Rational Engineering of XCaMPs, a Multicolor GECI Suite for In Vivo Imaging of Complex Brain Circuit Dynamics.

To decipher dynamic brain information processing, current genetically encoded calcium indicators (GECIs) are limited in single action potential (AP) detection speed, combinatorial spectral compatibility, and two-photon imaging depth. To address this, here, we rationally engineered a next-generation quadricolor GECI suite, XCaMPs. Single AP detection was achieved within 3-10 ms of spike onset, enabling measurements of fast-spike trains in parvalbumin (PV)-positive interneurons in the barrel cortex in vivo and recording three distinct (two inhibitory and one excitatory) ensembles during pre-motion activity in freely moving mice. In vivo paired recording of pre- and postsynaptic firing revealed spatiotemporal constraints of dendritic inhibition in layer 1 in vivo, between axons of somatostatin (SST)-positive interneurons and apical tufts dendrites of excitatory pyramidal neurons. Finally, non-invasive, subcortical imaging using red XCaMP-R uncovered somatosensation-evoked persistent activity in hippocampal CA1 neurons. Thus, the XCaMPs offer a critical enhancement of solution space in studies of complex neuronal circuit dynamics. VIDEO ABSTRACT.

Chronic Effects of Adaptive Servo-Ventilation Therapy on Mortality and the Urgent Rehospitalization Rate in Patients Experiencing Recurrent Admissions for Heart Failure　- A Multicenter Prospective Observational Study (SAVIOR-L).

BACKGROUND: This study investigated whether the chronic use of adaptive servo-ventilation (ASV) reduces all-cause mortality and the rate of urgent rehospitalization in patients with heart failure (HF).Methods and Results: This multicenter prospective observational study enrolled patients hospitalized for HF in Japan between 2019 and 2020 who were treated either with or without ASV therapy. Of 845 patients, 110 (13%) received chronic ASV at hospital discharge. The primary outcome was a composite of all-cause death and urgent rehospitalization for HF, and was observed in 272 patients over a 1-year follow-up. Following 1:3 sequential propensity score matching, 384 patients were included in the subsequent analysis. The median time to the primary outcome was significantly shorter in the ASV than in non-ASV group (19.7 vs. 34.4 weeks; P=0.013). In contrast, there was no significant difference in the all-cause mortality event-free rate between the 2 groups. CONCLUSIONS: Chronic use of ASV did not impact all-cause mortality in patients experiencing recurrent admissions for HF.

Early evaluation of CAR-T cell therapy response in R/R DLBCL patients using 18F-FDG PET/CT.

OBJECTIVE: CD19-targeted chimeric antigen receptor T (CAR-T) cell therapy provides a durable response in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). The role of fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) for early evaluation of response in patients with that immunotherapy was evaluated. SUBJECTS AND METHODS: Three separate 18F-FDG PET/CT examinations of 53 patients (29 males, 24 females; median 62 years old) with R/R DLBCL were conducted; before bridging therapy [time of decision (TD)], before CAR-T (tisagenlecleucel, n=37; lisocabtagenemaraleucel, n=16) infusion [time of CAR-T infusion (IT)], and one month (M1) after CAR-T infusion. Response was evaluated based on the Deauville 5-point scale and Lugano criteria. RESULTS: Among 21 patients (39.6%) with complete metabolic response (CMR) at IT-PET, 20 were able to continue CMR, while one showed progression at M1-PET. Among 32 patients (60.4%) with non-CMR at IT-PET, 12, 8, 4, and 8 showed CMR, partial metabolic response (PMR), (non-metabolic response (NMR), and progressive metabolic disease (PMD), respectively, at M1-PET as compared with IT-PET. Evaluations of M1-PET as compared with baseline TD-PET indicated 32, 7, 5, and 9 patients with CMR, PMR, NMR, and PMD, respectively. After a median 10.1 months, 26 patients showed progression and 13 had died from DLBCL. The 32 who achieved CMR showed significantly longer progression-free (P<0.0001) and overall survival (P<0.0001) periods as compared to the 21 non-CMR patients. CONCLUSION: Fluorine-18-FDG PET/CT findings obtained one month after CAR-T cell therapy showed accuracy for early response evaluation and prediction of progression in patients with R/R DLBCL.

Evaluation of 11 C-choline positron emission tomography/computed tomography for determining treatment response in castration-resistant prostate cancer patients.

OBJECTIVE: The utility of 11 C-choline positron emission tomography/computed tomography for determining treatment response as compared with prostate-specific antigen response and prognosis prediction in castration-resistant prostate cancer patients was investigated. METHODS: Eighty-four 11 C-choline-positron emission tomography/computed tomography scans before/after treatments with abiraterone (n = 12 patients), enzalutamide (n = 3), docetaxel (n = 9), cabazitaxel (n = 5), radiation therapy alone (n = 3), radiation therapy, enzalutamide, and/or abiraterone (n = 5), radium-223 (n = 4), and radiofrequency ablation (n = 1) in 42 castration-resistant prostate cancer patients were retrospectively examined. Prostate-specific antigen values were determined before and after treatment. Using the Kaplan-Meier method, the correlation of Positron Emission Tomography Response Criteria In Solid Tumors with prostate-specific antigen response and prognostic impact was evaluated. RESULTS: Pretreatment 11 C-choline-positron emission tomography/computed tomography findings identified local, lymph node, bone, and visceral metastasis in 12, 12, 29, and five patients, respectively. Following treatments, complete metabolic response was noted in one, partial metabolic response in eight, stable metabolic disease in 13, and progressive metabolic disease in 20. Mean prostate-specific antigen change for complete metabolic response, partial metabolic response, stable metabolic disease and progressive metabolic disease was -48.9%, -55.0% (range -92.4% to -19.1%), -4.2% (-33.2% to 35.1%), and 142.7% (30.7% to 373.8%), respectively, significantly greater in the progressive metabolic disease cases (P < 0.01). Positron Emission Tomography Response Criteria In Solid Tumors was well correlated with prostate-specific antigen change. Patients with no progression (complete metabolic response/partial metabolic response/stable metabolic disease) showed significantly longer cancer-specific survival than progressive metabolic disease (P < 0.005). Using pretreatment 11 C-choline-positron emission tomography/computed tomography results to divide into three groups; (a) local and/or lymph node metastasis without bone metastasis (n = 10), (b) <6 bone metastasis sites (n = 16), (c) ≥6 bone metastasis sites and/or visceral metastasis (n = 16), cancer-specific survival showed significant stratification (P < 0.001). CONCLUSIONS: 11 C-choline-positron emission tomography/computed tomography may reflect castration-resistant prostate cancer metastatic lesion activity for treatment response and prognosis evaluations.

Quality Indicators in Patient Referral Documents for Heart Failure in Japan.

This study examined quality indicators (QIs) for heart failure (HF) in patients' referral documents (PRDs).We conducted a nationwide questionnaire survey to identify information that general practitioners (GPs) would like hospital cardiologists (HCs) to include in PRDs and that HCs actually include in PRDs. The percentage of GPs that desired each item included in PRDs was converted into a deviation score, and items with a deviation score of ≥ 50 were defined as QIs. We rated the quality of PRDs provided by HCs based on QI assessment.We received 281 responses from HCs and 145 responses from GPs. The following were identified as QIs: 1) HF cause; 2) B-type natriuretic peptide (BNP) or N-terminal pro-BNP concentration; 3) left ventricular ejection fraction or echocardiography; 4) body weight; 5) education of patients and their families on HF; 6) physical function, and 7) functions of daily living. Based on QI assessment, only 21.7% of HCs included all seven items in their PRDs. HCs specializing in HF and institutions with many full-time HCs were independently associated with including the seven items in PRDs.The quality of PRDs for HF varies among physicians and hospitals, and standardization is needed based on QI assessment.

Impact of Induced Therapeutic Hypothermia by Intravenous Infusion of Ice-Cold Fluids After Hospital Arrival in Comatose Survivors of Out-of-Hospital Cardiac Arrest With Initial Shockable Rhythm.

BACKGROUND: The effect of in-hospital rapid cooling by intravenous ice-cold fluids for comatose survivors of out-of-hospital cardiac arrest (OHCA) is unclear.Methods and Results:From the J-PULSE-HYPO study registry, data for 248 comatose survivors with return of spontaneous circulation (ROSC) who were treated with therapeutic hypothermia (34℃ for 12-72 h) after witnessed shockable OHCA were extracted. Patients were divided into 2 groups by the median collapse-to-ROSC interval (18 min), and then into 2 groups by cooling method (rapid cooling by intravenous ice-cold fluids vs. standard cooling). The primary endpoint was favorable neurological outcome (Cerebral Performance Category of 1 or 2) at 30 days after OHCA. In the whole cohort, the shorter collapse-to-ROSC interval group had significantly higher favorable neurological outcome than the longer collapse-to-ROSC interval group (78.2% vs. 46.8%, P<0.001). In the shorter collapse-to-ROSC interval group, no significant difference was observed in favorable neurological outcome between the 2 cooling groups (rapid cooling group: 79.4% vs. standard cooling group: 77.0%, P=0.75). In the longer collapse-to-ROSC interval group, however, favorable neurological outcome was significant higher in the rapid cooling group than in the standard cooling group (60.7% vs. 33.3%, P<0.01) and the adjusted odds ratio after rapid cooling was 3.069 (95% confidence interval 1.423-6.616, P=0.004). CONCLUSIONS: In-hospital rapid cooling by intravenous ice-cold fluids improved neurologically intact survival in comatose survivors whose collapse-to-ROSC interval was delayed over 18 min after shockable OHCA.

Differences in Priorities for Heart Failure Management Between Cardiologists and General Practitioners in Japan.

BACKGROUND: The purpose of this study was to clarify the current status and issues of community collaboration in heart failure (HF) using a nationwide questionnaire survey.Methods and Results:We conducted a survey among hospital cardiologists and general practitioners (GPs) using a web-based questionnaire developed with the Delphi method, to assess the quality of community collaboration in HF. We received responses from 46 of the 47 prefectures in Japan, including from 281 hospital cardiologists and 145 GPs. The survey included the following characteristics and issues regarding community collaboration. (1) Hospital cardiologists prioritized medical intervention for preventing HF hospitalization and death whereas GPs prioritized supporting the daily living of patients and their families. (2) Hospital cardiologists have not provided information that meets the needs of GPs, and few regions have a community-based system that allows for the sharing of information about patients with HF. (3) In the transition to home care, there are few opportunities for direct communication between hospitals and community staff, and consultation systems are not well developed. CONCLUSIONS: The current study clarified the real-world status and issues of community collaboration for HF in Japan, especially the differences in priorities for HF management between hospital cardiologists and GPs. Our data will contribute to the future direction and promotion of community collaboration in HF management.

The association between neuromuscular blockade use during target temperature management and neurological outcomes.

BACKGROUND: To date, no study has comprehensively analyzed the association between neuromuscular blockade (NMB) during target temperature management (TTM) and the neurological outcomes after out-of-hospital cardiac arrest (OHCA) using a multicenter dataset. We aimed to examine the association between NMB during TTM after cardiac arrest and neurological outcomes after OHCA. METHODS: This study was a secondary analysis of the Japanese Population-based Utstein-style study with defibrillation and basic/advanced Life Support Education and implementation-Hypothermia (J-PULSE-HYPO) study registry. The exposure of the current study was the use of NMB during TTM. The primary outcome was favorable neurological outcome, i.e., a cerebral performance category of 1-2, at hospital discharge. RESULTS: Of the 452 patients with OHCA enrolled in the J-PULSE-HYPO study, 431 were analyzed. NMB was used in 353 patients (81.9%). Multivariable logistic regression analysis revealed that NMB use was not independently associated with favorable outcomes [odds ratio (OR), 0.96; 95% confidence interval (CI), 0.42-2.18; p = .918)] or survival at discharge (OR, 0.83; 95% CI, 0.31-2.02; p = .688). After adjusting the covariates, the predicted probabilities did not reveal significant differences between NMB use and non-NMB use in the respective mean (95% CI) values for favorable neurological outcomes [53.6 (50.2-57.0) % vs. 58.0 (50.4-65.6) %, p = .304], and survival rates [77.1 (74.7-79.5) % vs. 75.8 (70.5-81.0) %, p = .647]. CONCLUSIONS: The NMB use during TTM was not associated with favorable neurological outcomes and survival rate in patients with OHCA.

Comparison of Mortality Prediction Models on Long-Term Mortality in Hospitalized Patients With Acute Heart Failure　- The Importance of Accounting for Nutritional Status.

BACKGROUND: The ideal mortality prediction model (MPM) for acute heart failure (AHF) patients would have sufficient and stable predictive ability for long-term as well as short-term mortality. However, published MPMs for AHF predominantly predict short-term mortality up to 90 days, and their prognostic performance for long-term mortality remains unclear. Methods and Results: We analyzed 609 AHF patients in a prospective registry from January 2013 to May 2016. We compared the prognostic performance for long-term mortality among 8 systematically identified MPMs for AHF that predict short-term mortality up to 90 days from admission. The PROTECT 7-day model showed the highest c-index for long-term as well as short-term mortality among the studied MPMs. Sensitivity analyses revealed serum albumin and total cholesterol to be the most important variables, as dropping these variables resulted in a significant decline in c-index, when compared with other variables specific to the PROTECT 7-day model. Furthermore, significant improvements in c-index and net reclassification were observed when serum albumin or serum albumin plus total cholesterol was added to the studied MPMs, other than the PROTECT 7-day model. CONCLUSIONS: The PROTECT 7-day model demonstrated the highest predictive performance for long-term as well as short-term mortality in AHF patients among the published MPMs. Our findings indicate the importance of accounting for nutritional status such as serum albumin and total cholesterol in AHF patients when developing a MPM.

Elevated Plasma D-Dimer Level Is Associated With Short-Term Risk of Ischemic Stroke in Patients With Acute Heart Failure.

BACKGROUND AND PURPOSE: The incidence of heart failure increases the subsequent risk of ischemic stroke, and its risk could be higher in the short-term period after an acute heart failure (AHF) event. However, its determinants remain to be clarified. Plasma D-dimer level reflects fibrin turnover and exhibits unique properties as a biomarker of thrombosis. The aim of this study is to investigate whether D-dimer level is a determinant of short-term incidence of ischemic stroke in patients with AHF. METHODS: We examined 721 consecutive hospitalized AHF patients with plasma D-dimer level on admission from our prospective registry between January 2013 and May 2016. The study end points were incidence of ischemic stroke during hospitalization and at 30 days after admission. RESULTS: Of the total participants (mean age, 76 years; male, 60%; atrial fibrillation, 54%; mean left ventricular ejection fraction, 38%), in-hospital ischemic stroke occurred in 18 patients (2.5%) during a median hospitalization period of 21 days, and 30-day ischemic stroke occurred in 16 patients (2.2%). Higher D-dimer level on admission was an independent determinant of subsequent risk of in-hospital ischemic stroke even after adjustment by CHA2DS2-VASc score (odds ratio, 2.29; 95% confidence interval, 1.46-3.60; P<0.001) or major confounders, including age, atrial fibrillation, and antithrombotic therapy (odds ratio, 2.31; 95% confidence interval, 1.43-3.74; P<0.001). Subgroup analyses showed consistent findings in patients without atrial fibrillation (odds ratio, 2.46; 95% confidence interval, 1.39-4.54; P=0.002) and those without antithrombotic therapy (odds ratio, 2.79; 95% confidence interval, 1.53-5.57; P<0.001). Similar results were obtained for 30-day ischemic stroke as an alternative outcome. CONCLUSIONS: Elevated plasma D-dimer level on admission was significantly associated with increased incidence of ischemic stroke shortly after admission for AHF, suggesting a predictive role of D-dimer for short-term ischemic stroke events in patients with AHF. CLINICAL TRIAL REGISTRATION: URL: https://www.umin.ac.jp/ctr/index.htm. Unique identifier: UMIN000017024.

Randomized Phase II Trial of CapOX plus Bevacizumab and CapIRI plus Bevacizumab as First-Line Treatment for Japanese Patients with Metastatic Colorectal Cancer (CCOG-1201 Study).

PURPOSE: The aim of this randomized, multicenter, noncomparative, phase II trial was to investigate the efficacy and safety of two potential first-line treatments, capecitabine and oxaliplatin (CapOX) plus bevacizumab (BEV) and capecitabine and irinotecan (CapIRI) plus bevacizumab, in Japanese patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Patients with untreated mCRC were randomly assigned to receive either CapOX plus bevacizumab (CapOX/BEV arm: bevacizumab 7.5 mg/kg and oxaliplatin 130 mg/m2 on day 1 and oral capecitabine 2,000 mg/m2 on days 1-14, every 3 weeks) or CapIRI plus bevacizumab (CapIRI/BEV arm: bevacizumab 7.5 mg/kg and irinotecan 200 mg/m2 on day 1 and capecitabine 1,600 mg/m2 on days 1-14, every 3 weeks). The primary endpoint was overall response rate (ORR), and the secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. RESULTS: A total of 107 patients were enrolled. The intent-to-treat population comprised 54 patients in the CapOX/BEV arm and 53 patients in the CapIRI/BEV arm. The median follow-up period was 35.5 months. ORR was 56% in the CapOX/BEV arm and 55% in the CapIRI/BEV arm. Median PFS and OS were 12.4 and 26.7 months in the CapOX/BEV arm and 11.5 and 28.7 months in the CapIRI/BEV arm, respectively. The frequencies of hematological and nonhematological adverse events above grade 3 were 13% and 30% in the CapOX/BEV arm and 25% and 23% in the CapIRI/BEV arm, respectively. CONCLUSION: CapOX plus bevacizumab and CapIRI plus bevacizumab are equally effective and feasible as the first-line treatments in Japanese patients with mCRC. IMPLICATIONS FOR PRACTICE: The CCOG-1201 study was designed to evaluate the efficacy and safety of capecitabine and oxaliplatin plus bevacizumab and capecitabine and irinotecan plus bevacizumab as a first-line treatment in Japanese patients with metastatic colorectal cancer. This article reports on the trial and efforts to define the role of these regimens, including the effect of KRAS status and UGT1A1 polymorphisms in metastatic colorectal cancer.

The Impact of Heart Rate Response During 48-Hour Rewarming Phase of Therapeutic Hypothermia on Neurologic Outcomes in Out-of-Hospital Cardiac Arrest Patients.

OBJECTIVES: Bradycardia during therapeutic hypothermia has been reported to be a predictor of favorable neurologic outcomes in out-of-hospital cardiac arrests. However, bradycardia occurrence rate may be influenced by the target body temperature. During therapeutic hypothermia, as part of the normal physiologic response, heart rate decreases in the cooling phase and increases during the rewarming phase. We hypothesized that increased heart rate during the rewarming phase is another predictor of favorable neurologic outcomes. To address this hypothesis, the study aimed to examine the association between heart rate response during the rewarming phase and neurologic outcomes in patients having return of spontaneous circulation after out-of-hospital cardiac arrest. DESIGN: A secondary analysis of the Japanese Population-based Utstein style study with defibrillation and basic/advanced Life Support Education and implementation-Hypothermia registry, which was a multicenter prospective cohort study. SETTING: Fourteen hospitals throughout Japan. PATIENTS: Patients suffering from out-of-hospital cardiac arrest who received therapeutic hypothermia after the return of spontaneous circulation from 2005 to 2011. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: This study enrolled 452 out-of-hospital cardiac arrest patients, of which 354 were analyzed, and 80.2% survived to hospital discharge, of which 57.3% had a good neurologic outcome. Heart rate response was calculated using heart rate data recorded during therapeutic hypothermia in the abovementioned registry. Heart rate response in the rewarming phase (heart rate response-rewarming) was calculated as follows: (heart rate [post rewarming]-heart rate [pre rewarming])/heart rate (pre rewarming) × 100. The primary outcome was an unfavorable neurologic outcome at hospital discharge, that is, a Cerebral Performance Category of 3-5. Multivariable logistic regression analysis was performed to determine the association between heart rate response-rewarming and unfavorable neurologic outcomes. Multivariable logistic regression analysis showed that heart rate response-rewarming was independently associated with unfavorable outcomes (odds ratio [per 10% change], 0.86; 95% CI, 0.78-0.96; p = 0.004). CONCLUSIONS: Increased heart rate in the approximately 48-hour rewarming phase during therapeutic hypothermia was significantly associated with and was an independent predictor of favorable neurologic outcomes during out-of-hospital cardiac arrest.

Team-based parent training by child specialists helps maltreated children.

BACKGROUND: This study assessed the effects of the parent training (PT) technique, in which child specialists (CS) such as preschool and school teachers promote secure attachment in children with aberrant social behavior following maltreatment, using a team approach. METHODS: Child specialists confirmed the presence of child abuse, according to Japanese Ministry of Health, Labour and Welfare criteria. CS such as homeroom, special education-related, student guidance-related, nursing teachers and co-workers received a PT course conducted by the authors. A homeroom teacher provided classroom management to model good examples of social life for the target child. A nursing teacher and assistant offered individualized instruction to foster the formation of secure attachments by the target child. RESULT: Behavioral abnormalities in both school and home resolved in seven out of 12 cases. These subjects received the intervention for 2-4 years. In the other cases, behavioral abnormalities disappeared or decreased at school, but continued at home. Almost all children met the alternative criteria of attachment disorder proposed by Boris and Zeanah. One child met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for reactive attachment disorder. This intervention is significantly more effective for children who have yet to begin elementary school than those in elementary school. CONCLUSIONS: The PT technique as applied by CS using a team approach may be a useful intervention for fostering secure attachment in children with maltreatment who exhibit behavioral abnormalities. Early detection and intervention are necessary to successfully address the behavioral abnormalities of children with maltreatment.

The efficacy and safety of CapeOX plus bevacizumab therapy followed by capecitabine plus bevacizumab maintenance therapy in patients with metastatic colorectal cancer: a multi-center, single-arm, phase II study (CCOG-0902).

BACKGROUND: The aim of this study was to evaluate the efficacy and safety of CapeOX plus bevacizumab with a planned oxaliplatin stop-and-go strategy in Japanese patients with metastatic colorectal cancer (mCRC). METHODS: Patients with untreated mCRC were treated with 4 cycles of CapeOX plus bevacizumab therapy, followed by capecitabine plus bevacizumab maintenance therapy. Reintroduction of oxaliplatin was scheduled after 8 cycles of maintenance therapy or upon tumor progression. The primary endpoint was progression-free survival (PFS), and secondary end points included overall survival (OS), objective response rate to each treatment, reintroduction rate of oxaliplatin, frequency of peripheral sensory neuropathy (PSN), and safety. RESULTS: The 52 patients who received the protocol treatment were included in the evaluation of efficacy and safety. Median PFS and OS were 12.4 months (95% confidence interval [CI], 10.0-14.8) and 30.6 months (95% CI, 27.6-33.5), respectively. The objective response rates were 55.8% for the initial CapeOX plus bevacizumab therapy, 17.8% for capecitabine plus bevacizumab maintenance therapy, and 31.0% for reintroduced CapeOX plus bevacizumab therapy. The frequency of PSN was 63.5%, including 3.8% of patients with grade 3 PSN. No patients required treatment discontinuation because of PSN during the induction or maintenance therapy. CONCLUSIONS: CapeOX plus bevacizumab therapy with a planned oxaliplatin stop-and-go strategy is a feasible first-line treatment for Japanese patients with mCRC. TRIAL REGISTRATION: This trial is registered with the University Hospital Medical Information Network in 15 March 2010 ( UMIN000006478 ).

Impact of decreased serum albumin levels on acute kidney injury in patients with acute decompensated heart failure: a potential association of atrial natriuretic peptide.

Although hypoalbuminemia at admission is a risk for acute kidney injury (AKI) and mortality in patients with acute decompensated heart failure (ADHF), the clinical significance of decreased serum albumin levels (DAL) during ADHF therapy has not been elucidated. This study aimed to evaluate whether DAL was associated with AKI, and whether intravenous atrial natriuretic peptide (ANP) administration, which provides an effective treatment for ADHF but promotes albumin extravasation, was associated with DAL and AKI. A total of 231 consecutive patients with ADHF were enrolled. AKI was defined as ≥0.3 mg/dl absolute or 1.5-fold increase in serum creatinine levels within 48 h. AKI occurred in 73 (32%) of the 231 patients during ADHF therapy. The median value of decreases in serum albumin levels was 0.3 g/dl at 7 days after admission. When DAL was defined as ≥0.3 g/dl decrease in serum albumin levels, DAL occurred in 113 patients, and was independently associated with AKI. Of the 231 patients, 73 (32%) were treated with intravenous ANP. DAL occurred more frequently in patients receiving ANP than in those not receiving ANP (77 vs. 36%, p < 0.001), and ANP was independently associated with DAL. The incidence of AKI was higher in patients receiving ANP than in those not receiving ANP (48 vs. 24%, p < 0.001). ANP was independently associated with AKI. In conclusion, DAL is associated with AKI. Intravenous ANP administration may be one of the promoting factors of DAL, which leads to AKI, indicating a possible novel mechanism of AKI.

Self-Assembly of Giant Spherical Liquid-Crystalline Complexes and Formation of Nanostructured Dynamic Gels that Exhibit Self-Healing Properties.

Supramolecular self-assembly of 24 forklike mesogenic ligands and 12 transition metal ions led to the formation of giant spherical coordination complexes that exhibit liquid-crystalline (LC) phases. Self-healing LC supramolecular gels were also obtained through the introduction of these LC nanostructured supramolecular giant spherical complexes into dynamic covalent networks formed by cross-linkers and bifunctional polymers. The giant spherical structures of the PdII complexes with 72 rodlike moieties on the periphery were characterized by NMR, diffusion-ordered NMR spectroscopy, and mass spectrometry. These complexes are stable and exhibit lyotropic LC behavior, while the mesogenic ligands show thermotropic LC properties. The self-assembled LC structures of the spherical complexes can be tuned by the length of the rodlike moieties.

Generation of synchronized picosecond pulses by a 1.06-µm gain-switched laser diode for stimulated Raman scattering microscopy.

We propose that a gain-switched laser diode (GS-LD) can be used as a picosecond laser source for stimulated Raman scattering (SRS) microscopy. We employed a 1.06-µm GS-LD to generate ~13-ps pulses at a repetition rate of 38 MHz and amplified them to >100 mW with Yb-doped fiber amplifiers. The GS-LD was driven by 200-ps electrical pulses, which were triggered through a toggle flip-flop (T-FF) so that the GS-LD pulses were synchronized to Ti:sapphire laser (TSL) pulses at a repetition rate of 76 MHz. We found the timing jitter of GS-LD pulses to be approximately 2.7 ps in a jitter bandwidth of 7 MHz. We also show that the delay of electrical pulses can be less sensitive to the optical power of TSL pulses by controlling the threshold voltage of the T-FF. We demonstrate the SRS imaging of polymer beads and of HeLa cells with GS-LD pulses and TSL pulses, proving that GS-LD is readily applicable to SRS microscopy as a compact and stable pulse source.

1 MW peak-power subpicosecond optical pulse source based on a gain-switched laser diode.

We have generated optical pulses of 1.2 MW peak power and 0.6 ps duration using a 1060 nm band gain-switched laser diode pulse oscillator. Optical pulses are amplified by three-stage ytterbium-doped fiber amplifiers, and remarkable reductions of amplified spontaneous emission noise and temporal duration have been accomplished based on self-phase modulation in the middle-stage amplifier. After the main amplifier, optical pulses were temporally compressed by a grating pair, and this enabled generation of subpicosecond optical pulses with over 1 MW peak power.

Prognostic Impact of Functional Mitral Regurgitation in Patients Admitted With Acute Decompensated Heart Failure.

BACKGROUND: Functional mitral regurgitation (FMR) is a common complication of heart failure (HF) and worsens in acute decompensation. It is unclear whether FMR on admission or discharge determines the outcome. This study aimed to elucidate the prognostic significance of FMR on admission or discharge in patients admitted with acute decompensated HF. METHODS AND RESULTS: From 2006 to 2009, 349 patients admitted with acute decompensated HF were enrolled. They were followed with the composite endpoint of all-cause death and hospitalization for HF; 74 (21%) died and 113 (32%) developed the composite endpoint during 2.1±1.3 years. Moderate/severe FMR at discharge was associated with the composite endpoint (P=0.001), whereas that on admission was not. Multivariate Cox proportional hazard analysis showed that moderate/severe FMR (hazard ratio [95% confidence interval] =1.70 [1.03-2.73] P=0.04), logBNP, and NYHA class III/IV at discharge were independent determinants of the outcome. Moderate/severe FMR at discharge with BNP ≥200 pg/ml was prognostic, but BNP <200 pg/ml was no longer prognostic. CONCLUSIONS: Residual moderate/severe FMR after medical therapy for acute decompensated HF was associated with poor outcome, suggesting a potential target for further treatment of HF.

Time to Reperfusion in ST-Segment Elevation Myocardial Infarction Patients With vs. Without Pre-Hospital Mobile Telemedicine 12-Lead Electrocardiogram Transmission.

BACKGROUND: Prehospital ECG improves survival following ST-segment elevation myocardial infarction (STEMI). Although a new International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations placed new emphasis on the role of prehospital ECG, this technology is not widely used in Japan. We developed a mobile telemedicine system (MTS) that continuously transmits real-time 12-lead ECG from ambulances in a prehospital setting. This study was designed to compare reperfusion delay between STEMI patients with different prehospital transfer pathways. METHODS AND RESULTS: Between 2008 and 2012, 393 consecutive STEMI patients were transferred by ambulance to hospital (PCI-capable center); 301 patients who underwent primary percutaneous coronary intervention (PCI) were enrolled prospectively. We compared time to reperfusion between patients transferred to PCI-capable hospital using the MTS (MTS group, n=37), patients directly transferred from the field to PCI-capable hospital without the MTS (field transfer group, n=125) and patients referred from a PCI-incapable hospital (interhospital transfer group, n=139). Times to reperfusion in the MTS group were significantly shorter than in the other groups, yielding substantial benefits in patients who arrived at a PCI-capable hospital within 6 h after symptom onset. On multivariate analysis, MTS use was an independent predictor of <90-min door-to-device interval (OR, 4.61; P=0.005). CONCLUSIONS: Reperfusion delay was shorter in patients using MTS than in patients without it. (Circ J 2016; 80: 1624-1633).