Differences in extracellular fluid volume between acute heart failure patients with and without high systolic blood pressure

Aims Some reports have suggested that hypertensive acute heart failure (AHF) is caused by intravascular congestion, not interstitial congestion. We evaluated the differences in extracellular fluid volume assessed by bioelectrical impedance analysis (BIA) between AHF patients with and without high systolic blood pressure (sBP). Methods This prospective single-centre study (UMIN000030266) included 178 patients hospitalized due to AHF between September 2017 and August 2018. We calculated extracellular water (ECW), intracellular water (ICW), total body water (TBW), and ECW-to-TBW ratio (oedema index: EI) by BIA and evaluated conventional parameters as follows: weight, N-terminal pro brain natriuretic peptide values, and echocardiography parameters on admission and before discharge. One-year outcomes included all-cause death and re-admission due to heart failure. We compared patients with sBP > 140 mmHg on admission [clinical scenario 1 (CS1) group] and with sBP of Results The mean age of the patients was 79.5 +/- 11.1 years, and 48.9% of the patients were female. EI on admission of 83 patients in the CS1 group was lower than that of 95 patients in the non-CS1 group. The change in EI from admission to before discharge was no significant in the CS1 group but was significant in the non-CS1 group. Comparing the changes from admission to before discharge between the CS1 and the non-CS1 group, delta ECW, delta ICW, delta TBW, and delta EI of the CS1 group were significantly smaller than those of the non-CS1 group. During the 1-year follow-up period after discharge of the 178 patients, the numbers of deaths and re-admissions due to acute HF were 26 (15%) and 49 (28%), respectively. Patients with high EI before discharge [> 0.408 (median)] had significantly more cardiac events than patients with low EI [hazard ratio (HR): 2.15, 95% confidence interval (CI): 1.30-3.55]. Cox regression analysis revealed that higher EI as a continuous variable was significantly associated with worse outcome in non-CS1 group (HR: 1.46, 95% CI: 1.13-1.87), but not significantly associated with worse outcome in CS1 group (HR: 1.29, 95% CI: 0.98-1.69). Conclusions EI on admission in patients with high sBP was not elevated, and changes in ECW, ICW, TBW, and EI in patients with high sBP were smaller than those in patients without high sBP. EI measured by BIA could distinguish AHF with interstitial or intravascular congestion

Reducing Hemorrhagic Complication by Dabigatran Via Neurovascular Protection After Recanalization With Tissue Plasminogen Activator in Ischemic Stroke of Rat

This study assesses the risks and benefits of tissue plasminogen activator (tPA) treatment under oral anticoagulation with dabigatran compared with warfarin or vehicle control in transient middle cerebral artery occlusion (tMCAO). After pretreatment with warfarin (0.2 mg/kg/day), dabigatran (20 mg/kg/day), or vehicle (0.5% carboxymethyl cellulose sodium salt) for 7 days, tMCAO was induced for 120 min, followed by reperfusion and tPA (10 mg/kg/10 ml). Clinical parameters, including cerebral infarction volume, hemorrhagic volume, and blood coagulation, were examined. At 24 hr after reperfusion, markers for the neurovascular unit at the peri-ischemic lesion were immunohistochemically examined in brain sections, and MMP-9 activity was measured by zymography. Paraparesis and intracerebral hemorrhage volume were significantly improved in the dabigatran-pretreated group compared with the warfarin-pretreated group. A marked dissociation between astrocyte foot processes and the basal lamina or pericyte was observed in the warfarin-pretreated group, which was greatly improved in the dabigatran-pretreated group. Furthermore, a remarkable activation of MMP-9 in the ipsilateral warfarin-pretreated rat brain was greatly reduced in dabigatran-pretreated rats. The present study reveals that the mechanism of intracerebral hemorrhage with warfarin-pretreatment plus tPA in ischemic stroke rats is the dissociation of the neurovascular unit, including the pericyte. Neurovascular protection by dabigatran, which was first shown in this study, could partially explain the reduction in hemorrhagic complication by dabigatran reported from clinical study

Successful Delayed Aortic Surgery for a Patient with Ischemic Stroke Secondary to Aortic Dissection

The diagnosis of aortic dissection (AD) is sometimes difficult within the limited time window of recombinant tissue plasminogen activator (tPA) for ischemic stroke (IS). A 60-year-old man developed sudden left hemiparesis due to IS. During tPA infusion, his blood pressure dropped and consciousness declined. After transfer to our hospital, carotid duplex ultrasonography led to a diagnosis of AD. Emergency surgery was postponed because of the risk of hemorrhagic transformation. The patient successfully underwent aortic surgery on day 5 and was discharged with a remarkable improvement in his symptoms. Delayed surgery may avoid hemorrhagic transformation in patients with AD-induced IS who have received tPA

Efficacy and safety of cabazitaxel therapy in elderly (≥75 years) patients with castration-resistant prostate cancer: A multiinstitutional study

Background: There is little data on the outcome of cabazitaxel (CBZ) treatment of elderly patients with castration-resistant prostate cancer (CRPC). This study assessed the efficacy and safety of CBZ chemotherapy in patients with CRPC aged 75 years or older in a multiinstitutional study. Methods: We retrospectively reviewed the 74 patients with CRPC treated with CBZ enrolled in 10 institutions. Clinicopathological backgrounds, prognosis including prostate-specific antigen decline, time to treatment failure, progression-free survival, overall survival, and safety profiles were compared between younger (<75 years) and elder (≥75 years) patients. Results: In total, 74 patients were enrolled; 50 patients were younger than 75 years and 24 were ≥75 years. Clinicopathological characteristics were comparable between younger and elder patients, with the exception of serum albumin values at the time of CBZ treatment. The median prostate-specific antigen decline in younger and elder men was −8.8% and −32.3% from baseline, respectively. The median time to treatment failure, progression-free survival, and overall survival for younger and elder men were 0.24 and 0.33 years, 0.23 and 0.43 years, and 0.69 and 1.17 years, respectively. In addition, safety profiles were comparable between younger and elder patients. Conclusions: This multiinstitutional study suggests that patients with CRPC aged 75 years or older eligible for CBZ treatment can be treated safely and with noninferior efficacy compared with those younger than 75 years

Structural characterization of the circadian clock protein complex composed of KaiB and KaiC by inverse contrast-matching small-angle neutron scattering

The molecular machinery of the cyanobacterial circadian clock consists of three proteins: KaiA, KaiB, and KaiC. Through interactions among the three Kai proteins, the phosphorylation states of KaiC generate circadian oscillations in vitro in the presence of ATP. Here, we characterized the complex formation between KaiB and KaiC using a phospho-mimicking mutant of KaiC, which had an aspartate substitution at the Ser431 phosphorylation site and exhibited optimal binding to KaiB. Mass-spectrometric titration data showed that the proteins formed a complex exclusively in a 6:6 stoichiometry, indicating that KaiB bound to the KaiC hexamer with strong positive cooperativity. The inverse contrast-matching technique of small-angle neutron scattering enabled selective observation of KaiB in complex with the KaiC mutant with partial deuteration. It revealed a disk-shaped arrangement of the KaiB subunits on the outer surface of the KaiC C1 ring, which also serves as the interaction site for SasA, a histidine kinase that operates as a clock-output protein in the regulation of circadian transcription. These data suggest that cooperatively binding KaiB competes with SasA with respect to interaction with KaiC, thereby promoting the synergistic release of this clock-output protein from the circadian oscillator complex