Aortic Arch Plaques and the Long-Term Risk of Stroke and Cardiovascular Events in the Statin Era.

BACKGROUND: Aortic arch plaques are associated with an increased risk of ischemic stroke in patients with cryptogenic stroke or prior embolic events. However, this relationship is unclear in the community. We investigated (1) the long-term risk of stroke and cardiovascular events associated with arch plaques and (2) whether statin therapy prescribed for any indication modified the association. METHODS: A total of 934 stroke-free participants (72±9 years; 37% men) from the CABL study (Cardiovascular Abnormalities and Brain Lesion) were evaluated. Arch plaques were assessed by suprasternal transthoracic echocardiography; plaques ≥4 mm in thickness were classified as large plaques. The primary outcome was ischemic stroke; the secondary outcome was combined cardiovascular events (ischemic stroke, myocardial infarction, and cardiovascular death). The plaque-related risk of outcomes was also analyzed according to the presence of statin treatment. No plaque was used as a reference. RESULTS: Aortic arch plaques were present in 645 participants (69.1%), with large plaques in 114 (12.2%). During a mean follow-up of 11.3±3.6 years, 236 (25.3%) cardiovascular events occurred (76 ischemic strokes, 27 myocardial infarctions, and 133 cardiovascular deaths). Large arch plaques were independently associated with combined events (adjusted hazard ratio, 2.19 [95% CI, 1.40-3.43]) but not stroke alone (adjusted hazard ratio, 1.09 [95% CI, 0.50-2.38]). The association between large plaques and cardiovascular events was significant in participants receiving statins (adjusted hazard ratio, 2.57 [95% CI, 1.52-4.37]) but not in others; however, participants on statin treatment also had a worse risk profile (higher body mass index, greater frequencies of hypertension, diabetes, and coronary artery disease). CONCLUSIONS: Aortic arch plaques may be a marker of cardiovascular risk rather than a direct embolic stroke source in older adults without prior stroke. The efficacy of broader cardiovascular risk factors control, beyond cholesterol levels alone, for primary prevention of cardiovascular events in individuals with aortic arch plaques may require further investigation.

Phase II Study of Intraperitoneal Administration of Paclitaxel Combined with S-1 and Cisplatin for Gastric Cancer with Peritoneal Metastasis.

BACKGROUND: Intraperitoneal chemotherapy is promising for gastric cancer with peritoneal metastasis. Although a phase III study failed to show a statistically significant superiority of intraperitoneal paclitaxel combined with S-1 and intravenous paclitaxel, the sensitivity analysis suggested clinical efficacy. Thus, attempts to combine intraperitoneal paclitaxel with other systemic therapies with higher efficacy have been warranted. We sought to explore the efficacy of intraperitoneal paclitaxel with S-1 and cisplatin. PATIENTS AND METHODS: Gastric cancer patients with peritoneal metastasis were enrolled in the phase II trial. In addition to the established S-1 and cisplatin regimen every 5 weeks, intraperitoneal paclitaxel was administered on days 1, 8, and 22 at a dose of 20 mg/m2. The primary endpoint was overall survival rate at 1 year after treatment initiation. Secondary endpoints were progression-free survival and toxicity. RESULTS: Fifty-three patients were enrolled and fully evaluated for efficacy and toxicity. The 1-year overall survival rate was 73.6% (95% confidence interval 59.5-83.4%), and the primary endpoint was met. The median survival time was 19.4 months (95% confidence interval, 16.1-24.6 months). The 1-year progression-free survival rate was 49.6% (95% confidence interval, 34.6-62.9%). The incidences of grade 3/4 hematological and non-hematological toxicities were 43% and 47%, respectively. The frequent grade 3/4 toxicities included neutropenia (25%), anemia (30%), diarrhea (13%), and anorexia (17%). Intraperitoneal catheter and implanted port-related complications were observed in four patients. There was one treatment-related death. CONCLUSIONS: Intraperitoneal paclitaxel combined with S-1 and cisplatin is well tolerated and active in gastric cancer patients with peritoneal metastasis.

Racial Differences in Age-Related Changes in Left Ventricular Structural and Functional Echocardiographic Measurements Among Healthy Japanese and American Participants　- A Subanalysis of the World Alliance Society of Echocardiography Normal Values Study.

BACKGROUND: Age-related changes in left ventricular (LV) structure and function lower the threshold for the onset of heart failure with preserved ejection fraction (HFpEF). LV parameters change also with race; however, the racial differences in age-related changes in LV parameters with and without adjustment for body mass index (BMI), heart rate (HR), and blood pressure (BP) remain unclear.Methods and Results: We performed a subanalysis of the World Alliance Society of Echocardiography Normal Values Study, an international cross-sectional study that examined normal echocardiographic values in 15 countries. The age-related changes in 2-dimensional echocardiographic derived parameters including LV size, systolic function, and mass, were compared between healthy Japanese (n=227) and healthy White (n=98) and Black (n=69) American participants. In men, age-related changes in all parameters did not differ significantly among races. However, compared with Japanese women, White American women had a smaller body surface area (BSA)-indexed LV volume, BSA-indexed LV internal dimension at end-systole, BSA-indexed LV stroke volume, and LV mass index to BSA, and a larger LV ejection fraction with age, even after adjusting for BMI, HR, and BP. CONCLUSIONS: Age-related changes in LV structure and function, which are important for the pathophysiology of HFpEF, may differ by race. Therefore, future studies examining echocardiographic reference values for each age group in each race are needed.

Efficacy and Tolerability of Ivabradine for Cardiomyopathy in Patients with Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD) is an intractable X-linked myopathy caused by dystrophin gene mutations. Patients with DMD suffer from progressive muscle weakness, inevitable cardiomyopathy, increased heart rate (HR), and decreased blood pressure (BP). The aim of this study was to clarify the efficacy and tolerability of ivabradine treatment for DMD cardiomyopathy.A retrospective analysis was performed in 11 patients with DMD, who received ivabradine treatment for more than 1 year. Clinical results were analyzed before (baseline), 6 months after, and 12 months after the ivabradine administration.The initial ivabradine dose was 2.0 ± 1.2 mg/day and the final dose was 5.6 ± 4.0 mg/day. The baseline BP was 95/64 mmHg. A non-significant BP decrease to 90/57 mmHg was observed at 1 month but it recovered to 97/62 mmHg at 12 months after ivabradine administration. The baseline HR was 93 ± 6 bpm and it decreased to 74 ± 12 bpm at 6 months (P = 0.011), and to 77 ± 10 bpm at 12 months (P = 0.008). A linear correlation (y = 2.2x + 5.1) was also observed between the ivabradine dose (x mg/day) and HR decrease (y bpm). The baseline LVEF was 38 ± 12% and it significantly increased to 42 ± 9% at 6 months (P = 0.011) and to 41 ± 11% at 12 months (P = 0.038). Only 1 patient with the lowest BMI of 11.0 kg/m2 and BP of 79/58 mmHg discontinued ivabradine treatment at 6 months, while 1-year administration was well-tolerated in the other 10 patients.Ivabradine decreased HR and increased LVEF without lowering BP, suggesting it can be a treatment option for DMD cardiomyopathy.

Albumin-Globulin Ratio Indicates the Survival Outcome of Pancreatic Cancer Cases Who Underwent Preoperative Treatment and Curative Surgical Resection.

BACKGROUND: The pretreatment albumin-globulin ratio (AGR) is a frequently used inflammation-associated factor that has been reported to have associations with the survival outcomes of various malignancies. METHODS: We retrospectively analyzed 162 patients with pancreatic cancer who underwent preoperative treatment followed by curative surgery at Nagoya University Hospital between April 2010 and December 2020. Representative nutritional status indicators of neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), prognostic nutritional index (PNI), and albumin-globulin ratio (AGR) were calculated for each case. RESULTS: Among pretreatment blood examination parameters, only AGR (cutoff: 1.33) showed a significant difference in overall survival time (OS) and progression-free survival time (PFS) from the beginning of the preoperative treatment. Median PFS was 22.3 mo, in high AGR cases and 17.1 mo, in low AGR cases (P = 0.019). Median OS was 48.7 mo, in high AGR cases and 32.9 mo, in low AGR cases (P = 0.043). CONCLUSION: High pretreatment AGR may be a favorable prognostic factor for pancreatic cancer patients who received preoperative multimodal therapy followed by curative cancer resection. It may imply that nutritional status and inflammation control before the multimodal treatment affect the survival outcomes of pancreatic cancer cases and needs to be optimized.

Prevalence of glucose metabolism disorders and its association with left atrial remodelling before and after catheter ablation in patients with atrial fibrillation.

AIMS: To investigate the exact prevalence of glucose metabolism disorders, and their impact on left atrial (LA) remodelling and reversibility in patients with atrial fibrillation (AF). METHODS AND RESULTS: We examined 204 consecutive patients with AF who underwent their first catheter ablation (CA). Oral glucose tolerance test was used to evaluate glucose metabolism disorders in 157 patients without known diabetes mellitus (DM). Echocardiography was performed before and 6 months after CA. Oral glucose tolerance test identified abnormal glucose metabolism in 86 patients [11 with newly diagnosed DM, 74 with impaired glucose tolerance (IGT) and 1 with impaired fasting glucose (IFG)]. Ultimately, 65.2% of patients had abnormal glucose metabolism. Diabetes mellitus group had the worst LA reservoir strain and LA stiffness (both P < 0.05), while there was no significant difference in baseline LA parameters between normal glucose tolerance (NGT) group and IGT/IFG group. The prevalence of LA reverse remodelling (≥15% decrease in the LA volume index at 6 months after CA) was significantly higher in NGT group compared with IGT/IFG and DM group (64.1 vs. 38.6 vs. 41.5%, P = 0.006). Both DM and IFG/IGT carry a significant risk of lack of LA reverse remodelling independent of baseline LA size and AF recurrence. CONCLUSION: Approximately 65% of patients with AF who underwent their first CA had abnormal glucose metabolism. Patients with DM had significantly impaired LA function compared with non-DM patients. Impaired glucose tolerance/IFG as well as DM carries significant risk of unfavourable LA reverse remodelling. Our observations may provide valuable information regarding the mechanisms and therapeutic strategies of glucose metabolism-related AF.

Proposal of the Second Cutoff of Serum Carcinoembryonic Antigen Levels to Stratify Patients into Low, Intermediate, and High Risks at Recurrences after Curative Resection of Gastric Cancer.

INTRODUCTION: Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 are widely used for treating various cancers, with cutoff values of 5.0 ng/mL and 37.0 IU/mL, respectively. However, these cutoff values are not for specific diseases or purposes but are uniformly used for any disease and any purpose. It is also unclear as to whether patients are at equal risk of recurrence if they are below the cutoff values. This study aimed to investigate the optimal cutoff of serum tumor markers in the stratification of recurrence risk after curative resection of gastric cancer. METHODS: We constructed a nine-center integrated database of patients who received gastrectomy between January 2010 and December 2014 with a 5-year follow-up period. We determined the cutoff value of preoperative serum tumor marker levels correlated with postoperative recurrences and evaluated its performance in risk stratification for recurrences in 948 patients with stage II/III gastric cancer who underwent radical resection. RESULTS: The hazard ratio for postoperative recurrences increased at two points of preoperative CEA levels, 3.6 ng/mL and 5.0 ng/mL, which were set as cutoffs. These two cutoffs stratified relapse-free survival into three levels. CONCLUSIONS: By adding a second cutoff value for preoperative serum CEA, which was proposed specifically for the prediction of recurrences, patients can be stratified into low-, intermediate-, and high-risk recurrences after curative resection of gastric cancer.

Chapter 3: Management of kidney injury caused by cancer drug therapy, from clinical practice guidelines for the management of kidney injury during anticancer drug therapy 2022.

Cisplatin should be administered with diuretics and Magnesium supplementation under adequate hydration to avoid renal impairment. Patients should be evaluated for eGFR (estimated glomerular filtration rate) during the treatment with pemetrexed, as kidney injury has been reported. Pemetrexed should be administered with caution in patients with a CCr (creatinine clearance) < 45 mL/min. Mesna is used to prevent hemorrhagic cystitis in patients receiving ifosfamide. Febuxostat is effective in avoiding hyperuricemia induced by TLS (tumor lysis syndrome). Preventative rasburicase is recommended in high-risk cases of TLS. Thrombotic microangiopathy could be triggered by anticancer drugs and there is no evidence of efficacy of plasma exchange therapy. When proteinuria occurs during treatment with anti-angiogenic agents or multi-kinase inhibitors, dose reductions or interruptions based on grading should be considered. Grade 3 proteinuria and renal dysfunction require urgent intervention, including drug interruption or withdrawal, and referral to a nephrologist should be considered. The first-line drugs used for blood pressure elevation due to anti-angiogenic agents are ACE (angiotensin-converting enzyme) inhibitors and ARBs (angiotensin receptor blockers). The protein binding of drugs and their pharmacokinetics are considerably altered in patients with hypoalbuminemia. The clearance of rituximab is increased in patients with proteinuria, and the correlation with urinary IgG suggests similar pharmacokinetic changes when using other antibody drugs. AIN (acute interstitial nephritis) is the most common cause of ICI (immune checkpoint inhibitor)-related kidney injury that is often treated with steroids. The need for renal biopsy in patients with kidney injury that occurs during treatment with ICI remains controversial.

Drain Amylase Concentrations at 3 h After Gastrectomy Enhance Early Prediction of Postoperative Peripancreatic Inflammatory Fluid Collection.

BACKGROUND: Despite numerous studies of peripancreatic inflammatory fluid collection (PIFC) that report on the relevance of the drain amylase concentration (D-AMY), early prediction using this assay is problematic. This study aimed to investigate the clinical significance of measuring the D-AMY at 3 h after gastrectomy (POD0) for gastric cancer. METHODS: This retrospective analysis included consecutive patients who underwent gastrectomy combined with peripancreatic lymph node dissection. The predictive value of D-AMY on POD0 and postoperative day 1 (POD1) for clinically relevant PIFC was evaluated together or individually. RESULTS: Analyses were performed in 204 patients. Twenty (9.8%) patients experienced PIFC. D-AMY cutoffs of 721 IU/L on POD0 and 1695 IU/L on POD1 were determined using the receiver operating characteristic curve analysis for predicting PIFC. The D-AMY on POD0 had higher sensitivity (80%) but lower specificity (66.3%) for prediction of PIFC, compared with those of D-AMY on POD1 (65%, 89.1%, respectively). When combination marker analysis was performed, the highest risk group (D-AMY ≥ the cutoff values of POD0 and POD1) were associated with an elevated rate of occurrence (44%) and a high positive likelihood ratio (7.36) compared with those of the single cutoff group. The lowest risk group (D-AMY < the cutoff values on POD0 and POD1) was associated with a low rate of occurrence (2.5%) and low negative likelihood ratio (0.24) compared with those of the single cutoff group. CONCLUSIONS: Combined measurements of D-AMYs on POD0 and POD1 enhanced early prediction of PIFC after gastrectomy.

Prognostic impact of a microscopic positive margin in patients undergoing gastrectomy for gastric cancer: a propensity score­matched analysis of a multi­institutional dataset.

PURPOSE: We analyzed the effect of a microscopic positive margin on survival outcomes after gastrectomy for gastric cancer METHODS: We analyzed a multi-institutional dataset to study patients who underwent gastrectomy with curative intent between 2010 and 2014. We used propensity score matching to strictly balance the patients' oncological features, backgrounds, and postoperative treatment to compare the survival outcomes of those with microscopic positive margins and those with negative margins. RESULTS: Among 3029 patients, 32 (1.1%) had positive margins. After matching, we enrolled 128 patients in this retrospective analysis: 32 with a positive margin and 96 with a negative margin. The recurrence-free survival of the positive-margin group was significantly shorter than that of the negative-margin group (hazard ratio [HR], 1.62, 95% confidence interval, 1.00-2.63, p = 0.0485). Consistent results were observed for patients with pStages I-III disease (HR, 1.65, p = 0.0835), whereas the survival curves overlapped in those with pStage IV disease (HR, 1.29, p = 0.5934). The prevalence of overall recurrence in the positive-margin group was higher than that in the negative-margin group (75% vs 58%, p = 0.0917). This trend was consistent with locoregional recurrence (9% vs 3%) and distant recurrence (69% vs 55%). CONCLUSIONS: The survival of patients after curative gastrectomy for gastric cancer was worse in those with microscopic positive margins than in those with negative margins.

E-PASS scoring system serves as a predictor of short- and long-term outcomes in gastric cancer surgery.

PURPOSES: This study aimed to evaluate the estimation of the physiological ability and surgical stress (E-PASS) scoring system for predicting the short- and long-term outcomes in gastric cancer (GC) surgery. METHODS: We analyzed a multi-institutional dataset to study patients who underwent gastrectomy with a curative intent between 2010 and 2014. This study evaluated the associations between the optimal E-PASS score cutoff value and the following outcomes: (1) the incidence of postoperative complications in stage I-III GC patients and (2) the prognosis in stage II-III GC patients. RESULTS: A total of 2495 GC patients were included. A cutoff value of 0.419 was determined using the ROC curve analysis. Postoperative complications were observed more frequently in the E-PASS-high group than that in the E-PASS-low group (30% vs. 17%, p < 0.0001). Among pStage II-III GC patients (n = 1009), the overall survival time of the E-PASS-high group was significantly shorter than that of the E-PASS-low group (hazard ratio 2.08; 95% confidence interval 1.64-2.65; p < 0.0001). A forest plot revealed that E-PASS-high was associated with a greater prognostic factor for overall survival in most subgroups. CONCLUSIONS: The E-PASS scoring system may therefore be a useful predictor of the short- and long-term outcomes in patients with GC who have undergone radical gastrectomy.

Automatic Detection of Left Ventricular Dilatation and Hypertrophy from Electrocardiograms Using Deep Learning.

Left ventricular dilatation (LVD) and left ventricular hypertrophy (LVH) are risk factors for heart failure, and their detection improves heart failure screening. This study aimed to investigate the ability of deep learning to detect LVD and LVH from a 12-lead electrocardiogram (ECG). Using ECG and echocardiographic data, we developed deep learning and machine learning models to detect LVD and LVH. We also examined conventional ECG criteria for the diagnosis of LVH. We calculated the area under the receiver operating characteristic (AUROC) curve, sensitivity, specificity, and accuracy of each model and compared the performance of the models. We analyzed data for 18,954 patients (mean age (standard deviation): 64.2 (16.5) years, men: 56.7%). For the detection of LVD, the value (95% confidence interval) of the AUROC was 0.810 (0.801-0.819) for the deep learning model, and this was significantly higher than that of the logistic regression and random forest methods (P < 0.001). The AUROCs for the logistic regression and random forest methods (machine learning models) were 0.770 (0.761-0.779) and 0.757 (0.747-0.767), respectively. For the detection of LVH, the AUROC was 0.784 (0.777-0.791) for the deep learning model, and this was significantly higher than that of the logistic regression and random forest methods and conventional ECG criteria (P < 0.001). The AUROCs for the logistic regression and random forest methods were 0.758 (0.751-0.765) and 0.716 (0.708-0.724), respectively. This study suggests that deep learning is a useful method to detect LVD and LVH from 12-lead ECGs.

Postnatal development of mice with combined genetic depletions of lamin A/C, emerin and lamina-associated polypeptide 1.

Mutations in LMNA encoding lamin A/C and EMD encoding emerin cause cardiomyopathy and muscular dystrophy. Lmna null mice develop these disorders and have a lifespan of 7-8 weeks. Emd null mice show no overt pathology and have normal skeletal muscle but with regeneration defects. We generated mice with germline deletions of both Lmna and Emd to determine the effects of combined loss of the encoded proteins. Mice without lamin A/C and emerin are born at the expected Mendelian ratio, are grossly normal at birth but have shorter lifespans than those lacking only lamin A/C. However, there are no major differences between these mice with regards to left ventricular function, heart ultrastructure or electrocardiographic parameters except for slower heart rates in the mice lacking both lamin A/C and emerin. Skeletal muscle is similarly affected in both of these mice. Lmna+/- mice also lacking emerin live to at least 1 year and have no significant differences in growth, heart or skeletal muscle compared to Lmna+/- mice. Deletion of the mouse gene encoding lamina-associated protein 1 leads to prenatal death; however, mice with heterozygous deletion of this gene lacking both lamin A/C and emerin are born at the expected Mendelian ratio but had a shorter lifespan than those only lacking lamin A/C and emerin. These results show that mice with combined deficiencies of three interacting nuclear envelope proteins have normal embryonic development and that early postnatal defects are primarily driven by loss of lamin A/C or lamina-associated polypeptide 1 rather than emerin.

Impact of insulin resistance on subclinical left ventricular dysfunction in normal weight and overweight/obese japanese subjects in a general community.

BACKGROUND: Insulin resistance carries increased risk of heart failure, although the pathophysiological mechanisms remain unclear. LV global longitudinal strain (LVGLS) assessed by speckle-tracking echocardiography has emerged as an important tool to detect early LV systolic abnormalities. This study aimed to investigate the association between insulin resistance and subclinical left ventricular (LV) dysfunction in a sample of the general population without overt cardiac disease. METHODS: We investigated 539 participants who voluntarily underwent extensive cardiovascular health check including laboratory test and speckle-tracking echocardiography. Glycemic profiles were categorized into 3 groups according to homeostatic model assessment of insulin resistance (HOMA-IR): absence of insulin resistance (HOMA-IR < 1.5), presence of insulin resistance (HOMA-IR ≥ 1.5) and diabetes mellitus (DM). Multivariable logistic regression models were conducted to evaluate the association between abnormal glucose metabolism and impaired LVGLS (> - 16.65%). RESULTS: Forty-five (8.3%) participants had DM and 66 (12.2%) had abnormal HOMA-IR. LV mass index and E/e' ratio did not differ between participants with and without abnormal HOMA-IR, whereas abnormal HOMA-IR group had significantly decreased LVGLS (- 17.6 ± 2.6% vs. - 19.7 ± 3.1%, p < 0.05). The prevalence of impaired LVGLS was higher in abnormal HOMA-IR group compared with normal HOMA-IR group (42.4% vs. 14.0%) and similar to that of DM (48.9%). In multivariable analyses, glycemic abnormalities were significantly associated with impaired LVGLS, independent of traditional cardiovascular risk factors and pertinent laboratory and echocardiographic parameters [adjusted odds ratio (OR) 2.38, p = 0.007 for abnormal HOMA-IR; adjusted OR 3.02, p = 0.003 for DM]. The independent association persisted even after adjustment for waist circumference as a marker of abdominal adiposity. Sub-group analyses stratified by body mass index showed significant association between abnormal HOMA-IR and impaired LVGLS in normal weight individuals (adjusted OR 4.59, p = 0.001), but not in overweight/obese individuals (adjusted OR 1.62, p = 0.300). CONCLUSIONS: In the general population without overt cardiac disease, insulin resistance carries independent risk for subclinical LV dysfunction, especially in normal weight individuals.

Deep Learning Algorithm to Detect Cardiac Sarcoidosis From Echocardiographic Movies.

BACKGROUND: Because the early diagnosis of subclinical cardiac sarcoidosis (CS) remains difficult, we developed a deep learning algorithm to distinguish CS patients from healthy subjects using echocardiographic movies.Methods and Results:Among the patients who underwent echocardiography from January 2015 to December 2019, we chose 151 echocardiographic movies from 50 CS patients and 151 from 149 healthy subjects. We trained two 3D convolutional neural networks (3D-CNN) to identify CS patients using a dataset of 212 echocardiographic movies with and without a transfer learning method (Pretrained algorithm and Non-pretrained algorithm). On an independent set of 41 echocardiographic movies, the area under the receiver-operating characteristic curve (AUC) of the Pretrained algorithm was greater than that of Non-pretrained algorithm (0.842, 95% confidence interval (CI): 0.722-0.962 vs. 0.724, 95% CI: 0.566-0.882, P=0.253). The AUC from the interpretation of the same set of 41 echocardiographic movies by 5 cardiologists was not significantly different from that of the Pretrained algorithm (0.855, 95% CI: 0.735-0.975 vs. 0.842, 95% CI: 0.722-0.962, P=0.885). A sensitivity map demonstrated that the Pretrained algorithm focused on the area of the mitral valve. CONCLUSIONS: A 3D-CNN with a transfer learning method may be a promising tool for detecting CS using an echocardiographic movie.

Independent effect of visceral fat on left atrial phasic function in the general population.

BACKGROUND AND AIMS: Obesity increases the risk for atrial fibrillation (AF), although the impact of abdominal fat distribution on left atrial (LA) morphology and functional remodeling remains unclear. This study aimed to investigate whether increased abdominal adiposity is independently associated with impaired LA function and/or LA enlargement in a sample of the general population and to evaluate the role of adipokines in this association. METHODS AND RESULTS: The study cohort consisted of 527 participants (362 men; 57 ± 10 years) without overt cardiac disease who underwent laboratory testing, abdominal computed tomographic examination and echocardiography. Abdominal adiposity was quantitatively assessed as visceral fat area (VFA) and subcutaneous fat area (SFA) at the level of the umbilicus. Speckle-tracking echocardiography was performed to assess LA phasic function including reservoir, conduit and pump strain. LA reservoir and conduit strain decreased with increasing VFA quartiles (both p < 0.05), whereas no significant differences were observed in LA volume index and pump strain. When stratified by SFA, there were no significant differences in LA size and function across the quartiles. In multivariable analysis, VFA was significantly associated with LA conduit strain independent of cardiovascular risk factors, and pertinent laboratory and echocardiographic parameters (standardized ß = -0.136, p = 0.019). VFA was correlated with serum adiponectin level (r = -0.51, p < 0.001), but there was no association between adiponectin level and three LA phasic strains. CONCLUSION: In a sample of the general population, VFA accumulation was independently associated with worse LA conduit strain, which may be involved in the pathophysiological mechanism of obesity-related AF.

Accurate Prediction of Prognosis After Radical Resection of Gastric Cancer by the Modified Systemic Inflammation Score; a Multicenter Dataset Analysis.

BACKGROUND: The presence of chronic inflammation and nutritional status in cancer patients affects its prognosis. There is a clinical need for a prognostic predictor that is objective and accurate, and that can be easily evaluated by preoperative screening. We evaluated the importance and usefulness of the preoperative modified systemic inflammation score (mSIS) to predict the long-term outcome of patients undergoing curative resection for gastric cancer (GC). METHODS: Of the 3571 patients who underwent curative resection for GC in nine institutions between January 2010 and December 2014, 1764 patients who met the inclusion criteria were included. The mSIS was formulated according to the serum albumin level (ALB) and lymphocyte-to-monocyte ratio (LMR) as follows: mSIS 0 (ALB ≥ 4.0 g/dL and LMR ≥ 3.4), mSIS 1 (ALB < 4.0 g/dL or LMR < 3.4), and mSIS 2 (ALB < 4.0 g/dL and LMR < 3.4). RESULTS: Patients were categorized into preoperative mSIS 0 (n = 955), mSIS 1 (n = 584), and mSIS 2 (n = 225) groups. The overall survival times and the disease-free survival times of patients in preoperative mSIS 0,1 and 2 sequentially shortened (P < 0.0001), and mSIS 1 and 2 were identified as an independent prognostic factor (hazard ratio [HR] 1.35, 95% confidence interval [CI] 1.06-1.272, P = 0.0125 and HR 1.63, 95% CI 1.21-2.19, P = 0.0012). A stepwise increase in the prevalence of hematogenous recurrences was directly proportional to the mSIS. A forest plot revealed that mSIS 0,1 was associated with a greater risk of overall survival in most subgroups. CONCLUSION: Preoperative mSIS can be easily calculated, and it is suggested that it is useful as a prognostic predictor of patients with different disease stages, for stratifying and evaluating clinical outcomes.

Short-term outcomes of gastrectomy after neoadjuvant chemotherapy for clinical stage III gastric cancer: propensity score-matched analysis of a multi-institutional database.

PURPOSE: Preoperative chemotherapy for gastric cancer may be effective from the standpoint of compliance, although there is insufficient evidence of its efficacy. We analyzed a multicenter database to clarify whether preoperative chemotherapy influenced the short-term outcomes of gastrectomy. METHODS: We analyzed, retrospectively, 3571 patients who underwent gastrectomy between January, 2010 and December, 2014. Patients with clinical stage-III gastric adenocarcinoma were divided into a neoadjuvant chemotherapy (NAC) group and a non-NAC group. We performed propensity-matched comparative analysis to stratify the groups according to age, sex, tumor region, tumor type, preoperative stage, procedure, lymph node dissection, and tumor differentiation. Preoperative blood data, surgical findings, and postoperative complications were analyzed. RESULTS: Analysis of the matched NAC (n = 64) and non-NAC (n = 128) groups revealed that the preoperative values of neutrophils, platelets, and Hb were significantly lower in the NAC group. Blood loss during surgery was significantly higher, surgical times were longer, and the rate of repeat surgery was significantly lower in the NAC group; however, the rates of rehospitalization did not differ between the groups and mortality was 0% in both groups. Postoperative complications were not significantly different between the groups. CONCLUSIONS: NAC did not increase the complication rate of gastrectomy for gastric cancer.

Mitral Valvular Coaptation-Zone Area Is Associated with the Severity of Atherosclerosis Assessed by Cardio-Ankle Vascular Index.

Preservation of the mitral valve (MV) size is essential for valve function, and a reduced MV coaptation-zone area increases the risk of developing functional mitral regurgitation (FMR). We aimed to determine if the MV leaflet and coaptation-zone areas were associated with the severity of atherosclerosis assessed by cardio-ankle vascular index (CAVI) in patients with normal left ventricle (LV) systolic function and size by real-time 3D echocardiography (RT3DE).We performed RT3DE analysis in 66 patients with normal LV size and ejection fraction who underwent 2D echocardiography and CAVI. MV coaptation-zone areas were measured by custom 3D software and indexed by body surface area (BSA). The associations of clinical factors and mean CAVI with MV leaflet and coaptation-zone areas were evaluated by univariable and multivariable linear regression analyses.On univariable analysis, MV leaflet area/BSA was significantly associated with age (r = -0.335, P = 0.0069) and mean CAVI (r = -0.464, P < 0.001), and MV coaptation-zone area was significantly associated with age (r = -0.626, P < 0.001), hypertension (r = -0.626, P < 0.001), dyslipidemia (r = -0.626, P < 0.001), E/e' (r = -0.626, P < 0.001), and CAVI (r = -0.740, P < 0.001). On multivariable analysis, mean CAVI was independently associated only with MV leaflet area/BSA (standardized coefficient = -0.611, P < 0.001) and MV coaptation-zone area/BSA (standardized coefficient = -0.74, P < 0.001).In patients with normal LV systolic function and size, MV leaflet and coaptation-zone areas might be reduced according to advancing atherosclerosis. Patients with atherosclerosis might be at increased risk of developing FMR.

The Effectiveness of a Deep Learning Model to Detect Left Ventricular Systolic Dysfunction from Electrocardiograms.

Deep learning models can be applied to electrocardiograms (ECGs) to detect left ventricular (LV) dysfunction. We hypothesized that applying a deep learning model may improve the diagnostic accuracy of cardiologists in predicting LV dysfunction from ECGs. We acquired 37,103 paired ECG and echocardiography data records of patients who underwent echocardiography between January 2015 and December 2019. We trained a convolutional neural network to identify the data records of patients with LV dysfunction (ejection fraction < 40%) using a dataset of 23,801 ECGs. When tested on an independent set of 7,196 ECGs, we found the area under the receiver operating characteristic curve was 0.945 (95% confidence interval: 0.936-0.954). When 7 cardiologists interpreted 50 randomly selected ECGs from the test dataset of 7,196 ECGs, their accuracy for predicting LV dysfunction was 78.0% ± 6.0%. By referring to the model's output, the cardiologist accuracy improved to 88.0% ± 3.7%, which indicates that model support significantly improved the cardiologist diagnostic accuracy (P = 0.02). A sensitivity map demonstrated that the model focused on the QRS complex when detecting LV dysfunction on ECGs. We developed a deep learning model that can detect LV dysfunction on ECGs with high accuracy. Furthermore, we demonstrated that support from a deep learning model can help cardiologists to identify LV dysfunction on ECGs.