Is a composite score of physical performance measures more useful than usual gait speed alone in assessing functional status?

Overall physical performance can be represented by a composite score that is derived from upper and lower extremity performance measures. We aimed to identify whether composite scores of performance measures, particularly the lower extremity performance (LEP) score, upper extremity performance (UEP) score, and an overall score, are more accurate than usual gait speed (UGS) for assessing a wide range of functional status. We conducted a cross-sectional analysis on data from 701 community-dwelling older women (mean age 74.3 years). Trained testers measured UGS and the seven tests included in the composite scores. Using self-reported questionnaires, we assessed multiphasic functional status: physical function, higher-level functional capacity, mobility limitation, activities of daily living (ADLs), and falls. We compared the areas under the receiver operating characteristic curves (AUCs) of UGS with LEP, UEP, and overall scores for each status. We found no significant differences between the AUCs of UGS and LEP score for each status. The UEP score had significantly smaller AUCs for low physical function (0.73) and mobility limitation (0.78) than UGS alone (0.81 and 0.85, respectively), and the differences were substantial. Although the overall score had significantly greater AUCs for low higher-level functional capacity (0.83) and ADLs disability (0.83) than UGS alone (0.78 and 0.80, respectively), the differences were only 3-5%. The UGS should not be regarded solely as a measure of lower extremity function; this single test may represent overall physical performance. The UGS alone, which can be measured quickly and easily, suffice for assessing a wide range of functional status in older women.     

AAV8 vector expressing IL24 efficiently suppresses tumor growth mediated by specific mechanisms in MLL/AF4-positive ALL model mice

Mixed-lineage leukemia (MLL)/AF4-positive acute lymphoblastic leukemia (ALL) is a common type of leukemia in infants, which is associated with a high relapse rate and poor prognosis. IL24 selectively induces apoptosis in cancer cells and exerts immunomodulatory and antiangiogenic effects. We examined the effects of adeno-associated virus type 8 (AAV8) vector-mediated muscle-directed systemic gene therapy in MLL/AF4-positive ALL using IL24. In a series of in vitro studies, we examined the effects of AAV8-IL24-transduced C2C12 cell-conditioned medium. We also examined the effects of AAV8-IL24 in MLL/AF4 transgenic mice. The results revealed the effects of AAV8-IL24 in MLL/AF4-positive ALL both in vitro and in vivo. With regard to the mechanism of therapy using AAV8-IL24 in MLL/AF4-positive ALL, we demonstrated the antiangiogenicity and effects on the ER stress pathway and unreported pathways through inhibition of S100A6 and HOXA9, which is specific to MLL/AF4-positive ALL. Inhibition of S100A6 by IL24 was dependent on TNF-α and induced acetylation of p53 followed by activation of the caspase 8-caspase 3 apoptotic pathway. Inhibition of HOXA9 by IL24, which was independent of TNF-α, induced MEIS1 activation followed by activation of the caspase 8-caspase 3 apoptotic pathway. Thus, gene therapy using AAV8-IL24 is a promising treatment for MLL/AF4-positive ALL.     

Russell body gastritis

A 63-year-old woman who presented with chest and back pain underwent an upper gastrointestinal endoscopy which revealed elevated legion in the antrum mucosa. Histologic examinations of gastric biopsies were showing monoclonal proliferation plasma cells containing Russell bodies. Differential diagnosis from B-cell lymphoma and plasmacytoma is difficult, because of monoclonality. Molecular analyses of immunoglobulin heavy chain (IgH) gene demonstrated that gene rearrangement was negative. Thus, diagnosis of Russell body gastritis was made. The Giemsa stains were also showing infection of Helicobacter pylori (H.pylori). After eradication therapy for H.pylori, follow-up upper gastrointestinal endoscopy was performed. She then recovered.     

Moderate-to-vigorous physical activity and the risk of stroke recurrence in patients with a history of minor ischemic stroke in Japan: a retrospective analysis

Background: Physical activity (PA) is beneficial for stroke prevention; in particular, moderate-to-vigorous physical activity (MVPA). However, few studies have investigated its relationship with recurrent ischemic stroke (RIS).

Objectives: To clarify the relationship between MVPA and RIS and the burden of risk factors after a first-ever ischemic stroke.

Methods: A total of 45 outpatients (mean age 67.1 ± 10.2 years) who had previously experienced a transient ischemic attack or a minor non-cardioembolic ischemic stroke at a single hospital in Japan (mean 6.4 ± 4.2 years previously), were enrolled between March and June 2016. All patients wore an accelerometer around their hips for 10 days, and their percentage body fat (%BF) and visceral fat level (VFL) were measured by bioelectrical impedance. Retrospective information about the history of RIS and risk factors (blood pressure, lipoprotein cholesterol and estimated glomerular filtration rate) were extracted from the clinical records. Binary logistic regression models were used to estimate the relevance of the RIS history to MVPA and potential risk factors such as sociodemographic and clinical variables (obesity, smoking and hypertension).

Results: RIS occurred in 9 patients; they had significantly higher VFL (p = 0.007) and %BF (p = 0.007) values and lower MVPA (p = 0.011) values than patients without recurrence. A multivariate analysis of these factors indicated that age, VFL and MVPA were signi?cant independent predictors of RIS.

Conclusions: Patients with a history of mild ischemic stroke had low MVPA and high VFL values, which together may be a risk factor for RIS.     

Immunogenicity and Safety after Booster Vaccination of Diphtheria,Tetanus, and Acellular Pertussis in Young Adults: an Open Randomized Controlled Trial in Japan

The recent increase of pertussis in young adults in Japan is hypothesized to be due in part to waning protection from the acellular pertussis vaccine. While a booster immunization may prevent an epidemic of pertussis among these young adults, little is known about the safety and immunogenicity of such a booster with the diphtheria, tetanus, and acellular pertussis vaccine (DTaP), which is currently available in Japan. One hundred and eleven medical students with a mean age of 19.4 years were randomly divided into 2 groups of 55 and 56 subjects and received, respectively, 0.2 or 0.5 ml of DTaP. Immunogenicity was assessed by performing the immunoassay using serum, and the geometric mean concentration (GMC), GMC ratio (GMCR), seropositive rate, and booster response rate were calculated. Adverse reactions and adverse events were monitored for 7 days after vaccination. After booster vaccination in the two groups, significant increases were found in the antibodies against pertussis toxin, filamentous hemagglutinin, diphtheria toxoid, and tetanus toxoid, and the booster response rates for all subjects reached 100%. The GMCs and GMCRs against all antigens were significantly higher in the 0.5-ml group than in the 0.2-ml group. No serious adverse events were observed. Frequencies of local reactions were similar in the 2 groups, although the frequency of severe local swelling was significantly higher in the 0.5-ml group. These data support the acceptability of booster immunization using both 0.2 and 0.5 ml of DTaP for young adults for controlling pertussis. (This study was registered at UMIN-CTR under registration number UMIN000010672.)     

Complex anatomy surrounding the left atrial posterior wall: analysis with 3D computed tomography

Few studies have explored the topographic anatomy of the esophagus, posterior wall of the left atrium (LA), or fat pads using multidetector computed tomography (MDCT) to prevent the risk of esophageal injury during atrial fibrillation (AF) ablation. MDCT was performed in 110 consecutive patients with paroxysmal or persistent AF before the ablation procedure to understand the anatomic relationship of the esophagus. Two major types of esophagus routes were demonstrated. Leftward (type A) and rightward (type B) routes were found in 90 and 10% of the patients, respectively. A type A route had a larger mean size of the LA than type B. The fat pad was identifiable at the level of the inferior pulmonary vein in 91% of the patients without any predominance of either type. The thickness of the fat pad was thinner in the patients with a dilated LA (>42?mm) than in those with a normal LA size (??42?mm) (p?=?0.01). The results demonstrated that the majority of cases had a leftward route of the esophagus. There was a close association between the LA dilatation and fat pad thinning. With a dilated LA, the esophagus may become easily susceptible to direct thermal injury during AF ablation. Visualization of the anatomic relationship may contribute to the prevention of the potential risk of an esophageal injury.     

Biphasic effects of H. pylori infection on low-dose aspirin-induced gastropathy depending on the gastric acid secretion level

Background

The association of Helicobacter pylori infection with aspirin-induced gastropathy is controversial. H. pylori infection exerts diverse effects on gastric acid secretion. In this study, the interaction between H. pylori infection and aspirin was investigated with reference to the individual gastric acid secretion level in H. pylori-positive subjects.

Methods

Ninety-three (81 men, mean age: 70?years) long-term low-dose aspirin takers were prospectively enrolled. H. pylori infection was evaluated by serum IgG antibody determination, and gastrin-stimulated acid output was assessed with the endoscopic gastrin test. H. pylori-positive aspirin-takers were classified into 2 subgroups (hyposecretors and non-hyposecretors). The grade of gastric mucosal injury was assessed endoscopically according to the modified Lanza score; intensive aspirin-induced gastropathy was defined as a modified Lanza score of ??4. Multiple logistic regression analyses were used to adjust for potential confounders.

Results

With H. pylori-negative patients taken as the reference, H. pylori infection was found to be positively associated with intensive gastropathy among non-hyposecretors, with an odds ratio (OR) (95?% confidence interval [CI]) of 4.2 (1.1?C17.1), while the infection was negatively associated with gastropathy among hyposecretors, with an OR (95?% CI) of 0.3 (0.08?C0.9). Aspirin-induced gastropathy occurred preferentially in the antrum among H. pylori-positive non-hyposecretors, while it affected the fundus among H. pylori-positive hyposecretors.

Conclusion

The effect of H. pylori infection on the aspirin-induced gastropathy was biphasic depending on the individual gastric acid secretion level. In the presence of sufficient amounts of gastric acid, H. pylori infection and aspirin could synergistically damage gastric mucosal integrity, while in the absence of sufficient amounts of gastric acid, the synergistic effect could be completely counteracted and the infection could even suppress the aspirin-induced gastropathy.     

Comparison of PPIs and H2-receptor antagonists plus prokinetics for dysmotility-like dyspepsia

AIM: To compare efficacy of proton pump inhibitors (PPIs) with H₂-receptor antagonists (H₂RAs) plus prokinetics (Proks) for dysmotility-like symptoms in functional dyspepsia (FD).METHODS: Subjects were randomized to receive open-label treatment with either rabeprazole 10 mg od (n = 57) or famotidine 10 mg bid plus mosapride 5 mg tid (n = 57) for 4 wk. The primary efficacy endpoint was change (%) from baseline in total dysmotility-like dyspepsia symptom score. The secondary efficacy endpoint was patient satisfaction with treatment.RESULTS: The improvement in dysmotility-like dyspepsia symptom score on day 28 was significantly greater in the rabeprazole group (22.5% ± 29.2% of baseline) than the famotidine + mosapride group (53.2% ± 58.6% of baseline, P < 0.0001). The superior benefit of rabeprazole treatment after 28 d was consistent regardless of Helicobacter pylori status. Significantly more subjects in the rabeprazole group were satisfied or very satisfied with treatment on day 28 than in the famotidine + mosapride group (87.7% vs 59.6%, P = 0.0012). Rabeprazole therapy was the only significant predictor of treatment response (P < 0.0001), defined as a total symptom score improvement ≥ 50%.CONCLUSION: PPI monotherapy improves dysmotility-like symptoms significantly better than H₂RAs plus Proks, and should be the treatment of first choice for Japanese FD.