Impact of Cancer, Inflammation, and No Standard Risk Factors in Patients With Myocardial Infarction.

Background: The lack of standard modifiable cardiovascular risk factors (SMuRFs), including hypertension, diabetes, dyslipidemia, and smoking, is reportedly associated with poor outcomes in acute myocardial infarction (AMI). Among patients with no SMuRFs, cancer and chronic systemic inflammatory diseases (CSIDs) may be major etiologies of AMI. Objectives: The purpose of this study was to evaluate clinical characteristics and outcomes of patients with cancer, CSIDs, and no SMuRFs in AMI. Methods: This multicenter registry included 2,480 patients with AMI undergoing percutaneous coronary intervention. Patients were divided into 4 groups: active cancer, CSIDs, no SMuRFs, and those remaining. The coprimary endpoint was major adverse cardiovascular events (MACE) and major bleeding events, during hospitalization and after discharge. Results: Of 2,480 patients, 104 (4.2%), 94 (3.8%), and 120 (4.8%) were grouped as cancer, CSIDs, and no SMuRFs, respectively. During the hospitalization, MACE rates were highest in the no SMuRFs group, followed by the cancer, CSIDs, and SMuRFs groups (22.5% vs 15.4% vs 12.8% vs 10.2%; P < 0.001), whereas bleeding risks were highest in the cancer group, followed by the no SMuRFs, CSIDs, and SMuRFs groups (15.4% vs 10.8% vs 7.5% vs 4.9%; P < 0.001). After discharge, the rates of MACE (33.3% vs 22.7% vs 11.3% vs 9.2%; P < 0.001) and bleeding events (8.6% vs 6.7% vs 3.8% vs 2.9%; P = 0.01) were higher in the cancer group than in the CSIDs, no SMuRFs, and SMuRFs groups. Conclusions: Patients with active cancer, CSIDs, and no SMuRFs differently had worse outcomes after AMI in ischemic and bleeding endpoints during hospitalization and/or after discharge, compared with those with SMuRFs.

An effective plication technique for diaphragmatic eventration under thoracoscopy with laparoscopic image display.

Diaphragmatic eventration causes respiratory distress with the development of severe diaphragmatic compression of lung volume. While non-surgical treatment, such as physical therapy and pulmonary rehabilitation, is adequate for mild cases, surgical intervention is critical for severe diaphragmatic eventration. A 45-year-old man with respiratory fatigue was diagnosed with left diaphragmatic eventration and underwent surgery with diaphragmatic plication with double-row stapling under a video-assisted approach. Thoracoscopy with laparoscopic image display avoided visceral tissue involvement, and the double-stapling technique prevented diaphragmatic rupture and lowered the diaphragmatic level. The procedure improved the patient's respiratory function by reducing respiratory fatigue. This procedure is safe and effective for the thin and vulnerable diaphragmatic muscle.

Effects of Xanthine Oxidase Inhibition by Febuxostat on Lipid Profiles of Patients with Hyperuricemia: Insights from Randomized PRIZE Study.

Although patients with hyperuricemia and gout often have dyslipidemia, the effects of febuxostat, a xanthine oxidase inhibitor, on their lipid profiles are unclear. Thus, we performed a sub-analysis of the randomized PRIZE study in which the effects of febuxostat on carotid atherosclerosis were investigated in patients with hyperuricemia. The participants were randomized to the febuxostat or control group. The primary endpoint of this sub-analysis was changes in the patients' non-high-density lipoprotein cholesterol (HDL-C) levels from baseline to 6-month follow-up. Correlations between the changes in lipid profiles and cardiometabolic parameters were also evaluated. In total, 456 patients were included. From baseline to 6 months, non-HDL-C levels were significantly reduced in the febuxostat group (-5.9 mg/dL, 95% confidence interval [CI]: -9.1 to -2.8 mg/dL, p < 0.001), but not in the control group (-1.3 mg/dL, 95% CI: -4.4 to 1.8, p = 0.348). The reduction in non-HDL-C levels was more pronounced in women and correlated with changes in serum uric acid and estimated glomerular filtration rate levels only in the febuxostat group. In patients with hyperuricemia, febuxostat treatment was associated with reduced non-HDL-C levels from baseline to the 6-month follow-up compared to the control treatment, suggesting that the lipid-lowering effect of febuxostat should be considered when targeting dyslipidemia.

Volume-Outcome Relationships for Intra-Aortic Balloon Pump in Acute Myocardial Infarction.

BACKGROUND: Acute myocardial infarction (AMI) is a major scenario for the use of an intra-aortic balloon pump (IABP), particularly when complicated by cardiogenic shock, although the utilization of mechanical circulatory support devices varies widely per hospital. We evaluated the relationship, at the hospital level, between the volume of IABP use and mortality in AMI. METHODS AND RESULTS: Using a Japanese nationwide administrative database, 26,490 patients with AMI undergoing primary percutaneous coronary intervention (PCI) from 154 hospitals were included in this study. The primary endpoint was the observed-to-predicted in-hospital mortality ratio. Predicted mortality per patient was calculated using baseline variables and averaged for each hospital. The associations among PCI volume for AMI, observed and predicted in-hospital mortality, and observed and predicted IABP use were assessed per hospital. Of 26,490 patients, 2,959 (11.2%) were treated with IABP and 1,283 (4.8%) died during hospitalization. The annualized number of uses of IABP per hospital in AMI was 4.5. In lower-volume primary PCI centers, IABP was more likely to be underused than expected, and the observed-to-predicted in-hospital mortality ratio was higher than in higher-volume centers. CONCLUSIONS: A lower annual number of IABP use was associated with an increased mortality risk at the hospital level, suggesting that IABP use can be an institutional quality indicator in the setting of AMI.

A Novel Method to Localize Patency Capsule by Ileocolonoscopy Facilitates Endoscopic Assessment of the Small and Large Intestine in Patients with Crohn's Disease.

INTRODUCTION: Patients with Crohn's disease (CD) require an assessment of small bowel lesions, while difficulties exist in performing small intestinal examinations, especially in small-sized medical offices. Small bowel capsule endoscopy (SBCE) is handy and can be performed in most clinical settings. The only drawback of SBCE is a requirement of patency testing prior to the exam because it sometimes requires CT scanning to localize the ingested patency capsule (PC), which may be a substantial burden for the patient. We have developed a novel PC detection system named PICS (patency capsule, ileocolonoscopy, and small bowel capsule endoscopy) method by which we can avoid CT scanning. In the PICS method, ileocolonoscopy (ICS) is performed after 30-33 h of PC ingestion and the PC can be localized by ICS in patients who have not excreted the PC, and the entire intestine can be examined in combination with subsequent SBCE without additional bowel preparation. The aim of this study was to assess the usefulness and safety of the PICS method for CD patients. METHODS: CD patients who underwent PICS method from April 2021 to March 2023 were reviewed for clinical data, outcome of PICS method including the rates of PC detection by ICS, the number of patients underwent SBCE, and adverse events. Lewis score was used to assess SBCE results. RESULTS: The PICS method was performed in 54 patients. The median age of patients was 28.5 years old, and 64.8% of them were ileocolic type. The median disease duration was 10.5 months and 24.1% had history of small bowel resection. Five cases (9.3%) confirmed gastrointestinal patency by ICS, and none of the cases required CT scanning. One patient who could not be confirmed patency by ICS, and the other patient who excreted PC but was found ileal stenosis by ICS did not undergo SBCE. Remaining 52 patients received SBCE, and the median Lewis score of them was 0 (IQR 0, 450). There were no adverse events including small bowel obstruction by PC and SBCE retention in this series. CONCLUSION: The PICS method is not only feasible and safe but also convenient to assess disease extent in patients with CD. By localizing PC with ICS, additional CT scanning could be unnecessary for SBCE, which benefits both physicians and CD patients.

No standard modifiable cardiovascular risk factors in acute myocardial infarction: prevalence, pathophysiology, and prognosis.

Standard modifiable cardiovascular risk factors (SMuRFs), such as hypertension, diabetes, dyslipidemia, and current smoking, are associated with the development of atherosclerotic cardiovascular diseases including acute myocardial infarction (MI). Thus, therapeutic approaches against SMuRFs are important as primary and secondary prevention of cardiovascular diseases. In patients with acute MI, however, the prognosis is counterintuitively poor when SMuRFs are lacking. The growing evidence has explored the prevalence, pathophysiology, and prognosis of SMuRF-less patients in acute MI and suggested the potential underlying mechanisms. This review article summarizes the clinical evidence and relevance of the lack of SMuRFs in acute MI.

Plasma cell differentiation is regulated by the expression of histone variant H3.3.

The differentiation of B cells into plasma cells is associated with substantial transcriptional and epigenetic remodeling. H3.3 histone variant marks active chromatin via replication-independent nucleosome assembly. However, its role in plasma cell development remains elusive. Herein, we show that during plasma cell differentiation, H3.3 is downregulated, and the deposition of H3.3 and chromatin accessibility are dynamically changed. Blockade of H3.3 downregulation by enforced H3.3 expression impairs plasma cell differentiation in an H3.3-specific sequence-dependent manner. Mechanistically, enforced H3.3 expression inhibits the upregulation of plasma cell-associated genes such as Irf4, Prdm1, and Xbp1 and maintains the expression of B cell-associated genes, Pax5, Bach2, and Bcl6. Concomitantly, sustained H3.3 expression prevents the structure of chromatin accessibility characteristic for plasma cells. Our findings suggest that appropriate H3.3 expression and deposition control plasma cell differentiation.

Differential Prognostic Impact of Risk-Prediction Models for Heart Failure in Acute Myocardial Infarction: The Original and Revised Heart Failure Time-Points.

Background: We previously developed a risk-scoring system for heart failure (HF) in patients with acute myocardial infarction (MI), namely "HF time-points (HFTPs)". In the original HFTPs, the presence of HF on admission, during hospitalization, and at short-term follow-up was individually scored. This study examined whether the revised HFTPs, with additional scoring of previous HF, provide better predictivity. Methods: This multicenter registry included a total of 1331 patients with acute MI undergoing percutaneous coronary intervention. HF was evaluated at four time-points before and after acute MI onset: (1) a history of HF; (2) elevated natriuretic peptide levels on admission; (3) in-hospital HF events; and (4) elevated natriuretic peptide levels at a median of 31 days after the onset. When HF was present at each time-point, one point was assigned to a risk scoring system, namely the original and revised HFTPs, ranging from 0 to 3 and from 0 to 4. The primary endpoint was a composite of cardiovascular death and HF rehospitalization after discharge. Results: Of the 1331 patients, 65 (4.9%) had the primary outcome events during a median follow-up period of 507 (interquartile range, 335-1106) days. The increase in both original and revised HFTPs was associated with an increased risk of the primary outcomes in a stepwise fashion with similar diagnostic ability. Conclusions: The original and revised HFTPs were both predictive of long-term HF-related outcomes in patients with acute MI undergoing percutaneous coronary intervention. Yet, the original HFTPs may be sufficient to estimate HF risks after MI.

Diagnostic Ability of Manual Calcification Length Assessment on Non-Electrocardiographically Gated Computed Tomography for Estimating the Presence of Coronary Artery Disease.

Background: Coronary artery calcification score (CACS) on electrocardiography (ECG)-gated computed tomography (CT) is used for risk stratification of atherosclerotic cardiovascular disease, which requires dedicated analytic software. In this study, we evaluated the diagnostic ability of manual calcification length assessment on non-ECG-gated CT for epicardial coronary artery disease (CAD). Methods: A total of 100 patients undergoing both non-ECG-gated plain CT scans with a slice interval of 1.25 mm and invasive coronary angiography were retrospectively included. We manually measured the length of the longest calcified lesions of coronary arteries on each branch. The relationship between the number of coronary arteries with the length of coronary calcium > 5, 10, or 15 mm and the presence of epicardial CAD on invasive angiography was evaluated. Standard CACS was also evaluated using established software. Results: Of 100 patients, 49 (49.0%) had significant epicardial CAD on angiography. The median standard CACS was 346 [7, 1965]. In both manual calcium assessment and standard CACS, the increase in calcium burden was progressively associated with the presence of epicardial CAD on angiography. The receiver operating characteristic curve analysis showed similar diagnostic abilities of the two diagnostic methods. The best cut-off values for CAD were 2, 1, and 1 for the number of vessels with calcium > 5, 10, and 15 mm, respectively. Overall, the diagnostic ability of manual calcium assessment was similar to that of standard CACS > 400. Conclusions: Manual assessment of coronary calcium length on non-ECG-gated plain CT provided similar diagnostic ability for the presence of significant epicardial CAD on invasive angiography, as compared to standard CACS.

Type I interferon promotes the fate of Toll-like receptor 9-stimulated follicular B cells to plasma cell differentiation.

The activation and differentiation of B cells into plasma cells (PCs) play critical roles in the immune response to infections and autoimmune diseases. Toll-like receptor 9 (TLR9) responds to bacterial and viral DNA containing unmethylated CpG motifs and triggers immune responses in B cells; however, abnormal recognition of self-DNA by TLR9 can cause autoimmune diseases. When stimulated with TLR9 agonists, follicular (FO) B cells, a subset of B cells residing in the FO regions of secondary lymphoid organs, exhibit a propensity for activation but fail to give rise to PCs. The factors that enable the transition of TLR9-activated FO B cells from activation to differentiation into PCs remain unclear. In this study, we show that type I interferon-alpha (IFNα) signaling causes FO B cells activated by CpG stimulation to differentiate into PCs. Although CpG stimulation alone only temporarily increased interferon regulatory factor 4 (IRF4) expression in FO B cells, co-stimulation with both CpG and IFNα enhanced and maintained high IRF4 expression levels, ultimately enabling the cells to differentiate into PCs. Overexpression of IRF4 in FO B cells results in CpG-induced PC transition without IFN signaling. Furthermore, co-stimulation of TLR9 and IFNα receptors significantly enhanced mammalian target of rapamycin (mTOR) signaling, which regulates IRF4 expression and PC generation. These findings suggest that IFNα may play a key role in promoting the fate of PC differentiation in FO B cells activated by TLR9 stimulation.

Benchmarking System Monitoring on Quality Improvement in Percutaneous Coronary Intervention: A Nationwide Registry in Japan.

Background: Quality indicators (QIs) have been developed to improve and standardize care quality in percutaneous coronary intervention (PCI). In Japan, consecutive PCI procedures are registered in a nationwide database (the Japanese Percutaneous Coronary Intervention registry), which introduces a benchmarking system for comparing individual institutional performance against the national average. Objectives: The aim of this study was to assess the impact of the benchmarking system implementation on QI improvement at the hospital level. Methods: A total of 734,264 PCIs were conducted at 1,194 institutions between January 2019 and December 2021. In January 2018, a web-based benchmarking system encompassing 7 QIs for PCI at the institutional level, including door-to-balloon time and rate of transradial intervention, was introduced. The process by which institutions tracked their QIs was centrally monitored. Results: During the 3-year study period, the benchmarking system was reviewed at least once at 742 institutions (62.1%) (median 4 times; Q1-Q3: 2-7 times). The institutions that reviewed their records had higher PCI volumes. Among these institutions, although door-to-balloon time was not directly associated, the proportion of transradial intervention increased by 2.3% in the system review group during the initial year compared with 0.7% in their counterparts. However, in the subsequent year, the association between system reviews and QI improvement was attenuated. Conclusions: The implementation of a benchmarking system, reviewed by participating institutions in Japan, was partially associated with improved QIs during the first year; however, this improvement was attenuated in the subsequent year, highlighting the need for further efforts to develop effective and sustainable interventions to enhance care quality in PCI.

Perioperative Evaluation of the Physical Quality of Life of Patients with Non-Small Cell Lung Cancer: A Prospective Study.

Surgery is the most effective treatment for early-stage lung cancer; however, it poses a higher physical burden than other treatment options. Therefore, understanding the perioperative course of patients is important. Using the Short Form Health Survey 36, we prospectively measured the physical quality of life of patients who underwent anatomical pulmonary resection for non-small cell lung cancer at Shonan Kamakura General Hospital, Kanagawa, Japan (n = 87). In the preoperative setting, patients who had lower performance status and lived alone had significantly worse physical quality of life scores on multivariate analysis (regression coefficient (95% confidence interval), -9.37 (-13.43--5.32) and -10.22 (-13.74--7.40), respectively, p < 0.0001 for both). At 6 months postoperatively, patients who stopped smoking within 1 year preoperatively (stopped smoking within 1 year vs. remote or never smokers, 41.0 ± 10.5 vs. 48.6 ± 7.2, p = 0.002), had lower performance status (0 vs. 1-2, 49.3 ± 6.6 vs. 38.6 ± 9.6, p < 0.0001), lived alone (living alone vs. living with somebody, 41.6 ± 9.7 vs. 48.1 ± 7.9, p = 0.021), and had higher comorbid burden (Charlson comorbidity index <3 vs. ≥3, 48.2 ± 6.9 vs. 39.1 ± 14.7, p = 0.003) had significantly worse physical quality of life scores on univariate analysis. More recent smoking (regression coefficient (95% confidence interval), -4.90 (-8.78-1.0), p = 0.014), lower performance status (8.90 (5.10-12.70), p < 0.0001), living alone (5.76 (1.39-10.13), p = 0.01), and higher comorbid burden (-6.94 (-11.78--2.10), p = 0.006) were significant independent predictors of worse postoperative physical quality of life on multivariate analysis. Therefore, patients with these conditions might need additional support to maintain their physical condition after anatomical lung cancer surgery.

Thrombolytic therapy after cardiac arrest in patients with mechanical aortic valve thrombosis.

A 68-year-old woman with history of aortic valve replacement developed severe heart failure and cardiac arrest. Transesophageal echocardiography and cardiac computed tomography showed mechanical aortic valve thrombosis. Low-dose, ultraslow infusion of tissue-plasminogen activator was performed while the patient was in a critically ill condition, resulting in the improvement of thrombus burden and structural valve deterioration. Learning objectives: Mechanical valve thrombosis can be an underlying mechanism of severe heart failure, in which systemic thrombolytic therapy in a low-dose, ultraslow, and prolonged manner may improve clinical outcomes, even in critically ill patients.