Risk factors and outcomes associated with Left Ventricular Thrombus in patients with Peripartum Cardiomyopathy: An insight from National Inpatient Sample Database.

BACKGROUND: : We sought to assess the prevalence and impact of left ventricular thrombus (LVT) in patients with peripartum cardiomyopathy (PPCM). METHODS: : We performed a retrospective cohort study of all admissions with PPCM as the primary diagnosis from the Nationwide Inpatient Sample database over a 11-year period. Univariate analysis of all risk factors and outcomes and multivariable logistic regression analysis of certain variables were performed and represented as odds ratio (OR) with 95% confidence interval (CI). A p value of < 0.05 was considered statistically significant. Statistical analysis was performed using epiDisplay in 'R' studio. RESULTS: : In the time frame spanning 2005 -2014, 43,986 admissions with PPCM were found which included 43,534 without LVT and 452 patients with LVT. Black race was associated with a higher incidence of LV thrombus, (p value <0.001). Comorbidities more prevalent in the LVT group were smoking, drug abuse, pregnancy induced hypertension, diabetes with complications, valvular heart disease, connective tissue disorders, coagulopathy, anemia and depression. Adverse outcomes such as congestive heart failure, arrhythmias and stroke were higher in LVT group. Conversely, Caucasian race, obesity, preeclampsia (p <0.005) were higher in those without LVT. Mean length of stay (9 vs 5 days, p <0.001), in hospital mortality (3.32% vs 1.41%, p = 0.001) and mean hospitalization charges ($85,390 vs $48,033) were higher in those with LVT. However, on multivariate logistic regression, although stroke was higher in the LVT group (adjusted OR 5.51, 95% CI, 2.2, 13.81, 5.05, p 0.002), in-hospital mortality was not significantly different between the two groups (adjusted OR 1.17, 95% CI,0.32, 4.23, p = 0.817). CONCLUSION: : Our study showed that PPCM patients with LV thrombus had worse outcomes with respect to stroke, length of stay and in hospital mortality. Higher prevalence in patients with black race, complicated diabetes, peripheral vascular disease, valvular disease, coagulopathy, smoking, drug abuse, depression and psychoses calls for special attention to such high-risk groups for aggressive risk factor modification.

Burden of atrial fibrillation in patients with rheumatic diseases.

BACKGROUND: Studies have suggested that atrial fibrillation (AF) in patients with rheumatic diseases (RD) may be due to inflammation. AIM: To determine the highest association of AF among hospitalized RD patients and to determine morbidity and mortality associated with AF in hospitalized patients with RD. METHODS: The National inpatient sample database from October 2015 to December 2017 was analyzed to identify hospitalized patients with RD with and without AF. A subgroup analysis was performed comparing outcomes of AF among different RD. RESULTS: The prevalence of AF was 23.9% among all patients with RD (n = 3949203). Among the RD subgroup, the prevalence of AF was highest in polymyalgia rheumatica (33.2%), gout (30.2%), and pseudogout (27.1%). After adjusting for comorbidities, the odds of having AF were increased with gout (1.25), vasculitis (1.19), polymyalgia rheumatica (1.15), dermatopolymyositis (1.14), psoriatic arthropathy (1.12), lupus (1.09), rheumatoid arthritis (1.05) and pseudogout (1.04). In contrast, enteropathic arthropathy (0.44), scleroderma (0.96), ankylosing spondylitis (0.96), and Sjorgen's syndrome (0.94) had a decreased association of AF. The mortality, length of stay, and hospitalization costs were higher in patients with RD having AF vs without AF. Among the RD subgroup, the highest mortality was found with scleroderma (4.8%), followed by vasculitis (4%) and dermatopolymyositis (3.5%). CONCLUSION: A highest association of AF was found with gout followed by vasculitis, and polymyalgia rheumatica when compared to other RD. Mortality was two-fold higher in patients with RD with AF.

Cardiovascular Events in Patients with Thyroid Storm.

CONTEXT: Thyroid storm can present as a multitude of symptoms, the most significant being cardiovascular (CV). It is associated with various manifestations such as cardiac arrhythmia, heart failure, and ischemia. However, the frequencies of events and characteristics associated with patients that experience these events are not known. METHODS: Study cohort was derived from the National Inpatient Sample database from January 2012 to September 2015. Total hospitalizations of thyroid storm were identified using appropriate ICD-9 diagnostic codes. The analysis was performed using SAS. OBJECTIVE: To better understand the frequency and characteristics CV occurrences associated with thyroid storm, through a retrospective analysis of thyroid storm hospital admissions. DESIGN: The study cohort was derived from the National Inpatient Sample database from January 2012 to September 2015. SETTING: Total hospitalizations of thyroid storm were identified using International Classification of Diseases (ICD)-9 diagnostic codes. The analysis was performed using Statistical Analysis System (SAS). RESULTS: A total of 6380 adult hospitalizations were included in the final analysis, which includes 3895 hospitalizations with CV events (CEs). Most frequently associated CEs were arrhythmia (N = 3770) followed by acute heart failure (N = 555) and ischemic events (N = 150). Inpatient mortality was significantly higher in patients with CEs compared with those without CEs (3.5% vs 0.2%, P < 0.005). The median length of stay was also higher in patients with CEs compared with those without CEs (4 days vs 3 days, P < 0.0005). Atrial fibrillation was the most common arrhythmia type, followed by nonspecified tachycardia. CONCLUSIONS: In patients who were hospitalized due to thyroid storm and associated CEs significantly increased in-hospital mortality, length of stay, and cost. Patients with obesity, alcohol abuse, chronic liver disease, and COPD were more likely to have CEs. Patients with CV complications were at higher risk for mortality. In-hospital mortality increased with ischemic events and acute heart failure. Further evaluation is needed to further classify the type of arrhythmias and associated mortality.

Neurogenetic analysis of childhood disintegrative disorder.

BACKGROUND: Childhood disintegrative disorder (CDD) is a rare form of autism spectrum disorder (ASD) of unknown etiology. It is characterized by late-onset regression leading to significant intellectual disability (ID) and severe autism. Although there are phenotypic differences between CDD and other forms of ASD, it is unclear if there are neurobiological differences. METHODS: We pursued a multidisciplinary study of CDD (n = 17) and three comparison groups: low-functioning ASD (n = 12), high-functioning ASD (n = 50), and typically developing (n = 26) individuals. We performed whole-exome sequencing (WES), copy number variant (CNV), and gene expression analyses of CDD and, on subsets of each cohort, non-sedated functional magnetic resonance imaging (fMRI) while viewing socioemotional (faces) and non-socioemotional (houses) stimuli and eye tracking while viewing emotional faces. RESULTS: We observed potential differences between CDD and other forms of ASD. WES and CNV analyses identified one or more rare de novo, homozygous, and/or hemizygous (mother-to-son transmission on chrX) variants for most probands that were not shared by unaffected sibling controls. There were no clearly deleterious variants or highly recurrent candidate genes. Candidate genes that were found to be most conserved at variant position and most intolerant of variation, such as TRRAP, ZNF236, and KIAA2018, play a role or may be involved in transcription. Using the human BrainSpan transcriptome dataset, CDD candidate genes were found to be more highly expressed in non-neocortical regions than neocortical regions. This expression profile was similar to that of an independent cohort of ASD probands with regression. The non-neocortical regions overlapped with those identified by fMRI as abnormally hyperactive in response to viewing faces, such as the thalamus, cerebellum, caudate, and hippocampus. Eye-tracking analysis showed that, among individuals with ASD, subjects with CDD focused on eyes the most when shown pictures of faces. CONCLUSIONS: Given that cohort sizes were limited by the rarity of CDD, and the challenges of conducting non-sedated fMRI and eye tracking in subjects with ASD and significant ID, this is an exploratory study designed to investigate the neurobiological features of CDD. In addition to reporting the first multimodal analysis of CDD, a combination of fMRI and eye-tracking analyses are being presented for the first time for low-functioning individuals with ASD. Our results suggest differences between CDD and other forms of ASD on the neurobiological as well as clinical level.

The contribution of de novo coding mutations to autism spectrum disorder.

Whole exome sequencing has proven to be a powerful tool for understanding the genetic architecture of human disease. Here we apply it to more than 2,500 simplex families, each having a child with an autistic spectrum disorder. By comparing affected to unaffected siblings, we show that 13% of de novo missense mutations and 43% of de novo likely gene-disrupting (LGD) mutations contribute to 12% and 9% of diagnoses, respectively. Including copy number variants, coding de novo mutations contribute to about 30% of all simplex and 45% of female diagnoses. Almost all LGD mutations occur opposite wild-type alleles. LGD targets in affected females significantly overlap the targets in males of lower intelligence quotient (IQ), but neither overlaps significantly with targets in males of higher IQ. We estimate that LGD mutation in about 400 genes can contribute to the joint class of affected females and males of lower IQ, with an overlapping and similar number of genes vulnerable to contributory missense mutation. LGD targets in the joint class overlap with published targets for intellectual disability and schizophrenia, and are enriched for chromatin modifiers, FMRP-associated genes and embryonically expressed genes. Most of the significance for the latter comes from affected females.

De novo insertions and deletions of predominantly paternal origin are associated with autism spectrum disorder.

Whole-exome sequencing (WES) studies have demonstrated the contribution of de novo loss-of-function single-nucleotide variants (SNVs) to autism spectrum disorder (ASD). However, challenges in the reliable detection of de novo insertions and deletions (indels) have limited inclusion of these variants in prior analyses. By applying a robust indel detection method to WES data from 787 ASD families (2,963 individuals), we demonstrate that de novo frameshift indels contribute to ASD risk (OR = 1.6; 95% CI = 1.0-2.7; p = 0.03), are more common in female probands (p = 0.02), are enriched among genes encoding FMRP targets (p = 6 × 10(-9)), and arise predominantly on the paternal chromosome (p < 0.001). On the basis of mutation rates in probands versus unaffected siblings, we conclude that de novo frameshift indels contribute to risk in approximately 3% of individuals with ASD. Finally, by observing clustering of mutations in unrelated probands, we uncover two ASD-associated genes: KMT2E (MLL5), a chromatin regulator, and RIMS1, a regulator of synaptic vesicle release.