Although an interaction between gender and age has been shown to influence resuscitation outcomes in patients with out-of-hospital cardiac arrest (OHCA), this interaction has not been investigated in ...Asian populations. In this prospective, observational study, data from all cases of OHCA in Japan between 2005 and 2012 were obtained from the Japanese National Registry. We determined the relative excess risk due to interaction and the ratio of odds ratios (ORs) to assess the interaction effect of gender and age on the incidence of return of spontaneous circulation (ROSC) before hospital arrival, 1-month survival, and neurologically intact survival 1 month after OHCA. Male gender was associated with decreased ROSC and lower 1-month survival rates in patients with OHCA of presumed cardiac origin. Older age was associated with lower 1-month and neurologically intact survival rates in male patients with OHCA of presumed cardiac and noncardiac origin and with increased ROSC in male patients with OHCA of presumed cardiac origin. The relative excess risk due to interaction for ROSC in patients with OHCA of presumed cardiac origin was statistically significant (OR 0.19, 95% confidence interval CI 0.06 to 0.32). The ratio of ORs for ROSC was statistically significant in patients with OHCA of presumed cardiac origin (OR 1.25, 95% CI 1.05 to 1.47) and of noncardiac origin (OR 0.40, 95% CI 0.17 to 0.92). In conclusion, the interaction effect between age and gender on ROSC was positive in OHCA cases of presumed cardiac origin and negative in those of noncardiac origin.
Purpose
Meaningfully grouping individuals with tinnitus who share a common characteristics (ie, subgrouping, phenotyping) may help tailor interventions to certain tinnitus subgroups and hence reduce ...outcome variability. The purpose of this study was to test if the presence of tinnitus subgroups are discernible based on hearing‐related comorbidities, and to identify predictors of tinnitus severity for each subgroup identified.
Methods
An exploratory cross‐sectional study was used. The study was nested within an online survey distributed worldwide to investigate tinnitus experiences during the COVID‐19 pandemic. The main outcome measure was the tinnitus Handicap Inventory‐ Screening Version.
Results
From the 3400 respondents, 2980 were eligible adults with tinnitus with an average age of 58 years (SD = 14.7) and 49% (n = 1457) being female. A three‐cluster solution identified distinct subgroups, namely, those with tinnitus‐only (n = 1306; 44%), those presenting with tinnitus, hyperacusis, hearing loss and/or misophonia (n = 795; 27%), and those with tinnitus and hearing loss (n = 879; 29%). Those with tinnitus and hyperacusis reported the highest tinnitus severity (M = 20.3; SD = 10.5) and those with tinnitus and no hearing loss had the lowest tinnitus severity (M = 15.7; SD = 10.4). Younger age and the presence of mental health problems predicted greater tinnitus severity for all groups (β ≤ −0.1, P ≤ .016).
Conclusion
Further exploration of these potential subtypes are needed in both further research and clinical practice by initially triaging tinnitus patients prior to their clinical appointments based on the presence of hearing‐related comorbidities. Unique management pathways and interventions could be tailored for each tinnitus subgroup.
To develop precision medicine for atopic dermatitis (AD), it is critical to establish relevant biomarkers. However, the characteristics of various biomarkers have not been fully understood. We ...previously carried out the Biomarkers to Predict Clinical Improvement of AD in Patients Treated with Dupilumab (B-PAD) study, a comprehensive nationwide study in Japan, to explore biomarkers for AD.
The aim of this study is to find biomarkers associated with objective and subjective clinical findings in patients with moderate-to-severe AD based on the B-PAD study and to identify biomarkers sensitive enough to assess the severity of AD.
We performed the B-PAD study as a consortium composed of 19 medical facilities in Japan, enrolling 110 patients with moderate-to-severe AD. We evaluated the Eczema Area and Severity Index (EASI) for objective assessment as well as the Patient-Oriented Eczema Measure (POEM) and a numeric rating scale for pruritus (pruritis-NRS) for subjective assessment, measuring 19 biomarkers at baseline.
We found that 12, 6, and 7 biomarkers showed significant and positive associations with the EASI, POEM, and pruritis-NRS, respectively. Most of the biomarkers associated with either the POEM or the pruritis-NRS were included among the biomarkers associated with EASI. Of the biomarkers examined, CCL26/eotaxin-3 and SCCA2 were the most capable of assessing severity for EASI, as shown by the 2 kinds of receiver operating characteristic analyses, respectively, whereas lactate dehydrogenase was the best for both the POEM and pruritis-NRS, again using the 2 analyses.
We found biomarkers associated with the EASI, POEM, and pruritis-NRS, respectively, based on the B-PAD study. Moreover, we identified CCL26/eotaxin-3 and/or SCCA2 as the biomarkers having the greatest ability to assess severity in the EASI; lactate dehydrogenase did the same for the POEM and pruritis-NRS. These findings will be useful in treating patients with moderate-to-severe AD.
Osteopontin (OPN) is upregulated in several experimental models of cardiac fibrosis and remodeling. However, its direct effects remain unclear. We examined the hypothesis that OPN is important for ...the development of cardiac fibrosis and remodeling. Moreover, we examined whether the inhibitory effect of eplerenone (Ep), a novel aldosterone receptor antagonist, was mediated through the inhibition of OPN expression against cardiac fibrosis and remodeling. Wild-type (WT) and OPN-deficient mice were treated with angiotensin II (Ang II) for 4 weeks. WT mice receiving Ang II were divided into 2 groupsa control group and an Ep treatment group. Ang II treatment significantly elevated blood pressure and caused cardiac hypertrophy and fibrosis in WT mice. Ep treatment and OPN deficiency could reduce the Ang II–induced elevation of blood pressure and ameliorate the development of cardiac fibrosis, whereas Ep-only treatment abolished the development of cardiac hypertrophy. Most compelling, the reduction of cardiac fibrosis led to an impairment of cardiac systolic function and subsequent left ventricular dilatation in Ang II–treated OPN-deficient mice. These results suggest that OPN has a pivotal role in the development of Ang II–induced cardiac fibrosis and remodeling. Moreover, the effect of Ep on the prevention of cardiac fibrosis, but not cardiac hypertrophy, might be partially mediated through the inhibition of OPN expression.
Abstract Endocannabinoids are powerful modulators of synaptic transmission that act on presynaptic cannabinoid receptors. Cannabinoid receptor type 1 (CB1) is the dominant receptor in the CNS, and is ...present in many brain regions, including sensory cortex. To investigate the potential role of CB1 receptors in cortical development, we examined the developmental expression of CB1 in rodent primary somatosensory (barrel) cortex, using immunohistochemistry with a CB1-specific antibody. We found that before postnatal day (P) 6, CB1 receptor staining was present exclusively in the cortical white matter, and that CB1 staining appeared in the gray matter between P6 and P20 in a specific laminar pattern. CB1 staining was confined to axons, and was most prominent in cortical layers 2/3, 5a, and 6. CB1 null (−/−) mice showed altered anatomical barrel maps in layer 4, with enlarged inter-barrel septa, but normal barrel size. These results indicate that CB1 receptors are present in early postnatal development and influence development of sensory maps.
Advances in neurosurgical techniques and neuroimaging resolution questions the modern-day reliability of the Simpson grade for predicting meningioma recurrence. Therefore, we evaluated the ...reliability of predictors for recurrence and outcomes in detail in patients with non-skull base meningiomas (NSBMs).
We retrospectively analyzed data from consecutive 175 NSBMs underwent surgical resection. We performed Kaplan–Meier analyses of recurrence-free survival (RFS) according to Simpson and World Health Organization (WHO) grades. Predictors of RFS and clinical deterioration were estimated by univariate and multivariate analyses. Correlation between the Simpson grade and change in Karnofsky Performance Scale scores was assessed by Fisher's exact test.
Log-rank tests revealed significant correlations of both the Simpson and WHO grades with RFS for the overall cohort, convexity, and falx/tentorium meningioma. Unlike patients undergoing Simpson grade I and II resections, RFS in patients with WHO grade I and II/III tumors differed significantly from the early postoperative stage. Multivariate analysis identified tumor size, Simpson grade, and MIB-1 labeling index as significant predictors of RFS. Clinical deterioration was more frequent among patients undergoing less aggressive resection. Tumor location was the only significant predictor of clinical deterioration.
Our findings indicate that tumor size, Simpson and WHO grades, and MIB-1 labeling index are significant predictors of NSBM recurrence. Moreover, the risk of recurrence markedly decreases within the follow-up duration of 80 months. Aggressive resection appears to minimize the risk of recurrence without evidence of clinical deterioration. Follow-up schedules should be based on the WHO grade and extent of resection.
•Significant correlations were observed between Simpson grade and RFS for NSBMs.•Significant correlations were observed between the WHO grade and RFS for NSBMs.•RFS rates gradually decreased within 80 months, reaching a plateau thereafter.•Aggressive surgery minimizes the recurrence risk without evidence of poor outcome.•Follow-up schedules should be based on the WHO grade and extent of resection.
Summary
Background Darier disease (DD), an autosomal dominant genodermatosis characterized by warty papules and plaques over seborrhoeic areas, is caused by mutations in the ATP2A2 gene, which ...encodes the sarco/endoplasmic reticulum Ca2+ ATPase type 2 isoform (SERCA2). While markedly different clinical severity within DD‐affected family members is known, the pathomechanism has not been elucidated.
Objectives Based on the hypothesis that multiple ATP2A2 mutations might contribute to the pathomechanism, we have analysed two DD families in which the clinical severity differs markedly within a single pedigree, and, as controls, eight DD families without differing clinical severity.
Methods All the exons and intron–exon borders of ATP2A2 were directly sequenced from the genomic DNA extracted from all the subjects.
Results We identified the heterozygous mutations, G233R in pedigree 1 and C318R in pedigree 2, respectively, whereas no other ATP2A2 mutations in any of severely affected individuals were found. In eight DD pedigrees as control, we have found M1V, N39D, L180R, A838P and 2170 insertion G in each of five pedigrees, but no mutation was found in three DD pedigrees.
Conclusions Our results together with previous data indicate that the distribution of mutations is scattered over the entire ATP2A2 without any, as yet, discernible ‘hotspots’. The mutations in pedigrees 1 and 2 with intrafamiliar clinical differences occurred around the Ca2+‐binding sites on SERCA2, which might be associated with differences in clinical severity. These variations in ATP2A2 mutations alone cannot account for the clinical heterogeneity within DD pedigrees.
This study, following Japanese Registry of NeuroEndovascular Treatment 1 and 2 (JR-NET 1 & 2), shows an annual trend of cases including adverse events and clinical outcomes at 30 days after NET. ...JR-NET3 was registered by 749 cumulative total number of physicians, certified by the Japanese Society of Neuroendovascular Therapy in 166 centers, between 2010 and 2014. Medical information about the patients was anonymized and retrospectively registered through a website. A total of 40,177 patients were recruited, 632 patients were excluded because data of preprocedural status were not available. So we analyzed 39,545 patients retrospectively. The proportion of octogenarians is increasing year-by-year and 14.7% in 2014 compared with 10.4% in 2010. Most frequent target disease is intracranial aneurysm. For the proportion of the treatment of intracranial aneurysm, 50.0% in 2010, but that has decreased to 44.8% in 2014. However, number of procedures were increased from 3150 in 2010 to 3419 in 2014. Although before the positive clinical evidence of mechanical thrombectomy for acute ischemic stroke (AIS) was established, the proportion of endovascular treatment for AIS increased 13.8% in 2014 compared with 6.3% in 2010. The number of patients requiring neuroendovascular treatment in Japan is increasing since 2010–2013, but that declined a little in 2014 caused by study operation suspended at the end of 2013. The outcomes of such therapy are clinically acceptable. Details of each type of treatment will be investigated in sub-analyses of the database.
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