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Background: Pembrolizumab has been widely used in patients since its release, but information on cardiac Adverse Events (AEs) related to pembrolizumab remains lacking, particularly in Japanese populations. Objectives: This study aims to evaluate time to onset, incidence rates, and outcomes for pembrolizumab-induced cardiac AEs in patients with cancer using the Japanese Adverse Drug Event Report database. Methods: We analysed data for the period from April 2004 to March 2022. Data on cardiac AEs were extracted and relative risks of AEs were estimated using the reporting odds ratio. Results: We analysed 2,021,907 reports and identified 15,306 reports of AEs caused by pembrolizumab. Of these, 399 cardiac AEs were associated with pembrolizumab. Signals were detected for six cardiac AEs: myocarditis, immune-mediated myocarditis, pericardial effusion, cardiac tamponade, pericarditis, and pericarditis malignant. A histogram of median times to onset showed occurrence from 33 (21–97) days for immune-mediated myocarditis to 138 (67–168) days for pericarditis malignant, but some cases occurred even more than 1 year after the start of administration. Among these, myocarditis was the most frequently reported (27.1%), with fatal cases also reported. Conclusion: This study focused on cardiac AEs caused by pembrolizumab as post-marketing AEs. Patients should be monitored not only at the time of administration, but also over time for signs of these AEs, especially myocarditis, as some patients may have serious outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Cardiac adverse events (CAEs) have become a concern as serious adverse events (AEs) of nilotinib administration. No reports have described the incidence of CAEs associated with nilotinib in Japanese patients. Thus, we conducted this study to evaluate the risk of nilotinib-induced CAEs, time to onset, incidence rates, and post hoc outcomes using the Japanese Adverse Drug Event Report database. Methods: We analysed data for the period between April 2004 and March 2022. Data on CAEs were extracted, and relative risk of AEs was estimated using the reporting odds ratio. Results: We analysed 2,021,907 reports and identified 3,545 reports of AEs caused by nilotinib. Of these, 511 reports involved CAEs. Signals were detected for 19 CAEs. Of these, electrocardiogram QT prolonged was the most frequently reported (30.9%). Fatal outcomes were observed in eight AEs: cardiac failure, atrial fibrillation, acute myocardial infarction, pericardial effusion, myocardial infarction, cardiac arrest, pericarditis, and cardiac tamponade. Of these, acute myocardial infarction, myocardial infarction, pericarditis, and cardiac tamponade exhibited mortality rates >10%. A histogram of median times to onset showed nilotinib-associated AEs occurring 3–485 days after nilotinib administration. Conclusion: We focused on CAEs caused by nilotinib as post-marketing AEs. Some cases resulted in serious outcomes. Patients should be monitored for signs of onset of these AEs not only at the start of administration but for a long period of time. [ABSTRACT FROM AUTHOR]

Background: In the phase II JO25567 study (JapicCTI‐111390), erlotinib plus bevacizumab demonstrated a significant clinical benefit in Japanese patients with epidermal growth factor receptor mutation‐positive (EGFR+) non‐small cell lung cancer (NSCLC). Here, we present an exploratory analysis investigating the impact of baseline pleural/pericardial effusion (PPE) on patient outcomes. Methods: Patients with stage IIIB/IV or postoperative recurrent EGFR+ NSCLC were randomized 1:1 to receive erlotinib (150 mg/day) plus bevacizumab (15 mg/kg every 3 weeks) or erlotinib monotherapy. Progression‐free survival (PFS), overall survival (OS), objective response rate (ORR), and safety were evaluated according to the presence or absence of baseline PPE. Results: The population comprised 152 patients, 66 with baseline PPE and 86 without. Median PFS was longer with erlotinib plus bevacizumab than with erlotinib alone, with (hazard ratio [HR] 0.45; 95% confidence interval [CI]: 0.25–0.82) or without (HR 0.62; 95% CI: 0.37–1.04) baseline PPE. Median OS was also prolonged with erlotinib plus bevacizumab relative to erlotinib regardless of the presence (HR 0.82; 95% CI: 0.46–1.47) or absence (HR 0.84; 95% CI: 0.46–1.55) of baseline PPE. ORR was higher with erlotinib plus bevacizumab (70.0%) than with erlotinib (55.6%) in patients with baseline PPE, but similar (68.9% vs. 70.7%) in patients without. Most common grade ≥3 adverse events were hypertension and rash in the erlotinib plus bevacizumab arm, and rash in the erlotinib arm, regardless of baseline PPE status. Conclusions: Erlotinib plus bevacizumab may be a beneficial treatment strategy in patients with EGFR+ NSCLC, especially for those with baseline PPE. [ABSTRACT FROM AUTHOR]

There has been continuing discussion regarding the treatment strategy for acute type A intramural hematoma (IMH). Most patients are treated conservatively in Japan; hence, predicting fatal events and stratifying risks based on results normally obtained on hospital arrival are important. We aimed to examine the incidences and risk factors of death or need for surgery for acute type A IMH in patients receiving medical treatment and to identify high-risk patients using clinical findings on hospital arrival. From 2011 to 2016, 57 consecutive patients (mean age 72.5 years; male 36.8%) diagnosed with acute type A IMH who were receiving treatment at Shizuoka City Shizuoka Hospital were retrospectively included. Primary endpoint was a composite of cardiovascular death and operation within 1 year after onset. To evaluate sensitivity and specificity of the risk factors and risk score, we estimated the area under the receiver operating characteristic (ROC) curve. Mean follow-up duration was 621 days. Mean systolic blood pressure (SBP) was 129 mmHg. Computed tomography (CT) on arrival showed a mean ascending aorta diameter of 46 mm. Ulcer-like projection (ULP) in the ascending aorta and pericardial effusion (PE) were seen in 33% and 42% of cases, respectively. Twenty-eight patients (49.1%) reached the primary endpoint (cardiovascular death, 7 cases [12.3%]; operation, 21 cases [36.8%]). In univariate analysis of admission values, the primary endpoint group had significantly lower SBP (113.0 ± 28.5 vs 144.3 ± 33.5 mmHg), higher ascending aorta diameter (49.5 ± 8.1 vs 43.6 ± 5.9 mm), and higher frequency of ULP (53.8% vs 13.8%) and PE (58.6% vs 25.0%) than the event-free group. Multivariate analysis showed that ULP on admission CT was a significant predictor of the primary endpoint. The risk score was considered using these risk factors. On admission, the primary endpoint could be predicted with 89.7% sensitivity and 75% specificity (area under the ROC curve 0.823) if the patient had ULP and/or > 2 of the following factors: SBP < 120 mmHg, ascending aorta diameter > 45 mm, and PE. SBP and CT findings on arrival were significantly associated with cardiovascular death and the need for surgery in patients with acute type A IMH receiving initial medical therapy. The novel risk score was useful for predicting cardiovascular death and surgery. [ABSTRACT FROM AUTHOR]

Cardiac erosion is a rare serious complication following Amplatzer septal occluder (ASO) placement for atrial septal defect. Although multiple risk factors have been found, a useful predictor to prevent it has not been established yet. In 12 patients who developed erosion between 2005 and 2016 in Japan, we retrospectively observed patients' characteristics and transesophageal echocardiography findings immediately before and after ASO placement and at erosion onset. We compared risk factors of erosion, including absent aortic rim, device size/body weight ratio, device shape, or Valsalva sinus wall deformation pressed by either disk-edge, the maximum depth of which from the standard curve of the Valsalva wall was defined as Dent, between the 12 patients and 95 patients with Valsalva sinus wall deformation immediately after placement who did not develop erosion for 5 ± 3 years. Of the 12 patients, nine developed pericardial effusion with eight cardiac tamponade and three aorta-atrium fistula; all were surgically rescued. Surgical findings revealed that erosion in all patients occurred at the right and/or left atrial roof beside the Valsalva in the non-coronary cusp on which the disk-edge seemed to be pressing. The mean Dent immediately after the placement in patients with erosion was significantly deeper than without (2.48 ± 0.32 vs. 1.28 ± 0.38; p < 0.001). There were no differences in the other risk factors between the two groups. Dent is believed to be a useful indicator of erosion development after ASO placement. If Dent is > 2.0 mm, it is desirable to change the size or to replace the device. [ABSTRACT FROM AUTHOR]

Background: A challenging decision exists as whether to abandon or remove noninfectious superfluous leads during lead revisions or cardiac implantable electronic device (CIED) upgrades. There is insufficient data in the Asian population to guide decision making. Methods: This study investigated the safety and efficacy of transvenous lead extractions (TLEs) in a high‐volume Japanese center. Among a total of 341 patients who underwent lead revisions or CIED upgrades between 2008 and 2018, 53 patients (16%) who underwent TLEs to remove the superfluous leads were analyzed. Results: Indications for TLE were vascular issues (60%), recalled leads (21%), growth of the body size (6%), abandoned leads in young patients (6%), switch to a subcutaneous implanted cardiac defibrillator (4%), need for an MRI conditional CIED (2%), and risks of vascular injury (2%). The population included 29 patients (55%) with nonfunctional leads and 24 (45%) with functional abandoned leads. A total of 74 target leads (mean 1.4 leads/person, median lead age 6.7 years) were extracted with a complete removal achieved in 98%. All coexisting leads, intended for continued use, were not damaged. All new leads (mean 1.4 leads/person) that had been simultaneously implanted during the TLE procedures were successfully implanted. There was one minor complication (2%) involving a pericardial effusion but it did not affect the hemodynamics. Conclusions: In this Japanese single center experience, the removal of noninfectious superfluous leads with TLEs seemed to be a safe and effective therapeutic option. [ABSTRACT FROM AUTHOR]

Aims: Transseptal puncture (TSP) has become a common approach in catheter ablation of arrhythmia originating from the left atrium. In paediatric patients, however, TSP can be a challenge due to narrower access vessels and small left atrial size, and the safety of TSP in smaller children is yet to be understood. The purpose of this study was to retrospectively evaluate the feasibility and safety of TSP in children weighing below 30 kg.Methods and Results: Among 655 paediatric patients who underwent catheter ablation of arrhythmia between July 2009 and April 2015, 43 cases having structurally normal hearts, weighing <30 kg and requiring TSP were included in the study. Age, height, body weight, diagnosis, and complications during TSP and catheter ablation were evaluated. The median age, height, and body weight (range) were 7.0 years (0.3-11.1), 116.8 cm (54.0-138.4 cm) and 21.5 kg (4.3-29.6 kg), respectively. Diagnosis included manifest (n = 27; 62.8%) and concealed accessory pathway (n = 14; 32.6%) and atrial tachycardia (n = 2; 4.6%). In 10 cases (23.2%), TSP using radiofrequency energy was performed. None of the patients had major complications. Pericardial effusion was recorded as a minor complication in one patient (2.3%).Conclusion: TSP was feasible, safe, and of low risk of complications in children weighing <30 kg. [ABSTRACT FROM AUTHOR]

Background: We evaluated malignancy according to the characteristics of pericardial fluid in symptomatic Japanese patients undergoing pericardiocentesis and computed tomography (CT)., Methods: This was a retrospective, single-center, observational study of 125 symptomatic patients undergoing pericardiocentesis. The patients were classified into two groups: a malignancy group and a non-malignancy group, according to the primary disease and cytology of the pericardial effusion (PE). We compared the pericardial fluid sample and CT measurements between both groups., Results: All patients were diagnosed as having exudative PE by Light's criteria. PE with malignant cells was demonstrated in 76.8% of the malignancy group patients. Pericardial to serum lactate dehydrogenase (LDH) ratio > 0.6, as one of Light's criteria, was associated with malignancy (p = 0.017). Lower serum brain natriuretic peptide (BNP) concentration was also associated with malignancy (BNP: 126.9 ± 89.8 pg/ml vs 409.2 ± 97.7 pg/ml, malignancy vs non-malignancy groups, respectively; p = 0.037). A significant difference was observed in pericardial fluid glucose level between the malignancy and non-malignancy groups (pericardial fluid glucose: 78.24 ± 48.29 mg/dl vs 98.41 ± 44.85, respectively; p = 0.048). Moreover, CT attenuation values (Hounsfield units (HU)) tended to be higher in the malignancy group vs the non-malignancy group (22.7 [interquartile range (IQR), 17.4-26.0] vs 17.4 [IQR, 13.7-26.4], respectively; p = 0.08). The sensitivity and specificity of pericardial fluid glucose level ≤ 70 mg/dl and CT attenuation values > 20 HU were 40.9% and 89.6%, respectively, in the malignancy group. The positive- and negative predictive values of pericardial fluid glucose level ≤ 70 mg/dl and CT attenuation values > 20 HU were 85.7% and 50.0%, respectively, in the malignancy group. Pericardial fluid glucose level ≤ 70 mg/dl and CT attenuation values > 20 HU were cutoff values associated with malignancy (p = 0.012)., Conclusions: Lower pericardial fluid glucose level with higher CT attenuation values may suggest malignancy-related PE.

The article presents a case study of a 20-month-old girl who was admitted to the hospital with compensated shock and hypoxia along with dyspnea and deteriorated respiration. It talks about the girl being diagnosed with non-typeable Haemophilus influenzae pericarditis which was detected through chest radiography.

A 67-year-old man diagnosed with clinical Stage Ⅳ gastric cancer was administered nivolumab as fourth-line chemotherapy. After 9 courses, he was emergently admitted with complaints of low blood pressure and general malaise. On the fourth hospital day, he had high-grade fever and elevated serum C-reactive protein. Computed tomography showed a moderate amount of pericardial effusion. He was administered 1.7 mg/kg of methylprednisolone and improved rapidly. A hormonal blood examination showed his adrenal gland disorder. This is the first case in our country of pericardial effusion as an immune-reactive adverse event, which is not well known in Japan.

There are few reports about the clinical results of proton beam therapy for esophageal cancer in a large population. The purpose of this study was to evaluate the clinical results of proton beam therapy for esophageal cancer in a large population using a multicentered database. Between January 2009 and December 2013, patients newly diagnosed with esophageal cancer and who had received proton beam therapy were retrospectively recruited from a database of four proton beam therapy centers in Japan. Two hundred and two patients (including 90 inoperable patients) fulfilled the inclusion criteria, and 100 patients (49.5%) had stage III/IV cancer (Union for International Cancer Control 8th). The 3-year and 5-year overall survival rate was 66.7% and 56.3%, respectively. The five-year local control rate was 64.4%. There were two patients with grade three pericardial effusion (1%) and a patient with grade three pneumonia (0.5%). No grade 4 or higher cardiopulmonary toxicities were observed (Common Terminology Criteria for Adverse Events version 4.0). This study suggests that proton beam therapy for esophageal cancer was not inferior in efficacy and had lower rates of toxicities in comparison to photon radiotherapy. Therefore, proton beam therapy can serve as an alternate treatment for patients with esophageal cancer. [ABSTRACT FROM AUTHOR]

Aims: To clarify the prognosis and prognostic factors in pulmonary arterial hypertension (PAH) patients in real-world medical practice in the Tokai area in Japan., Main Methods: We conducted a retrospective, multicenter observational study. The data of 81 patients diagnosed with Dana Point group 1 or 1' PAH was collected from January 2005 to January 2013. The primary outcome was all-cause death., Key Findings: The patients consisted of 34 cases of idiopathic PAH (IPAH), 28 of connective tissue-associated PAH (CTD-PAH), 16 of congenital heart disease-associated PAH (CHD-PAH) and others. Mean age was 51 years and mean observation period was 46 months. The systolic blood pressure (BPs) was 117±23 mm Hg. Pericardial effusion was observed in 27.0% of patients. The mean right atrial pressure (mRAP) was 10.2±7.3 mm Hg. In the univariate Cox regression analysis, WHO-FCS III & IV, a cardiac index (CI)<2.5 L/min/m(2), and the presence of pericardial effusion at baseline were significantly associated with all-cause death. In the multivariate analysis, the pericardial effusion (HR 3.3, 95% CI 1.03-10.63, p=0.04) and mRAP (HR 3.2, 95% CI 1.03-9.83, p=0.04) or CI<2.5 L/min/m(2) (HR 3.89, 95% CI 1.05-14.45, p=0.04) were the independent predictors of mortality., Significance: The presence of pericardial effusion and mRAP or CI<2.5 L/min/m(2) at diagnosis indicated high mortality., (Copyright © 2014. Published by Elsevier Inc.)