Left atrial strain time integral evaluated by two-dimensional speckle tracking predicts left atrial appendage dysfunction in patients with acute ischemic stroke.

Cardioembolic stroke is a serious disease with poor prognosis, whose main embolic source is the left atrial appendage (LAA). Left atrial (LA) strain evaluated by the two-dimensional (2D) speckle tracking technique has been proposed. However, the commonly used peak LA strain reflects only LA reservoir function. The LA strain also includes indicators of the other LA functions, such as booster pump function, which reflects active contraction of the LA. This study aimed to investigate whether a newly developed parameter, the left atrial strain time integral (LASTI), can evaluate LAA dysfunction more accurately in patients with acute stroke. We measured LA strain using a 2D speckle tracking method in 168 patients with acute stroke and 20 age-matched control subjects. LASTI was calculated as the area under the LA strain curve in one cardiac cycle. LAA dysfunction was defined as LAA thrombus and/or severe spontaneous echo contrast by transesophageal echocardiography. LASTI was significantly lower in patients with LAA dysfunction than those without. LASTI was a better correlation with LAA blood flow velocity measured by transesophageal echocardiography than peak LA strain. Multivariate logistic regression analysis showed that LASTI was an independent predictor of LAA dysfunction after adjustment for conventional risk factors. LASTI can be a feasible parameter for predicting LAA dysfunction in patients with acute stroke.

Improved cerebral blood flow and hippocampal blood flow in stroke-free patients after catheter ablation of atrial fibrillation.

INTRODUCTION: Atrial fibrillation (AF) is a risk factor for reduced cerebral blood flow (CBF) and cognitive dysfunction, even in stroke-free patients. We aimed to test the hypothesis that CBF and hippocampal blood flow (HBF), measured with arterial spin labeling magnetic resonance imaging (MRI), improve after catheter ablation of AF to achieve sinus rhythm (SR). METHODS: A total of 84 stroke-free patients (63.1 ± 9.1 years; paroxysmal AF, n = 50; non-paroxysmal AF, n = 34) undergoing AF catheter ablation were included. MRI studies were done before, 3 months, and 12 months after the procedure with CBF and HBF measurements. RESULTS: Baseline CBF and HBF values in 50 paroxysmal AF patients were used as controls. Baseline CBF was higher in patients with paroxysmal AF than with non-paroxysmal AF (100 ± 32% vs. 86 ± 28%, p = .04). Patients with non-paroxysmal AF had increased CBF 3 months after AF ablation (86 ± 28% to 99 ± 34%, p = .03). Differences in CBF and HBF were greater in the group with AF restored to SR (p < .01). Both CBF and HBF levels at 12 months were unchanged from the 3 months level. Successful rhythm control by catheter ablation was an independent predictor of an increase in CBF > 17.5%. The Mini-Mental State Examination score improved after ablation (p = .02). CONCLUSION: SR restoration with catheter ablation was associated with improved CBF and HBF at 3 months, maintenance of blood flow, and improved cognitive function at 12 months.

Hypokalemia, Kidney Function, and Clinical Outcomes in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is an increasing health problem associated with high morbidity and mortality rates. Several reports have shown an association between hypokalemia and clinical outcomes in patients with heart failure (HF). However, the association of hypokalemia with kidney function and clinical outcomes in patients with HFpEF remains unclear.Methods and Results: We measured serum potassium levels and kidney function in 454 patients with HFpEF (mean age 76 years; 55% men) at admission. Hypokalemia (K+<3.5 mmol/L) and hyperkalemia (K+>5.0 mmol/L) were identified in 58 (12.7%) and 11 (2.4%) patients, respectively. Patients with hypokalemia showed renal tubular damage (RTD), defined as a urinary ß2-microglobulin to creatinine ratio ≥300 µg/gCr, preserved estimated glomerular filtration rate (eGFR), and plasma volume expansion. Multivariate logistic analysis demonstrated that RTD, preserved eGFR, and plasma volume expansion were significantly associated with hypokalemia. During the median follow-up period of 1,000 days, 82 HF-related events occurred. Kaplan-Meier analysis showed that patients with hypokalemia had a higher rate of HF-related events than those without hypokalemia. Multivariate Cox proportional hazard regression analysis demonstrated that hypokalemia was significantly associated with HF-related events after adjusting for confounding factors. CONCLUSIONS: Hypokalemia is affected by kidney function, notably RTD, in patients with HFpEF. Hypokalemia is a risk factor for HF-related events in patients with HFpEF.

Growth Differentiation Factor 15 and Clinical Outcomes in Japanese Patients With Heart Failure.

BACKGROUND: Heart failure (HF) is an increasing health problem associated with a high mortality rate. Growth differentiation factor (GDF) 15, a stress response cytokine belonging to the transforming growth factor-ß superfamily, is associated with poor clinical outcomes in a broad spectrum of cardiovascular diseases. However, the prognostic usefulness of GDF15 in Japanese patients with HF remains unclear.Methods and Results: We measured serum concentrations of GDF15 and B-type natriuretic peptide (BNP) in 1,201 patients with HF. All patients were prospectively followed for a median period of 1,309 days. In all, 319 HF-related events and 187 all-cause deaths occurred during the follow-up period. Kaplan-Meier analysis demonstrated that, among GDF15 tertiles, the highest tertile group had the greatest risk of HF-related events and all-cause mortality. Multivariate Cox proportional hazard regression analysis demonstrated that the serum GDF15 concentration was an independent predictor of HF-related events and all-cause deaths after adjusting for confounding risk factors. Serum GDF15 improved the prediction capacity for all-cause deaths and HF-related events with a significant net reclassification index and integrated discrimination improvement. Subgroup analysis in patients with HF with preserved ejection fraction also showed the prognostic usefulness of GDF15. CONCLUSIONS: Serum GDF15 concentrations were associated with HF severity and clinical outcomes, indicating that GDF15 could provide additional clinical information to track the health status of patients with HF.

Safety and Efficacy of Bis-Glyceryl Ascorbate as Prophylaxis for Hand-Foot Skin Reaction: A Single-Arm, Open-Label Phase I/II Study (DGA Study).

BACKGROUND: Hand-foot skin reaction (HFSR) induced by multiple tyrosine kinase inhibitors (TKIs) is a serious side effect that can cause treatment interruption or decreased dosing. This study was conducted to evaluate the safety and efficacy of bis-glyceryl ascorbate (Amitose bis(di)-glyceryl ascorbate [DGA])-containing cream (DGA cream) for the prevention of sunitinib-induced HFSR. METHODS: A single-arm, open-label phase I/II study was conducted, targeting patients with metastatic renal cell carcinoma (mRCC) who were receiving sunitinib therapy with a schedule of 2 weeks on/1 week off. The participants applied DGA cream to both palmar and plantar surfaces in combination with a moisturizing agent as standard-of-care prophylaxis during two sunitinib treatment cycles (6 weeks). The primary endpoint in phase I was safety defined as dermatological abnormalities and it was determined in the first five participants. The primary endpoint in phase II was efficacy defined as development of grade 1 or higher HFSR defined by Common Terminology Criteria for Adverse Events within 6 weeks and it was determined on a full analysis set (FAS) defined as the population including all participants who used DGA cream once in the study duration. Efficacy in the per protocol set (PPS) defined as the population excluding seven patients whose study treatment was interrupted was evaluated as a secondary endpoint. RESULTS: Twenty-four patients were enrolled as a FAS. No dermatological abnormalities occurred in the first 5 patients enrolled in the phase I study. Three patients developed HFSR (grade 1: n = 2, grade 2: n = 1) in the observation period. The HFSR incidence rate was 12.5% (3/24; 95% confidence interval [CI]: 2.7%-32.4%) in the FAS, which was significantly lower than the incidence rate predefined as a threshold of 33.3% by a previous report from our hospital (P = .030). The incidence rate in the 17 patients of the PPS was 17.6% (3/17; 95%CI: 3.8%-43.4%). CONCLUSION: DGA cream may be safe and effective in the prophylaxis of HFSR in mRCC patients who receive sunitinib therapy (Trial ID: jRCTs051180051).

Association between thrombolysis in myocardial infarction grade and clinical outcome after emergent percutaneous coronary intervention in patients with acute myocardial infarction who have suffered out-of-hospital cardiac arrest: the Yamagata AMI registry.

Despite improvements in the survival rate of acute myocardial infarction (AMI), out-of-hospital cardiac arrest (OHCA) due to AMI is still a devastating condition. Thrombolysis in myocardial infarction (TIMI) grade is used to classify coronary reperfusion after percutaneous coronary intervention (PCI), but it remains unclear whether TIMI grade after emergent PCI is associated with short-term mortality in patients with AMI who have suffered OHCA. We analyzed data collected from 2012 to 2017 and recorded in the Yamagata AMI registry, which is a multicenter surveillance conducted in all institutions in Yamagata prefecture. Among 3332 patients with AMI, 254 had suffered OHCA. There were 564 deaths during the 30 days after the onset of AMI. The survival rate was lower in patients who had suffered OHCA than in those who had not (40% vs. 87%; P < 0.0001). Patients with AMI who had suffered OHCA were divided into three groups based on TIMI grade (TIMI III group, n = 70; TIMI ≤ II group, n = 21; and no coronary angiography [non-CAG] group, n = 163). The survival rates in the TIMI III, TIMI ≤ II, and non-CAG groups were 87%, 38%, and 5%, respectively. Kaplan-Meier analysis demonstrated that the survival rate was highest in the TIMI III group. Multivariate Cox proportional hazard regression analysis demonstrated that TIMI III was closely associated with survival after adjustment for confounding factors. Achieving TIMI grade III during emergent PCI is crucial to improve survival in patients with AMI who have suffered OHCA.

Albumin-to-globulin ratio predicts clinical outcomes of heart failure with preserved ejection fraction in women.

Despite advances in medicine, heart failure with preserved ejection fraction (HFpEF) remains an increasing health concern associated with a high mortality rate. Research has shown sex-based differences in the clinical characteristics of patients with HF; however, definitive biomarkers for poor clinical outcomes of HFpEF in women are unavailable. We focused on the albumin-to-globulin ratio (AGR), a biomarker for malnutrition and inflammation and investigated its usefulness as a predictor of clinical outcomes of HFpEF in women. We measured the AGR in consecutive 224 women with HFpEF and 249 men with HFpEF. There were 69 cardiac events in women with HFpEF and 69 cardiac events in men with HFpEF during the follow-up period. The AGR decreased with advancing New York Heart Association functional class in women with HFpEF. Patients were categorized into three groups based on AGR tertiles. Kaplan-Meier analysis showed that among the three groups, the risk for cardiac events and HF-associated rehospitalizations was the highest in the lowest tertile in women with HFpEF. Univariate and multivariate Cox proportional hazard regression analyses showed that after adjustment for confounding risk factors, the AGR was an independent predictor of cardiac events and HF-associated rehospitalizations in women with HFpEF, but not in men with HFpEF. The addition of AGR to the risk factors significantly improved the net reclassification and integrated discrimination indices in women with HFpEF. This is the first study that highlights the significant association between the AGR and the severity and clinical outcomes of HFpEF in women. Addition of AGR to the risk factors improved its prognostic value for clinical outcomes, which indicates that this variable may serve as a useful clinical biomarker for HFpEF in women.

Perfusion Balloon Is Useful for Preventing Obstruction of Left Main Coronary Artery During Transcatheter Aortic Valve Implantation.

The incidence of acute coronary obstruction during transcatheter aortic valve implantation (TAVI) is low (< 1.0%); however, it is associated with high mortality. An 83-year-old female with a history of chest pain and syncope was diagnosed with severe aortic stenosis. Computed tomography showed severely calcified aortic leaflets with a low left coronary ostial height of 7.8 mm, which indicates a high risk of coronary obstruction. TAVI was performed using the right femoral artery approach under general anesthesia. To prevent coronary obstruction and minimize coronary flow obstruction, coronary protection of the left main tract (LMT) via the left radial artery was established with a perfusion balloon. We crossed a 23 mm Sapien 3 transcatheter heart valve and settled it at an appropriate position on the aortic valve. After inflation of the perfusion balloon at the LMT, we started rapid ventricular pacing, and deployed the Sapien 3 using the KBI technique. Hemodynamics were stable and aortography showed excellent coronary flow with no stenosis of the LMT ostium. This strategy may serve as a useful method to prevent coronary obstruction and minimize coronary ischemia.

Left Atrial Filling Time Index (LAFTI) Evaluated by 2D Speckle Tracking Echocardiography Predicts Poor Cardiac Prognosis in Patients with Heart Failure.

Left atrial (LA) dysfunction is known to be a more sensitive prognostic marker than left ventricular (LV) dysfunction in patients with heart failure (HF). Persistent LA overload increases LA stiffness which impairs LA relaxation. The aim of this study was to investigate whether LA filling time is associated with clinical outcomes in patients with HF. Two-dimensional speckle tracking echocardiography (2DSTE) was performed at discharge, to measure LA and LV strain in 179 HF patients admitted to our hospital. The LA filling time index (LAFTI) was defined as the time from onset of the R wave to the peak LA systolic strain divided by the R-R interval. All patients were prospectively followed with cardiac events including cardiac death and rehospitalization for HF. There were 64 cardiac events during a median follow-up period of 451 days. There were no significant differences in heart rate, severity of HF at discharge, etiology of HF, severity of mitral regurgitation, or LV global longitudinal strain between the cardiac event group and no cardiac event group. Patients with cardiac events had significantly higher levels of brain natriuretic peptide (BNP), ratio of the E wave to e' (E/e'), left atrial volume index (LAVI), and lower LAFTI than those without. Kaplan-Meier analysis showed that patients with lower LAFTI were associated with higher cardiac event rates. Multivariate Cox hazard analysis showed that LAFTI was independently associated with the cardiac events after adjustment for confounding factors. In conclusion, LAFTI is a feasible predictor for cardiac events in patients with HF.

Quantitative Difference in Solubility of Diastereomeric (2H/1H)-Isotopomers.

Many achiral organic compounds become chiral by an isotopic substitution of one of the enantiotopic moieties in their structures. Although spectroscopic methods can recognize the molecular chirality due to an isotopic substitution, the effects of isotopically chiral compounds in enantioselective reactions have remained unsolved because the small chirality arises only from the difference between the number of neutrons in the atomic nuclei. The difference between the diastereomeric isotopomers of reactive sources should be the key to these effects. However, the energy difference between them is difficult to calculate, even using present computational methods, and differences in physical properties have not yet been reported. Here, we demonstrate that the small energy difference between the diastereomeric isotopomers at the molecular level can be enhanced to appear as a solubility difference between the diastereomeric (2H/1H) isotopomers of α-aminonitriles, synthesized from an isotopically chiral amine, achiral aldehyde, and HCN. This small, but measurable, difference induces the chiral (d/l) imbalance in the suspended α-aminonitrile; therefore, a second enhancement in the solid-state chirality proceeds to afford a highly stereoimproved aminonitrile (>99% selectivity) whose handedness arises completely from the excess enantiomer of isotopically chiral amine, even in a low enantiomeric excess and low deuterium-labeling ratio. Because α-aminonitriles can be hydrolyzed to chiral α-amino acids with the removal of an isotope-labeling moiety, the current sequence of reactions represents a highly enantioselective Strecker amino acid synthesis induced by the chiral hydrogen (2H/1H) isotopomer. Thus, hydrogen isotopic chirality links directly with the homochirality of α-amino acids via a double enhancement of α-aminonitrile, the chiral intermediate of a proposed prebiotic mechanism.

Prognostic significance of the controlling nutritional (CONUT) score in patients with acute coronary syndrome.

BACKGROUND: Malnutrition is an independent predictor of adverse outcomes in patients with acute coronary syndrome. The controlling nutritional (CONUT) score has been applied to assess nutritional status, and has been reported to be associated with poor prognosis in patients with heart failure. However, the prognostic impact of the CONUT score in patients with acute coronary syndrome (ACS) remains to be elucidated. METHODS: We evaluated the CONUT score in 196 patients with ACS who underwent percutaneous coronary intervention. We divided the patients into four groups according to CONUT score (undernutrition degree: normal, CONUT 0-1 (reference); mild, CONUT 2-4; moderate, CONUT 5-8; severe, CONUT 9-12). The endpoint of the present study was composite events including all-cause death, acute coronary syndrome, target vessel revascularization, and stroke. RESULTS: The median CONUT score was significantly higher in patients with composite events than in those without events (P = 0.0058). Kaplan-Meier analysis revealed that a significantly higher event rate in patients with severe malnutrition (log-rank test, P = 0.0222). In the multivariate Cox proportional hazards analysis, CONUT score was independently associated with composite events after adjustment for confounding factors (adjusted hazard ratio 1.284, 95% confidence interval 1.126-1.457, P = 0.0003). CONCLUSION: Higher CONUT scores were associated with unfavorable outcomes in patients with ACS. Malnutrition assessed by the CONUT score may provide valuable prognostic information in patients with ACS.

Impact of pre-operative coronary artery disease on the clinical outcomes of patients with aortic aneurysms.

Aortic aneurysm is an increasingly important public health problem with high morbidity and mortality. It is associated with coronary artery disease (CAD), which is a comorbidity of high incidence that is reported to worsen perioperative complications and long-term clinical outcomes in patients with an aortic aneurysm. Patients with significant coronary artery stenosis may require coronary revascularization and/or optimal medical therapy in the perioperative period of aneurysm surgery. However, the prognostic impact of non-significant coronary artery stenosis not indicated for coronary revascularization on clinical outcomes of patients with aortic aneurysms remains unclear. We performed coronary angiography on 239 consecutive patients with thoracic and abdominal aortic aneurysms before endovascular aortic repair or surgical repair. The patients were divided into the following 3 groups according to the severity of stenosis of major coronary arteries: non-CAD group (with < 25% stenosis), non-significant CAD group (with ≥ 25% but < 75% stenosis), and significant CAD group (with ≥ 75% stenosis). CAD was diagnosed in 133 (56%) patients consisting of 48 (20%) patients with non-significant CAD and 85 (36%) patients with significant CAD. Thirty-nine major adverse cardiovascular and cerebrovascular events (MACCEs) occurred in a median follow-up period of 723 days. Kaplan-Meier analysis revealed that the risk of MACCEs was higher in the significant and non-significant CAD groups than in the non-CAD group. Multivariate Cox proportional hazard regression analysis showed that the risk of MACCEs was equally high in the non-significant CAD and significant CAD groups compared to that in the non-CAD group after adjustment for confounding factors. CAD is significantly associated with poor outcomes in patients with aortic aneurysms, irrespective of the significance of CAD.

Efficacy and safety of 0.0584% hydrocortisone aceponate topical spray and systemic oclacitinib combination therapy in dogs with atopic dermatitis: a randomized, double-blinded, placebo-controlled trial.

BACKGROUND: Oclacitinib is an effective systemic therapy for dogs with atopic dermatitis (AD). Few studies have evaluated concurrent topical treatment with oclacitinib in dogs. OBJECTIVES: To evaluate the efficacy and safety of combination therapy of oclacitinib and 0.0584% hydrocortisone aceponate (HCA) spray in dogs with AD. ANIMALS: Eighteen dogs with AD. METHODS AND MATERIALS: This study was a randomized, double-blinded, placebo-controlled trial. All dogs were treated with oclacitinib (0.4-0.6 mg/kg twice daily for 14 days, then once daily for 14 days) and randomized to receive either HCA spray or placebo spray, applied once daily for seven days then every other day through to Day (D)28. Clinical assessments included the Canine Atopic Dermatitis Extent and Severity Index, 4th iteration (CADESI-4) and the pruritus Visual Analog Scale (PVAS) every seven days, and blood and urine tests every 14 days. RESULTS: The mean CADESI-4 and PVAS scores were significantly reduced on D7 and D14 compared to D0 in both groups (P < 0.05). From D14 to D21, CADESI-4 and PVAS scores were significantly increased in the placebo group (P < 0.005), and not in the HCA-treated group. The mean reduction from baseline of the HCA-treated group was significantly higher than that of the placebo group for the PVAS and CADESI-4 on D21 (59.9% versus 27.6%, P = 0.0216) and D28 (56.0% versus 30.5%, P = 0.0109), respectively. One dog in the HCA-treated group was withdrawn as a consequence of developing diarrhoea. CONCLUSION: Topical application of 0.0584% HCA spray may be useful for preventing exacerbation of pruritus and clinical lesions when tapering oclacitinib therapy in dogs with AD.

The impact of kidney dysfunction categorized by urinary to serum creatinine ratio on clinical outcomes in patients with heart failure.

Kidney dysfunction (KD) is closely associated with poor clinical outcome in patients with heart failure (HF). KD is classified as intrinsic and pre-renal KD. However, the impact of each KD on the clinical outcome in patients with HF has not yet been fully elucidated. We measured the urinary to serum creatinine (UC/SC) ratio, a marker for intrinsic and pre-renal KD, in 1009 consecutive patients with HF at admission. There were 314 cardio-renal events including HF and advanced end-stage renal dysfunction during the median follow-up period of 1154 days. There were 63 (6%) patients with intrinsic KD (UC/SC ratio < 20), 118 (12%) patients with intermediate KD (UC/SC ratio 20-40), 607 (60%) patients with pre-renal KD (UC/SC ratio > 40), and 221 (22%) patients with no KD. Multivariate Cox's proportional hazard regression analysis demonstrated that intrinsic and intermediate KDs were significantly associated with poor clinical outcome. The prediction model for cardio-renal events was significantly improved by the addition of UC/SC ratio to the confounding risk factors. Subgroup analysis in patients with HF with severely reduced glomerular filtration rates showed that the prevalence rates of intrinsic, intermediate, and pre-renal KDs were 23%, 30%, and 47%, respectively. The cardio-renal event rate was the highest in the intrinsic KD group compared with that in the other groups. Intrinsic KD was closely associated with extremely poor clinical outcome in patients with HF. The UC/SC ratio could provide important clinical information for the treatment and management of KD in patients with HF.

[Monotherapy using a direct oral anticoagulant (apixaban) for catheter thrombosis and pulmonary thromboembolism in a patient with ulcerative colitis: a case report].

A 20-year-old woman with ulcerative colitis flare was admitted to Fukui Red Cross Hospital. During treatment with granulocyte and monocyte apheresis (GMA), the patient complained of chest discomfort and was diagnosed with pulmonary thromboembolism with central intravenous catheter thrombosis. Apixaban, a direct oral anticoagulant (DOAC), was used as monotherapy for anticoagulation, and thromboembolism was resolved without complication. Among extraintestinal complications in patients with ulcerative colitis, pulmonary thromboembolism can be a life-threatening condition and requires prompt anticoagulant therapy. Although the effectiveness of conventional pharmacological anticoagulation using warfarin and heparin has been reported, the efficacy of DOAC monotherapy remains controversial. DOAC monotherapy may be considered and innovative therapeutic strategy for a thromboembolic condition in patients with ulcerative colitis.

Prolonged total atrial conduction time evaluated with tissue Doppler imaging predicts poor cardiac prognosis in patients with heart failure.

Prolonged total atrial conduction time is caused by atrial remodeling. Left atrial remodeling is associated with poor outcome in patients with heart failure (HF). This study aimed to investigate whether prolonged total atrial conduction time predicts poor prognosis in patients with HF. We performed transthoracic echocardiography in 100 patients (65 men; mean age 68 ± 13 years) who were hospitalized for HF. Total atrial conduction time was defined as the duration from P wave onset on electrocardiography to peak A' wave on tissue Doppler imaging (TDI) echocardiography (PA-TDI duration). There were 37 cardiac events (37%) during a median follow-up period of 414 days. The PATDI duration was significantly longer in patients with cardiac events than in those without (150 ± 18 ms vs 133 ± 19 ms; P < 0.05). There were no significant differences in left ventricular end-diastolic dimensions and ejection fractions between patients with and without cardiac events. Patients with HF were divided into 3 groups according to tertiles of the PA-TDI duration. Kaplan-Meier analysis showed that the highest tertile of PA-TDI duration was associated with the greatest risk among patients with HF. Multivariate Cox proportional hazard analysis showed that the PA-TDI duration was an independent predictor of cardiac events, leading to the conclusion that prolonged PA-TDI duration was a feasible predictor of cardiac prognosis in patients with HF.

Direct comparison of prognostic ability of cardiac biomarkers for cardiogenic stroke and clinical outcome in patients with stroke.

Despite many recent advances in medicine, cardiogenic stroke is still a health problem with a high mortality rate. Cardiac biomarkers have been reported to be useful indicators for cardiogenic stroke and subsequent cerebrovascular events. However, there are no data directly comparing the cardiac biomarkers in stroke patients. We measured atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), N-terminal pro-brain natriuretic peptide (NT-proBNP), and high-sensitivity troponin T (hsTnT) levels and performed transthoracic and transesophageal echocardiography in 282 stroke patients. There were 108 cases of cardiogenic stroke and 47 cases of major adverse cardiovascular and cerebrovascular events (MACCE) during the follow-up period. Association with left atrial function and left atrial appendage function appeared somewhat stronger for BNP and NT-proBNP than ANP and hsTnT. Multivariate logistic analysis demonstrated that cardiac biomarkers excluding ANP were significantly associated with cardiogenic stroke in stroke patients, multivariate Cox's proportional hazards regression analysis demonstrated that all biomarkers were significantly associated with MACCE after adjustment for confounding risk factors. Receiver operating characteristic curve analysis showed that the C indices of BNP and NT-proBNP for cardiogenic stroke and MACCE were almost equal, but significantly greater than those of ANP and hsTnT. Both BNP and NT-proBNP levels are useful predictors of cardiogenic stroke and subsequent MACCE superior to ANP and hsTnT in stroke patients.

Left atrial remodeling index is a feasible predictor of poor prognosis in patients with acute ischemic stroke.

Left atrial (LA) functional remodeling as well as LA structural remodeling are associated with incident LA appendage (LAA) thrombus formation. This study aimed to elucidate whether combined assessment of LA functional and structural remodeling can predict LAA dysfunction and recurrent cerebrovascular events in patients with acute ischemic stroke. We performed transthoracic and transesophageal echocardiography in 196 patients within 7 days after acute ischemic stroke. Peak systolic LA strain was evaluated using 2D speckle tracking imaging. We defined the ratio of LA peak systolic strain to LA volume index (LAVI) as the LA remodeling index (LARI). All patients were prospectively followed for recurrent cerebrovascular events. We divided patients into four groups according based on the LARI quartile. LAA dysfunction increased with decreasing LARI. In total, 52 recurrent cerebrovascular events were noted during the median follow-up period of 700 days. Patients with recurrent cerebrovascular events had lower LARI than those without recurrent events (0.50 ± 0.45 vs. 1.10 ± 0.95, P < 0.001). Kaplan-Meier analysis showed that patients with lower LARI were more susceptible to recurrent cerebrovascular events than those with higher LARI. Multivariate Cox proportional hazard regression analysis showed that LARI was an independent predictor of recurrent cerebrovascular events after adjustment for confounding factors. Net reclassification index improved with the addition of LARI to basic predictors. LARI is a novel feasible parameter for LAA dysfunction and can predict recurrent cerebrovascular events in patients with acute ischemic stroke.

Increased plasma xanthine oxidoreductase activity deteriorates coronary artery spasm.

Increased reactive oxygen species (ROS) contributes to the development of endothelial dysfunction, which is involved in coronary artery spasm (CAS). Xanthine oxidoreductase (XOR) plays a pivotal role in producing both uric acid and ROS. However, the association between plasma XOR activity and CAS has not been elucidated. The aim of this study was to investigate whether plasma XOR activity is associated with CAS. We measured XOR activity in 104 patients suspected for CAS, who presented without significant coronary artery stenosis and underwent intracoronary acetylcholine provocation tests. CAS was provoked in 44 patients and they had significantly higher XOR activity as compared with those without CAS. The patients were divided into three groups based on the XOR activity. The prevalence rate of CAS was increased with increasing XOR activity. A multivariate logistic regression analysis showed that the 3rd tertile group exhibited a higher incidence of CAS as compared with the 1st tertile group [odds ratio (OR) 6.9, P = 0.001) and the 2nd tertile group (OR 3.2, P = 0.033) after adjustment for conventional CAS risk factors, respectively. The C index was significantly improved by the addition of XOR activity to the baseline model based on CAS risk factors. Furthermore, the 3rd tertile group had the highest incidence of severe spasm defined as total obstruction, flow-limiting stenosis, diffuse spasm, multivessel spasm, and/or lethal arrhythmia. This is a first report to elucidate the association of plasma XOR activity with CAS. Increased plasma XOR activity is significantly associated with CAS.

Clear Cell Carcinoma of the Uterine Cervix Presented as a Submucosal Tumor Arising in a Background of Cervical Endometriosis.

Clear cell carcinoma (CCC) of the uterine cervix without prenatal diethylstilbestrol exposure is rare, and its etiology is unclear. We present a case of cervical CCC presenting as a submucosal tumor, which strongly suggests an association between cervical endometriosis and cervical CCC. A 56-year-old postmenopausal Japanese woman visited a gynecologic clinic with a complaint of watery vaginal discharge. A few atypical cells suggesting adenocarcinoma were detected in a cervical cytologic specimen. Magnetic resonance imaging revealed a cystic lesion with a solid component at the uterine cervix. Under a tentative diagnosis of cervical cancer, surgery was performed. Although a freshly resected specimen initially showed no tumorous lesion in the cervical mucosa, cutting of the mucosa revealed a solid tumor with a final diagnosis of CCC. The findings of aggregation of hemosiderin-laden macrophages and ectopic endometrium adjacent to the tumor strongly suggest that this tumor arose from cervical endometriosis.