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A 42-year-old man with a history of acute myocarditis after streptococcal pharyngitis developed recurrent fulminant myocarditis. Endomyocardial biopsy revealed myocyte degeneration, interstitial edema, and neutrophil infiltration. The patient's cardiac function deteriorated rapidly, and he died despite mechanical circulatory support. Autopsy revealed neutrophil infiltration, interstitial edema, and micro-abscesses containing masses of streptococci and neutrophilic phagocytosis within the myocardium. The patient did not meet the diagnostic criteria for acute rheumatic fever; thus, he was diagnosed with non-rheumatic streptococcal myocarditis. Non-rheumatic streptococcal myocarditis rarely recurs, but it can be fulminant upon recurrence. LEARNING OBJECTIVE: We report a rare case of recurrent fulminant non-rheumatic streptococcal myocarditis. Endomyocardial biopsy and autopsy revealed neutrophil infiltration and micro-abscesses containing bacterial masses of streptococci and neutrophilic phagocytosis in the myocardium. The patient did not meet the diagnostic criteria for acute rheumatic fever; thus, he was diagnosed with non-rheumatic streptococcal myocarditis. Non-rheumatic streptococcal myocarditis rarely recurs, but it can be fulminant upon recurrence.

Supplementary Figure S2. NAE inhibitory effects of TAS4464. (A) E1 inhibitory effects of TAS4464 on HCT116 cells. Cells were treated with TAS4464 for 1 h. (B) Competition assay with non-labeled TAS4464. HCT116 cells were pre-treated with non-labeled TAS4464 (10, 100, 1000, 10000 nmol/L) and treated with 100 nmol/L 14C TAS4464 for 4 hours. (C) Dual-color detection of NEDD8 and UBC12. CCRF-CEM cells were treated with 100 nmol/L of TAS4464 for 1 to 24 h.

NEDD8-activating enzyme (NAE) is an essential E1 enzyme of the NEDD8 conjugation (neddylation) pathway, which controls cancer cell growth and survival through activation of cullin-RING ubiquitin ligase complexes (CRL). In this study, we describe the preclinical profile of a novel, highly potent, and selective NAE inhibitor, TAS4464. TAS4464 selectively inhibited NAE relative to the other E1s UAE and SAE. TAS4464 treatment inhibited cullin neddylation and subsequently induced the accumulation of CRL substrates such as CDT1, p27, and phosphorylated IκBα in human cancer cell lines. TAS4464 showed greater inhibitory effects than those of the known NAE inhibitor MLN4924 both in enzyme assay and in cells. Cytotoxicity profiling revealed that TAS4464 is highly potent with widespread antiproliferative activity not only for cancer cell lines, but also patient-derived tumor cells. TAS4464 showed prolonged target inhibition in human tumor xenograft mouse models; weekly or twice a week TAS4464 administration led to prominent antitumor activity in multiple human tumor xenograft mouse models including both hematologic and solid tumors without marked weight loss. As a conclusion, TAS4464 is the most potent and highly selective NAE inhibitor reported to date, showing superior antitumor activity with prolonged target inhibition. It is, therefore, a promising agent for the treatment of a variety of tumors including both hematologic and solid tumors. These results support the clinical evaluation of TAS4464 in hematologic and solid tumors.

Supplementary materials including cell line, antibodies information and methods including pharmacokinetics and signature score.

Supplementary Table S1. Antiproliferative activity against a panel of cancer cell lines.

The Impella 5.0 is an axial-flow percutaneous ventricular assist device used in patients with cardiogenic shock. Although the recommended period of use is 10 days or less, weaning can be delayed because of ongoing hemodynamic instability. In clinical practice, this device sometimes malfunctions during long-term management with heparin and must be replaced; however, the relationship between the duration of support with the initial and replacement Impella 5.0 and the changes in value of the purge system has not been fully elucidated. From July 2018 to May 2021, Impella 5.0 was implanted and used for more than 10 days in 11 patients at our institution. Four patients required Impella replacement because of device malfunction and the second Impella had purge system malfunction in all cases. The second Impella was used for a significantly shorter time than the first Impella (p = 0016). We calculated the ratio of purge pressure to purge flow rate and found that the ratio exceeded 50 mm Hg/mL/h in all cases with purge system malfunction. In conclusion, it is important to construct a treatment strategy considering the duration of use, because the risk of purge system malfunction is high after replaced Impella 5.0.

Aims In recent decades, haemodynamic parameters have been estimated for risk stratification and determining treatment strategies for patients with non‐ischaemic dilated cardiomyopathy (DCM). In various invasive procedures, the cardiac pumping capability is defined as cardiac power output (CPO), which is calculated by multiplying cardiac output by the mean arterial pressure. Lower CPO values in advanced heart failure predict adverse outcomes. However, few studies discuss the prognostic value of CPO in mild‐to‐moderate phase patients. This study aimed to determine the value of the cardiac power index (CPI) obtained from the resting CPO for predicting the prognosis of patients with New York Heart Association Functional Class II or III DCM. Methods and results From March 2000 to January 2020, a total of 623 cardiomyopathy patients were evaluated for haemodynamic parameters. Patients with secondary cardiomyopathy, ischaemic cardiomyopathy, valvular heart disease, and Class IV cardiomyopathy were excluded. A total of 176 DCM patients fulfilled the criteria for inclusion. Patients were 51.7 ± 12.5 years old (mean ± standard deviation) with a mean left ventricular ejection fraction of 32.1 ± 9.2%. The patients were divided into two groups by their median CPI (CPI

Impella 5.0 circulatory support via subclavian artery (SA) access may be a safe approach for patients undergoing cardiac rehabilitation (CR). In this case series, we retrospectively analyzed the demographic characteristics, physical function, and CR data of six patients who underwent Impella 5.0 implantation via the SA prior to left ventricular assist device (LVAD) implantation between October 2013 and June 2021. The median age was 48 years, and one patient was female. Grip strength was maintained or increased in all patients before LVAD implantation (pre-LVAD) compared to after Impella 5.0 implantation. The pre-LVAD knee extension isometric strength (KEIS) was less than 0.46 kgf/kg in two patients and more than 0.46 kgf/kg in three patients (unavailable KEIS data, n = 1). With Impella 5.0 implantation, two patients could ambulate, one could stand, two could sit on the edge of the bed, and one remained in bed. One patient lost consciousness during CR due to decreased Impella flow. There were no other serious adverse events. Impella 5.0 implantation via the SA allows mobilization, including ambulation, prior to LVAD implantation, and CR can be performed relatively safely.

Aims Left ventricular reverse remodelling (LVRR) is a well‐established predictor of a good prognosis in patients with dilated cardiomyopathy (DCM). The prediction of LVRR is important when developing a long‐term treatment strategy. This study aimed to assess the clinical predictors of LVRR and establish a scoring system for predicting LVRR in patients with DCM that can be used at any institution. Methods and results We consecutively enrolled 131 patients with DCM and assessed the clinical predictors of LVRR. LVRR was defined as an absolute increase in left ventricular ejection fraction (LVEF) from ≥10% to a final value of >35%, accompanied by a decrease in left ventricular end‐diastolic dimension (LVEDD) ≥ 10% on echocardiography at 1 ± 0.5 years after a diagnosis of DCM. The mean patient age was 50.1 ± 11.9 years. The mean LVEF was 32.2 ± 9.5%, and the mean LVEDD was 64.1 ± 12.5 mm at diagnosis. LVRR was observed in 45 patients (34%) at 1 ± 0.5 years. In a multivariate analysis, hypertension [odds ratio (OR): 6.86; P = 0.002], no family history of DCM (OR: 10.45; P = 0.037), symptom duration 5 in receiver‐operating characteristic curve analysis (area under the curve: 0.89; P 5 was an independent predictor compared with the presence of late gadolinium enhancement on cardiovascular magnetic resonance or the severity of fibrosis on endomyocardial biopsy (OR: 11.79; 95% confidence interval: 2.40–58.00; P = 0.002). Conclusions The LVRR predicting score using five predictors including hypertension, no family history of DCM, symptom duration

Many patients with dilated cardiomyopathy (DCM) progress to heart failure (HF), although some demonstrate left ventricular (LV) reverse remodeling (LVRR), which is associated with better outcomes. The pulmonary artery diameter (PAD) to ascending aortic diameter (AoD) ratio has been used as a prognostic predictor in patients with HF, although this tool's usefulness in predicting LVRR remains unknown.Methods and Results: Data from a prospective observational study of 211 patients diagnosed in 2000-2020 with DCM were retrospectively analyzed. Sixty-nine patients with New York Heart Association class I or II HF were included. LVRR was observed in 23 patients (33.3%). The mean LV ejection fraction (29%) and LV end-diastolic dimension (64.5 mm) were similar in patients with and without LVRR. The PAD/AoD ratio was significantly lower in patients with LVRR than those without (81.4% vs. 92.4%, respectively; P=0.003). The optimal PAD/AoD cut-off value for detecting LVRR was 0.9 according to the receiver operating characteristic curve analysis. Multivariate analysis identified a PAD/AoD ratio ≥0.9 as an independent predictor of presence/absence of LVRR. Cardiac events were significantly more common in patients with a PAD/AoD ratio ≥0.9 than those with a ratio0.9, after a median follow up of 2.5 years (log-rank, P=0.007).The PAD/AoD ratio can predict LVRR in patients with DCM.

Autotaxin (ATX) promotes myocardial inflammation, fibrosis, and the subsequent cardiac remodelling through lysophosphatidic acid production. However, the prognostic impact of serum ATX in non-ischaemic dilated cardiomyopathy (NIDCM) has not been clarified. We investigated the prognostic impact of serum ATX in patients with NIDCM.We enrolled 104 patients with NIDCM (49.8 ± 13.4 years, 76 men). We divided the patients into two groups using different cutoffs of median serum ATX levels for men and women: high-ATX group and low-ATX group. Cardiac events were defined as a composite of cardiac death and heart failure resulting in hospitalization. Median ATX level was 203.5 ng/mL for men and 257.0 ng/mL for women. Brain natriuretic peptide levels [224.0 (59.6-689.5) pg/mL vs. 96.5 (40.8-191.5) pg/mL, P = 0.010] were higher in the high-ATX group than low-ATX group, whereas high-sensitivity C-reactive protein and collagen volume fraction levels in endomyocardial biopsy samples were not significantly different between the two groups. Kaplan-Meier survival analysis revealed that the event-free survival rate was significantly lower in the high-ATX group than low-ATX group (log-rank; P = 0.007). Cox proportional hazard analysis revealed that high-ATX was an independent determinant of composite cardiac events. In both sexes, serum ATX levels did not correlate with high-sensitivity C-reactive protein levels and collagen volume fraction but had a weak correlation with brain natriuretic peptide levels (men; spearman's rank: 0.274, P = 0.017, women; spearman's rank: 0.378, P = 0.048).High serum ATX levels can be associated with increasing adverse clinical outcomes in patients with NIDCM. These results indicate serum ATX may be a novel biomarker or therapeutic target in NIDCM.

Heart failure (HF) is a systemic inflammatory disease that causes hypotrophy and skeletal muscle loss. The Global Leadership Initiative on Malnutrition (GLIM) criteria have been developed as a novel evaluation index for malnutrition, with reported usefulness in HF caused by ischemic heart disease. However, reports on the usefulness of malnutrition evaluated by the GLIM criteria in non-ischemic dilated cardiomyopathy (NIDCM) and its relationship with psoas muscle volume are lacking. We investigated the prognostic value of malnutrition evaluated using the GLIM criteria and its association with psoas muscle volume in patients with NIDCM. We enrolled 139 consecutive patients with NIDCM between December 2000 and June 2020. Malnutrition was evaluated using the GLIM criteria on admission. The median follow-up period was 4.7 years. Cardiac events were defined as a composite of cardiac death, hospitalization for worsening HF, and lethal arrhythmia. Furthermore, we measured the psoas muscle volume using computed tomography volumetry in 48 patients. At baseline, the median age was 50 years, and 132 patients (95.0%) had New York Heart Association functional class I or II HF. The median psoas muscle volume was 460.8 cm

Immunomodulatory drugs (IMiDs) thalidomide, lenalidomide, and pomalidomide (Pom) bind to cereblon (CRBN) and trigger proteasomal degradation of neo-substrates IKZF1/3 leading to multiple myeloma (MM) cell apoptosis. Pomalidomide (Pom) also binds albeit weakly to p53-related protein kinase (PRPK, aka TP53RK), an understudied kinase reported to be associated with poor prognosis in MM patients. Here, we developed a series of IMiDs based on Pom and conducted a structure-activity relationship (SAR) study to identify a potent and selective PRPK binder. Structural analysis showed that IMiDs bind PRPK in a fundamentally different way from CRBN, and suggested specific derivatization to improve affinity. We employed a structure-guided strategy to develop compound TXM-02-118, which exhibited nanomolar affinityfor PRPK in binding assays, and showed high selectivity for PRPK over CRBN. Overall, the work represents an initial effort to develop tool compounds for studying PRPK. Moreover, it illustrates how a single class of molecules can use different recognition elements to bind diverse targets using fundamentally different binding poses. This has broad implications for chemical probe and lead compound selectivity profiling, and argues for more wide-spread use of global proteomics or similar methodologies.

The spleen is an important immune organ that releases erythrocytes and monocytes and destroys aged platelets. It also reserves 20-30% of the total blood volume, and its size decreases in hypovolemic shock. However, the clinical significance of splenic size in patients with heart failure (HF) remains unclear. We retrospectively analyzed the data of 206 patients with clinically stable HF gathered between January 2001 and August 2020 and recorded in a single-center registry. All patients underwent right heart catheterization and computed tomography (CT). Splenic size was measured using CT volumetry. The primary outcomes were composite cardiac events occurring for the first time during follow-up, namely, cardiac death and hospitalization for worsening HF. The median splenic volume and splenic volume index (SVI) were 118.0 mL and 68.9 mL/m

Background The spleen is an important organ that stores blood, releases erythrocytes or monocytes, and destroys no-longer-needed platelets. It can reserve 20–30% of the total blood volume, and its size is reduced in hypovolemic shock. However, the clinical significance of the spleen size in patients with heart failure (HF) remains unclear. Purpose The purpose of this study was to investigate the relationship between spleen size, hemodynamic parameters, and prognosis in patients with HF. Methods A total of 219 patients with clinically stable HF were enrolled. All patients underwent right heart catheterisation and computed tomography. The spleen size was measured using computed tomography volumetry. In addition, spleen volume was assessed using the spleen volume index (SVI), corrected for body surface area. Cardiac events were composite endpoints of cardiac death, hospitalisation for worsening HF, fatal arrhythmias, implantation of cardiac devices, implantation of left ventricular assist devices, and unexpected percutaneous coronary intervention or cardiac surgery. Spearman's rank correlation coefficient was used to examine the relationship between spleen volume and hemodynamic parameters. Multivariate Cox hazard regression models were used to investigate whether SVI was an independent determinant of cardiac events. Results Of the 219 patients (median age, 54 [interquartile range] 46–64 years), 145 (66%) were males. The median (interquartile range) spleen volume and SVI was 118.0 (91.5–156.0) mL and 67.8 (54.9–87.2) mL/m2, respectively. SVI was positively correlated with cardiac output (r=0.269, P Conclusion The spleen size may affect the prognosis in patients with HF, reflecting haemodynamics, including systemic circulating blood volume status and sympathetic nerve activity. Funding Acknowledgement Type of funding sources: None. Figure 1Figure 2

Background Left ventricular reverse remodeling (LVRR) is an important predictor for a good prognosis in patients with dilated cardiomyopathy (DCM). Previous reports indicated the pulmonary artery diameter (PAD) to ascending aortic diameter (AoD) ratio as a predictor of adverse outcomes in heart failure patients. However, the impact of the PAD/AoD ratio for predicting LVRR in patients with DCM is unknown. Aim The aim of this study is to investigate the association between PAD/AoD ratio and LVRR in patients with DCM. Methods From a prospective study, clinically stable DCM patients who were investigated the LVRR on echocardiography and underwent CT at baseline were enrolled. LVRR is defined as left ventricular (LV) ejection fraction increase of 10% and a decrease in indexed LV end-diastolic diameter of 10% compared to those at baseline. PAD and AoD data was collected with nonenhanced computed tomography images at baseline. Results In sixty-nine patients (mean age 50.0±13.3 years), the mean LV ejection fraction was 29.8%, and mean LV end-diastolic dimension was 64.5mm, and both of which data was no significant difference between patients with or without LVRR. LVRR was observed in 23 (33.3%) patients. The PAD/AoD ratio was significantly lower in patients with LVRR than without LVRR (81.4% vs. 92.4%, p=0.003). By ROC analysis, the best cut-off for the detection of LVRR was found for a PAD/AoD ratio of 0.9. From multivariate analyses, PAD/AoD ratio was identified as a significant predictor of LVRR. After a median follow-up duration of 2.5 years, the DCM patients with PAD/AoD≥0.9 revealed a significant higher cardiac event than those with PAD/AoD Conclusions The PAD/AoD ratio is useful for predicting LVRR in patients with DCM. The DCM patients with high PAD/AoD ratio had a poor long-term outcome. Funding Acknowledgement Type of funding sources: None. ROC curve for LVRR predictionKaplan-Meier survival curves

Background Autotaxin (ATX) has been reported to promote myocardial inflammation and subsequent cardiac remodeling through lysophosphatidic acid (LPA) production. However, the prognostic impact of ATX has not been clarified in dilated cardiomyopathy (DCM). Purpose We aimed to investigate the prognostic impact of ATX in patients with DCM. Methods We enrolled 104 DCM patients (49.8 years, 76 males). The subjects underwent blood sampling, echocardiography, cardiac catheterization, and endomyocardial biopsy. Gender differences in serum ATX levels have been reported, thus we divided the subjects into two groups using median serum ATX levels for men and women: High-ATX group and Low-ATX group. All patients were followed up by expert cardiologists. The cardiac event was defined as a composite of cardiac death and hospitalization for worsening heart failure. Results Eighty-nine percent of the subjects were classified as New York Heart Association functional class I or II. Female patients had higher serum ATX levels than male patients, with median values of 257.0 ng/mL and 203.5 ng/mL, respectively (Figure A). The average left ventricular ejection fraction and brain natriuretic peptide levels were 30.6% and 122.5 pg/mL. In survival analysis, cumulative event-free probability was significantly lower in High ATX group (p=0.007, Figure B). In Cox proportional hazards analysis, High-ATX was one of the independent predictors of composite cardiac events (Hazards Ratio, 2.575; p=0.043). On the other hand, high sensitive C-reactive protein and collagen volume fraction in myocardial samples were not significant predictors. Conclusion High serum ATX level was associated with poor prognosis in patients with DCM. Funding Acknowledgement Type of funding sources: None. Gender difference in autotaxin levelsSurvival analysis of cardiac events

Atypical fractures commonly arise in the subtrochanteric region or the femoral shaft, whereas those of the upper extremities are rare. Only 15 fractures in 13 patients have been described in the English literature. The management of such fractures has not been established. We describe a patient with an atypical fracture of the ulnar diaphysis, which required revision surgery to achieve the union of the fracture site. Teriparatide together with low-intensity pulsed ultrasound contributed to bone healing. Further studies are needed to determine the optimal strategy for treating atypical fractures of the ulna.

NEDD8-activating enzyme (NAE) is an essential E1 enzyme of the NEDD8 conjugation (neddylation) pathway, which controls cancer cell growth and survival through activation of cullin-RING ubiquitin ligase complexes (CRL). In this study, we describe the preclinical profile of a novel, highly potent, and selective NAE inhibitor, TAS4464. TAS4464 selectively inhibited NAE relative to the other E1s UAE and SAE. TAS4464 treatment inhibited cullin neddylation and subsequently induced the accumulation of CRL substrates such as CDT1, p27, and phosphorylated IκBα in human cancer cell lines. TAS4464 showed greater inhibitory effects than those of the known NAE inhibitor MLN4924 both in enzyme assay and in cells. Cytotoxicity profiling revealed that TAS4464 is highly potent with widespread antiproliferative activity not only for cancer cell lines, but also patient-derived tumor cells. TAS4464 showed prolonged target inhibition in human tumor xenograft mouse models; weekly or twice a week TAS4464 administration led to prominent antitumor activity in multiple human tumor xenograft mouse models including both hematologic and solid tumors without marked weight loss. As a conclusion, TAS4464 is the most potent and highly selective NAE inhibitor reported to date, showing superior antitumor activity with prolonged target inhibition. It is, therefore, a promising agent for the treatment of a variety of tumors including both hematologic and solid tumors. These results support the clinical evaluation of TAS4464 in hematologic and solid tumors.

The titration of cardioprotective agents is essential for successful treatment of heart failure (HF) patients with reduced left ventricular ejection fraction. However, hypotension is one of the limiting factors for titration. Ivabradine reduces heart rate without compromising systolic function by prolonging diastolic filling time. Herein two cases of dilated cardiomyopathy (DCM) are presented in which ivabradine improved blood pressure (BP)-limited tolerability and allowed for further titration of cardioprotective agents. In both cases, the introduction of ivabradine raised the BP, which permitted further increase of the dose of renin-angiotensin system inhibitors or beta-blockers. One major hypothesized mechanism of ivabradine-induced BP elevation has been postulated to be an increase in stroke volume due to prolonged ventricular diastolic filling time. However, ivabradine is not expected to increase BP for all HF patients. In those with small and poorly compliant ventricles with severe diastolic or restricted dysfunction, decreased heart rate and prolonged diastole may excessively suppress compensatory mechanisms, and thus may not lead to increased cardiac output and BP. In contrast, ivabradine potentially increases BP and improves BP-limited tolerability of cardioprotective agents in DCM patients with a large and compliant heart. In addition, subsequent titration of cardioprotective agents may provide additional cardiac reverse remodeling. Learning objective: Ivabradine is usually used for heart failure patients with reduced ejection fraction when the tolerability of cardioprotective agents is maximized. This agent has no direct cardiac contractility-suppressing action. It potentially increases blood pressure and improves tolerability of cardioprotective agents in patients with a large and compliant heart such as dilated cardiomyopathy. Furthermore, subsequent titration of cardioprotective agents may provide additional cardiac reverse remodeling.

Introduction: Several studies have evaluated prognostic value of heart rate (HR) change during hospitalization in patients with acute heart failure (AHF). However, the relationship between HR change in early phase after admission and prognosis have not been fully elucidated. Hypothesis: The aim of this study was to evaluate the prognostic value of HR change in early phase in patients with AHF. Methods: We used a data of multicenter retrospective registry for the consecutive hospitalized patients due to AHF since January 2012 to March 2019. Patients were divided into three groups according to tertiles of HR at admission: lower tertile, HR 108 bpm. And, (HR [at admission] - HR [at 12 hour after admission]) * 100 / HR [at admission] was calculated as HR change (%). Results: Total of 1625 patients were analyzed. The median HR at admission was 96 bpm, and HR decreased to 81 bpm at 12 hours after admission (p < 0.001). Larger HR change was observed according to increase in HR at admission (HR change; lower tertile, 1.0%; middle tertile, 12.5%, higher tertile, 38.0%, p < 0.001). In Kaplan-Meier analysis, the cumulative event-free rates in the composite endpoint of death and re-hospitalization due to AHF showed better according to higher HR at admission (p < 0.001, log-rank) (Figure). After dividing the patient into two groups in each tertiles based on the median HR change, the cumulative event-free rates were comparable between higher HR change group and lower HR change group in all tertiles (Figure). Cox proportional hazards analysis showed that HR change was not the independent predictors of composite endpoint adjusted by covariates in each tertile (lower tertile, p = 0.81; middle tertile, p = 0.78; higher tertile, p = 0.90). Conclusions: HR decreased significantly until 12 hours after admission. However, HR change in early phase did not have prognostic value in patients with AHF.

Introduction: Interstitial fibrosis of myocardium is an important component of cardiac dysfunction. Myofibroblasts, which are activated fibroblasts, contribute to interstitial fibrosis in dilated cardiomyopathy (DCM). Recently, human epididymal body protein 4 (HE4) has attracted attention as a marker specific to myofibroblasts. Hypothesis: We hypothesized that the circulating serum HE4 levels were associated with future cardiac events in DCM. Methods: We enrolled 44 DCM patients with stable heart failure (HF) condition. Patients with cancer were excluded. We collected blood samples from peripheral vain (PV), ascending aorta (Ao), and coronary sinus (CS) during cardiac catheterization. They were divided into two groups at the median of PV HE4 levels: High PV group (>69 pmol/L); n=22, Low PV group (-0.15 pmol/L); n=22, Low CS-Ao group ( Results: The mean age, left ventricular ejection fraction (LVEF), and plasma BNP level were 56 years, 32%, and 205 pg/mL. Between two groups, there were no significant differences in age, gender, LVEF, left ventricular end-diastolic diameter, cardiac index, and pulmonary capillary wedge pressure. However, estimated glomerular filtration rate was significantly lower in the High PV group (p=0.025). Survival analysis revealed that the High PV group had a higher rate of cardiac events ( Figure ). However, there was no difference between two CS-Ao groups. As for the pathological analysis, not only the peripheral HE4 level but CS-Ao HE4 level did not significantly correlate with collagen volume fraction in biopsy samples. Conclusion: Elevated circulating HE4 is associcated with poor prognosis in ambulatory patients with NIDCM. However, transcardiac gradient of plasma HE4 level might not be associated.

Yuji Kasukawa, Naohisa Miyakoshi, Michio Hongo, Yoshinori Ishikawa, Daisuke Kudo, Masazumi Suzuki, Takashi Mizutani, Ryouta Kimura, Yuichi Ono, Yoichi Shimada Department of Orthopedic Surgery, Akita University Graduate School of Medicine, Akita, Japan Abstract: Lumbar kyphosis and the decreased mobility of the lumbar spine increase the risk of falls and impair both the quality of life and the ability to perform activities of daily living. However, in the elderly Japanese population, little is known about the age-related changes and sex-related differences in muscle strength, including of the upper and lower extremities and back extensors. An adequate kyphotic or lordotic angle has also not been determined. In this study, we evaluated the age-related changes in muscle strength and spinal kyphosis in 252 males and 320 females ≥50years of age. Grip, back extensor, hip flexor, and knee extensor strength; thoracic and lumbar kyphosis; and spinal inclination in the neutral standing position were assessed, together with the range of motion of the thoracic and lumbar spine and spinal inclination. Grip strength, back extensor strength, and the strength of the hip flexors and knee extensors decreased significantly with aging, both in males (P

Reducing radiation exposure is a very important issue in interventional cardiology techniques such as percutaneous coronary intervention. Although novel techniques to reduce radiation exposure are valuable, we should also reconsider older techniques. Digital zoom has been available in Japan from 2005. Digital zoom enlarges an 8-inch field of view (FOV) by 1.2 times, allowing visualization of a 6.7-inch FOV without FOV switching. We identified 2101 suitable cases of percutaneous intervention (PCI) and divided them into two groups according to the use of digital zoom; 1195 patients were included in the digital zoom group and 906 patients in the conventional group. We collected data regarding the reference air kerma (RAK) and dose-area product (DAP). We calculated RAK and DAP per minute fluoroscope time (RAK/min, DAP/min, respectively). There were intergroup differences in RAK, DAP, RAK/min, and DAP/min (digital zoom group vs conventional group; RAK, 1590 mGy [990–2410] vs 1850 [1220–2720], p

In the original publication of this article [1], the values of PH in the Table 4 are wrong.

The molecular chaperone heat shock protein 90 (HSP90) is a promising target for cancer therapy, as it assists in the stabilization of cancer-related proteins, promoting cancer cell growth, and survival. A novel series of HSP90 inhibitors were discovered by structure-activity relationship (SAR)-based optimization of an initial hit compound 11a having a 4-(4-(quinolin-3-yl)-1 H-indol-1-yl)benzamide structure. The pyrazolo[3,4- b]pyridine derivative, 16e (TAS-116), is a selective inhibitor of HSP90α and HSP90β among the HSP90 family proteins and exhibits oral availability in mice. The X-ray cocrystal structure of the 16e analogue 16d demonstrated a unique binding mode at the N-terminal ATP binding site. Oral administration of 16e demonstrated potent antitumor effects in an NCI-H1975 xenograft mouse model without significant body weight loss.

Malnutrition is one of the important risk factors for postoperative complications. Transferrin, prealbumin, and retinol-binding protein, so-called rapid turnover proteins (RTPs), may be the better indicators for early detection of nutritional deficits. However, few studies have described the impact of serum RTP levels on postoperative surgical site infection (SSI) in spine surgery. The purpose of this study was to investigate the relationship between preoperative serum RTPs and postoperative SSI. The data of 105 patients (64 male, 41 female; average age 64.4 years; age range 20–88 years) who underwent spine surgery in a single institution between 2014 and 2015 were retrospectively analyzed. Preoperative total lymphocyte count, serum albumin, transferrin, prealbumin, retinol-binding protein, pre-and postopeartive C-reactive protein (CRP), white blood cell count (WBC), and total lymphocyte count were evaluated. Postoperative CRP, WBC, and total lymphocyte count were repeated two or three times/week until hospital discharge. A broad spectrum penicillin or second generation cephalosporin was administered as a prophylactic antibiotic to each patient. When repeated CRP elevation or lymphopenia (no more than 10% or 1000/μL) after postoperative day 3 or 4 was observed, possible SSI was diagnosed. Variables between possible SSI group and non-SSI group were compared using Mann–Whitney U or Chi square test. All variables on univariate analysis were included in multiple logistic regression analysis to identify risk factors for possible postoperative SSI. Thirty-five patients were diagnosed with possible SSI. The mean operative time of possible SSI group was significantly longer (p = 0.036), preoperative total lymphocyte count and serum prealbumin level of possible SSI group were significantly lower (p = 0.002, p = 0.048, respectively) than that of non-SSI group. On univariate analysis, operative time (p = 0.012), preoperative total lymphocyte count (p = 0.041), serum albumin level (p = 0.038), and serum prealbumin level (p = 0.044) were significant contributors to possible SSI, and multiple logistic regression analysis revealed that operative time was the significant contributor to possible SSI (odds ratio 1.008, 95% confidence interval (CI) 1.001–1.015, p = 0.024). A low prealbumin level is a possible risk factor for early-stage SSI in spine surgery, though it was not statistically significant; operative time was the most important indicator of SSI on multivariate analysis.

The purpose of this study was to compare postcontraction hyperemia after electrical stimulation between patients with upper extremity paralysis caused by upper motor neuron diseases and healthy controls. Thirteen healthy controls and eleven patients with upper extremity paralysis were enrolled. The blood flow in the basilic vein was measured by ultrasound before the electrical stimulation of the biceps brachii muscle and 30 s after the stimulation. The stimulation was performed at 10 mA and at a frequency of 70 Hz for 20 s. The mean blood flow in the healthy control group and in upper extremity paralysis group before the electrical stimulation was 60 ± 20 mL/min (mean ± SD) and 48 ± 25 mL/min, respectively. After the stimulation, blood flow in both groups increased to 117 ± 23 mL/min and 81 ± 41 mL/min, respectively. We show that it is possible to measure postcontraction hyperemia using an ultrasound system. In addition, blood flow in both groups increased after the electrical stimulation because of postcontraction hyperemia. These findings suggest that evaluating post contraction hyperemia in patients with upper extremity paralysis can assess rehabilitation effects.

Background Serum lactate level can predict clinical outcomes in some critical cases. In the clinical setting, we noted that patients undergoing extracorporeal cardiopulmonary resuscitation (ECPR) and with poor serum lactate improvement often do not recover from cardiopulmonary arrest. Therefore, we investigated the association between lactate clearance and in-hospital mortality in cardiac arrest patients undergoing ECPR. Methods Serum lactate levels were measured on admission and every hour after starting ECPR. Lactate clearance [(lactate at first measurement − lactate 6 h after)/lactate at first measurement × 100] was calculated 6 h after first serum lactate measurement. All patients who underwent ECPR were registered retrospectively using opt-out in our outpatient’s segment. Result In this retrospective study, 64 cases were evaluated, and they were classified into two groups according to lactate clearance: high-clearance group, > 65%; low-clearance group, ≤ 65%. Surviving discharge rate of high-clearance group (12 cases, 63%) is significantly higher than that of low-clearance group (11 cases, 24%) (p

We report the case of a 13-year-old girl who presented with cardiac collapse secondary to compression of the left main coronary artery (LMCA) between the pulmonary artery and the ascending aorta. In the acute phase, we performed aortography, intra-vascular ultrasound (IVUS), coronary computed tomography angiography (CCTA), transthoracic echocardiography (TTE), and transesophageal echocardiography (TEE). Aortography and CCTA showed that her LMCA was located between her pulmonary artery and the ascending aorta. IVUS and TEE showed that her LMCA was narrowed owing to compression by both great vessels during systole with release of the pressure during diastole. TTE and TEE showed that the left coronary artery flow was faster in the systole than that observed in the diastole. She was initially treated at our hospital but was transferred to another hospital for an unroofing operation. This was a rare case of a patient presenting with a coronary artery anomaly causing cardiac collapse. We conclude that her LMCA stenosis secondary to compression and narrowing of the great vessels led to her cardiac collapse. .