Airway wall structure assessed by endobronchial ultrasonography and bronchial hyperresponsiveness in patients with asthma

金沢大学医薬保健研究域医学系Background and Objective: The purpose of this study was to evaluate the relationship between the wall structure assessed by using endobronchial ultrasonography (EBUS) and bronchial hyperresponsiveness in patients with asthma. Methods: Twenty-four patients with stable asthma and 11 individuals without asthma were studied. EBUS was performed with a radial 20-MHz ultrasonic probe inserted into the intermediate bronchus undergoing flexible bronchoscopy to assess the airway wall structure. The percentage of airway wall thickness {WT%; defined as [(ideal outer diameter-ideal luminal diameter)/ideal outer diameter] × 100} was determined by EBUS. We measured bronchial hyperresponsiveness to methacholine [the provocative concentration of methacholine causing a decrease of 20% or more in forced expiratory volume in 1 s (PC20)]. Results: Percentage wall thickness measured by EBUS was significantly greater in patients with asthma than that in subjects without asthma (P < 0.01). The evaluation of the laminar structure using EBUS indicated that the thickness of the second layer in patients with asthma was greater than that in subjects without asthma (P < 0.05). PC20 was negatively correlated with the thickness of the second layer (r=0.52, P < 0.01) but was not significantly correlated with other layers in patients with asthma. Conclusions: The evaluation of the bronchial mural structure using EBUS might be advantageous for assessing the relationship between airway wall remodeling and bronchial hyperresponsiveness. © 2010 Lippincott Williams & Wilkins

High Levels of Copper, Zinc, Iron and Magnesium, but not Calcium, in the Cerebrospinal Fluid of Patients with Fahr's Disease

Patients with marked calcification of the basal ganglia and cerebellum have traditionally been referred to as having Fahr's disease, but the nomenclature has been criticized for including heterogeneous etiology. We describe 3 patients with idiopathic bilateral striatopallidodentate calcinosis (IBSPDC). The patients were a 24-year-old man with mental deterioration, a 57-year-old man with parkinsonism and dementia, and a 76-year-old woman with dementia and mild parkinsonism. The former 2 patients showed severe calcification of the basal ganglia and cerebellum, and the latter patient showed severe calcification of the cerebellum. We found significantly increased levels of copper (Cu), zinc (Zn), iron (Fe) and magnesium (Mg), using inductively coupled plasma mass spectrometry in the CSF of all these 3 patients. The increased levels of Cu, Zn, Fe and Mg reflect the involvement of metabolism of several metals and/or metal-binding proteins during the progression of IBSPDC. More numerous patients with IBSPDC should be examined in other races to clarify the common mechanism of the disease and to investigate the specific treatment

Sox21 Regulates Anapc10 Expression and Determines the Fate of Ectodermal Organ

The transcription factor Sox21 is expressed in the epithelium of developing teeth. The present study aimed to determine the role of Sox21 in tooth development. We found that disruption of Sox21 caused severe enamel hypoplasia, regional osteoporosis, and ectopic hair formation in the gingiva in Sox21 knockout incisors. Differentiation markers were lost in ameloblasts, which formed hair follicles expressing hair keratins. Molecular analysis and chromatin immunoprecipitation sequencing indicated that Sox21 regulated Anapc10, which recognizes substrates for ubiquitination-mediated degradation, and determined dental-epithelial versus hair follicle cell fate. Disruption of either Sox21 or Anapc10 induced Smad3 expression, accelerated TGF-beta 1-induced promotion of epithelial-to-mesenchymal transition (EMT), and resulted in E-cadherin degradation via Skp2. We conclude that Sox21 disruption in the dental epithelium leads to the formation of a unique microenvironment promoting hair formation and that Sox21 controls dental epithelial differentiation and enamel formation by inhibiting EMT via Anapc10.Peer reviewe

A comparison between hospital follow‐up and collaborative follow‐up in patients with acute heart failure

AIMS: There are no previous studies focusing on collaborative follow-ups between hospitals and clinics for patients discharged after acute heart failure (AHF) in Japan. The purpose of this study was to determine the status of collaboration between hospitals and clinics for patients with AHF in Japan and to compare patient characteristics and clinical outcomes using a large Japanese observational database. METHODS AND RESULTS: Of 4056 consecutive patients hospitalized for AHF in the Kyoto Congestive Heart Failure registry, we analysed 2862 patients discharged to go home, who were divided into 1674 patients (58.5%) followed up at hospitals with index hospitalization (hospital follow-up group) and 1188 (41.5%) followed up in a collaborative fashion with clinics or other general hospitals (collaborative follow-up group). The primary outcome was a composite of all-cause death or heart failure (HF) hospitalization within 1 year after discharge. Previous hospitalization for HF and length of hospital stay longer than 15 days were associated with hospital follow-up. Conversely, ≥80 years of age, hypertension, and cognitive dysfunction were associated with collaborative follow-up. The cumulative 1-year incidence of the primary outcome, all cause death, and cardiovascular death were similar between the hospital and collaborative follow-up groups (31.6% vs. 29.6%, P = 0.51, 13.1% vs, 13.9%, P = 0.35, 8.4% vs. 8.2%, P = 0.96). Even after adjusting for confounders, the difference in risk for patients in the hospital follow-up group relative to those in the collaborative follow-up group remained insignificant for the primary outcome, all-cause death, and cardiovascular death (HR: 1.11, 95% CI: 0.97-1.27, P = 0.14, HR: 1.10, 95% CI: 0.91-1.33, P = 0.33, HR: 0.96, 95% CI: 0.87-1.05, P = 0.33). The cumulative 1-year incidence of HF hospitalization was higher in the hospital follow-up group than in the collaborative follow-up group (25.5% vs. 21.3%, P = 0.02). The risk of HF hospitalization was higher in the hospital follow-up group than in the collaborative follow-up group (HR: 1.19, 95% CI: 1.01-1.39, P = 0.04). CONCLUSIONS: In patients hospitalized for AHF, 41.5% received collaborative follow-up after discharge. The risk of HF hospitalization was higher in the hospital follow-up group than in the collaborative follow-up, although risk of the primary outcome, all-cause death, and cardiovascular death were similar between groups

Risk Factors and Clinical Outcomes of Nonhome Discharge in Patients With Acute Decompensated Heart Failure: An Observational Study

Background: No clinical studies have focused on the factors associated with discharge destination in patients with acute decompensated heart failure. Methods and Results: Of 4056 consecutive patients hospitalized for acute decompensated heart failure in the KCHF (Kyoto Congestive Heart Failure) registry, we analyzed 3460 patients hospitalized from their homes and discharged alive. There were 3009 and 451 patients who were discharged to home and nonhome, respectively. We investigated the factors associated with nonhome discharge and compared the outcomes between home discharge and nonhome discharge. Factors independently and positively associated with nonhome discharge were age ≥80 years (odds ratio [OR], 1.76; 95% CI, 1.28–2.42), body mass index ≤22 kg/m2 (OR, 1.49; 95% CI, 1.12–1.97), poor medication adherence (OR, 2.08; 95% CI, 1.49–2.88), worsening heart failure (OR, 2.02; 95% CI, 1.46–2.82), stroke during hospitalization (OR, 3.74; 95% CI, 1.75–8.00), functional decline (OR, 12.24; 95% CI, 8.74–17.14), and length of hospital stay >16 days (OR, 4.14; 95% CI, 3.01–5.69), while those negatively associated were diabetes mellitus (OR, 0.69; 95% CI, 0.51–0.94), cohabitants (OR, 0.62; 95% CI, 0.46–0.85), and ambulatory state before admission (OR, 0.25; 95% CI, 0.18–0.36). The cumulative 1‐year incidence of all‐cause death was significantly higher in the nonhome discharge group than in the home discharge group. The nonhome discharge group compared with the nonhome discharge group was associated with a higher adjusted risk for all‐cause death (hazard ratio, 1.66; P<0.001). Conclusions: The discharge destination of patients with acute decompensated heart failure is influenced by factors such as prehospital social background, age, body mass index, low self‐care ability, events during hospitalization (worsening heart failure, stroke, etc), functional decline, and length of hospital stay; moreover, the prognosis of nonhome discharge patients is worse than that of home discharge patients. Registration Information: clinicaltrials.gov. Identifier: NCT02334891

Prognostic value of reduction in left atrial size during a follow-up of heart failure: an observational study

OBJECTIVE: The association between sequential changes in left atrial diameter (LAD) and prognosis in heart failure (HF) remains to be elucidated. The present study aimed to investigate the link between reduction in LAD and clinical outcomes in patients with HF. DESIGN: A multicentre prospective cohort study. SETTING: This study was nested from the Kyoto Congestive Heart Failure registry including consecutive patients admitted for acute decompensated heart failure (ADHF) in 19 hospitals throughout Japan. PARTICIPANTS: The current study population included 673 patients with HF who underwent both baseline and 6-month follow-up echocardiography with available paired LAD data. We divided them into two groups: the reduction in the LAD group (change <0 mm) (n=398) and the no-reduction in the LAD group (change ≥0 mm) (n=275). PRIMARY AND SECONDARY OUTCOMES: The primary outcome measure was a composite of all-cause death or hospitalisation for HF during 180 days after 6-month follow-up echocardiography. The secondary outcome measures were defined as the individual components of the primary composite outcome measure and a composite of cardiovascular death or hospitalisation for HF. RESULTS: The cumulative 180-day incidence of the primary outcome measure was significantly lower in the reduction in the LAD group than in the no-reduction in the LAD group (13.3% vs 22.2%, p=0.002). Even after adjusting 15 confounders, the lower risk of reduction in LAD relative to no-reduction in LAD for the primary outcome measure remained significant (HR 0.59, 95% CI 0.36 to 0.97 p=0.04). CONCLUSION: Patients with reduction in LAD during follow-up after ADHF hospitalisation had a lower risk for a composite endpoint of all-cause death or HF hospitalisation, suggesting that the change of LAD might be a simple and useful echocardiographic marker during follow-up

Improved and new-onset anemia during follow-up in patients with acute decompensated heart failure

There was no previous report on the prognostic impact of new-onset or improved anemia after discharge from acute decompensated heart failure (ADHF).We analyzed 771 patients with ADHF and who were followed in multicenters in Japan was divided into 4 groups based on the hemoglobin values at discharge and 6-month index visit: 373 patients (48.4%) with persistent anemia, 87 patients (11.3%) with new-onset anemia, 91 patients (11.8%) with improved anemia, and 220 patients (28.5%) without anemia.The primary outcome measure was a composite of all-cause death or HF hospitalization after index visit. The cumulative 6-month incidences of the primary outcome measure were 25.2% for persistent anemia, 18.5% for new onset anemia, 9.0% for improved anemia, and 9.2% for no anemia (log-rank P < .001). Compared with the no anemia group, the excess risk for the primary outcome measure remained significant in the persistent anemia group [hazard ratio (HR) 2.70, 95% confidence interval (95% CI), 1.45-5.44, P = .001] and in the new-onset anemia group (HR 2.73, 95% CI 1.19-6.25, P = .02), while it was not significant in the improved anemia group (HR 1.69, 95% CI 0.68-4.03, P = .25).Persistent and new-onset anemia at 6-month visit were associated with a subsequent higher risk for all-cause death or HF hospitalization in patients with ADHF, suggesting the importance of detecting anemia during follow-up

Left atrial reverse remodeling improves risk stratification in patients with heart failure with recovered ejection fraction

We aimed to investigate the relationship between left atrial (LA) reverse remodeling and prognosis of heart failure (HF) with recovered ejection fraction (EF) (HFrecEF). Among 1, 246 patients with acute heart failure enrolled in the prospective longitudinal follow-up study, 397 patients with HF with mildly-reduced EF and with reduced EF at discharge were analyzed. Echocardiography was performed during the index hospitalization and at the 6-month follow-up after discharge. They were divided into non-HFrecEF (n = 227) and HFrecEF (n = 170) groups. The primary outcome measure was a composite of all-cause death or hospitalization for HF. The cumulative 180-day incidence of the primary outcome measure after follow-up echocardiography was significantly lower in the HFrecEF group than in the non-HFrecEF group (8.9% versus 23.4%, log-rank P = 0.0002). LA reverse remodeling was associated with a lower cumulative 6-month incidence of the primary outcome measure in the HFrecEF group (4.7% versus 18.0%; HR: 0.27, 95%CI: 0.09-0.79, P = 0.01), but not in the non-HFrecEF group (24.4% versus 22.6%; HR: 1.13, 95%CI: 0.65-1.96, P = 0.28) with a significant LA reverse remodeling-by-HFrecEF interaction (P for interaction = 0.02). Combination of left ventricular and atrial reverse remodeling may help in improving HF risk stratification

Serum cholinesterase as a prognostic biomarker for acute heart failure

[Aims]The association between serum cholinesterase and prognosis in acute heart failure (AHF) remains to be elucidated. We investigated the serum cholinesterase level at discharge from hospitalization for AHF and its association with clinical outcomes in patients with AHF. [Methods and results]Among 4056 patients enrolled in the Kyoto Congestive Heart Failure multicentre registry, we analysed 2228 patients with available serum cholinesterase data. The study population was classified into three groups according to serum cholinesterase level at discharge: low tertile (<180 U/L, N = 733), middle tertile (≥180 U/L and <240 U/L, N = 746), and high tertile (≥240 U/L, N = 749). Patients in the low tertile had higher tricuspid pressure gradient, greater inferior vena cava diameter, and higher brain natriuretic peptide (BNP) levels than those in the high tertile. The cumulative 1-year incidence of the primary outcome measure (a composite endpoint of all-cause death and hospitalization for HF) was higher in the low and middle tertiles than in the high tertile [46.5% (low tertile) and 31.4% (middle tertile) vs. 22.1% (high tertile), P < 0.0001]. After adjustment for 26 variables, the excess risk of the low tertile relative to the high tertile for the primary outcome measure remained significant (hazard ratio 1.37, 95% confidence interval 1.10–1.70, P = 0.006). Restricted cubic spline models below the median of cholinesterase demonstrated incrementally higher hazards at low cholinesterase levels. [Conclusions]Low serum cholinesterase levels are associated with congestive findings on echocardiography, higher BNP, and higher risks for a composite of all-cause death and HF hospitalization in patients with AHF

Lower In-Hospital Mortality With Beta-Blocker Use at Admission in Patients With Acute Decompensated Heart Failure

[Background] It remains unclear whether beta‐blocker use at hospital admission is associated with better in‐hospital outcomes in patients with acute decompensated heart failure. [Methods and Results] We evaluated the factors independently associated with beta‐blocker use at admission, and the effect of beta‐blocker use at admission on in‐hospital mortality in 3817 patients with acute decompensated heart failure enrolled in the Kyoto Congestive Heart Failure registry. There were 1512 patients (39.7%) receiving, and 2305 patients (60.3%) not receiving beta‐blockers at admission for the index acute decompensated heart failure hospitalization. Factors independently associated with beta‐blocker use at admission were previous heart failure hospitalization, history of myocardial infarction, atrial fibrillation, cardiomyopathy, and estimated glomerular filtration rate <30 mL/min per 1.73 m2. Factors independently associated with no beta‐blocker use were asthma, chronic obstructive pulmonary disease, lower body mass index, dementia, older age, and left ventricular ejection fraction <40%. Patients on beta‐blockers had significantly lower in‐hospital mortality rates (4.4% versus 7.6%, P<0.001). Even after adjusting for confounders, beta‐blocker use at admission remained significantly associated with lower in‐hospital mortality risk (odds ratio, 0.41; 95% CI, 0.27–0.60, P<0.001). Furthermore, beta‐blocker use at admission was significantly associated with both lower cardiovascular mortality risk and lower noncardiovascular mortality risk. The association of beta‐blocker use with lower in‐hospital mortality risk was relatively more prominent in patients receiving high dose beta‐blockers. The magnitude of the effect of beta‐blocker use was greater in patients with previous heart failure hospitalization than in patients without (P for interaction 0.04). [Conclusions] Beta‐blocker use at admission was associated with lower in‐hospital mortality in patients with acute decompensated heart failure