Biology‐Driven Gene‐Gene Interaction Analysis of Age‐Related Cataract in the eMERGE Network

Bioinformatics approaches to examine gene‐gene models provide a means to discover interactions between multiple genes that underlie complex disease. Extensive computational demands and adjusting for multiple testing make uncovering genetic interactions a challenge. Here, we address these issues using our knowledge‐driven filtering method, Biofilter, to identify putative single nucleotide polymorphism (SNP) interaction models for cataract susceptibility, thereby reducing the number of models for analysis. Models were evaluated in 3,377 European Americans (1,185 controls, 2,192 cases) from the Marshfield Clinic, a study site of the Electronic Medical Records and Genomics (eMERGE) Network, using logistic regression. All statistically significant models from the Marshfield Clinic were then evaluated in an independent dataset of 4,311 individuals (742 controls, 3,569 cases), using independent samples from additional study sites in the eMERGE Network: Mayo Clinic, Group Health/University of Washington, Vanderbilt University Medical Center, and Geisinger Health System. Eighty‐three SNP‐SNP models replicated in the independent dataset at likelihood ratio test P < 0.05. Among the most significant replicating models was rs12597188 (intron of CDH1)–rs11564445 (intron of CTNNB1). These genes are known to be involved in processes that include: cell‐to‐cell adhesion signaling, cell‐cell junction organization, and cell‐cell communication. Further Biofilter analysis of all replicating models revealed a number of common functions among the genes harboring the 83 replicating SNP‐SNP models, which included signal transduction and PI3K‐Akt signaling pathway. These findings demonstrate the utility of Biofilter as a biology‐driven method, applicable for any genome‐wide association study dataset.     

Increased risk of death and readmission after hospital discharge of critically ill patients in a developing country: a retrospective multicenter cohort study

Purpose

To describe long-term mortality and hospital readmissions of patients admitted to Brazilian intensive care units (ICU).

Methods

Retrospective cohort study of adult patients admitted to Brazilian hospitals affiliated to the Public Healthcare System from 10 state capitals. ICU patients were paired to non-ICU patients by frequency matching (ratio 1:2), according to postal code and admission semester. Hospitalization records were linked through deterministic linkage to national mortality data. Primary outcome was mortality up to 1 year. Other outcomes were mortality and readmissions at 30 and 90 days and 3 years. Multiple Cox regressions were used adjusting for age, sex, cancer diagnosis, type of hospital, and surgical status.

Results

We included 324,594 patients (108,302 ICU and 216,292 non-ICU). ICU patients had increased hospital length of stay [9 (5–17) vs. 3 (1–6) days, p?<?0.001] and mortality (18.5 vs. 3.6%, p?<?0.001) versus non-ICU patients. One year after discharge, ICU patients were more frequently readmitted to hospital (25.4 vs. 17.4%, p?<?0.001) and to ICU (31.4 vs. 7.3%, p?<?0.001) than controls. Mortality up to 1 year was also higher for ICU patients (14.3 vs. 3.9%, p?<?0.001). A significant interaction between surgical status and mortality was found, with adjusted hazard ratios (HRs) up to 1 year of 2.7 [95% confidence interval (CI) 2.5–2.9] for surgical patients, and 3.4 (95%CI 3.3–3.5) for medical patients. The risk for death and readmission diminished over time up to 3 years.

Conclusions

In a public healthcare system of a developing country, ICU patients have excessive long-term mortality and frequent readmissions. The ICU burden tended to reduce over time after hospital discharge.

     

Association of acidosis with coagulopathy and transfusion requirements in liver transplantation

Journal of Thrombosis and Thrombolysis - The relationship between acidosis and coagulopathy has long been described in vitro and in trauma patients, but not yet in orthotopic liver transplantation...     

Low density neutrophils in patients with juvenile idiopathic arthritis.

OBJECTIVES: (1) To study the correlation among conventional clinical and laboratory parameters and the relation between the number of lymphocytes and neutrophils (L/N) in cell suspensions from peripheral blood of patients with juvenile idiopathic arthritis (JIA). (2) To evaluate the L/N relation of JIA patients after an 8 year follow-up period. METHODS: Fifty-one JIA patients (25 female, disease course: 19 systemic, 15 polyarticular, 17 pauciarticular) were enrolled in the study. To measure the L/N relation, we used Boyum's method: The leucocyte separation was done by centrifugation of peripheral blood on Ficoll-Hypaque (FH) gradient, and the number of lymphocytes, monocytes, and neutrophils in 500 cells was determined. The following clinical and laboratory parameters were evaluated: disease activity, number of active and limited joints, functional capacity, erythrocyte sedimentation rate (ESR), and C reactive protein (CRP). Twenty-four healthy children were used as controls. We also studied 13/51 patients from our Pediatric Rheumatology Unit who had been evaluated by the same method 8 years before. RESULTS: We observed the lowest L/N relation in patients with active disease, especially those with polyarticular course. A statistical correlation was also observed with the acute-phase reactants (ESR and CRP, p < 0.05). The majority of patients who had presented a low L/N relation at the first evaluation (8 years before) had a worse outcome. CONCLUSION: The measure of L/N relation from peripheral blood could be used as an auxiliary tool in the assessment of the activity and outcome of JIA patients, especially at disease onset.     

Water-based resistance training program with isolated concentric action improves physical functional capacity and muscular strength in older women

Background

Resistance training has proven to be an excellent method for counteracting aging physical dysfunctions. However, its application in the liquid environment is not yet fully elucidated.

Aim

To investigate the effects of water-based resistance training (WBRT) with the concentric phase performed as fast as possible, compared to conventional resistance training (CRT), on physical functional capacity, muscle strength, and body composition in older women.

Methods

Thirteen healthy older women participated in the WBRT and 11 in the CRT. Estimation statistics focused on the effect size of the experiment/intervention were used. We also analyzed the intervention effect based on the percentage delta between WBRT and CRT.

Results

The WBRT group showed a negative large effect (d?=?? 0.922; p?=?0.0274) for the timed up and go, and a large effect for chair rise in 30″ and the elbow flex test (d?=?1.58; p?=?0.0012; d?=?2.8; p?=?0.01) respectively. Intervention comparisons based on the delta percentage between WBRT and CRT presented an intermediate effect (d?=?0.606; p?=?0.157) for the stair climb, a large effect (d?=?0.988; p?=?0.0282) for the timed up and go, and a large negative effect [d?=?? 1.32 (90.0% CI ? 1.92, ? 0.646); p?=?0.0038] for the elbow flex test. Concentric extensor-flexor peak torque (60°/s) showed an intermediate effect (d?=?0.749; p?=?0.0876; d?=?0.65; p?=?0.122 respectively). Body fat (%) demonstrated an intermediate effect (d?=?0.523; p?=?0.234).

Conclusion

WBRT with the concentric phase performed as fast as possible was able to improve physical functional capacity and maximal knee extension strength of older women.

     

Morphofunctional characteristics of the right ventricle in Chagas' dilated cardiomyopathy

Right ventricular involvement is a typical characteristic of Chagas' disease, and it has been described especially in the early stages of the disease. However, the role of right ventricular dysfunction in cardiac failure due to Chagas' cardiomyopathy has not been well established. Seventy-four patients with positive serology tests for Trypanosoma cruzi and Chagas' dilated cardiomyopathy characterized by left ventricular dilatation and systolic dysfunction were studied. Clinical history, physical exam, ECG, chest X-ray and Doppler echocardiogram with color flow mapping were obtained in all. Mean age was 47.5+/-12.9 and 51 were males (69%). Sixty-five patients (88%) were in NYHA functional classes I and II. Mild systolic dysfunction was present in 35 (47%) while in 18 (24%), dysfunction was moderate and in 21 (28%) it was severe. In 43 patients (58%), only the left ventricle was involved by echocardiographic criteria; the remaining 31 patients (42%) showed biventricular involvement. No patient had isolated involvement of the right ventricle. Greater dilation of the right ventricle was associated with larger diastolic (p<0.002) and systolic (p<0.001) diameters of the left ventricle. Systolic pulmonary artery pressure was obtained non-invasively in 54 patients. Pulmonary hypertension was associated with right ventricular dilation (p<0.005) and with systolic dysfunction of the left ventricle (p<0.001). In this group of patients with Chagas' dilated cardiomyopathy, right ventricular dysfunction was present when there was associated and significant involvement of the left ventricle and with higher levels of pulmonary pressure.     

Late coronary artery recanalization effects on left ventricular remodelling and contractility by magnetic resonance imaging.

AIMS: To assess the recanalization effects of post-myocardial infarction (MI) on left ventricular (LV) remodelling and contractility in relation to conservative therapy. METHODS AND RESULTS: Thirty-six patients with occluded infarct-related artery between 12 h and 14 days post-anterior MI were randomized to percutaneous coronary intervention (PCI group) or conservative therapy (no-PCI group). Magnetic resonance imaging was performed at enrollment and after 6 months. The left ventricle was divided into infarct, adjacent, and remote segments. There was no difference in relation to LV volume between groups at the 6 month follow-up. Change in LV ejection fraction was favourable to the PCI group: 5.00% vs. -0.76%, P=0.012. Change in circumferential shortening (Ecc) of the remote segments in the PCI group was significantly better than in the no-PCI group: -1.67+/-6.30% vs. 0.29+/-6.02%, P<0.001. Infarct size and LV mass were similar between groups. CONCLUSIONS: Late recanalization improved LV ejection fraction and myocardial contractility in late follow-up, but did not change the ventricular volumes. Improvement in the left ventricle global and regional contractility may benefit the long-term outcome in post-MI patients with sustained patency of the infarct-related artery.     

Onabotulinumtoxin type A improves lower urinary tract symptoms and quality of life in patients with human T cell lymphotropic virus type 1 associated overactive bladder

Aim

To evaluate the efficacy of the onabotulinum toxin type A in the treatment of HTLV-1 associated overactive bladder and its impact on quality of life (QoL).