Successful Management of Terminal Delirium With Transdermal Blonanserin Patch in a Terminally Ill Cancer Patient.

Delirium is a distressing condition in terminally ill cancer patients, often treated with antipsychotics. Administering them orally, subcutaneously, or intravenously can be challenging in severely agitated patients. Transdermal antipsychotic patches offer an alternative, but their use for terminal delirium remains underexplored. We present the case of a 73-year-old man with advanced diffuse large B cell lymphoma who developed severe mixed delirium during third-line chemotherapy. Nonpharmacological interventions and oral risperidone plus intravenous haloperidol failed to improve his condition. Subsequently, a transdermal blonanserin patch was applied, resulting in the resolution of hallucinations on day 1 and agitation on day 3, allowing improved communication. The patch was easily applied daily without notable adverse events. However, he deteriorated a week later with an estimated survival of days, ultimately requiring continuous midazolam for refractory agitation. This case underscores the potential of transdermal blonanserin patches for delirium in terminally ill cancer patients, emphasizing the need for future prospective studies.

Low-carbohydrate diets containing plant-derived fat but not animal-derived fat ameliorate heart failure.

Cardiovascular disease (CVD) is a global health burden in the world. Although low-carbohydrate diets (LCDs) have beneficial effects on CVD risk, their preventive effects remain elusive. We investigated whether LCDs ameliorate heart failure (HF) using a murine model of pressure overload. LCD with plant-derived fat (LCD-P) ameliorated HF progression, whereas LCD with animal-derived fat (LCD-A) aggravated inflammation and cardiac dysfunction. In the hearts of LCD-P-fed mice but not LCD-A, fatty acid oxidation-related genes were highly expressed, and peroxisome proliferator-activated receptor α (PPARα), which regulates lipid metabolism and inflammation, was activated. Loss- and gain-of-function experiments indicated the critical roles of PPARα in preventing HF progression. Stearic acid, which was more abundant in the serum and heart of LCD-P-fed mice, activated PPARα in cultured cardiomyocytes. We highlight the importance of fat sources substituted for reduced carbohydrates in LCDs and suggest that the LCD-P-stearic acid-PPARα pathway as a therapeutic target for HF.

Native T1 mapping in early diffuse and limited systemic sclerosis, and its association with diastolic function.

BACKGROUND: Systemic sclerosis (SSc) is divided into diffuse and limited cutaneous SSc (dcSSc and lcSSc). The dcSSc subtype has more severe internal organ damage. This study aimed to assess whether cardiovascular magnetic resonance (CMR) parametric mapping could detect early cardiac involvement and evaluate differences between these two subtypes. METHODS: Eighty SSc patients (37 dcSSc and 43 lcSSc) underwent CMR at 3.0 T (Philips Healthcare, Best, The Netherlands) in our hospital between July 2018 and July 2021. We analyzed myocardial damage by CMR parametric mapping and compared it with clinical data. RESULTS: The median duration of the disease was 10.2 months. The left ventricular ejection fraction was preserved in both groups. DcSSc had significantly higher native T1 (1333.4 ±â€¯71.2 ms vs. 1295.0 ±â€¯42.7 ms, p = 0.006) and extracellular volume fraction (32.6 ±â€¯4.1 % vs. 30.3 ±â€¯4.0 %, p = 0.018) in the mid-ventricular septum as compared to lcSSc, although there were no differences in T2 values. Native T1 values were positively correlated with the E/e' ratio and left atrial volume indices evaluated by transthoracic echocardiography in overall SSc and dcSSc, but not in lcSSc. Logistic regression analysis revealed that native T1 was an independent predictor of left ventricular diastolic dysfunction in SSc patients (odds ratio, 1.194; 95 % confidence interval, 1.021-1.396; p = 0.026). Native T1 was higher in SSc patients with progressive skin lesions. Additionally, there were positive correlations between brain natriuretic peptide, New York Heart Association functional classification, and native T1. CONCLUSIONS: CMR parametric mapping is a useful tool for detecting myocardial changes. Native T1 was the most sensitive parameter for identifying diffuse myocardial changes in the early stages of SSc and was associated with left ventricular diastolic function. DcSSc had more severe myocardial involvement than lcSSc; therefore, the use of CMR parametric mapping may aid in its prediction.

The effect of immunosuppressive therapy on cardiac involvements in anti-mitochondrial antibody-positive myositis.

AIMS: Anti-mitochondrial antibody (AMA)-positive myositis is frequently associated with various cardiac involvements, such as arrhythmia and left ventricular (LV) dysfunction. However, the efficacy of immunosuppressive therapy in these complications remains unknown. This study aimed to investigate the cardiac response to immunosuppressive therapy in patients with AMA-positive myositis. METHODS AND RESULTS: The clinical data of 15 AMA-positive myositis patients with cardiac involvement were retrospectively collected at our centre. To evaluate the effects of immunosuppressive therapy, echocardiographic and laboratory data of patients who received glucocorticoid therapy with additional immunosuppressants (n = 6) and those who did not (n = 6) were compared. Also, the characteristics of patients with or without >5% LV ejection fraction (LVEF) decline during the follow-up period (n = 5 vs. n = 7) were compared. Thirteen patients (87%) had arrhythmias, and eight patients (53%) had LV wall motion abnormalities. Although arrhythmias decreased after treatment, reduced LVEF and LV wall motion abnormalities persisted. Further investigation revealed an increased LV end-systolic dimension and reduced LVEF in patients without additional immunosuppressive therapy, while those in patients with additional immunosuppressive therapy were maintained. Six of seven patients (86%) without LVEF decline received additional immunosuppressive therapy, whereas no patients with LVEF decline had additional immunosuppressive therapy. CONCLUSIONS: Cardiac involvement in AMA-positive myositis may worsen even with glucocorticoid monotherapy, and there might be some associations between the change of LV function and additional immunosuppressive therapy.

Delayed diagnosis of severe traumatic tricuspid regurgitation after traffic injury.

Traumatic accidents sometimes cause primary traumatic tricuspid regurgitation (TR), and the diagnosis is occasionally delayed due to the load adaptability of the right ventricle, which may lead to fatal outcomes. Here, we report a case of a 28-year-old man with traumatic TR, which presented with late-onset exertional dyspnea 5 years after a blunt chest injury from a bicycle accident. The chordae tendineae of anterior tricuspid leaflet was ruptured with right heart dilatation, and he underwent surgical tricuspid valvuloplasty. For the patients having a chest traumatic accident, echocardiographic screening is recommended considering TR occurrence. .

Successful treatment of recurrent cardiac sarcoidosis with the combination of corticosteroid and methotrexate monitored by 18F-fluoro-2-deoxyglucose positron emission tomography: case series.

Background: The standard treatment for cardiac sarcoidosis (CS) is corticosteroids, including prednisolone (PSL). Previous studies have shown that the addition of methotrexate (MTX) to PSL is effective for steroid-refractory and recurrent cases. 18F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) is an essential tool for the diagnosis of CS. However, it is unclear whether FDG-PET is useful for detecting recurrence of CS and monitoring the effectiveness of PSL and MTX combination therapy. Case summary: We detected CS recurrence during PSL treatment using FDG-PET. Patient 1 was accompanied by increased FDG uptake in other organs, Patient 2 was complicated with a decrease in left ventricular ejection fraction, and Patient 3 showed enlargement of the late gadolinium enhancement area, which was compatible with the recurrence of CS. We successfully monitored the inflammation activity by FDG-PET and treated recurrent CS by increasing the PSL dose and adding MTX to suppress inflammation. Discussion: FDG-PET is useful for detecting CS recurrence and monitoring the effectiveness of PSL and MTX combination therapy. Serial FDG-PET scans indicated that it might be more difficult to suppress inflammation in recurrent CS than in the initial treatment. The use of FDG-PET is necessary to monitor long-term disease activity.

Recovery of sinus rhythm by tafamidis in patients with wild-type transthyretin amyloid cardiomyopathy with atrial arrhythmias.

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a life-threatening infiltrative disease in elderly patients. Atrial arrhythmias (AAr) are common in patients with ATTR-CM. However, AAr treatment in these patients is challenging. In this case, a patient diagnosed with wild-type ATTR-CM suffered atrial fibrillation (AF) for ~1 year, according to the data of his self-monitoring and regular electrocardiogram. This AF reverted to normal sinus rhythm a few months after the initiation of tafamidis without administering an antiarrhythmic drug. Tafamidis may be beneficial as alternative antiarrhythmic therapy in patients with ATTR-CM.

Detection of Profound Myocardial Damage by Cardiac MRI in a Patient with Severe Cardiotoxicity Induced by Anti-HER2 Therapy.

Anti-HER2 therapy has greatly improved the long-term prognosis of patients with HER2-positive breast cancer. Meanwhile, by interfering with the protective effects of neuregulin-1/HER2 signaling on stressed cardiomyocytes, anti-HER2 therapy occasionally induces reversible cancer therapeutics-related cardiac dysfunction (CTRCD). Cardiac magnetic resonance (CMR) parametric mapping or myocardial feature-tracking, in combination with late gadolinium enhancement (LGE) imaging, has the potential to detect changes in the myocardium in anti-HER2 therapy-related cardiac dysfunction. Here we report a breast cancer patient who experienced life-threatening CTRCD after treatment with trastuzumab plus pertuzumab. This case showed multiple transmural LGE-positive myocardial lesions in CMR imaging and high native T1 and T2 values in CMR parametric mapping, which was apparently more extensive than those observed in most patients with anti-HER2 therapy-related cardiac dysfunction. Consistent with profound myocardial damage indicated by CMR, her cardiac function was not fully restored despite intensive care and cardioprotective drug therapy. These findings suggest the potential usefulness of LGE imaging and parametric mapping by CMR for the assessment of myocardial injury to determine the clinical severity of anti-HER2 therapy-related cardiac dysfunction.

CXCR7 ameliorates myocardial infarction as a ß-arrestin-biased receptor.

Most seven transmembrane receptors (7TMRs) are G protein-coupled receptors; however, some 7TMRs evoke intracellular signals through ß-arrestin as a biased receptor. As several ß-arrestin-biased agonists have been reported to be cardioprotective, we examined the role of the chemokine receptor CXCR7 as a ß-arrestin-biased receptor in the heart. Among 510 7TMR genes examined, Cxcr7 was the most abundantly expressed in the murine heart. Single-cell RNA-sequencing analysis revealed that Cxcr7 was abundantly expressed in cardiomyocytes and fibroblasts. Cardiomyocyte-specific Cxcr7 null mice showed more prominent cardiac dilatation and dysfunction than control mice 4 weeks after myocardial infarction. In contrast, there was no difference in cardiac phenotypes between fibroblast-specific Cxcr7-knockout mice and control mice even after myocardial infarction. TC14012, a specific agonist of CXCR7, significantly recruited ß-arrestin to CXCR7 in CXCR7-expressing cells and activated extracellular signal-regulated kinase (ERK) in neonatal rat cardiomyocytes. Cxcr7 expression was significantly increased and ERK was activated in the border zone of the heart in control, but not Cxcr7 null mice. These results indicate that the abundantly expressed CXCR7 in cardiomyocytes may play a protective role in the heart as a ß-arrestin-biased receptor and that CXCR7 may be a novel therapeutic target for myocardial infarction.

Omega-3 fatty acid prevents the development of heart failure by changing fatty acid composition in the heart.

Some clinical trials showed that omega-3 fatty acid (FA) reduced cardiovascular events, but it remains unknown whether omega-3 FA supplementation changes the composition of FAs and their metabolites in the heart and how the changes, if any, exert beneficial effects on cardiac structure and function. To clarify these issues, we supplied omega-3 FA to mice exposed to pressure overload, and examined cardiac structure and function by echocardiography and a proportion of FAs and their metabolites by gas chromatography and liquid chromatography-tandem mass spectrometry, respectively. Pressure overload induced cardiac hypertrophy and dysfunction, and reduced concentration of all FAs' components and increased free form arachidonic acid and its metabolites, precursors of pro-inflammatory mediators in the heart. Omega-3 FA supplementation increased both total and free form of eicosapentaenoic acid, a precursor of pro-resolution mediators and reduced free form arachidonic acid in the heart. Omega-3 FA supplementation suppressed expressions of pro-inflammatory cytokines and the infiltration of inflammatory cells into the heart and ameliorated cardiac dysfunction and fibrosis. These results suggest that omega-3 FA-induced changes of FAs composition in the heart have beneficial effects on cardiac function via regulating inflammation.

Variable Cardiac Responses to Immunosuppressive Therapy in Anti-Mitochondrial Antibody-Positive Myositis.

We describe a case of anti-mitochondrial antibody-positive myositis associated with cardiovascular involvement. An electrophysiological study (EPS) showed binodal dysfunction, and cardiac magnetic resonance (CMR) imaging revealed left ventricular dysfunction with diffuse, patchy T2 high-intensity areas and late gadolinium enhancement indicative of inflammation and fibrosis. The left ventricular dysfunction was successfully treated with immunosuppressive therapy as documented by CMR. Persistence of conduction system dysfunction was confirmed by EPS, and a pacemaker was implanted. CMR and EPS concisely documented the variable cardiac response to treatment in anti-mitochondrial antibody-positive myositis. We demonstrate the utility of cardiac investigations in this rare disorder.

High-throughput single-molecule RNA imaging analysis reveals heterogeneous responses of cardiomyocytes to hemodynamic overload.

BACKGROUND: The heart responds to hemodynamic overload through cardiac hypertrophy and activation of the fetal gene program. However, these changes have not been thoroughly examined in individual cardiomyocytes, and the relation between cardiomyocyte size and fetal gene expression remains elusive. We established a method of high-throughput single-molecule RNA imaging analysis of in vivo cardiomyocytes and determined spatial and temporal changes during the development of heart failure. METHODS AND RESULTS: We applied three novel single-cell analysis methods, namely, single-cell quantitative PCR (sc-qPCR), single-cell RNA sequencing (scRNA-seq), and single-molecule fluorescence in situ hybridization (smFISH). Isolated cardiomyocytes and cross sections from pressure overloaded murine hearts after transverse aortic constriction (TAC) were analyzed at an early hypertrophy stage (2 weeks, TAC2W) and at a late heart failure stage (8 weeks, TAC8W). Expression of myosin heavy chain ß (Myh7), a representative fetal gene, was induced in some cardiomyocytes in TAC2W hearts and in more cardiomyocytes in TAC8W hearts. Expression levels of Myh7 varied considerably among cardiomyocytes. Myh7-expressing cardiomyocytes were significantly more abundant in the middle layer, compared with the inner or outer layers of TAC2W hearts, while such spatial differences were not observed in TAC8W hearts. Expression levels of Myh7 were inversely correlated with cardiomyocyte size and expression levels of mitochondria-related genes. CONCLUSIONS: We developed a new image-analysis pipeline to allow automated and unbiased quantification of gene expression at the single-cell level and determined the spatial and temporal regulation of heterogenous Myh7 expression in cardiomyocytes after pressure overload.

Spinal Cord Swelling After Surgery in Cervical Spondylotic Myelopathy: Relationship With Intramedullary Gd-DTPA Enhancement on MRI.

STUDY DESIGN: This is a prospective multicenter study. SUMMARY OF BACKGROUND DATA: Postoperative spinal cord swelling has been reported in patients with cervical spondylotic myelopathy. In the cases of the spinal cord swelling, the involvement in the intramedullary gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) enhancement on magnetic resonance imaging (MRI) was referred. OBJECTIVE: The prevalence and clinical relevance of postoperative spinal cord swelling and its relationship with intramedullary Gd-DTPA enhancement in patients with cervical spondylotic myelopathy were investigated. SUBJECTS AND METHODS: A total of 683 consecutive patients with cervical spondylotic myelopathy who underwent laminoplasty were examined. T1, T2, and Gd-DTPA-enhanced MRI were performed before surgery. Patients with intramedullary Gd-DTPA enhancement were allocated to the enhancement group. Fifty consecutive cases who did not exhibit intramedullary Gd-DTPA enhancement were allocated to the nonenhancement group. Both groups underwent MRI examinations at 1 month and 1 year after surgery. RESULTS: The prevalence of spinal cord swelling in the enhancement group (26%) was significantly higher than that in the nonenhancement group (4%) (P=0.0038). At 1 year after surgery, spinal cord swelling had resolved in all patients in the nonenhancement group, while it persisted in 3 of 13 patients (23%) in the enhancement group. On multiple regression analysis, intramedullary Gd-DTPA enhancement rather than the spinal cord swelling showed a significant influence in terms of recovery of the Japanese Orthopedic Association score. CONCLUSIONS: Surgical outcomes of patients with postoperative swelling should be evaluated separately according to the presence or absence of intramedullary Gd-DTPA enhancement on MRI. Spinal cord swelling associated with intramedullary Gd-DTPA enhancement was indicative of poor prognosis.

Axillofemoral Bypass Markedly Improved Acute Decompensated Heart Failure and Kidney Injury in a Patient with Severely Calcified Stenosis of Thoracoabdominal Aorta (Atypical Aortic Coarctation).

Atypical aortic coarctation (AAC) has been reported to occur anywhere along the aorta, except for the ascending aorta. The associated symptoms include hypotension in the lower half of the body, secondary hypertension in the upper half of the body, and heart failure. Here we present an 80-year-old Asian woman complaining of progressive exertional dyspnea. She was diagnosed with acute decompensated heart failure and kidney injury due to severely calcified stenosis of the thoracoabdominal aorta, the so called AAC. She received hemodiafiltration, and pulmonary congestion improved in part. Generally, surgical treatments are quite invasive in elderly patients. Endovascular stent graft placement is less invasive, however, fracture and rupture should be considered at severely calcified lesions like this case. Therefore, we selected extra-anatomical axillofemoral bypass. Her recovery after the surgery was remarkable. In a few days, she became free from hemodiafiltration, intravenous diuretics, and oxygen administration. We thought the contributive factors are the increase in kidney blood flow and the correction of afterload mismatch. The decrease in pulse pressure may reflect the reduction in systemic arterial compliance by axillofemoral bypass. The operative mortality of axillofemoral bypass was reported to be acceptable, although the patency of the axillofemoral bypass graft was not high enough. In conclusion, axillofemoral bypass is effective and feasible for elderly patients with acute decompensated heart failure and kidney injury due to AAC.

Bilateral Subclavian Vein Occlusion in a SAPHO Syndrome Patient Who Needed an Implantable Cardioverter Defibrillator.

A 79-year-old Asian man was hospitalized because of progressive exertional dyspnea with decreasing left ventricular ejection fraction and frequent non-sustained ventricular tachycardia. Pre-procedure venography for implantable cardioverter defibrillator (ICD) implantation showed occlusion of the bilateral subclavian veins. In consideration of subcutaneous humps in the sterno-clavicular area and palmoplantar pustulosis, we diagnosed him as having synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome and speculated that it induced peri-osteal chronic inflammation in the sterno-clavicular area, resulting in occlusion of the adjacent bilateral subclavian veins. An automatic external defibrillator (AED) was installed in the patient's house and total subcutaneous ICD was considered. Venous thrombosis in SAPHO syndrome is not frequent but has been reported. To the best of our knowledge, this is the first case of bilateral subclavian vein occlusion in a SAPHO syndrome patient who needs ICD implantation.

Risk of acetabular protrusion is low in rheumatoid arthritis patients treated with bipolar hemiarthroplasty for displaced femoral neck fractures without rheumatoid change in hip joints.

OBJECTIVES: The aim of this study was to analyze the radiological outcomes of bipolar hemiarthroplasty after displaced femoral neck fractures of non-arthritic hip joints in rheumatoid arthritis patients. METHODS: We retrospectively investigated 25 hip joints in 23 rheumatoid arthritis patients who underwent bipolar hemiarthroplasty for displaced femoral neck fracture of non-arthritic hip joints. All patients were female with an average age of 69.8 years (range 51-83 years). Mean follow-up duration was 8.4 years (range 5-12 years). Radiographs taken immediately, 1 year after surgery and most recently, were collected for each case. Radiographic measurement of the migration distance of the outer-head prosthesis in the direction of vertical, horizontal and medial to Köhler's line was undertaken at 1 year after surgery and most recently. RESULTS: No patients had hip-related pain after surgery. No case indicated apparent central migration and >3-mm migration of the hemisphere in each direction. There was no significant change in migration distance between evaluation at 1 year after surgery and most recently. CONCLUSIONS: We conclude that risk of acetabular protrusion appears to be low in patients of rheumatoid arthritis treated with bipolar hemiarthroplasty for displaced femoral neck fractures of non-arthritic hip joints in the medium term.