Shock and unresponsiveness to repeated courses of intravenous immunoglobulin in Kawasaki disease: a nationwide database study.

BACKGROUND: We aimed to investigate the clinical implications of unresponsiveness to single or repeated courses intravenous immunoglobulin (IVIG) and Kawasaki disease (KD) shock syndrome in patients with KD in an era of a single brand of IVIG. METHODS: Data were collected from National Health Insurance database 2010-2013. Characteristics of the KD patients were analyzed, including age, gender, shock, and associated coronary aneurysms. RESULTS: There were 3043 KD patients (male: 1872) identified. Among them, 46 (1.51%) had KDSS, 261 patients (8.5%) had IVIG unresponsiveness, and 225 patients (7.4%) developed coronary aneurysms. Moreover, 51 patients did not respond to the second course IVIG therapy, i.e., re-IVIG unresponsiveness. KDSS was associated with the occurrence of IVIG unresponsiveness (P < 10-4) and re-IVIG unresponsiveness (P = 0.02). In addition to male gender and KD shock syndrome, IVIG unresponsiveness (OR: 2.18, 95% CI: 1.48-3.22, P = 0.001) and re-IVIG unresponsiveness (OR: 2.87, 95% CI: 1.40-5.89, P = 0.004) were both independent risk factors for coronary aneurysms. CONCLUSIONS: In a nationwide KD cohort, both IVIG unresponsiveness and re-IVIG unresponsiveness increase the risk of coronary aneurysms. Such observation addresses the importance of refining the treatment for IVIG unresponsiveness, at least in those with KD shock syndrome.

Cardiac manifestations and prognostic implications of hereditary transthyretin amyloidosis associated with transthyretin Ala97Ser.

BACKGROUND: The cardiac manifestations of late-onset hereditary transthyretin amyloidosis with p.A97S variant have not been extensively studied, and the prognostic factors remain unclear. METHODS: The clinical profile, echocardiography, and ECG of patients diagnosed with ATTR p.A97S polyneuropathy between 2000 and 2016 were retrospectively collected. 67 patients with ATTR p.A97S were collected. RESULTS: A total of 82% of patients met the criteria for left ventricular (LV) hypertrophy. Reduced global longitudinal strain (GLS) was noted in 42.1% of patients, and 14% of patients had a relative apical sparing pattern. A low voltage pattern in the ECG was observed in 31.3% of patients, while 64.2% presented with a pseudoinfarction pattern. End-systolic LV inner dimension (HR: 2.25 (95% CI: 1.01-5.01), p = 0.048), reduced GLS (HR: 5.26 (1.08-25.0), p = 0.039), relative apical longitudinal strain (RALS>1, HR: 8.57 (1.69-43.3), p = 0.009), increased E/A ratio (HR: 6.51 (1.17-36.4), p = 0.033), and increased QRS duration (HR: 1.02 (1.00-1.04), p = 0.05) were correlated with reduced survival in univariate analysis. Multivariate analysis revealed reduced RALS was significantly correlated with reduced survival (HR: 13.00 (1.81-93.45), p = 0.011). CONCLUSION: Our findings reveal that ATTR p.A97S is a cardiomyopathy as well as a polyneuropathic syndrome. Routine use of more contemporary echocardiographic techniques are recommended to identify cardiac amyloidosis and provide prognostic information.

Comparative Efficacy of Noninvasive Neurostimulation Therapies for Acute and Subacute Poststroke Dysphagia: A Systematic Review and Network Meta-analysis.

OBJECTIVE: To investigate the effectiveness of noninvasive neurostimulation therapies in patients with poststroke dysphagia. DATA SOURCES: Electronic databases, including Embase, PubMed, Scopus, and the Cochrane Library, were searched up to May 31, 2018. STUDY SELECTION: All published randomized controlled trials (RCTs) comparing neurostimulation therapies, including repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), surface neuromuscular electrical stimulation (sNMES), and pharyngeal electrical stimulation (PES), in patients with acute and subacute poststroke dysphagia were included. Nineteen RCTs were enrolled in the meta-analysis. DATA EXTRACTION: Full texts were independently reviewed. Two independent raters assessed the risk of bias of RCTs with the Cochrane risk-of-bias tool. The primary outcome measure was swallowing function evaluated before and after neurostimulation therapy. DATA SYNTHESIS: Both pairwise and network meta-analysis revealed that rTMS, tDCS, and sNMES significantly improved poststroke dysphagia compared with placebo. Differences in functional improvement between PES and placebo were not significant. Based on probability ranking, rTMS seemed the best treatment among the 4 neurostimulation therapies. In the network meta-analysis, rTMS showed the best efficacy compared with placebo (standardized mean difference=1.02, 95% confidence interval, 0.61-1.43). CONCLUSIONS: Among the 4 noninvasive neurostimulation therapies, rTMS, tDCS, and sNMES were effective for treating poststroke dysphagia; furthermore, rTMS may be the most effective therapy according to probability ranking.

Sleep apnea may be associated with suicidal ideation in adolescents.

Suicide is a major threat to adolescent health. Sleep problems increase the risk of adolescent suicidal behavior, but the role of sleep-disordered breathing (e.g., sleep apnea) is unclear. We investigated whether sleep apnea had an effect on suicidal ideation that was independent of depression and perceived stress. We examined a series of sleep variables with suicidal ideation in 746 fifth and seventh graders using self-reported questionnaires to assess time in bed, sleep quality, insomnia, and sleep apnea while controlling depression and perceived stress. Overall, 8.8% of students aged 10-14 years reported having recent suicidal ideation, and 33% or 3.8%, depending on the screening criteria, reported having suspected sleep apnea. The sleep variables were all associated with an increased risk of suicidal ideation, but the magnitude of effects was largely attenuated when depression and perceived stress were included in the models. Suspected sleep apnea using daytime sleepiness as a screening criterion was independently associated with suicidal ideation (odds ratio = 2.25, p < 0.05). Suspected sleep apnea was associated with suicidal ideation that was partly independent of depression and stress, which reveals the pertinence of screening for sleep apnea among school students and designing proper prevention strategies for reducing youth suicidal behavior.

Primary cardiac sarcomas: A multi-national retrospective review.

BACKGROUND: Primary cardiac sarcoma (PCS) is a rare but often fatal disease. The current study aimed to analyze the impact of baseline demographics, local and systemic therapies in a contemporary cohort. METHODS: Clinical records of PCS across six institutions in three continents were reviewed. Kaplan-Meier method was used to estimate survival. Cox proportional hazard model was used to determine variables impacting progression-free survival (PFS) or overall survival (OS). RESULTS: Sixty-one patients with PCS (1996-2016) were identified. The median age at diagnosis was 46 (range 18-79); 36% (n = 22) presented with metastatic disease. The most common histology was angiosarcoma (n = 24, 39%). A total of 46 patients received surgery (75%) but only 5 (8%) patients achieved R0 resection. Multi-modality treatment to the primary tumor was given to 28 patients (46%; localized disease 23/39 (59%); metastatic disease 5/22 (23%)). The median OS for the entire cohort was 17.5 months (95% CI 9.5-20.6), with seven (11%) patients surviving longer than 36 months. On multi-variate analysis, age <65 (P = 0.01) was the only significant favorable prognostic factor. For first-line palliative chemotherapy, the median PFS was 4.4 months (95% CI 2.9-7.7 months). The best response for first-line chemotherapy was 32% (CR = 1, PR = 9). No significant improvement in OS was identified in patients presenting throughout the 20-year period of this review. CONCLUSION: Younger age at diagnosis was associated with improved outcome although the prognosis of PCS remains poor. Given the lack of improvement in survival, further dedicated research is required.

SP110 Polymorphisms Are Genetic Markers for Vulnerability to Latent and Active Tuberculosis Infection in Taiwan.

One-fourth of the human population is estimated to have been exposed to Mycobacterium tuberculosis (Mtb) and carries the infection in its latent form. This latent infection presents a lifelong risk of developing active tuberculosis (TB) disease, and persons with latent TB infection (LTBI) are significant contributors to the pool of active TB cases. Genetic polymorphisms among hosts have been shown to contribute to the outcome of Mtb infection. The SP110 gene, which encodes an interferon-induced nuclear protein, has been shown to control host innate immunity to Mtb infection. In this study, we provide experimental data demonstrating the ability of the gene to control genetic susceptibility to latent and active TB infection. Genetic variants of the SP110 gene were investigated in the Taiwanese population (including 301 pulmonary TB patients, 68 LTBI individuals, and 278 healthy household contacts of the TB patients), and their association with susceptibility to latent and active TB infection was examined by performing an association analysis in a case-control study. We identified several SNPs (rs7580900, rs7580912, rs9061, rs11556887, and rs2241525) in the SP110 gene that are associated with susceptibility to LTBI and/or TB disease. Our studies further showed that the same SNPs may have opposite effects on the control of susceptibility to LTBI versus TB. In addition, our analyses demonstrated that the SP110 rs9061 SNP was associated with tumor necrosis factor-α (TNFα) levels in plasma in LTBI subjects. The results suggest that the polymorphisms within SP110 have a role in controlling genetic susceptibility to latent and active TB infection in humans. To the best of our knowledge, this is the first report showing that the SP110 variants are associated with susceptibility to LTBI. Our study also demonstrated that the identified SP110 SNPs displayed the potential to predict the risk of LTBI and subsequent TB progression in Taiwan.

Conditioning adaptive combination of P-values method to analyze case-parent trios with or without population controls.

Detection of rare causal variants can help uncover the etiology of complex diseases. Recruiting case-parent trios is a popular study design in family-based studies. If researchers can obtain data from population controls, utilizing them in trio analyses can improve the power of methods. The transmission disequilibrium test (TDT) is a well-known method to analyze case-parent trio data. It has been extended to rare-variant association testing (abbreviated as "rvTDT"), with the flexibility to incorporate population controls. The rvTDT method is robust to population stratification. However, power loss may occur in the conditioning process. Here we propose a "conditioning adaptive combination of P-values method" (abbreviated as "conADA"), to analyze trios with/without unrelated controls. By first truncating the variants with larger P-values, we decrease the vulnerability of conADA to the inclusion of neutral variants. Moreover, because the test statistic is developed by conditioning on parental genotypes, conADA generates valid statistical inference in the presence of population stratification. With regard to statistical methods for next-generation sequencing data analyses, validity may be hampered by population stratification, whereas power may be affected by the inclusion of neutral variants. We recommend conADA for its robustness to these two factors (population stratification and the inclusion of neutral variants).