Pulmonary Nocardiosis With Endobronchial Involvement Caused by Nocardiaaraoensis.

We report a rare case of pulmonary nocardiosis with endobronchial involvement caused by Nocardia araoensis. A 79-year-old man with a history of asthma and a previous right upper lobectomy for lung cancer and organizing pneumonia presented with cough and dyspnea. He presented with right bronchial stenosis associated with various mucosal lesions, including ulcerative and exophytic lesions. N araoensis was detected in sputum samples collected via bronchoscopy. The mucosal lesions improved after a 2-week course of meropenem. After a further 6 months of oral sulfamethoxazole-trimethoprim treatment, the mucosal lesions completely disappeared. Based on bronchoscopic and pathophysiologic findings, the patient was diagnosed with pulmonary nocardiosis with endobronchial involvement. Nocardiosis should be considered in the differential diagnosis of endobronchial mucosal lesions.

HAS-Flow May Be an Adequate Method for Evaluating Human T-Cell Leukemia Virus Type 1 Infected Cells in Human T-Cell Leukemia Virus Type 1-Positive Rheumatoid Arthritis Patients Receiving Antirheumatic Therapies: A Retrospective Cross-Sectional Observation Study.

The study aims to assess the usefulness of human T-cell leukemia virus type 1 (HTLV-1)-infected cell analysis using flow cytometry (HAS-Flow) as a monitoring method for adult T-cell leukemia (ATL) development in HTLV-1-positive patients with rheumatoid arthritis (RA) under treatment with antirheumatic therapies. A total of 13 HTLV-1-negative and 57 HTLV-1-positive RA patients participated in this study, which was used to collect clinical and laboratory data, including HAS-Flow and HTLV-1 proviral load (PVL), which were then compared between the two groups. CADM1 expression on CD4+ cells in peripheral blood (PB) was used to identify HTLV-1-infected cells. The population of CADM1+ CD4+ cells was significantly higher in HTLV-1-positive RA patients compared to HTLV-1-negative RA patients. The population of CADM1+ CD4+ cells was correlated with HTLV-1 PVL values. There were no antirheumatic therapies affecting both the expression of CADM1 on CD4+ cells and PVLs. Six HTLV-1-positive RA patients who indicated both high HTLV-1 PVL and a predominant pattern of CADM1+ CD7neg CD4+ cells in HAS-Flow can be classified as high-risk for ATL progression. HAS-Flow could be a useful method for monitoring high-risk HTLV-1-positive RA patients who are at risk of developing ATL during antirheumatic therapies.

Association of Clostridium butyricum Therapy Using the Live Bacterial Product CBM588 with the Survival of Patients with Lung Cancer Receiving Chemoimmunotherapy Combinations.

The gut microbiota has emerged as a key regulator of immune checkpoint inhibitor (ICI) efficacy. Therapeutic approaches aimed at manipulating the microbiota through targeted reconstitution to enhance cancer treatment outcomes have garnered considerable attention. A single live microbial biotherapeutic bacterium, Clostridium butyricum MIYAIRI 588 strain (CBM588), has been shown to enhance the effects of ICI monotherapy in patients with advanced lung cancer. However, whether CBM588 affects the outcomes of chemoimmunotherapy combinations in lung cancer remains unknown. We hypothesized that CBM588 augments the effect of chemoimmunotherapy combinations and restores diminished effectiveness in patients with non-small cell lung cancer (NSCLC) receiving dysbiosis-inducing drugs. To validate this hypothesis, we retrospectively analyzed 106 patients with stage IV or recurrent metastatic NSCLC consecutively treated with chemoimmunotherapy combinations. A survival analysis was performed employing univariate and multivariate Cox proportional hazard models with inverse probability of treatment weighting (IPTW) using propensity scores. Forty-five percent of patients received Clostridium butyricum therapy. CBM588 significantly extended overall survival in patients with NSCLC receiving chemoimmunotherapy. The favorable impact of CBM588 on the efficacy of chemoimmunotherapy combinations varied based on tumor-programmed cell death ligand 1 (PD-L1) expression. The survival benefit of CBM588 in the PD-L1 <1% cohort was higher than that in the PD-L1 1-49% and PD-L1 ≥ 50% cohorts. Furthermore, CBM588 was associated with improved overall survival in patients receiving proton pump inhibitors and/or antibiotics. CBM588-induced manipulation of the commensal microbiota holds the potential to enhance the efficacy of chemoimmunotherapy combinations, warranting further exploration of the synergy between CBM588 and immunotherapy.

Clinical Implications and Molecular Characterization of Drebrin-Positive, Tumor-Infiltrating Exhausted T Cells in Lung Cancer.

T cells express an actin-binding protein, drebrin, which is recruited to the contact site between the T cells and antigen-presenting cells during the formation of immunological synapses. However, little is known about the clinical implications of drebrin-expressing, tumor-infiltrating lymphocytes (TILs). To address this issue, we evaluated 34 surgical specimens of pathological stage I-IIIA squamous cell lung cancer. The immune context of primary tumors was investigated using fluorescent multiplex immunohistochemistry. The high-speed scanning of whole-slide images was performed, and the tissue localization of TILs in the tumor cell nest and surrounding stroma was automatically profiled and quantified. Drebrin-expressing T cells were characterized using drebrin+ T cells induced in vitro and publicly available single-cell RNA sequence (scRNA-seq) database. Survival analysis using the propensity scores revealed that a high infiltration of drebrin+ TILs within the tumor cell nest was independently associated with short relapse-free survival and overall survival. Drebrin+ T cells induced in vitro co-expressed multiple exhaustion-associated molecules. The scRNA-seq analyses confirmed that the exhausted tumor-infiltrating CD8+ T cells specifically expressed drebrin. Our study suggests that drebrin-expressing T cells present an exhausted phenotype and that tumor-infiltrating drebrin+ T cells affect clinical outcomes in patients with resectable squamous cell lung cancer.

Readiness of Advance Care Planning Among Patients With Cardiovascular Disease.

Background: Advance care planning (ACP) is a widely advocated strategy to improve outcomes at end-of-life care for patients suffering from heart failure (HF). However, finding the right time to start ACP is challenging for healthcare providers because it is often a sensitive issue for patients with HF and their families. We interviewed patients with cardiovascular diseases regarding ACP readiness and investigated the relationship between the ACP desire and multiple clinical prognostic parameters. Method: Eighty-one patients (average age 81.8 ± 10.3 years old, 42 men, 62 cases of HF) who introduced cardiac rehabilitation were inquired about previous ACP experience, a desire for ACP, understanding of their cardiovascular diseases, and lifestyle-associated questionnaires. Multiple logistic regression analyses were employed to identify the clinical parameters associated with ACP desire. Patients who desired ACP were also asked about their preferences for medical care at the end-of-life. Results: Nine patients (11.1%) had previous experience with ACP, and 28 (34.6%) preferred to implement ACP. Patients who did not want to implement ACP were 54.3%. Patients with HF showed a higher acceptance rate of ACP (odds ratio [OR] 5.56, p = 0.015). Interestingly, patients harboring skeletal muscle frailty showed lower ACP acceptance, while patients with non-frailty rather positively wanted to implement ACP. Two types of prognosis evaluation scales, such as the Enhanced Feedback for Effective Cardiac Treatment (EFFECT) risk score and the Japanese Version of Supportive and Palliative Care Indicators Tool (SPICT-JP), identified 31 patients (38.3%) needing ACP; however, 19 (61.3%) did not want ACP. The wish not to attempt resuscitation and life-prolonging treatment at the end-of-life reached approximately 70% among patients who requested ACP. Conclusions: Although patients with HF tended to be ready for implementing ACP, the presence of skeletal muscle frailty was negatively associated with ACP preference. Indeed, patients who should be considered ACP were not carried out and did not desire it. Earlier introduction of ACP into patients before having skeletal muscle frailty may be considered.

Heterogeneous Tumor-Immune Microenvironments between Primary and Metastatic Tumors in a Patient with ALK Rearrangement-Positive Large Cell Neuroendocrine Carcinoma.

Evolution of tumor-immune microenviroments (TIMEs) occurs during tumor growth and dissemination. Understanding inter-site tumor-immune heterogeneity is essential to harness the immune system for cancer therapy. While the development of immunotherapy against lung cancer with driver mutations and neuroendocrine tumors is ongoing, little is known about the TIME of large cell neuroendocrine carcinoma (LCNEC) or anaplastic lymphoma kinase (ALK) rearrangement-positive lung cancer. We present a case study of a 32-year-old female patient with ALK-rearrangement-positive LCNEC, who had multiple distant metastases including mediastinal lymph-node, bilateral breasts, multiple bones, liver and brain. Multiple biopsy samples obtained from primary lung and three metastatic tumors were analyzed by fluorescent multiplex immunohistochemistry. Tissue localizations of tumor-infiltrating lymphocytes in the tumor nest and surrounding stroma were evaluated. T cell and B cell infiltrations were decreased with distance from primary lung lesion. Although each tumor displayed a unique TIME, all tumors exhibited concomitant regression after treatment with an ALK-inhibitor. This study provides the first evidence of the coexistence of distinct TIME within a single individual with ALK-rearrangement-positive LCNEC. The present study contributes to our understanding of heterogeneous TIMEs between primary and metastatic lesions and provides new insights into the complex interplay between host-immunity and cancer cells in primary and metastatic lesions.

Successful treatment by pembrolizumab in a patient with end-stage renal disease with advanced non-small cell lung cancer and high PD-L1 expression.

We report a 66-year-old Japanese male with end-stage renal disease (ESRD) and advanced non-small cell lung cancer (NSCLC) who was on hemodialysis. The patient harbored high programmed death ligand 1 (PD-L1) expression and was successfully treated with pembrolizumab. Laboratory examination upon diagnosis showed elevated serum creatinine (6.58 mg/dL). We administered pembrolizumab (200 mg/body) and repeated every 3 weeks. His renal dysfunction gradually progressed, hemodialysis was initiated after eight courses of pembrolizumab, and the antitumor effect was maintained at five months after hemodialysis initiation. Therefore, pembrolizumab can be administered for patients with ESRD and advanced NSCLC, who harbor high PD-L1 expression, during preparation for hemodialysis.

Reversible Restrictive Lung Disease in Pseudomesotheliomatous Carcinoma in a Lung Harboring a HER2-mutation.

Pseudomesotheliomatous carcinoma of the lung is very rare, and reversible restrictive lung disease with pseudomesotheliomatous carcinoma has not yet been previously reported. We herein report a patient with HER2-positive non-small-cell lung cancer (NSCLC) showing pseudomesotheliomatous carcinoma who was successfully treated with bevacizumab combination chemotherapy. A 56-year-old Japanese woman with advanced NSCLC presented with dyspnea. We administered chemotherapy with cisplatin (75 mg/m2) plus pemetrexed (500 mg/m2) plus bevacizumab (15 mg/kg), followed by pemetrexed plus bevacizumab. After eight cycles of maintenance chemotherapy, chest CT demonstrated a marked tumor reduction and an improvement of the right lung volume. The vital capacity was thereafter found to have significantly increased according to pulmonary function tests.

Severe interstitial pneumonia associated with anti-PD-1 immune checkpoint antibody after talc slurry pleurodesis.

A 70-year-old Japanese man with recurrent squamous cell carcinoma of the head and neck presented with severe interstitial pneumonia associated with nivolumab, after talc slurry pleurodesis. Following the development of malignant pleural effusion, he underwent chest drainage and was administered intrathoracic talc as a pleurodesis. Two weeks later, we administered nivolumab (3mg/kg) to be repeated every 2 weeks. However, on day 12, chest computed tomography scan demonstrated diffuse non-segmental ground-glass opacity and mild bronchiectasis. We diagnosed interstitial pneumonia associated with nivolumab. Although corticosteroid pulse therapy was initiated, the patient died of respiratory failure on day 14.

Impact of milrinone on mitral annular velocity in patients with congestive heart failure.

PURPOSE: The purpose of this study is to assess the impact of milrinone on mitral annular velocity in patients with congestive heart failure. METHOD: We studied 27 patients with congestive heart failure. All patients underwent transthoracic echocardiography both before and after administration of milrinone. We measured the early transmitral velocity (E) and the mitral annular early diastolic velocity (Ea). The ratio of E to Ea (E/Ea) was calculated. After the baseline echocardiography, milrinone was administered as a continuous infusion at a rate of 0.25 µg/kg/min. Echocardiographic measurements were repeated 4 h after milrinone was begun. RESULTS: After administration of milrinone, Ea was significantly increased, while E/Ea was significantly decreased. The population of 27 patients was divided into 20 (74 %) with left ventricular ejection fraction (LVEF) <50 % and seven (26 %) with LVEF ≥50 %. Ea was significantly increased in both groups, while E/Ea was significantly decreased. CONCLUSION: Even low-dose milrinone produced an improvement in left ventricular (LV) diastolic function, as evidenced by an increase in Ea, and falls in LV filling pressures, as determined by a decrease in E/Ea, in patients with congestive heart failure throughout a wide range of LV systolic function.

Add-on therapy of EPA reduces oxidative stress and inhibits the progression of aortic stiffness in patients with coronary artery disease and statin therapy: a randomized controlled study.

AIM: We examined the anti-oxidant mechanisms of combined therapy of eicosapentaenoic acid (EPA) plus statin on the progression of atherosclerosis. METHODS: Patients receiving statin therapy for dyslipidemia and with coronary artery disease (CAD) were assigned randomly in an open-label manner to the EPA (1,800 mg/day) -plus-statin group (n= 25; combined-therapy group) or to the statin-only group (n= 25), and followed for 48 weeks. At baseline and 48 weeks after enrollment, oxidative stress, brachial-ankle pulse wave velocity (baPWV) and stiffness parameter ß-index of the carotid were measured. RESULTS: The lipid profile remained unchanged throughout the study. Although the median value of baPWV increased more in the statin-only group than in the combined-therapy group, this difference was not significant (p= 0.29); however, a decrease in baPWV was associated with combined-therapy treatment by multiple regression analysis adjusted for age and mean blood pressure (p= 0.04). In addition, the ß-index of the carotid was lower in the combined-therapy group than in the statin-only group (p= 0.02). Furthermore, although the difference in the reduction of the urinary concentration of 8-isoprostane between the two groups did not reach statistical significance, this concentration was significantly lower in the combined-therapy group with higher baseline levels (≥ 183 pg/mL · Cr) of urinary 8-isoprostane (p= 0.004). CONCLUSIONS: EPA may reduce oxidative stress and inhibit the progression of arterial stiffness more efficiently than statin-only therapy in patients with dyslipidemia and CAD.

Effects of mineralocorticoid receptor antagonist spironolactone on atrial conduction and remodeling in patients with heart failure.

BACKGROUND: Spironolactone was shown to reduce mortality in patients with heart failure (HF). However, the effect of spironolactone on the incidence of atrial fibrillation remains unknown. Therefore, we examined the effects of spironolactone on atrial conduction and remodeling in patients with HF. METHODS AND RESULTS: A total of 21 patients with HF were divided into either spironolactone group (n=11) or control group (n=10). The patients were followed up for 12 months. Blood examination, echocardiogram, and signal-averaged electrocardiogram were performed at study enrollment and after 3 and 12 months of treatment. In the spironolactone group, atrial natriuretic peptide tended to reduce, left atrium dimension was significantly smaller, the ratio of E wave to A wave tended to improve, and P-duration was significantly shortened. CONCLUSIONS: Spironolactone improves atrial conduction and remodeling in patients with HF.

Defibrillation efficacy of a subcutaneous array lead: A case report.

We report a case of Brugada syndrome with a high defibrillation threshold (DFT) in whom a subcutaneous array lead was used to lower the DFT in combination with a transvenous right ventricular defibrillation lead. The patient had previously received pacemaker implantation due to sick sinus syndrome. An implantable cardioverter defibrillator (ICD) with a transvenous right ventricular defibrillation lead alone required a high DFT. A subcutaneous array lead improved defibrillation efficacy in combination with a right ventricular lead. These data suggest that a subcutaneous array lead facilitates implantation of an effective ICD lead system in patients requiring a high DFT.

Cardio-ankle vascular index is superior to brachial-ankle pulse wave velocity as an index of arterial stiffness.

Both cardio-ankle vascular index (CAVI) and brachial-ankle pulse wave velocity (baPWV) are noninvasive methods to estimate arterial stiffness. The purpose of this study is to determine whether CAVI or baPWV is superior as an index of arterial stiffness. One hundred and thirty patients with chest pain syndrome who underwent coronary angiography (CAG) were included in this study. We obtained intima-media-thickness (IMT) and the stiffness parameter beta of the carotid artery by carotid ultrasounds (CU). The peak early diastolic velocity (E), deceleration time of E (EDCT), peak atrial systolic velocity (A) of transmitral flow and left ventricular mass index (LVMI) were obtained by echocardiography. CAVI, baPWV, total cholesterol (T-C), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and triglycerides (TG) were measured before CAG. There was a significant correlation between CAVI and baPWV (r = 0.64, p < 0.01). Both CAVI and baPWV were significantly correlated with age, IMT and beta (age: r = 0.64, p < 0.01 for CAVI, and r = 0.48, p < 0.01 for baPWV; IMT: r = 0.40, p < 0.01, and r = 0.31, p < 0.01; beta: r = 0.36, p < 0.01 and r = 0.25, p < 0.01). However, only CAVI was correlated with the parameters of left ventricular diastolic indices from echocardiography (E/A: r = 0.44, p < 0.01; EDCT: r = 0.36, p < 0.01). Additionally, LDL-C and T-C/HDL-C were also associated with only CAVI (LDL-C: r = 0.26, p < 0.02; T-C/HDL-C: r = 0.30, p < 0.01), not baPWV. Finally, only CAVI was significantly higher in the group with angina pectoris than in the normal group (9.708 +/- 1.423 vs. 9.102 +/- 1.412; p = 0.0178). All parameters associated with atherosclerosis suggested that CAVI was superior to baPWV as a parameter of arterial stiffness.

Cardio-ankle vascular index is a new noninvasive parameter of arterial stiffness.

BACKGROUND: Beta is an index of arterial stiffness independent of blood pressure. Beta of the thoracic descending aorta (TDA) has been obtained by transesophageal echocardiography (TEE) and the cardio-ankle vascular index (CAVI) is a new noninvasive estimation of beta. METHODS AND RESULTS: The purpose of this study was to evaluate the accuracy and usefulness of CAVI and to compare it with other parameters of arteriosclerosis by carotid ultrasound (CU). The instantaneous dimensional change of the TDA on TEE was measured simultaneously with systemic pressure of the brachial artery in 70 patients in sinus rhythm. There were significant correlations between CAVI and age (r=0.65, p<0.01), and CAVI and the beta from TEE (Aobeta) (r=0.67, p<0.01). Next, 110 patients with chest pain syndrome underwent CU and measurement of CAVI, intima - media thickness (IMT), plaque score and beta. There were significant relationships between CAVI and IMT (r=0.42, p<0.01), and between CAVI and beta (r=0.39, p<0.01). CAVI of the group diagnosed with plaque was significant higher than that of the normal group (9.872+/-1.464 vs 9.038+/-1.377, p=0.0039). CONCLUSIONS: CAVI is measured easily and noninvasively and is a new index of arterial stiffness that is independent of blood pressure.

Chronic stage left ventricular aneurysm and thrombus after myocardial infarction.

A 60-year-old man had acute myocardial infarction 13 years ago. After percutaneous coronary intervention, the follow-up left ventriculography (8 years ago) showed dyskinesia in the anterolateral and apical segments of the wall. Following this, there was no change in the clinical symptom. After 6 years the patient discontinued aspirin without seeking medical advice. In this year, a thrombus was found in the left ventricle, and thrombectomy was performed. Left ventricular aneurysm has always been a risk for thrombogenesis in any stage, and a periodic follow-up including an echocardiogram and anticoagulation therapy is necessary.

Tricuspid pouch can cause systemic embolization in adulthood.

A 63-year-old-man with significant left hemiplegia was admitted to hospital. He had experienced a transient cerebral ischemic attack 10 years ago. Computed tomography revealed hypodensity along the right lateral ventricle, which corresponded to the left paralysis. Echocardiography and left ventricular angiography revealed an aneurysm of the membranous septum (AMS) without a ventricular septal defect (VSD). Therefore, the embolism was thought to be of cardiac origin, but surgery revealed that it was not caused by AMS. The aneurysm was created when the septal leaflet of tricupid valve formed a giant capsule during the process of natural closure of the VSD. It was a large pouch, 2.0 cm in diameter, adjacent to the septal leaflet. Anomalies of the tricuspid valve, including pouches, can resemble AMS.

[Cardioversion of amiodarone-insensitive atrial fibrillation by bepridil in heart failure: two case reports].

Two patients presented with atrial fibrillation which was refractory to amiodarone but successfully treated with bepridil. A 76-year-old man with ischemic cardiomyopathy, non-sustained ventricular tachycardia (NSVT) and atrial fibrillation received amiodarone for NSVT, which disappeared but atrial fibrillation was sustained. A month after receiving amiodarone, interstitial pneumonia occurred. Interstitial pneumonia was improved after amiodarone was discontinued, but NSVT occurred again. He received bepridil, when NSVT and atrial fibrillation disappeared. An 83-year-old man with dilated cardiomyopathy, NSVT, and atrial fibrillation received amiodarone for NSVT, which disappeared but atrial fibrillation was sustained. Five months after receiving amiodarone, interstitial pneumonia occurred. Interstitial pneumonia was improved after amiodarone was discontinued, but NSVT occurred again. He received bepridil, when NSVT and atrial fibrillation disappeared.

Effects of ambient temperature steps on thermal comfort requirements.

The purpose of this study was to determine the thermal comfort requirements for steps in temperature. Thirty male subjects were exposed for 50 min to a 34 or 37 degrees C condition, and then quickly transferred to a cooler environment of 31, 28, 25, and 22 degrees C for 50 min. Mean skin temperature was continuously measured, and the subjects reported their thermal sensation and comfort sensation every 2 min. Just after the step changes, the mean skin temperature immediately decreased, while the thermal sensation overshot and gradually rose again. Both the skin temperature and the thermal sensation seemed to reach a constant level within about 20 min. However, there were differences in the mean skin temperature and the neutral temperature derived from the correlation between the ambient temperature and the thermal sensation even 50 min after the steps, due to the thermal environmental condition before the changes of temperature. The change in the neutral temperature with time was expressed as two attenuating equations. These equations indicate that there is an obvious difference between the neutral temperatures due to the thermal condition before step changes, and that it takes >50 min after the step changes to reach the steady state. It is expected that these equations predict in quantitative terms the thermal comfort requirements within a given experimental condition.

Significance of predischarge BNP on one-year outcome in decompensated heart failure--comparative study with echo-Doppler indexes.

BACKGROUND: Cardiac natriuretic peptides and echo-Doppler indexes are important as prognostic indicators of congestive heart failure (CHF). However, differences between etiologies have not been fully investigated. This study aimed to assess the prognostic value of transmitral flow (TMF) and B-type natriuretic peptide (BNP) on admission or predischarge in patients with acutely decompensated CHF of ischemic and nonischemic etiologies. METHODS AND RESULTS: We studied 52 patients with chronic CHF, 31 with old myocardial infarction (OMI), and 21 with idiopathic dilated cardiomyopathy (DCM), admitted for emergency acute decompensation. Patients underwent echo-Doppler study and measurement of plasma BNP on admission and predischarge. The combined index of BNP with echo-Doppler indexes were calculated. Pulmonary capillary wedge pressure (PCWP) and cardiac index were measured on admission. All were followed for 1 year, and those rehospitalized (R group) were compared with those with a stable clinical course (S group). TMF and BNP on admission were similar between DCM and OMI groups. During follow up, 9 with OMI and 10 with DCM were rehospitalized. There were no statistical differences in TMF or BNP levels on admission between the R and S groups. However, the predischarge BNP level was significantly higher in the R group than in the S. Kaplan-Meier curves revealed the influence of predischarge BNP on prognosis. CONCLUSION: Predischarge BNP, not BNP on admission, levels are considered predictive of rehospitalization for decompensation within a year. There were no differences between BNP and echo-Doppler indexes with regard to the CHF etiology.