Calcium channel blockers may reduce the development of long COVID in females.

With the rising numbers of patients infected with severe acute respiratory syndrome coronavirus 2, long coronavirus disease 2019 (COVID-19)-a sequelae of COVID-19-has become a major problem. Different sexes and age groups develop different long COVID symptoms, and the risk factors for long COVID remain unclear. Therefore, we performed subgroup analyses of patients with COVID-19, classifying them into different groups. In this multicenter cohort study, using an original questionnaire, we examined patients (≥18 years old) diagnosed with COVID-19 from November 2020 to March 2022 and hospitalized at participating medical facilities. In total, 1066 patients were registered (361 female, 620 male). Hypertension was the most common comorbidity (n = 344; 32.5%). Females with hypertension were significantly less likely to develop long COVID symptoms than those without hypertension (odds ratio [OR] 0.51, 95% confidence interval [CI] 0.27-0.98; p = 0.043). In females, Ca channel blocker administration, rather than having hypertension, was significantly associated with reductions in the frequency of alopecia (OR 0.14, 95% CI 0.03-0.67, p = 0.015), memory impairment (OR 0.14, 95% CI 0.02-0.82, p = 0.029), sleeping disorders (OR 0.17, 95% CI 0.04-0.67, p = 0.012), tinnitus (OR 0.23, 95% CI 0.05-0.98, p = 0.047), sputum (OR 0.31, 95% CI 0.10-0.92, p = 0.035), and fever (OR 0.33, 95% CI 0.12-0.93, p = 0.036). Several long COVID symptoms, including alopecia, were significantly negatively associated with Ca channel-blocker administration in female patients with long COVID. Calcium channel blockers may reduce the development of long COVID in females.

Use of the neutrophil-to-lymphocyte ratio and an oxygen requirement to predict disease severity in patients with COVID-19.

We investigated the association between complete blood count, including neutrophil-to-lymphocyte ratio (NLR) in combination with patient characteristics, and coronavirus disease (COVID-19) outcomes to identify the best prognostic indicator. We analyzed data of patients with confirmed COVID-19 from the nationwide database of the Japan COVID-19 Task Force between February 2020 and November 2021. A composite outcome was defined as the most severe condition, including noninvasive positive-pressure ventilation, high-flow nasal cannula, invasive mechanical ventilation, extracorporeal membrane oxygenation, or death. Of 2425 patients in the analysis, 472 (19.5%) experienced a composite outcome. NLR was the best predictor of composite outcomes, with an area under the curve (AUC) of 0.81, and a sensitivity and specificity of 72.3% and 75.7%, respectively, using a cut-off value of 5.04. The combination of NLR and an oxygen requirement on admission had the highest AUC (0.88). This simple combination may help identify patients at risk of progression to severe disease.

Apixaban-Associated Diffuse Alveolar Hemorrhage in an Elderly Man with Multiple Complications.

BACKGROUND Diffuse alveolar hemorrhage (DAH) caused by direct oral anticoagulants (DOACs) has increased in recent years with the increase in prescriptions of DOACs. Generally, DOACs are considered to have a lower bleeding risk than the traditional anticoagulant, warfarin. However, major bleeding, including DAH, due to DOACs can be seen in clinical practice, and there are few reports to elucidate when DOAC-associated alveolar hemorrhage occurs and whether DOAC-induced DAH has a trigger. CASE REPORT An 80-year-old man diagnosed and treated for atrial fibrillation with apixaban 2.5 mg twice daily for 1 year before admission, underwent 2 invasive medical procedures over a short period of time. Hemoptysis began after the procedures. He experienced shortness of breath and rapidly progressive hypoxic respiratory failure. His postsurgical oxygen saturation level dropped rapidly. Chest radiography and computed tomography images showed pulmonary infiltration and ground-glass opacity in both lungs. Apixaban treatment was discontinued, and mechanical ventilation was initiated. Bronchoalveolar lavage cytology revealed hemosiderin-laden macrophages. A diagnosis of diffuse alveolar hemorrhage (DAH) was made. In previous reports about DAH caused by DOACs, most patients had bleeding triggers; drug interactions in patients taking DOACs are one of such triggers. Although DOACs are relatively safe for elderly patients, DAH can occur in patients receiving either early-stage or long-term treatment. CONCLUSIONS The onset of DOAC-associated DAH is not limited to the early stages of medication initiation. Various triggers can induce DAH in patients receiving DOACs.

Analysis of adverse drug events in pulmonary Mycobacterium avium complex disease using spontaneous reporting system.

BACKGROUND: In Japan, Mycobacterium avium complex lung disease (MAC-LD) is the most common in nontuberculous mycobacterial lung disease. Patients often experience adverse events, resulting in the discontinuation of treatment, which causes treatment failure. The JADER (Japanese Adverse Drug Event Report) database is a database of adverse events that allows us to collect real-world data on adverse events. We can collect large-scale data cost-effectively and detect signals of potential adverse events such as reporting odds ratio (ROR) by using spontaneous reporting systems. In this study, we aimed to elucidate the adverse events of clarithromycin (CAM), ethambutol (EB), and rifampicin (RFP) using the JADER database. METHODS: We included cases of MAC-LD between April 2004 and June 2017. We investigated sex, age, and medications that may have caused the adverse events, outcomes, and time of onset. We calculated the safety signal index as the ROR. Time-to-event analysis was performed using the Weibull distribution. RESULTS: The total number of adverse events of CAM, EB, and RFP was 2780, with 806 patients. In the overall adverse events, hematologic and lymphatic disorders were the most common adverse events, with 17.3%, followed by eye disorders (16.6%), and hepatobiliary disorders (14.0%). The outcomes were as follows: recovery, 40.0%; remission, 27.1%; non-recovery, 11.2%; and death, 7.1%. Regarding the most common onset time of CAM, EB, and RFP was within 120 days at 40%, 181-300 days at 43.6%, and within 120 days at 88.5%. For CAM, the RORs of infections and infestations, hepatobiliary system disorders, and immune system disorders were 4.13 (95% confidence interval [CI], 2.3-7.44), 2.61 (95% CI, 1.39-4.91), and 2.38 (95% CI, 1.04-5.44). For EB, the ROR of eye disorders was 215.79 (95% CI, 132.62-351.12). For RFP, the RORs of renal and urinary tract disorders and investigations were 7.03 (95% CI, 3.35-14.77) and 6.99 (95% CI, 3.22-15.18). The ß value of EB was 2.07 (95% CI, 1.48-2.76), which was classified as a wear-out failure type. CONCLUSIONS: For MAC-LD, the adverse event which has the highest ROR is infections and infestations in CAM, eye disorders in EB, renal and urinary tract disorders in RFP. Adverse events of EB occur after 180 days, whereas the adverse events of CAM and RFP occur early in the course of treatment.

Transcatheter coil embolization for large pulmonary arteriovenous fistulae through an artificial tricuspid ball valve.

Pulmonary arteriovenous fistulae (PAFs) occur congenitally or are acquired. A PAF can cause hypoxemia, sudden death from rupture, abscess formation, and embolism. Treatment for PAF is transcatheter embolization or surgery. Transcatheter embolization is the first choice of treatment; however, this treatment is impossible to perform if a patient has had tricuspid or pulmonary valve replacement. In this paper, we describe a case of PAFs complicated with tricuspid valve replacement with a ball valve (which had been performed 40 years earlier) that was treated with transcatheter embolization. .

Effect of low back pain on the muscles controlling the sitting posture.

[Purpose] The purpose of the current study was to reveal the association between posture control and muscle activity by measuring the trunk and hip joint muscle activities in the upright and slump sitting positions in both the healthy participants and patients with recurrent lower back pain. [Participants and Methods] We recruited eleven patients of recurrent lower back pain and ten healthy participants. During the maintenance of the two types of posture, upright and slump, we collected the surface electromyography data. We assessed the following muscles: rectus abdominis, external oblique, thoracic erector spinae, lumbar erector spinae, internal oblique, lumbar multifidus, iliacus, serratus anterior, rectus femoris, tensor fascia latae, and gluteus maximus. We studied the differences in spinal-pelvic curvature and muscle activity between the upright and slump positions in each group. [Results] In the healthy group, comparison of the muscle activity in upright and slump positions for both the trunk (external oblique, internal oblique, lumbar erector spinae, and lumbar multifidus), and the hip muscles (iliacus and gluteus maximus) showed a significant decrease in activity in the slump position. In the group with recurrent lower back pain, although the external oblique, lumbar erector spinae and lumbar multifidus showed reduced activity in slump position, these values were smaller when compared to those in the healthy group. [Conclusion] This study aimed to clarify the relationship between posture (upright and slump) and the activity of the trunk and hip joint muscles in the healthy participants and the patients with recurrent lower back pain. The results indicated that postural changes caused by recurrent lower back pain significantly affected the activity of the muscles involved in controlling the posture.

Cardiac mitofusin-1 is reduced in non-responding patients with idiopathic dilated cardiomyopathy.

Prognosis of severe heart failure remains poor. Urgent new therapies are required. Some heart failure patients do not respond to established multidisciplinary treatment and are classified as "non-responders". The outcome is especially poor for non-responders, and underlying mechanisms are largely unknown. Mitofusin-1 (Mfn1), a mitochondrial fusion protein, is significantly reduced in non-responding patients. This study aimed to elucidate the role of Mfn1 in the failing heart. Twenty-two idiopathic dilated cardiomyopathy (IDCM) patients who underwent endomyocardial biopsy of intraventricular septum were included. Of the 22 patients, 8 were non-responders (left ventricular (LV) ejection fraction (LVEF) of < 10% improvement at late phase follow-up). Electron microscopy (EM), quantitative PCR, and immunofluorescence studies were performed to explore the biological processes and molecules involved in failure to respond. Studies in cardiac specific Mfn1 knockout mice (c-Mfn1 KO), and in vitro studies with neonatal rat ventricular myocytes (NRVMs) were also conducted. A significant reduction in mitochondrial size in cardiomyocytes, and Mfn1, was observed in non-responders. A LV pressure overload with thoracic aortic constriction (TAC) c-Mfn1 KO mouse model was generated. Systolic function was reduced in c-Mfn1 KO mice, while mitochondria alteration in TAC c-Mfn1 KO mice increased. In vitro studies in NRVMs indicated negative regulation of Mfn1 by the ß-AR/cAMP/PKA/miR-140-5p pathway resulting in significant reduction in mitochondrial respiration of NRVMs. The level of miR140-5p was increased in cardiac tissues of non-responders. Mfn1 is a biomarker of heart failure in non-responders. Therapies targeting mitochondrial dynamics and homeostasis are next generation therapy for non-responding heart failure patients.

Stent malapposition occurred 17 days following percutaneous coronary intervention for a severe calcified lesion in acute myocardial infarction.

The occurrence of stent malapposition and coronary artery aneurysm (CAA) during the early phase of drug-eluting stent (DES) implantation is rare. This report presents the case of a 55-year-old man who underwent DES implantation to the left circumflex artery with full-arc severe calcified lesion owing to inferior acute myocardial infarction. Coronary angiography and optical coherence tomography (OCT) at 17 days following percutaneous coronary intervention (PCI) revealed stent malapposition and CAA of diameter 6.5 mm in the distal part of the stented vessel. OCT findings at 5 months following PCI revealed a dilated CAA of diameter 7.5 mm and a luminal structure outside the stent. Based on these findings, it was suggested that the cause of CAA in the early phase following DES implantation to the severe calcified lesion was related to coronary sequelae of Kawasaki disease. .

Dynamic left ventricular outflow tract obstruction complicated with takotsubo cardiomyopathy: The acute phase of takotsubo cardiomyopathy manifests latent left ventricular outflow tract obstruction.

Dynamic left ventricular (LV) outflow tract (LVOT) obstruction is sometimes complicated with takotsubo cardiomyopathy (TC). The present case involves a 70-year-old woman with chest discomfort. Seven years earlier, transthoracic echocardiography revealed LVOT obstruction due to a sigmoid-shaped septum. She underwent urgent cardiac catheterization for suspected acute coronary syndrome. She was diagnosed as having TC with LVOT obstruction. After undergoing conservative treatment, her LV function normalized and the LVOT obstruction resolved. After the LV wall motion normalized, administering an intravenous infusion of dobutamine again provoked LVOT obstruction. In this situation, the presence of TC manifested latent LVOT obstruction. .

Clinical Predictors of Recurrent Ventricular Arrhythmias in Secondary Prevention Implantable Cardioverter Defibrillator Recipients With Coronary Artery Disease　- Lower Left Ventricular Ejection Fraction and Incomplete Revascularization.

BACKGROUND: The implantable cardioverter defibrillator (ICD) is a standard prevention therapy for patients at high risk for sudden cardiac death (SCD) due to life-threatening ventricular arrhythmia (VA), that is, ventricular fibrillation and ventricular tachycardia. However, clinical predictors of recurrent VA in secondary prevention ICD recipients with coronary artery disease (CAD) remain unknown. Methods and Results: We followed up 96 consecutive patients with CAD undergoing ICD implantation for secondary prevention of SCD. Long-term rates and clinical predictors of appropriate ICD therapy (ICD-Tx) for VA were analyzed. Appropriate ICD-Tx occurred in 41 (42.7%) patients during a median follow-up of 2.4 years (interquartile range, 0.9-6.1). These patients had significantly greater left ventricular end-diastolic diameter (62.3±1.3 vs. 54.6±1.1 mm, P<0.001), lower left ventricular ejection fraction (LVEF; 36.3±2.0% vs. 45.7±1.8%, P<0.001), and more incomplete revascularization (ICR; 70.7% vs. 45.5%, P=0.014) than those without appropriate ICD-Tx. Multivariable analysis showed that LVEF (hazards ratio [HR], 0.950; 95% CI: 0.925-0.975; P<0.001) and ICR (HR, 2.293; 95% CI: 1.133-4.637; P=0.021) were significant predictors of appropriate ICD-Tx for VA. CONCLUSIONS: Lower LVEF and ICR were independent predictors of recurrent VA in secondary prevention ICD recipients with CAD.

Efficacy of Corticosteroid Treatment for Refractory Multivessel Vasospastic Coronary Angina with Hypereosinophilia.

A 43-year-old man was diagnosed with acute myocardial infarction (AMI) due to multivessel coronary vasospasm. Accordingly, two coronary vasodilators were administered, and he was discharged without an angina attack. However, from the following day, he reported frequent chest pain and was re-hospitalized. Despite adding multiple coronary vasodilators, it was difficult to completely suppress the angina attack. He also demonstrated hypereosinophilia from the onset of AMI, and his eosinophil count gradually increased up to 6,238/µL. After corticosteroid administration was started, the vasospasm was completely controlled, and his eosinophil count normalized. He remained free from angina attacks for two years with corticosteroid therapy.

Low-Dose Erythropoietin in Patients With ST-Segment Elevation Myocardial Infarction (EPO-AMI-II)　- A Randomized Controlled Clinical Trial.

BACKGROUND: Erythropoietin (EPO) has antiapoptotic and tissue-protective effects, but previous clinical studies using high-dose EPO have not shown cardioprotective effects, probably because of platelet activation and a lack of knowledge regarding the optimal dose. In contrast, a small pilot study using low-dose EPO has shown improvement in left ventricular function without adverse cardiovascular events.Methods and Results:We performed a multicenter (25 hospitals), prospective, randomized, double-blind, placebo-controlled, dose-finding study to clarify the efficacy and safety of low-dose EPO in patients with ST-segment elevation myocardial infarction (STEMI) under the Evaluation System of Investigational Medical Care of the Ministry of Health, Labor and Welfare of Japan. In total, 198 STEMI patients with low left ventricular ejection fraction (LVEF <50%) were randomly assigned to receive intravenous administration of EPO (6,000 or 12,000 IU) or placebo within 6 h of successful percutaneous coronary intervention. At 6 months, there was no significant dose-response relationship in LVEF improvement among the 3 groups tested (EPO 12,000 IU: 5.4±9.3%, EPO 6,000 IU: 7.3±7.7%, Placebo: 8.1±8.3%, P=0.862). Low-dose EPO also did not improve cardiac function, as evaluated by 99 mTc-MIBI SPECT or NT-proBNP at 6 months and did not increase adverse events. CONCLUSIONS: Administration of low-dose EPO did not improve LVEF at 6 months in STEMI patients (UMIN000005721).

Percutaneous Coronary Intervention for a Patient with Left Main Coronary Compression Syndrome.

Left main coronary compression syndrome rarely occurs in patients with severe pulmonary hypertension. A 65-year-old woman with severe pulmonary hypertension due to an atrial septal defect suffered from angina on effort. Cardiac computed-tomography and coronary angiography revealed considerable stenosis of the left main coronary artery (LMA) caused by compression between the dilated main pulmonary artery trunk and the sinus of valsalva. Stenting of the LMA under intravascular ultrasound imaging was effective for the treatment of angina. We herein report the diagnosis and management of this condition with a brief literature review.

Aortic Regurgitation Presenting with Recurrent Detachment of a Prosthetic Valve, as the First Presenting Symptom of Cardiovascular Behçet's Disease.

A 33-year-old man with severe aortic regurgitation underwent initial aortic valve replacement (AVR). During the 2 years after AVR, 3 reoperations for prosthetic valve detachment were required. During hospitalization, he had no typical clinical findings, with the exception of a persistent inflammatory reaction; a pseudo-aneurysm around the Bentall graft developed 27 days after the 4th operation. This unique clinical course suggested the possibility of Behçet's disease. In the 8 years of follow-up after the administration of prednisolone, the pseudo-aneurysm did not become enlarged and the detachment of the prosthetic valve was not observed. We herein present a case of cardiovascular Behçet's disease, with a review of the literature.

Dual Antiplatelet Therapy Guided by CYP2C19 Polymorphisms after Implantation of Second-Generation Drug-Eluting Stents for Management of Acute Coronary Syndrome.

Prasugrel, a novel P2Y12 receptor inhibitor, is administered to patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI), but it can increase the risk of bleeding. The Japanese exhibit weaker responses to clopidogrel than other races because of CYP2C19 polymorphisms; thus, it is unclear whether these patients should continue dual antiplatelet therapy (DAPT) using prasugrel or switch to clopidogrel in the chronic phase. Here we evaluated the clinical outcomes of DAPT guided by CYP2C19 polymorphisms after implantation of second-generation drug-eluting stents (DESs) for ACS management. Patients with ACS receiving PCI via DES from November 2011 to March 2015 were divided into two groups: conventional DAPT with clopidogrel (n = 41) and gene-guided DAPT (n = 24). In the gene-guided DAPT group, all patients with ACS were given DAPT using prasugrel as soon as possible; extensive and intermediate metabolizers receiving PCI for the first time were switched to clopidogrel at least 2 weeks after discharge, and intermediate metabolizers with repeated ACS and poor metabolizers continued on DAPT using prasugrel. Notably, gene-guided DAPT significantly reduced major adverse cardiovascular/cerebrovascular events (MACCEs; 22.0% versus 4.2%, hazard ratio [HR]: 0.15, 95% confidence interval [CI]: 0.01-0.81; P = 0.0247). Hemorrhagic complications were observed in 3.1% of patients receiving conventional DAPT and absent in the gene-guided group. Moreover, multivariate analysis showed that gene-guided DAPT significantly decreased MACCE incidence (HR: 0.15, 95% CI: 0.01-0.81; P = 0.033). Collectively, these data suggest that CYP2C19 polymorphism analysis may improve treatment decisions in patients with ACS receiving DES-PCI.

Transient increase in systemic interferences in the superficial layer and its influence on event-related motor tasks: a functional near-infrared spectroscopy study.

Functional near-infrared spectroscopy (fNIRS) is a widely utilized neuroimaging tool in fundamental neuroscience research and clinical investigation. Previous research has revealed that task-evoked systemic artifacts mainly originating from the superficial-tissue may preclude the identification of cerebral activation during a given task. We examined the influence of such artifacts on event-related brain activity during a brisk squeezing movement. We estimated task-evoked superficial-tissue hemodynamics from short source­detector distance channels (15 mm) by applying principal component analysis. The estimated superficial-tissue hemodynamics exhibited temporal profiles similar to the canonical cerebral hemodynamic model. Importantly, this task-evoked profile was also observed in data from a block design motor experiment, suggesting a transient increase in superficial-tissue hemodynamics occurs following motor behavior, irrespective of task design. We also confirmed that estimation of event-related cerebral hemodynamics was improved by a simple superficial-tissue hemodynamic artifact removal process using 15-mm short distance channels, compared to the results when no artifact removal was applied. Thus, our results elucidate task design-independent characteristics of superficial-tissue hemodynamics and highlight the need for the application of superficial-tissue hemodynamic artifact removal methods when analyzing fNIRS data obtained during event-related motor tasks.

Case studies in poststroke hemiplegic patients using SEMUL: a passive 2-DOF rehabilitation robot.

Following stroke, rehabilitation exercises paired with medical treatment are important for the recovery and maintenance of upper limb function. We developed a 2-DOF passive haptic system for upper limb rehabilitation and software focusing on reaching exercises, known as the coin collecting program, which provides training and evaluation of motor function, particularly dexterity. Past studies have revealed quantitative, reproducible evaluation indices using this software. In this paper, we compared case studies of post-stroke patients with results from healthy participants, and confirmed the reliability of the evaluation indices in grading or scoring motor skills.