Effects of hypoxia in the diabetic corneal stroma microenvironment.

Corneal dysfunctions associated with Diabetes Mellitus (DM), termed diabetic keratopathy (DK), can cause impaired vision and/or blindness. Hypoxia affects both Type 1 (T1DM) and Type 2 (T2DM) surprisingly, the role of hypoxia in DK is unexplored. The aim of this study was to examine the impact of hypoxia in vitro on primary human corneal stromal cells derived from Healthy (HCFs), and diabetic (T1DMs and T2DMs) subjects, by exposing them to normoxic (21% O2) or hypoxic (2% O2) conditions through 2D and 3D in vitro models. Our data revealed that hypoxia affected T2DMs by slowing their wound healing capacity, leading to significant alterations in oxidative stress-related markers, mitochondrial health, cellular homeostasis, and endoplasmic reticulum health (ER) along with fibrotic development. In T1DMs, hypoxia significantly modulated markers related to membrane permeabilization, oxidative stress via apoptotic marker (BAX), and protein degradation. Hypoxic environment induced oxidative stress (NOQ1 mediated reduction of superoxide in T1DMs and Nrf2 mediated oxidative stress in T2DMs), modulation in mitochondrial health (Heat shock protein 27 (HSP27), and dysregulation of cellular homeostasis (HSP90) in both T1DMs and T2DMs. This data underscores the significant impact of hypoxia on the diabetic cornea. Further studies are warranted to delineate the complex interactions.

Phytochemical profiling and biological activities of Diplazium esculentum (Retz.) Sw.: an edible vegetable fern.

OBJECTIVES: Diplazium esculentum (Retz.) Sw. is an edible vegetable fern of the Himalayan region with high nutritional and therapeutic value owing to its richness in various secondary metabolites and both macro and micronutrients. CONTENT: This updated review discusses the general traditional use, ethnopharmacology, phytochemistry, nutritional value, pharmacology, and toxicity concerns of D. esculentum. SUMMARY: The plant parts, viz. rhizomes, shoots, fronds and leaves, have immense ethnomedicinal importance, being traditionally used to cure several health disorders. Among other pharmacological effects, this botanical reveals excellent anti-inflammatory, analgesic, antifungal, antibacterial, antioxidant, anti-leishmanial, antioxidant, anaphylactic, antipyretic, anthelmintic and hepatoprotective activities, directly attributed to the presence of many secondary metabolites. From a pharmacological point of view, the excellent antioxidant potential of D. esculentum suggests its promising use for nutraceutical or functional food formulation purposes. OUTLOOK: Considering the evidences on popular ethnomedicinal uses of D. esculentum as an edible vegetable, its immense bio-potential, and multiple pharmacological roles, there is a huge need to evaluate its therapeutic applications in light of standard clinical trials.

Hidradenitis Suppurativa in the United States: Insights From the National Inpatient Sample (2008-2017) on Contemporary Trends in Demographics, Hospitalization Rates, Chronic Comorbid Conditions, and Mortality.

Background Hidradenitis suppurativa (HS) is a clinical condition characterized by the formation of painful lumps under the skin. It often affects intertriginous areas like armpits and groin. There is a paucity of contemporary data on patient and hospital-level characteristics of HS in the United States. Methods We analyzed the Nationwide Inpatient Sample (NIS) for retrospective analysis to calculate the frequency and yearly rates of HS hospitalizations, demographic variations, rates of comorbidities, and length of stay. Results The rate of hospitalizations with HS as a primary diagnosis increased from 7.9 per 100,000 all-cause hospitalizations in 2008 to 11.6 per 100,000 all-cause hospitalizations in 2017 (p < 0.0001). The mean age ± standard error of hospitalized patients was 39.5 ± 0.2 years. The age group of 18-34 years was the most affected. Women showed a higher preponderance of the disease than men (56.6% vs. 43.5%, p < 0.0001). The Black race was the most affected out of all the racial groups (59.9%). Most hospitalizations were in large, urban teaching hospitals. Hypertension (34.9%), skin and subcutaneous tissue infections (26.5%), and diabetes mellitus (25.9%) were the most common comorbidities. Out of the total hospitalizations with HS, 12.7% were found to have a major or extreme loss of function and 3.5% were at a major or extreme likelihood of dying. Conclusions HS disproportionately affects young adults, women, and Black patients. A significant proportion of these patients are at a major risk of major loss of bodily function or death. Prospective studies are needed to identify the risk factors for hospitalizations in these patient populations and devise appropriate prevention and treatment strategies.

The Omic Insights on Unfolding Saga of COVID-19.

The year 2019 has seen an emergence of the novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease of 2019 (COVID-19). Since the onset of the pandemic, biological and interdisciplinary research is being carried out across the world at a rapid pace to beat the pandemic. There is an increased need to comprehensively understand various aspects of the virus from detection to treatment options including drugs and vaccines for effective global management of the disease. In this review, we summarize the salient findings pertaining to SARS-CoV-2 biology, including symptoms, hosts, epidemiology, SARS-CoV-2 genome, and its emerging variants, viral diagnostics, host-pathogen interactions, alternative antiviral strategies and application of machine learning heuristics and artificial intelligence for effective management of COVID-19 and future pandemics.

Safety and feasibility of robotic assisted percutaneous coronary intervention compared to standard percutaneous coronary intervention- a systematic review and meta-analysis.

OBJECTIVE: Robotically assisted PCI offers a great alternative to S-PCI. This has gained even more relevance during the COVID-19 pandemic era however safety of R-PCI compared to S-PCI has not been studied well. This study explores the safety and efficacy of robotically assisted PCI (R-PCI) compared to standard PCI (S-PCI) for the treatment of coronary artery disease (CAD). METHODS: PubMed, Scopus, Ovid, and Google scholar databases were searched for studies comparing R-PCI to S-PCI. Outcomes included clinical success, procedure time, fluoroscopy time, contrast use and radiation exposure. RESULTS: Theauthors included 5 studies comprising 1555 patients in this meta-analysis. Clinical success was comparable in both arms (p = 0.91). Procedure time was significantly longer in R-PCI group (risk ratio: 5.52, 95% confidence interval: 1.85 to 9.91, p = 0.003). Compared to S-PCI, patients in R-PCI group had lower contrast use (meandifference: -19.88, 95% confidence interval: -21.43 to -18.33, p < 0.001), fluoroscopy time (mean difference:-1.82, 95% confidence interval: -3.64 to -0.00, p = 0.05) and radiation exposure (mean difference:-457.8, 95% confidence interval: -707.14 to -208.14, p < 0.001). CONCLUSION: R-PCI can achieve similar success as S-PCI at the expense of longer procedural times. However, radiation exposure and contrast exposure were lower in the R-PCI arm.

Ecotoxicity of as-synthesised copper nanoparticles on soil bacteria.

Release of metallic nanoparticles in soil poses a serious threat to the ecosystem as they can affect the soil properties and impose toxicity on soil microbes that are involved in the biogeochemical cycling. In this work, in vitro ecotoxicity of as-synthesised copper nanoparticles (CuNPs) on Bacillus subtilis (MTCC No. 441) and Pseudomonas fluorescens (MTCC No. 1749), which are commonly present in soil was investigated. Three sets of colloidal CuNPs with identical physical properties were synthesised by chemical reduction method with per batch yield of 0.2, 0.3 and 0.4 gm. Toxicity of CuNPs against these soil bacteria was investigated by MIC (minimum inhibitory concentration), MBC (minimum bactericidal concentration), cytoplasmic leakage and ROS (reactive oxygen species) assay. MIC of CuNPs were in the range of 35-60 µg/ml and 35-55 µg/ml for B. subtilis and P. fluorescens respectively, while their MBC ranged from 40-70 µg/ml and 40-60 µg/ml respectively. MIC and MBC tests reveal that Gram-negative P. fluorescens was more sensitive to CuNPs as compared to Gram positive B. subtilis mainly due to the differences in their cell wall structure and composition. CuNPs with smaller hydrodynamic size (11.34 nm) were highly toxic as revealed by MIC, MBC tests, cytoplasmic leakage and ROS assays, which may be due to the higher active surface area of CuNPs and greater membrane penetration. Leakage of cytoplasmic components and generation of extra-cellular oxidative stress by reactive oxygen species (ROS) causes cell death. The present study realizes in gauging the negative impact of inadvertent release of nanoparticles in the environment, however, in situ experiments to know its overall impact on soil health and soil microflora can help in finding solution to combat ecotoxicity of nanoparticles.

Characteristics and Outcomes of Patients Admitted With Type 2 Myocardial Infarction.

Type 2 myocardial infarction (Type 2 MI) is a common problem and carries a high diagnostic uncertainty. Large studies exploring outcomes in type 2 MI are lacking. Nationwide Readmission Database (2017) was queried using the International Classification of Diseases codes (ICD-10-CM) to identify type 2 MI patients. Characteristics, in-hospital outcomes, 30-day readmissions, and predictors of in-hospital mortality as well as 30-day readmissions were explored. We identified 21,738 patients with a diagnosis of type 2 MI. Most common primary diagnosis at presentation included infection/sepsis (27.5%), hypertensive heart disease (15.3%) and pulmonary diseases (8.5%). Overall, in-hospital mortality and 30-day readmission for patients with type 2 MI were 9.0% and 19.1% respectively. On multivariable analysis, significant predictors of increased in-hospital mortality included male gender, coexisting atrial fibrillation/flutter, peripheral vascular disease, coagulopathy, malignancy, and fluid/electrolyte abnormalities. Significant predictors of 30-day readmission were coexisting diabetes mellitus, atrial fibrillation/ flutter, carotid artery stenosis, anemia, COPD, CKD and prior history of myocardial infarction, A primary diagnosis of sepsis, pulmonary issues including respiratory failure, neurological conditions including stroke carried highest risk of mortality however readmission risk was not influenced by primary diagnosis at presentation. In conclusion, approximately 1 in 10 patients admitted for type 2 MI died during admission, and nearly 1 in 5 patients were readmitted at 30 days after discharge. In-hospital mortality varied based on associated primary diagnosis at presentation. Proposed predictive model for mortality and 30-day readmission in our study can help to target high risk patients for post-Type 2 MI care.

Oxidative Stress Induced Cytotoxicity of Colloidal Copper Nanoparticles on RAW 264.7 Macrophage Cell Line.

Copper is an essential trace mineral that plays an important role in various physiological processes of human body and also possesses excellent antimicrobial properties, however its high dose results in the formation of free-radicals, which can induce cytotoxicity through chromosomal and DNA damage. Therefore, cytotoxicity of colloidal copper nanoparticles (CuNPs) on murine macrophage cell line (RAW 264.7) was studied to understand the correlation between the cytotoxicity and the nanoparticle yield. Three identical sets of CuNPs with similar physical properties having hydrodynamic particle size of 11-14 nm were prepared by chemical reduction method with target yield of 0.2 g, 0.3 g and 0.4 g. CuNPs exhibited dose-dependent (0.001-100 µg/mL) cytotoxicity due to the mitochondrial damage as indicated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide) assay. Oxidative stress induced by reactive oxygen species (ROS) in RAW 246.7 macrophage cell lines exposed to CuNPs was the primary cause of observed cytotoxicity in all CuNPs test samples. Morphological changes in cells also indicated strong dose-dependent oxidative damage by CuNPs. IC50 (half maximal inhibitory concentration) values of CuNPs were independent of nanoparticle yield. This suggests that per batch variation in CuNPs yield from 0.2 g to 0.4 g had no negative correlation with their toxicity that makes CuNPs a potential candidate for further development of nanotherapeutics and anticancer drugs.

Trends and outcomes of venous thromboembolism in adult hospitalizations with acute myeloid leukemia: analysis of nationwide inpatient sample from 2010 to 2014.

Background: Venous thromboembolism (VTE) occurs frequently in acute myeloid leukemia (AML) patients. There are no population-based studies from the United States (U.S.) analyzing this association. The study aims to analyze the trends, predictors of mortality, and outcomes of VTE in AML patients.Methods: We analyzed the publicly available Nationwide Inpatient Sample (NIS) for years 2010-2014. Hospitalizations due to AML were identified by previously validated International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes as the primary diagnosis. VTE was identified by ICD-9-CM codes as secondary diagnosis. Hospitalizations with age less than 18 years of age were excluded. The trends and outcomes were determined using Chi-squared (χ2) test and multivariate regression models.Results: From 2010 to 2014, there were 313,282 hospitalizations with a primary diagnosis of AML and 1,633 hospitalizations (0.1%) had VTE as a concurrent diagnosis. There was a significant increase in the proportion of AML hospitalizations with VTE from 0.47% in 2010 to 0.56% in 2014 (P = 0.014). Multivariable regression analysis showed that the odds of in-hospital mortality were not higher in AML hospitalizations with VTE (odds ratio [OR] 1.11; 95% confidence interval [CI] 0.81-1.52; P = 0.5) than those without VTE. Age group above 84 years carried the highest risk of mortality (OR 3.20; 95% CI 2.77-3.70; P < 0.0001) in AML-VTE patients. Black (OR 1.23; 95% CI 1.13-1.35; P < 0.0001) and uninsured patients (OR 1.50; 95% CI 1.31-1.73; P < 0.0001) were at significantly higher odds of in-hospital mortality amongst the AML-VTE hospitalizations.Conclusion: The proportion of AML hospitalizations with VTE continues to rise in the U.S. After adjusting for confounders, increasing age, Black race, and lack of insurance were found to have higher risk of in-hospital mortality in the AML-VTE cohort. The odds of in-hospital mortality in AML hospitalizations with VTE are not higher than those without VTE.

Short term outcomes after transcatheter mitral valve repair.

BACKGROUND: Outcome data following transcatheter mitral valve repair (TMVR) with the MITRACLIP® device are scarce outside the pivotal randomized controlled trials. METHODS: The Nationwide Readmission Data base (NRD) was utilized for years 2013-2017 to identify the study population. Thirty-day readmission pattern, in-hospital complications, causes of readmissions, and multivariate predictors for readmission, complications and mortality were explored. RESULTS: We noted a total of 14,647 index admissions related to MITRACLIP of which 48% of procedures were performed at high volume centers (Annual hospital volume ≥ 25). A total of 15% of patients were readmitted within 30 days of discharge most frequently due to cardiac causes. Approximately 33% of patients were discharged within 24 h of the procedure. The in-hospital mortality rate was 2.8% and in-hospital complication rate was 14.6%. The most common complications were cardiac complications (8.2%), bleeding related complications (5.9%) and vascular complications (0.65%). On multivariate modeling, female sex, CHF, Atrial fibrillation, prior PCI, COPD, CKD, transfer to skilled nursing facility, length of stay ≥2 days were associated with a high risk of readmission. Additionally, coagulopathy, chronic kidney disease and lengthier hospital stays were associated with high risk of complication or death. CONCLUSION: The 30-day readmission rate following commercial treatment with the MITRACLIP device is 15%. Half of these admission were from a cardiac etiology. Heart failure, atrial arrhythmias and clip related complications round out the top 3 cardiac reasons for readmission. There was no impact of hospital size, teaching status or case volume on mortality and in hospital complication rates.

Harnessing antifungal immunity in pursuit of a Staphylococcus aureus vaccine strategy.

Staphylococcus aureus (S. aureus) is one of the most common bacterial infections worldwide, and antibiotic resistant strains such as Methicillin-Resistant S. aureus (MRSA) are a major threat and burden to public health. MRSA not only infects immunocompromised patients but also healthy individuals and has rapidly spread from the healthcare setting to the outside community. However, all vaccines tested in clinical trials to date have failed. Immunocompromised individuals such as patients with HIV or decreased levels of CD4+ T cells are highly susceptible to S. aureus infections, and they are also at increased risk of developing fungal infections. We therefore wondered whether stimulation of antifungal immunity might promote the type of immune responses needed for effective host defense against S. aureus. Here we show that vaccination of mice with a fungal ß-glucan particle (GP) loaded with S. aureus antigens provides protective immunity to S. aureus. We generated glucan particles loaded with the four S. aureus proteins ClfA, IsdA, MntC, and SdrE, creating the 4X-SA-GP vaccine. Vaccination of mice with three doses of 4X-SA-GP promoted protection in a systemic model of S. aureus infection with a significant reduction in the bacterial burden in the spleen and kidneys. 4X-SA-GP vaccination induced antigen-specific Th1 and Th17 CD4+ T cell and antibody responses and provided long-term protection. This work suggests that the GP vaccine system has potential as a novel approach to developing vaccines for S. aureus.

Transcatheter Aortic Valve Implantation Readmissions in the Current Era (from the National Readmission Database).

Transcatheter aortic valve implantation (TAVI) has become the mainstream treatment for severe aortic stenosis. Despite improvement in device iteration and operator experience rigorous outcome data outside the scope of clinical trials is lacking. Nationwide readmission database 2016 and 2017 was utilized to identify the study population. International Classification of Disease,10th edition codes were used to identify TAVI admissions. Outcomes of interest were the 90-day readmission pattern and in hospital complications of the TAVI procedure. A total of 73,784 TAVI related index admissions were identified in the Nationwide Readmission Database in 2016 to 2017. Forty four percent of patients undergoing TAVI in that timeframe were discharged within 48 hours of their procedure. 16,343 patients (22.2%) were readmitted within 90 days after discharge. Major cardiac co-morbidities like heart failure were prevalent more often in the group of patients that were readmitted within 90 days. Noncardiac causes however accounted for two thirds of these readmissions. The median time to 90-day readmission was 31 days. Multivariate analysis showed that nonagenarians, patients undergoing transapical TAVI, and patients with a higher comorbidity burden were more likely to be readmitted within 90 days. In conclusion, almost half of TAVI patients in the US are discharged within 48 hours after their procedure and 20% of all TAVI patients are readmitted within 90 days. Most readmissions are due to noncardiac causes.

Influence of Influenza Infection on In-Hospital Acute Myocardial Infarction Outcomes.

Influenza is associated with significant morbidity in the United States but its influence on in-hospital outcomes in patients with AMI has not been well studied. The Nationwide Readmission Database (NRD) from 2010 to 2014 was queried using the International Classification of Diseases-Ninth edition, Clinical Modification (ICD-9-CM) codes to identify all patients ≥18 years who were admitted for AMI with and without concurrent influenza. Propensity score matching was used to adjust patients' baseline characteristics and co-morbidities. In-hospital mortality, 30-day readmission rates, in-hospital complications, and resource utilization were analyzed. We identified a total of 2,428,361 patients admitted with AMI, of whom 3,006 (0.12%) had coexisting influenza. We noted significantly higher in-hospital mortality (7.7% vs 5.6%, p <0.01) and 30-day readmission rates (15.8% vs 14.1%, p <0.01) in patients with influenza compared with those without it. After propensity matching, the differences in in-hospital mortality and 30-day readmission were no longer statistically significant between the groups. Patients with influenza had a higher incidence of acute kidney injury (30.9% vs 24.6%, p <0.01), acute respiratory failure (50.2% vs 32.2%, p <0.01), need for mechanical ventilation (13.9% vs 9.2%, p <0.01), and sepsis (10% vs 3.8%, p <0.01) in the matched cohort. Patients with influenza had longer hospital stays (8.4 days vs 6.4 days, p <0.01) and mean costs of care (26,200USD vs 23,400USD, p <0.01). In conclusion, AMI patients with concomitant influenza infection had higher in-hospital mortality, 30-day readmission, in-hospital complications, and higher resource utilization compared with those without influenza.

Short-term outcomes associated with inpatient ventricular tachycardia catheter ablation.

BACKGROUND: Utilization of catheter ablation of ventricular tachycardia (VT) has steadily increased in recent years. Exploring short-term outcomes is vital in health care planning and resource allocation. METHODS: The Nationwide Readmissions Database from 2010 to 2014 was queried using the ICD-9 codes for VT (427.1) and catheter ablation (37.34) to identify study population. Incidence, causes of 30-day readmission, in-hospital complications as well as predictors of 30-day readmissions, complications, and cost of care were analyzed. RESULTS: Among 11 725 patients who survived to discharge after index admission for VT ablation, 1911 (16.3%) were readmitted within 30 days. Paroxysmal VT was the most common cause of 30-day readmission (39.51%). Dyslipidemia, chronic kidney disease (CKD), previous CABG, congestive heart failure (CHF), chronic pulmonary disease, and anemia predicted increased risk of 30-day readmissions. The overall in-hospital complication rate was 8.2% with vascular and cardiac complications being the most common. Co-existing CKD and CHF and the need for mechanical circulatory support (MCS) predicted higher complication rates. Similarly increasing age, CKD, CHF, anemia, in-hospital use of MCS or left heart catheterization, teaching hospital, and disposition to nursing facilities predicted higher cost. CONCLUSION: Approximately one in six patients was readmitted after VT ablation, with paroxysmal VT being the most common cause of the readmission. A complication rate of 8.2% was noted. We also identified a predictive model for increased risk of readmission, complication, and factors influencing the cost of care that can be utilized to improve the outcomes related to VT ablation.

Causes, Trends, and Predictors of 90-Day Readmissions After Spontaneous Coronary Artery Dissection (from A Nationwide Readmission Database).

Spontaneous coronary artery dissection (SCAD) is a frequently missed diagnosis in patients presenting with acute coronary syndrome (ACS). Our aim was to evaluate the causes, trends, and predictors of 90-day hospital readmission in patients presenting with SCAD. The Nationwide Readmissions Database (2013 to 2014) was utilized to identify patients with primary discharge diagnosis of SCAD using the International Classification of Diseases, Ninth Revision, Clinical Modification, diagnostic code 414.12. The primary outcome was 90-day readmission. Among 11,228 patients admitted with the primary diagnosis of SCAD, 2,424 patients (21.6%) were readmitted within 90 days (68% women, 82% <65 years of age). Common causes for 90-day readmission were ACS (25%), acute heart failure (11%), acute respiratory failure (7%), and arrhythmias (5%). Multivariate predictors of 90-day readmissions were hypertension, chronic obstructive pulmonary disease, peripheral arterial disease, discharge to facility and increased length of stay (LOS) during index admission. Multivariate predictors of increased healthcare-related costs were older age, female gender, discharge to facility, and increased LOS. Over half of the readmissions (52%) occurred in first 30 days after discharge. In conclusion, we found a high rate of rehospitalization among SCAD patients, particularly within the first 30 days of index hospitalization. ACS, heart failure, and acute respiratory failure were the most common reasons for readmission. Hypertension, chronic obstructive pulmonary disease, peripheral arterial disease, and increased LOS were independent predictors of readmission. Further studies are warranted to confirm these predictors of readmission in this high-risk population.

Outcomes and Resource Utilization Associated With Readmissions After Atrial Fibrillation Hospitalizations.

Background Atrial fibrillation is the most common arrhythmia worldwide. Data regarding 30-day readmission rates after discharge for atrial fibrillation remain poorly reported. Methods and Results The Nationwide Readmission Database (2010-2014) was queried using the International Classification of Diseases, Ninth Revision (ICD-9) codes to identify study population. Incidence, etiologies of 30-day readmission and predictors of 30-day readmissions, and cost of care were analyzed. Among 1 723 378 patients who survived to discharge, 249 343 (14.4%) patients were readmitted within 30 days. Compared with the readmitted group, the nonreadmitted group had higher utilization of electrical cardioversion and catheter ablation. Atrial fibrillation was the most common cause of readmission (24.1%). Median time to 30-day readmission was 13 days. Advancing age, female sex, and longer stay during index hospitalization predicted higher 30-day readmissions, whereas private insurance, electrical cardioversion, catheter ablation, higher income, and elective admissions correlated with lower 30-day readmission. Comorbidities such as heart failure, neurological disorder, chronic obstructive pulmonary disease, diabetes mellitus, chronic kidney disease, chronic liver failure, coagulopathy, anemia, peripheral vascular disease, and electrolyte disturbance, correlated with increased 30-day readmissions and cost burden. Trend analysis showed a progressive decline in 30-day readmission rates from 14.7% in 2010 to 14.3% in 2014 (P trend, <0.001). Conclusions Approximately 1 in 7 patients were readmitted within 30 days of discharge, with symptomatic atrial fibrillation being the most common cause. We identified a predictive model for increased risk of readmissions and treatment expense. Electrical cardioversion during index admission was associated with a significant reduction in 30-day readmissions and service charges. The 30-day readmissions correlated with a substantial rise in the cost of care.

Burden and trends of arrhythmias in hypertrophic cardiomyopathy and its impact of mortality and resource utilization.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) accounts for significant morbidity and mortality worldwide. Arrhythmias are considered the main cause of mortality, however, there is paucity of data relating to trends of arrhythmia and associated outcomes in HCM patients. METHODS: Nationwide Inpatient Sample from 2003 to 2014 was analyzed. HCM related hospitalizations were identified using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD9-CM) code 425.1 and 425.11 in all diagnosis fields. RESULTS: Overall, there was an increase in number of hospitalizations related to arrhythmias among HCM patients from 7784 in 2003 to 8380 in 2014 (relative increase 10.5%, P < 0.001). The increase was most significant in patients ≥ 80 years and those with higher comorbidity burden. Atrial fibrillation (AF) was the most frequently occurring arrhythmia however atrial flutter (AFL) witnessed the highest rise during the study period. In general, there was a down trend in mortality with the greatest reduction occurring in patients with ventricular fibrillation/flutter (VF/VFL). The mean length of stay was higher if patients had arrhythmia, which led to increased cost of care from $16105 in 2003 to $19310 in 2014 (relative increase 22.9%, P < 0.001). CONCLUSION: There is overall decline in HCM related hospitalizations but rise in hospitalization among HCM patients with arrhythmias. HCM with arrhythmia accounts for significant inpatient mortality coupled with prolonged hospital stay and increased cost of care. However, there is an encouraging downtrend in the mortality most likely because of improved clinical practice, cardiac screening and primary and secondary prevention strategies.

Malassezia Is Associated with Crohn's Disease and Exacerbates Colitis in Mouse Models.

Inflammatory bowel disease (IBD) is characterized by alterations in the intestinal microbiota and altered immune responses to gut microbiota. Evidence is accumulating that IBD is influenced by not only commensal bacteria but also commensal fungi. We characterized fungi directly associated with the intestinal mucosa in healthy people and Crohn's disease patients and identified fungi specifically abundant in patients. One of these, the common skin resident fungus Malassezia restricta, is also linked to the presence of an IBD-associated polymorphism in the gene for CARD9, a signaling adaptor important for anti-fungal defense. M. restricta elicits innate inflammatory responses largely through CARD9 and is recognized by Crohn's disease patient anti-fungal antibodies. This yeast elicits strong inflammatory cytokine production from innate cells harboring the IBD-linked polymorphism in CARD9 and exacerbates colitis via CARD9 in mouse models of disease. Collectively, these results suggest that targeting specific commensal fungi may be a therapeutic strategy for IBD.

Trends in Incidence and Outcomes of Pregnancy-Related Acute Myocardial Infarction (From a Nationwide Inpatient Sample Database).

Acute myocardial infarction (AMI) during pregnancy is rare but fatal complication. Recent incidence of pregnancy related AMI and trends in the related outcomes are unknown. The Nationwide Inpatient Sample database was utilized from years 2005 to 2014. International Classification of Disease-Ninth Revision were used to identify pregnancy related admissions and AMI. Primary outcome was incidence and trend of AMI related to pregnancy and Secondary outcomes were trends in mortality, resource utilization, and predictors of AMI during pregnancy. Simple logistic regression model was used to calculate predictors of AMI during pregnancy. p Values for trends were generated by Cochrane-Armitage test for categorical variables and simple linear regression for continuous variables. A total of 43,437,621 pregnancy related hospitalization and 3,786 cases of AMI (86% ante-partum and 14% postpartum) were noted during study period. The incidence of AMI during the study period was 8.7 per 100,000 pregnancies with an overall increase in incidence during the study period (relative increase of 18.9%, p <0.001). There was a concomitant decrease in mortality (relative decrease of 40.05%, p <0.001), cost of care (relative decrease of 8.70%, p <0.001), and length of stay (relative decrease of 13.53%, p <0.001). Significant predictors of AMI during pregnancy were higher age of pregnancy, black race, co-morbidities such as hypertension, thrombophilia, diabetes milletus, substance abuse, smoking, hyperlipidemia, heart failure, deep venous thrombosis, transfusion, fluid and electrolyte imbalance, and postpartum complications such as hemorrhage, infection, and depression. In conclusion, the incidence of AMI 2005 to 2014 rose with a concomitant decrease in mortality and resource utilization. High-risk patient characteristics were identified which could be utilized for resource allocation to further improve outcomes.

Expansion of commensal fungus Wallemia mellicola in the gastrointestinal mycobiota enhances the severity of allergic airway disease in mice.

The gastrointestinal microbiota influences immune function throughout the body. The gut-lung axis refers to the concept that alterations of gut commensal microorganisms can have a distant effect on immune function in the lung. Overgrowth of intestinal Candida albicans has been previously observed to exacerbate allergic airways disease in mice, but whether subtler changes in intestinal fungal microbiota can affect allergic airways disease is less clear. In this study we have investigated the effects of the population expansion of commensal fungus Wallemia mellicola without overgrowth of the total fungal community. Wallemia spp. are commonly found as a minor component of the commensal gastrointestinal mycobiota in both humans and mice. Mice with an unaltered gut microbiota community resist population expansion when gavaged with W. mellicola; however, transient antibiotic depletion of gut microbiota creates a window of opportunity for expansion of W. mellicola following delivery of live spores to the gastrointestinal tract. This phenomenon is not universal as other commensal fungi (Aspergillus amstelodami, Epicoccum nigrum) do not expand when delivered to mice with antibiotic-depleted microbiota. Mice with Wallemia-expanded gut mycobiota experienced altered pulmonary immune responses to inhaled aeroallergens. Specifically, after induction of allergic airways disease with intratracheal house dust mite (HDM) antigen, mice demonstrated enhanced eosinophilic airway infiltration, airway hyperresponsiveness (AHR) to methacholine challenge, goblet cell hyperplasia, elevated bronchoalveolar lavage IL-5, and enhanced serum HDM IgG1. This phenomenon occurred with no detectable Wallemia in the lung. Targeted amplicon sequencing analysis of the gastrointestinal mycobiota revealed that expansion of W. mellicola in the gut was associated with additional alterations of bacterial and fungal commensal communities. We therefore colonized fungus-free Altered Schaedler Flora (ASF) mice with W. mellicola. ASF mice colonized with W. mellicola experienced enhanced severity of allergic airways disease compared to fungus-free control ASF mice without changes in bacterial community composition.