 vs 0.5 per 100 vessel years; log-rank P < 0.0001) and in patients with HRP compared to those without HRP (3.6 vs 0.8 per 100 vessel years; log-rank P = 0.0001). POC-FFRCT <0.80 and the presence of HRP were the independent predictors of cardiac events (HR: 16.67; 95% CI: 2.63-105.39; P = 0.002) compared with POC-FFRCT ≥0.8 and absent HRP. For the vessels with POC-FFRCT <0.80 and HRP, a significantly higher rate of adverse events was observed in patients who did not undergo revascularization compared with those revascularized (16.4 vs 1.4 per 100 vessel years; log-rank P = 0.006). CONCLUSIONS: POC-FFRCT <0.80 and the presence of HRP were the independent predictors of cardiac events, and revascularization of HRP lesions with abnormal POC-FFRCT was associated with a lower event rate.

Coronary computed tomography angiographic detection of in-stent restenosis via deep learning reconstruction: a feasibility study.

OBJECTIVES: Evaluation of in-stent restenosis (ISR), especially for small stents, remains challenging during computed tomography (CT) angiography. We used deep learning reconstruction to quantify stent strut thickness and lumen vessel diameter at the stent and compared it with values obtained using conventional reconstruction strategies. METHODS: We examined 166 stents in 85 consecutive patients who underwent CT and invasive coronary angiography (ICA) within 3 months of each other from 2019-2021 after percutaneous coronary intervention with coronary stent placement. The presence of ISR was defined as percent diameter stenosis ≥ 50% on ICA. We compared a super-resolution deep learning reconstruction, Precise IQ Engine (PIQE), and a model-based iterative reconstruction, Forward projected model-based Iterative Reconstruction SoluTion (FIRST). All images were reconstructed using PIQE and FIRST and assessed by two blinded cardiovascular radiographers. RESULTS: PIQE had a larger full width at half maximum of the lumen and smaller strut than FIRST. The image quality score in PIQE was higher than that in FIRST (4.2 ± 1.1 versus 2.7 ± 1.2, p < 0.05). In addition, the specificity and accuracy of ISR detection were better in PIQE than in FIRST (p < 0.05 for both), with particularly pronounced differences for stent diameters < 3.0 mm. CONCLUSION: PIQE provides superior image quality and diagnostic accuracy for ISR, even with stents measuring < 3.0 mm in diameter. CLINICAL RELEVANCE STATEMENT: With improvements in the diagnostic accuracy of in-stent stenosis, CT angiography could become a gatekeeper for ICA in post-stenting cases, obviating ICA in many patients after recent stenting with infrequent ISR and allowing non-invasive ISR detection in the late phase. KEY POINTS: • Despite CT technology advancements, evaluating in-stent stenosis severity, especially in small-diameter stents, remains challenging. • Compared with conventional methods, the Precise IQ Engine uses deep learning to improve spatial resolution. • Improved diagnostic accuracy of CT angiography helps avoid invasive coronary angiography after coronary artery stenting.

Resting echocardiographic parameters can exclude significant coronary artery disease: A comparison with coronary computed tomography angiography.

INTRODUCTION: Coronary computed tomography angiography (CCTA) is known to have a high negative predictive value (NPV) in identifying coronary artery disease (CAD). This study aimed to examine whether resting echocardiographic parameters could exclude significant CAD on CCTA. METHODS: We recruited 142 patients who had undergone both CCTA and echocardiography within a 3-month window. Based on the CCTA findings, patients were divided into two groups: Group A (non-significant CAD, defined as all coronary segments having <50% stenosis) and Group B (significant CAD). Resting echocardiographic parameters were compared between the two groups to identify predictors of non-significant CAD on CCTA. RESULTS: A total 92 patients (mean age, 68 ± 13 years; males, 62%) were eligible for this study; 50 in Group A and 42 in Group B. Among the various echo parameters, left atrial volume index (LAVI) and left ventricular (LV) global longitudinal strain (GLS) were significantly lower in Group A (23.5 ± 7.6 vs. 33.6 ± 7.4 mL/m2 , p < .001; -20.2 ± 1.8% vs. -16.8 ± 2.0%, p < .001, respectively). Analysis of the receiver operating characteristic curve revealed that the cutoff value to exclude significant CAD on CCTA was 29.0 mL/m2 for LAVI (NPV 80.8%) and -18.1% for GLS (NPV 80.7%). The NPV increased to 95.0% when these parameters were combined (LAVI < 29.0 mL/m2 and GLS < -18.1%). CONCLUSION: The combination of resting LAVI and GLS was clinically useful in excluding significant CAD via CCTA.

Development of a novel model for intraarticular adhesion in rat knee joint.

In this study, a novel rat model of knee joint adhesion was developed, and its formation was analyzed quantitatively over time. Thirty-nine Wistar rats were randomly divided into intact control (n = 3) and experimental (n = 36) groups. The latter was equally divided into three groups according to the experimental intervention: fixed with deep bending of the knee joint (group I), fixed after incision of the capsule (group II), and fixed after exposure of the patellofemoral joint to artificial patellar subluxation (group III). All rats were subdivided according to their joint immobilization period (1, 2, or 4 weeks). Thereafter, the limited range of motion of the knee joint with (limited knee range of motion) and without (limited knee joint intrinsic range of motion) skin and muscles were measured. The lengths of adhesions of the anterior knee joint and posterior capsules were evaluated histologically. The limited intrinsic range of motion of the knee joint was found to be increased in groups II and III compared to that in group I 4 weeks after immobilization. Adhesions were confirmed within 1 week after immobilization in groups II and III. The length of the adhesions in group III was significantly longer than in other groups at 2 weeks and remained longer than in group I at 4 weeks. This model may contribute to the assessment of the adhesion process and development of new therapeutic avenues following trauma or surgical invasion.

Geriatric nutritional risk index as readmission predictor in older adults with heart failure irrespective of ejection fraction.

Objectives: Malnutrition is associated with an increased risk of hospital readmission for heart failure in patients with acute decompensated heart failure (ADHF). Therefore, evaluation of the nutritional status in patients with ADHF may be important. The geriatric nutritional risk index (GNRI), the controlling nutritional status (CONUT) score, and the prognostic nutritional index (PNI) are widely used objective indexes for evaluation of the nutritional status. The present study was performed to determine the best nutritional index for predicting the prognosis in older adults with ADHF. Methods: We retrospectively studied 167 older adults (>65 years of age) who were admitted with ADHF from January 2012 to December 2015 and discharged alive. The objective nutritional status was evaluated using the GNRI, CONUT score, and PNI at admission. The endpoint of this study was unplanned hospitalization for worsening heart failure (WHF) within 1 year after discharge. Results: During the follow-up period, 58 patients were readmitted for WHF. In the multivariate Cox analysis, only the GNRI (p<0.0001) was independently associated with readmission for WHF among the three nutritional indexes. Kaplan-Meier analysis revealed that patients in the low-GNRI group (<90 as determined by receiver operating characteristic curve analysis) had a significantly greater risk of 1-year hospital readmission for WHF (p<0.0001; hazard ratio, 6.1; 95% confidence interval, 3.5-10.5). Conclusion: Among the objective nutritional indexes, the GNRI is the best predictor of readmission for WHF within 1 year after discharge in older adults with ADHF.

Ultrasound therapy for a week promotes regeneration and reduces pro-inflammatory macrophages in a rat sciatic nerve autograft model.

Peripheral nerve injury causes long-term motor dysfunction. Ultrasound (US) therapy is expected to accelerate peripheral nerve regeneration. However, its optimal usage and effects on macrophage phenotypes during peripheral nerve regeneration remain unknown. In this study, we investigated the optimal duration of US therapy and its effects on macrophage phenotype. Twenty-seven rats with autologous sciatic nerve grafting were divided into three groups: two received US therapy (1 MHz frequency, intensity of 140 mW/cm2, 20% duty cycle, 5 min/day) for one (US1) or 4 weeks (US4), and one group received sham stimulation. Immunohistochemistry was performed 3 and 7 days after injury in another set of 12 rats. Eight weeks after the injury, the compound muscle action potential amplitude of the gastrocnemius in the US1 and US4 groups was significantly higher than that in the sham group. The toe-spreading test showed functional recovery, whereas the gait pattern during treadmill walking did not recover. There were no significant differences in motor function, histomorphometry, or muscle weight between groups. Immunohistochemistry showed that US therapy decreased the number of pro-inflammatory macrophages seven days after injury. Therefore, US therapy for both one or 4 weeks can similarly promote reinnervation and reduce proinflammatory macrophages in autograft model rats.

Multimodality imaging to identify lipid-rich coronary plaques and predict periprocedural myocardial injury: Association between near-infrared spectroscopy and coronary computed tomography angiography.

Background: This study compares the efficacy of coronary computed tomography angiography (CCTA) and near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) in patients with significant coronary stenosis for predicting periprocedural myocardial injury during percutaneous coronary intervention (PCI). Methods: We prospectively enrolled 107 patients who underwent CCTA before PCI and performed NIRS-IVUS during PCI. Based on the maximal lipid core burden index for any 4-mm longitudinal segments (maxLCBI4mm) in the culprit lesion, we divided the patients into two groups: lipid-rich plaque (LRP) group (maxLCBI4mm ≥ 400; n = 48) and no-LRP group (maxLCBI4mm < 400; n = 59). Periprocedural myocardial injury was a postprocedural cardiac troponin T (cTnT) elevation of ≥5 times the upper limit of normal. Results: The LRP group had a significantly higher cTnT (p = 0.026), lower CT density (p < 0.001), larger percentage atheroma volume (PAV) by NIRS-IVUS (p = 0.036), and larger remodeling index measured by both CCTA (p = 0.020) and NIRS-IVUS (p < 0.001). A significant negative linear correlation was found between maxLCBI4mm and CT density (rho = -0.552, p < 0.001). Multivariable logistic regression analysis identified maxLCBI4mm [odds ratio (OR): 1.006, p = 0.003] and PAV (OR: 1.125, p = 0.014) as independent predictors of periprocedural myocardial injury, while CT density was not an independent predictor (OR: 0.991, p = 0.22). Conclusion: CCTA and NIRS-IVUS correlated well to identify LRP in culprit lesions. However, NIRS-IVUS was more competent in predicting the risk of periprocedural myocardial injury.

Volume-based 18 F-FDG PET analysis of cardiac sarcoidosis using the descending aorta as a reference tissue.

OBJECTIVE: 18 F-FDG PET can be used to calculate the threshold value of myocardial volume based on the mean standardised uptake value (SUV mean ) of the aorta to detect highly integrated regions of cardiac sarcoidosis. The present study investigated the myocardial volume when the position and number of volumes of interest (VOIs) were changed in the aorta. METHODS: The present study examined PET/computed tomography images of 47 consecutive cardiac sarcoidosis cases. VOIs were set at three locations in the myocardium and aorta (descending thoracic aorta, superior hepatic margin and near the pre-branch of the common iliac artery). The volume was calculated for each threshold using 1.1-1.5 times the SUV mean (median of three cross-sections) of the aorta as the threshold to detect high myocardial 18 F-FDG accumulation. The detected volume, correlation coefficient with the visually manually measured volume and the relative error were also calculated. RESULTS: The optimum threshold value for detecting high 18 F-FDG accumulation was 1.4 times that of the single cross-section of the aorta and showed the smallest relative errors of 33.84% and 25.14% and correlation coefficients of 0.974 and 0.987 for single and three cross-sections, respectively. CONCLUSION: The SUV mean of the descending aorta may be detected in good agreement with the visual high accumulation by multiplying the same threshold constant for both single and multiple cross-sections.

Serum angiotensin-converting enzyme levels indicating early sarcoidosis diagnosis and immunosuppressive therapy efficacy.

AIMS: This study aimed to determine the new cut-off value of serum angiotensin-converting enzyme (ACE) levels for detecting patients with sarcoidosis and to examine the change in ACE levels after the initiation of immunosuppressive therapy. METHODS AND RESULTS: We retrospectively examined patients in whom serum ACE levels were measured for suspected sarcoidosis between 2009 and 2020 in our institution. For patients diagnosed with sarcoidosis, changes in ACE levels were also observed. Of the 3781 patients (51.1% men, 60.1 ± 17.0 years old), 477 were excluded for taking ACE inhibitors and/or immunosuppression agents or those with any diseases affecting serum ACE levels. In 3304 patients including 215 with sarcoidosis, serum ACE levels were 19.6 IU/L [interquartile range, 15.1-31.5] in patients with sarcoidosis and 10.7 [8.4-16.5] in those without sarcoidosis (P < 0.01), and the best cut-off value was 14.7 IU/L with 0.865 of the area under the curves. Compared with the current ACE cut-off of 21.4, the sensitivity improved from 42.3 to 78.1 at the new cut-off, although specificity slightly decreased from 98.6 to 81.7. The ACE level significantly decreased more in those with immunosuppression therapy than in those without it (P for interaction <0.01), although it decreased in both groups (P < 0.01). CONCLUSIONS: Because the sensitivity for detecting sarcoidosis is comparatively low at the current standard value, further examinations are needed for patients suspected of sarcoidosis with relatively high ACE levels in the normal range. In patients with sarcoidosis, ACE levels decreased after the initiation of immunosuppression therapy.

Long-term prognostic value of changes in left ventricular global longitudinal strain in patients with heart failure with preserved ejection fraction.

BACKGROUND: Left ventricular (LV) global longitudinal strain (GLS) has emerged as a more sensitive index than LV ejection fraction (LVEF) for detecting subclinical LV dysfunction. We examined whether changes in GLS values are associated with the long-term prognosis of patients with a preserved LVEF and acute decompensated heart failure (HF). METHODS: We studied 100 consecutive patients (mean age: 71 years) who were hospitalized for HF with preserved ejection fraction (HFpEF) and had a preserved LVEF (≥ 50%) in both the acute and stable phases. We performed two-dimensional speckle-tracking echocardiography in the acute (GLS-acute) and stable (GLS-stable) phases at a median of 2 and 347 days after admission, respectively, and calculated the rate of change of the absolute value of GLS-stable with respect to that of GLS-acute. An improved GLS was defined as a rate of change in GLS ≥ 16%, and a non-improved GLS was a rate of change < 16%. The primary endpoint was the occurrence of major cardiovascular events (MACE). RESULTS: During a mean follow-up period of 1218 days, MACE occurred in 26 patients, including 8 all-cause deaths and 18 readmissions for HF. The rate of change in GLS for patients with MACE was lower than compared to those without MACE (10.6% vs 26.0%, p < 0.001). Multivariate Cox regression analyses indicated the rate of change in GLS was an independent predictor of MACE (p < 0.001). A non-improved GLS was correlated with a high risk of MACE. CONCLUSION: Changes in GLS values could be useful for the long-term risk stratification of patients hospitalized for HFpEF and persistently preserved LVEF.

Rationale and Design of Rivaroxaban Estimation With Warfarin in Atrial Fibrillation Patients With Coronary Stent Implantation (REWRAPS).

Background: Recent major randomized trials revealed the superiority of non-vitamin K antagonist oral anticoagulants (NOACs) over vitamin K antagonists (VKAs) from 6 months to 2 years after percutaneous coronary intervention (PCI). However, whether NOAC monotherapy superiority over warfarin continues in real-world patients with a history of atrial fibrillation (AF), coronary stenting, and underlying chronic kidney disease (CKD) >1 year after PCI (e.g., at 5 years) has not been established. Methods and Results: In the Rivaroxaban Estimation with Warfarin in Atrial Fibrillation Patients with Coronary Stent Implantation (REWRAPS) study (NCT02024230), a multicenter, prospective, non-randomized, open-label, physician-initiated efficacy and safety study in Japan, 493 patients received either rivaroxaban or warfarin. The primary efficacy endpoint was major adverse cardiac and cerebrovascular events (MACCE), consisting of cardiac and stroke death, non-fatal myocardial infarction, non-fatal stroke, systemic embolism, and coronary revascularization. The primary safety endpoint was major bleeding (Bleeding Academic Research Consortium 3 and 5). The primary composite endpoint was net adverse clinical events (NACE), defined as a combination of all-cause death and major bleeding. Conclusions: Completion of REWRAPS will provide, for the first time, evidence as to whether rivaroxaban is superior or non-inferior to warfarin with regard to the primary efficacy (MACCE), safety (major bleeding), or combined (all-cause death, major bleeding) endpoints in real-world patients with AF, coronary stenting, and underlying CKD an average of 5 years after PCI.

Ultrasound Stimulation Inhibits Morphological Degeneration of Motor Endplates in the Denervated Skeletal Muscle of Rats.

Recovery of motor function after peripheral nerve injury requires treatment of the neuromuscular junction (NMJ), as well as the injured nerve and skeletal muscle. The purpose of this study was to examine the effects of ultrasound (US) stimulation on NMJ degeneration after denervation using a rat model of peroneal nerve transection. Twelve-week-old male Wistar rats were randomly assigned to 3 groups: US stimulation, sham stimulation, and intact. US or sham stimulation was performed on the left tibialis anterior (TA) muscle starting the day after peroneal nerve transection for 5 minutes daily under anesthesia. Four weeks later, the number and morphology of the motor endplates were analyzed to assess NMJ in the TA muscle. The endplates were classified as normal, partially fragmented, or fully fragmented for morphometric analysis. In addition, the number of terminal Schwann cells (tSCs) per endplate and percentage of endplates with tSCs (tSC retention percentage) were calculated to evaluate the effect of tSCs on NMJs. Our results showed that endplates degenerated 4 weeks after transection, with a decrease in the normal type and an increase in the fully fragmented type in both the US and sham groups compared to the intact group. Furthermore, the US group showed significant suppression of the normal type decrease and a fully fragmented type increase compared to the sham group. These results suggest that US stimulation inhibits endplate degeneration in denervated TA muscles. In contrast, the number of endplates and tSC and tSC retention percentages were not significantly different between the US and sham groups. Further investigations are required to determine the molecular mechanisms by which US stimulation suppresses degeneration.

The Acute-Phase Ambulation Program Improves Clinical Outcome for Acute Heart Failure.

It remains unclear whether the acute-phase ambulation program (AAP) improves the prognosis of heart failure (HF) patients. We examined the association between the initiation of AAP and the prognosis of patients with worsening HF. We enrolled 560 consecutive patients admitted due to worsening HF from March 2019 to April 2021. Our hospital introduced AAP in May 2020, but we did not perform AAP until April 2020. We retrospectively compared cardiac events within 180 days after discharge between patients admitted before April 2020 (conventional group) and after May 2020 (AAP group). Primary endpoints were all-cause mortality and readmission for worsening HF. The Kaplan-Meier survival curves showed a significantly lower event rate in the AAP group in HF readmission or the primary endpoint (p = 0.020 and p = 0.014). The occurrence of the primary endpoint was associated with age, history of HF, systolic blood pressure, medications including renin-angiotensin system inhibitors or angiotensin receptor blocker, hemoglobin, NT-proBNP, and AAP participation. After adjusting for these parameters and sex, participation in AAP was an independent factor associated with a reduced risk of primary endpoint occurrence (hazard ratio of 0.62 (0.41-0.95), p = 0.028). The AAP for patients with acute HF might lead to improved short-term prognosis and should be considered for implementation.

Ultrasound Therapy of Injury Site Modulates Gene and Protein Expressions in the Dorsal Root Ganglion in a Sciatic Nerve Crush Injury Rat Model.

The aim of this study was to verify the effects of ultrasound on dorsal root ganglion (DRG) neurons at the injury site in a rat model of sciatic nerve crush injury. We evaluated the mRNA expression of neurotrophic and pro-inflammatory factors by quantitative reverse transcription polymerase chain reaction 7 and 14 d post-injury. We also evaluated the protein levels of brain-derived neurotrophic factor (BDNF) 7 and 14 d post-injury. Axon regeneration and motor function analyses were performed 21 days after injury to confirm the facilitative effect of ultrasound on nerve regeneration. In the ultrasound group, BDNF and interleukin-6 mRNA expression of the DRG was significantly reduced 7 d post-injury. Compared with the sham group, the BDNF protein expression of the DRG in the ultrasound group remained at a higher level 14 d post-injury. Motor function, myelinated fiber density and myelin sheath thickness were significantly higher in the ultrasound group than in the sham group 21 d post-injury. These results indicate that ultrasound therapy at the injury site promotes nerve regeneration and modulates gene and protein expression in the DRG of a rat model of a sciatic nerve crush injury.

An autopsy case report of fulminant myocarditis: Following mRNA COVID-19 vaccination.

There have been few case reports on fatal outcomes in patients with acute myocarditis after mRNA coronavirus disease 2019 (COVID-19) vaccination. In most cases of myocarditis after mRNA COVID-19 vaccination, the myocarditis is mild, and the prognosis is good. Here we report an autopsy case of fulminant myocarditis following mRNA COVID-19 vaccination. Learning objective: The global distribution of the mRNA coronavirus disease 2019 vaccine requires consideration of appropriate treatment for postvaccination myocarditis. Eosinophil-mediated immunological injury to cardiomyocytes can be involved in the cause of fulminant inflammation from the pathological findings of postvaccination myocarditis.

Cortical nicotinic enhancement of tone-evoked heightened activities and subcortical nicotinic enlargement of activated areas in mouse auditory cortex.

Systemic nicotine administration regulates neuronal activities in mouse auditory cortex. How nicotine regulates the spread of the activities across auditory cortical areas is not well known. We investigate this using flavoprotein fluorescence imaging. 20 kHz amplitude-modulated (AM) tones increased the peak intensity of flavoprotein fluorescence in presumptive primary auditory cortex (A1). 5 kHz AM tones activated at least three cortical areas, which are presumably A1, anterior auditory field, and secondary auditory cortex. Nicotine enlarged tone-activated cortical areas and enhanced both 20 kHz and 5 kHz tone-evoked fluorescence intensities at their respective, optimal frequency peak sites and at non-optimal frequency peak sites in A1. The extent of this enhancement was greater at non-optimal frequency sites than at optimal frequency sites. A cortical injection of dihydro-ß-erythroidine, an inhibitor of nicotinic acetylcholine receptors composed of α4 and ß2-subunits (α4ß2*-nAChRs), blocked the enhancement of fluorescence intensity at the peak sites but did not appear to block the enlargement of activated areas. These results suggest that nicotine exposure activates cortical α4ß2*-nAChRs to enhance tone-evoked local neuronal activities at an optimal frequency site. The nicotine-induced enlargement of a tone-activated area may depend on the nicotinic enhancement of cortical inputs or other activities.

[Coexistence of Lung Adenocarcinoma and Non-caseous Epithelioid Granuloma Possibly due to Systemic Sarcoidosis in the Same Lesion].

A lung cancer coexists with non-caseous epithelioid granulomas (NEG) in the same lesion is uncommon. A 62-year-old female was referred to our hospital for examination of a right lung S3 nodule which was recently increasing in its size. Positron emission tomography-computed tomography (PET-CT) examination revealed positive signals at the S3 nodule as well as mediastinal lymph nodes, apex of heart and right pleura. Pathological examination revealed the S3 nodule coexisting with both adenocarcinoma and NEG. The differential diagnosis between the systemic sarcoidosis and sarcoid reaction is usually important in such a case. Since the pleura and mediastinal lymph nodes contained many NEGs, the adenocarcinoma arising based on the systemic sarcoidosis was possibly suggested in the present case.