Feasibility of left atrial strain assessment using cardiac computed tomography in patients with paroxysmal atrial fibrillation.

PURPOSE: To evaluate the feasibility of left atrial strain (LAS) assessment using cardiac computed tomography (CT) in patients with paroxysmal atrial fibrillation (PAF). METHODS: This retrospective single-center study included 98 patients with PAF who underwent cardiac CT and echocardiography before the first catheter ablation. LAS was analyzed using cardiac CT (CT-LAS) and speckle-tracking echocardiography (STE; STE-LAS). LA reservoir (LASr), conduit (LASc), and pump strain (LASp) were calculated by averaging LAS measured in 4- and 2-chamber views. The results were compared using Pearson's correlation coefficients, paired t-tests, and Bland-Altman analysis. Intraclass correlation coefficients (ICCs) were used to evaluate reproducibility. RESULTS: CT-LAS could be analyzed in all patients, while STE-LAS could be analyzed in 53 (54%) patients. LASr, LASc, and LASp showed significant correlations between CT- and STE-LAS: LASr, r = 0.68, p < 0.001; LASc, r = 0.47, p < 0.001; LASp, r = 0.67, p < 0.001. LASr, LASc, and LASp of CT- and STE-LAS were 23.7 ± 6.0% and 22.1 ± 6.7%, 11.1 ± 3.6% and 11.1 ± 4.1%, and 12.6 ± 4.6% and 11.0 ± 4.1%, respectively. LASr and LASp were significantly higher in CT-LAS than that in STE-LAS (p = 0.023 for LASr and p = 0.001 for LASp). CT-LAS showed excellent reproducibility. The intra- and interobserver ICCs were 0.96 to 0.99 and 0.89 to 0.90, respectively. CONCLUSION: CT-LAS was successfully analyzed in more patients than STE-LAS and was highly reproducible. The findings suggest that CT-LAS is feasible for patients with PAF.

Effects of Heart Rate Variability Biofeedback Training on Anxiety Reduction and Brain Activity: a Randomized Active-Controlled Study Using EEG.

Heart rate variability biofeedback (HRVBF) is a promising anxiety-reducing intervention that increases vagally-mediated heart rate variability (vmHRV) through slow-paced breathing and feedback of heart rhythm. Several studies have reported the anxiety-reducing effects of HRVBF; however, some studies have reported such training as ineffective. Furthermore, the effects of training and underlying brain activity changes remain unclear. This study examined the anxiety-reducing effects of HRVBF training and related brain activity changes by randomly assigning participants, employing an active control group, and measuring anxiety-related attentional bias using the emotional Stroop task and electroencephalography (EEG). Fifty-five healthy students with anxiety were randomly assigned to the HRVBF or control groups, and 21 in the HRVBF group and 19 in the control group were included in the analysis. Both groups performed 10 training sessions of 20 min each within 3 weeks. They were assessed using resting vmHRV, event-related potential (ERP), time-frequency EEG, attentional bias, and the State-Trait Anxiety Inventory-JYZ (STAI-JYZ) before and after training. The results demonstrated increased resting vmHRV in the HRVBF group compared to the control group after training. However, no differences were observed in ERP, time-frequency EEG, attentional bias, and STAI-JYZ. Participants with higher pre-training resting vmHRV achieved higher heart rhythm coherence in HRVBF training and had reduced attentional bias. This study suggests that individuals with higher resting vmHRV are more likely to be proficient in HRVBF training and benefit from its anxiety-reducing effects. The findings contribute to participant selection to benefit from HRVBF training and modification of the training protocols for non-responders.Clinical trial registrationOrganization: University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR), JapanRegistration number: UMIN000047096Registration date: March 6, 2022.

Four-dimensional computed tomography is useful for detection of apical sparing of cardiac amyloidosis.

A 73-year-old male was admitted because of recurrent syncope. He was diagnosed with transient bradycardia caused by a 2:1 atrioventricular block, and he underwent cardiac computed tomography (CT) using 320 detector-row CT to screen for coronary artery disease. Significant coronary artery stenosis was not detected, but diffuse late iodinate enhancement was found on the epi-myocardium and endo-myocardium of the interventricular septum, and endo-myocardium of the anterior and lateral left ventricular (LV) myocardium (LVM) on CT. The ejection fraction and global longitudinal strain (LS) of LVM were 53.97% and - 9.87% on CT. Apical sparing was present, meaning the LS of LV apical segments were preserved compared with basal segments on CT. Pathological findings of LVM demonstrated loss of myocardial cells and extra-cellular amyloid deposition on the direct fast scarlet staining. He was finally diagnosed with transthyretin amyloidosis.

Personalizing cardiovascular risk prediction for patients with systemic lupus erythematosus.

OBJECTIVE: Cardiovascular disease (CVD) risk is increased in SLE and underestimated by general population prediction algorithms. We aimed to develop a novel SLE-specific prediction tool, SLECRISK, to provide a more accurate estimate of CVD risk in SLE. METHODS: We studied patients in the Brigham and Women's Hospital SLE cohort. We collected one-year baseline data including the presence of traditional CVD factors and SLE-related features at cohort enrollment. Ten-year follow-up for the first major adverse cardiovascular event (MACE; myocardial infarction (MI), stroke, or cardiac death) began at day +1 following the baseline period (index date). ICD-9/10 codes identified MACE were adjudicated by board-certified cardiologists. Least absolute shrinkage and selection operator regression selected SLE-related variables to add to the American College of Cardiology/American Heart Association (ACC/AHA) Pooled Cohort Risk Equations 10-year risk Cox regression model. Model fit statistics and performance (sensitivity, specificity, positive/negative predictive value, c-statistic) for predicting moderate/high 10-year risk (≥7.5 %) of MACE were assessed and compared to ACC/AHA, Framingham risk score (FRS), and modified FRS (mFRS). Optimism adjustment internal validation was performed using bootstrapping. RESULTS: We included 1,243 patients with 90 MACEs (46 MIs, 36 strokes, 19 cardiac deaths) over 8946.5 person-years of follow-up. SLE variables selected for the new prediction algorithm (SLECRISK) were SLE activity (remission/mild vs. moderate/severe), disease duration (years), creatinine (mg/dL), anti-dsDNA, anti-RNP, lupus anticoagulant, anti-Ro positivity, and low C4. The sensitivity for detecting moderate/high-risk (≥7.5 %) of MACE using SLECRISK was 0.74 (95 %CI: 0.65, 0.83), which was better than the sensitivity of the ACC/AHA model (0.38 (95 %CI: 0.28, 0.48)). It also identified 3.4-fold more moderate/high-risk patients than the ACC/AHA. Patients who were moderate/high-risk according to SLECRISK but not ACC/AHA, were more likely to be young women with severe SLE and few other traditional CVD risk factors. Model performance between SLECRISK, FRS, and mFRS were similar. CONCLUSION: The novel SLECRISK tool is more sensitive than the ACC/AHA for predicting moderate/high 10-year risk for MACE and may be particularly useful in predicting risk for young females with severe SLE. Future external validation studies utilizing cohorts with more severe SLE are needed.

Herpes Simplex Virus Encephalitis in Patients With Autoimmune Conditions or Exposure to Immunomodulatory Medications.

BACKGROUND AND OBJECTIVES: Among infectious etiologies of encephalitis, herpes simplex virus type 1 (HSV-1) is most common, accounting for ∼15%-40% of adult encephalitis diagnoses. We aim to investigate the association between immune status and HSV encephalitis (HSVE). Using a US Medicaid database of 75.6 million persons, we evaluated the association between HSVE and autoimmune conditions, exposure to immunosuppressive and immunomodulatory medications, and other medical comorbidities. METHODS: We used the US Medicaid Analytic eXtract data between 2007 and 2010 from the 29 most populated American states. We first examined the crude incidence of HSVE in the population. We then age and sex-matched adult cases of HSVE with a sufficient enrollment period (12 months before HSVE diagnosis) to a larger control population without HSVE. In a case-control analysis, we examined the association between HSVE and exposure to both autoimmune disease and immunosuppressive/immunomodulatory medications. Analyses were conducted with conditional logistic regression progressively adjusting for sociodemographic factors, Charlson Comorbidity Index, and non-autoimmune comorbidities. RESULTS: Incidence of HSVE was ∼3.01 per 105 person-years among adults. A total of 951 HSVE cases and 95,100 age and sex-matched controls were compared. The HSVE population had higher rates of medical comorbidities than the control population. The association of HSVE and autoimmune conditions was strong (adjusted odds ratio (OR) 2.6; 95% CI 2.2-3.2). The association of HSVE and immunomodulating medications had an OR of 2.2 (CI 1.9-2.6), also after covariate adjustment. When both exposures were included in regression models, the associations remained robust: OR 2.3 (CI 1.9-2.7) for autoimmune disease and 2.0 (CI 1.7-2.3) for immunosuppressive and immunomodulatory medications. DISCUSSION: In a large, national population, HSVE is strongly associated with preexisting autoimmune disease and exposure to immunosuppressive and immunomodulatory medications. The role of antecedent immune-related dysregulation may have been underestimated to date.

Coronary computed tomography angiography for clinical practice.

Coronary artery disease (CAD) is a common condition caused by the accumulation of atherosclerotic plaques. It can be classified into stable CAD or acute coronary syndrome. Coronary computed tomography angiography (CCTA) has a high negative predictive value and is used as the first examination for diagnosing stable CAD, particularly in patients at intermediate-to-high risk. CCTA is also adopted for diagnosing acute coronary syndrome, particularly in patients at low-to-intermediate risk. Myocardial ischemia does not always co-exist with coronary artery stenosis, and the positive predictive value of CCTA for myocardial ischemia is limited. However, CCTA has overcome this limitation with recent technological advancements such as CT perfusion and CT-fractional flow reserve. In addition, CCTA can be used to assess coronary artery plaques. Thus, the indications for CCTA have expanded, leading to an increased demand for radiologists. The CAD reporting and data system (CAD-RADS) 2.0 was recently proposed for standardizing CCTA reporting. This RADS evaluates and categorizes patients based on coronary artery stenosis and the overall amount of coronary artery plaque and links this to patient management. In this review, we aimed to review the major trials and guidelines for CCTA to understand its clinical role. Furthermore, we aimed to introduce the CAD-RADS 2.0 including the assessment of coronary artery stenosis, plaque, and other key findings, and highlight the steps for CCTA reporting. Finally, we aimed to present recent research trends including the perivascular fat attenuation index, artificial intelligence, and the advancements in CT technology.

Arthroscopically Assisted Coracoclavicular (CC) Stabilization Using a Suture Button Device for Lateral Clavicle Fractures with CC Ligament Injury.

Background: Lateral clavicle fractures represent approximately 10-15% of all clavicle fractures. However, controversy exists regarding the optimal surgical treatment because of instability associated with the coracoclavicular (CC) ligament injury and a small lateral fragment. The purpose of this study was to evaluate the radiological and clinical outcomes of arthroscopically assisted CC stabilization using a suture button device for lateral clavicle fractures accompanied by CC ligament injury. Methods: A retrospective observational study involved six patients with modified Neer type IIB fractures, which were treated with the technique and followed for 12 months. Postoperative range of motion (ROM) and X-rays were evaluated every 3 months. Shoulder functional scores (University of California Los Angeles score, Japanese Orthopedics Association score) and visual analog scale (VAS) scores for pain (at rest, at night, and during motion) and for satisfaction were analyzed 12 months after surgery. Results: Early phase ROM recovery and excellent outcomes were achieved. All patients achieved bone union. Slight superior clavicle displacement and bone hole dilation occurred with no critical complications. Conclusions: Arthroscopically assisted CC stabilization with a suture button device for unstable lateral clavicle fractures can produce satisfactory radiological and clinical results.

Analysis of Homo- and Heterotriple Helix Formation of Collagen Model Peptides and Evaluation of Their Stability in a Biological Environment.

Self-assembled materials have attracted attention and have been extensively studied because the reversibility of noncovalent interactions allows them to possess various properties, such as stimulus responsiveness and self-healing. Collagen model peptides have an amino acid sequence characteristic of the triple helix region of collagen and exhibit repeatable triple helix formation. Many studies of their applications have used homotrimers, and although some studies on heterotrimers have been reported, few have clarified the details. If the characteristics of heterotrimers can be revealed, they are expected to be applied as new self-assembled materials. In this study, we analyzed the detailed self-assembling properties of hetero- and homohelices formed by (proline-proline-glycine)10 (PPG)10 and (proline-hydroxyproline-glycine)10 (POG)10 to evaluate the potential of the helices for biomedical application. Fluorescein isothiocyanate-labeled (PPG)10 (F(PPG)10) and (POG)10 (F(POG)10) were synthesized to analyze the heterotriple helix formation using concentration quenching based on triple helix formation. When (PPG)10 was added to F(POG)10, the fluorescence intensity did not reach a plateau, while the fluorescence intensity reached about 100% in the other pairs such as (POG)10-F(POG)10, (PPG)10-F(PPG)10, and (POG)10-F(PPG)10. The critical triple helix formation concentration was 7 µM for the heterotrimer prepared under 1:2 mixing conditions of (PPG)10 and (POG)10, 320 µM for [(PPG)10]3, and 4 µM for [(POG)10]3, indicating that the triple helix formation concentration of the heterotrimer is almost half that of [(POG)10]3 but 45 times higher than [(PPG)10]3. Furthermore, the heterotrimer formed at 37 °C was stable after 5 days, which was the same as [(POG)10]3. These results suggest that heterotrimers have different association properties from homotrimers and are expected to be applied in nanotechnology and biomaterials as new self-assembled materials.

Strong Diagnostic Performance of Single Energy 256-row Multidetector Computed Tomography with Deep Learning Image Reconstruction in the Assessment of Myocardial Fibrosis.

Objective Although magnetic resonance imaging (MRI) is the gold standard for evaluating abnormal myocardial fibrosis and extracellular volume (ECV) of the left ventricular myocardium (LVM), a similar evaluation has recently become possible using computed tomography (CT). In this study, we investigated the diagnostic accuracy of a new 256-row multidetector CT with a low tube-voltage single energy scan and deep-learning-image reconstruction (DLIR) in detecting abnormal late enhancement (LE) in LVM. Methods We evaluated the diagnostic performance of CT for detecting LE in LVM and compared the results with those of MRI as a reference. We also measured the ECV of the LVM on CT and compared the results with those on MRI. Patients or Materials We analyzed 50 consecutive patients who underwent cardiac CT, including a late-phase scan and MRI, within three months of suspected cardiomyopathy. All patients underwent 256-slice CT (Revolution CT Apex; GE Healthcare) with a low tube-voltage (70 kV) single energy scan and DLIR for a late-phase scan. Results In patient- and segment-based analyses, the sensitivity, specificity, and accuracy of detection of LE on CT were 94% and 85%, 100% and 95%, and 96% and 93%, respectively. The ECV of LVM per patient on CT and MRI was 33.0% ±6.2% and 35.9% ±6.1%, respectively. These findings were extremely strongly correlated, with a correlation coefficient of 0.87 (p <0.0001). The effective radiation dose on late-phase scanning was 2.4±0.9 mSv. Conclusion The diagnostic performance of 256-row multislice CT with a low tube voltage and DLIR for detecting LE and measuring ECV in LVM is credible.

[Enhancement of mast cells activation by ATP via P2X4 receptor].

Adenosine-5'-triphosphate (ATP) is an important intracellular energy currency, but it is released extracellularly in response to various stimuli and acts as an intercellular signaling molecule by stimulating various P2 receptors. ATP and ADP are stored in synaptic vesicles and secretory granules, and are released extracellularly upon stimulation, playing important roles in neurotransmission and platelet aggregation. Furthermore, considerable amount of ATP is released by mechanical stimuli such as skin scraping or by cell damage, which in turn activates immune cells to promote inflammatory responses. Mast cells (MCs) are derived from hematopoietic stem cells and play a central role in type I allergic reactions. MCs are activated by IgE-mediated antigen recognition, leading to type I allergic reactions. MCs express P2X7 receptors that are activated by high concentrations of ATP (>0.5 |mM), and reported to aggravate inflammatory bowel disease and dermatitis. In contrast, role of MC P2 receptors that respond to lower concentrations of ATP remains to be investigated. We investigated in detail the effects of ATP in mouse bone marrow-derived MCs, and found that lower concentrations of ATP (<100 |µM) promotes IgE-dependent and GPCR-mediated degranulation via the ionotropic P2X4 receptor. In mouse allergic models, P2X4 receptor signal promote MC-mediated allergic responses through comprehensively increasing the sensitivity of MCs to different stimuli. Since ATP is known to be released from various cells upon mechanical stimuli such as cell damage or scratching, inhibition of P2X4 receptor signaling may represent a novel strategy to abrogate allergic reaction.

Improving the accuracy of automated gout flare ascertainment using natural language processing of electronic health records and linked Medicare claims data.

BACKGROUND: We aimed to determine whether integrating concepts from the notes from the electronic health record (EHR) data using natural language processing (NLP) could improve the identification of gout flares. METHODS: Using Medicare claims linked with EHR, we selected gout patients who initiated the urate-lowering therapy (ULT). Patients' 12-month baseline period and on-treatment follow-up were segmented into 1-month units. We retrieved EHR notes for months with gout diagnosis codes and processed notes for NLP concepts. We selected a random sample of 500 patients and reviewed each of their notes for the presence of a physician-documented gout flare. Months containing at least 1 note mentioning gout flares were considered months with events. We used 60% of patients to train predictive models with LASSO. We evaluated the models by the area under the curve (AUC) in the validation data and examined positive/negative predictive values (P/NPV). RESULTS: We extracted and labeled 839 months of follow-up (280 with gout flares). The claims-only model selected 20 variables (AUC = 0.69). The NLP concept-only model selected 15 (AUC = 0.69). The combined model selected 32 claims variables and 13 NLP concepts (AUC = 0.73). The claims-only model had a PPV of 0.64 [0.50, 0.77] and an NPV of 0.71 [0.65, 0.76], whereas the combined model had a PPV of 0.76 [0.61, 0.88] and an NPV of 0.71 [0.65, 0.76]. CONCLUSION: Adding NLP concept variables to claims variables resulted in a small improvement in the identification of gout flares. Our data-driven claims-only model and our combined claims/NLP-concept model outperformed existing rule-based claims algorithms reliant on medication use, diagnosis, and procedure codes.

Immunomodulator use, risk factors and management of flares, and mortality for patients with pre-existing rheumatoid arthritis after immune checkpoint inhibitors for cancer.

OBJECTIVE: To investigate immunomodulator use, risk factors and management for rheumatoid arthritis (RA) flares, and mortality for patients with pre-existing RA initiating immune checkpoint inhibitors (ICI) for cancer. METHODS: We performed a retrospective cohort study of all patients with RA meeting 2010 ACR/EULAR criteria that initiated ICI for cancer at Mass General Brigham or Dana-Farber Cancer Institute in Boston, MA (2011-2022). We described immunomodulator use and changes at baseline of ICI initiation. We identified RA flares after baseline, categorized the severity, and described the management. Baseline factors were examined for RA flare risk using Fine and Gray competing risk models. We performed a landmark analysis to limit the potential for immortal time bias, where the analysis started 3 months after ICI initiation. Among those who survived at least 3 months, we examined whether RA flare within 3 months after ICI initiation was associated with mortality using Cox regression. RESULTS: Among 11,901 patients who initiated ICI for cancer treatment, we analyzed 100 pre-existing RA patients (mean age 70.3 years, 63 % female, 89 % on PD-1 monotherapy, 50 % lung cancer). At ICI initiation, 71 % were seropositive, 82 % had remission/low RA disease activity, 24 % were on glucocorticoids, 35 % were on conventional synthetic disease-modifying antirheumatic drugs (DMARDs), and 10 % were on biologic or targeted synthetic DMARDs. None discontinued glucocorticoids and 3/35 (9 %) discontinued DMARDs in anticipation of starting ICI. RA flares occurred in 46 % (incidence rate 1.84 per 1000 person-months, 95 % CI 1.30, 2.37); 31/100 flared within 3 months of baseline. RA flares were grade 1 in 16/46 (35 %), grade 2 in 25/46 (54 %), and grade 3 in 5/46 (11 %); 2/46 (4 %) required hospitalization for RA flare. Concomitant immune-related adverse events occurred in 15/46 (33 %) that flared. A total of 72/100 died during follow-up; 21 died within 3 months of baseline. Seropositivity had an age-adjusted sdHR of 1.95 (95 % CI 1.02, 3.71) for RA flare compared to seronegativity, accounting for competing risk of death. Otherwise, no baseline factors were associated with RA flare, including cancer type, disease activity, RA duration, and deformities. 9/46 (20 %) patients had their ICI discontinued/paused due to RA flares. In the landmark analysis among 79 patients who survived at least 3 months, RA flare in the first 3 months was not associated with lower mortality (adjusted HR 1.24, 95 % CI 0.71, 2.16) compared to no RA flare. CONCLUSION: Among patients with pre-existing RA, few changed immunomodulator medications in anticipation of starting ICI, but RA flares occurred in nearly half. RA flares were mostly mild and treated with typical therapies. Seropositivity was associated with RA flare risk. A minority had severe RA flares requiring disruption of ICI, and RA flares were not associated with mortality.

Rheumatoid arthritis, quantitative parenchymal lung features, and mortality among smokers.

OBJECTIVES: There have been limited investigations of the prevalence and mortality impact of quantitative computed tomography (QCT) parenchymal lung features in rheumatoid arthritis (RA). We examined the cross-sectional prevalence and mortality associations of QCT features, comparing RA and non-RA participants. METHODS: We identified participants with and without RA in COPDGene, a multicentre cohort study of current or former smokers. Using a k-nearest neighbor quantifier, high resolution CT chest scans were scored for percentage of normal lung, interstitial changes, and emphysema. We examined associations between QCT features and RA using multivariable linear regression. After dichotomizing participants at the 75th percentile for each QCT feature among non-RA participants, we investigated mortality associations by RA/non-RA status and quartile 4 vs quartiles 1-3 of QCT features using Cox regression. We assessed for statistical interactions between RA and QCT features. RESULTS: We identified 82 RA cases and 8820 non-RA comparators. In multivariable linear regression, RA was associated with higher percentage of interstitial changes (ß = 1.7 ± 0.5, p= 0.0008) but not emphysema (ß = 1.3 ± 1.7, p= 0.44). Participants with RA and >75th percentile of emphysema had significantly higher mortality than non-RA participants (HR 5.86, 95%CI 3.75-9.13) as well as RA participants (HR 5.56, 95%CI 2.71-11.38) with ≤75th percentile of emphysema. There were statistical interactions between RA and emphysema for mortality (multiplicative p= 0.014; attributable proportion 0.53, 95%CI 0.30-0.70). CONCLUSIONS: Using machine learning-derived QCT data in a cohort of smokers, RA was associated with higher percentage of interstitial changes. The combination of RA and emphysema conferred >5-fold higher mortality.