Need for cardiac implantable electronic devices and long-term follow-up in recipients of orthotopic heart transplants.

BACKGROUND: Cardiac pacemaker implantation after orthotopic heart transplantation declined dramatically after development of the bicaval anastomosis technique. However, much less is known about the rate, indications, and predictors of device implantation procedures with the current surgical technique. OBJECTIVE: The purpose of this study was to evaluate the indications, patient characteristics, incidence, and survival related to cardiac implantable electronic device (CIED) implantation after heart transplantation. METHODS: This was a single-center study of 399 consecutive adult recipients of orthotopic heart transplants with bicaval anastomosis from 1991 to 2017. The primary end point was freedom from pacemaker or implantable cardioverter-defibrillator (ICD) implantation, and the secondary end point was all-cause mortality. RESULTS: At the time of transplantation, the mean age of recipients was 50 ± 12 years and that of donors 31 ± 12 years. CIEDs were implanted in 8% of recipients (n = 31): 11 pacemakers (35%) for sinus node dysfunction, 17 (55%) for high-grade heart block, and 3 ICDs (10%) for the primary prevention of sudden cardiac death. Early CIED implantation (<30 days) was rare and absent for sinus node dysfunction. The risk for CIED implantation increased progressively during follow-up (0-30 years; median 11 years), with low-, moderate-, and high-risk periods between 0 and 10, between 10 and 20, and between 20 and 30 years, respectively. Recipients receiving CIEDs survived longer after transplantation (21 years vs 13 years; P < .01). Recipients receiving pacemakers for heart block were more likely to receive older donor hearts at the time of transplantation. CONCLUSION: The risk of pacemaker implantation increases progressively, while ICD implantation is rare. Donor age is the predominant risk factor for subsequent heart block. Early sinus node dysfunction requiring permanent pacing is rare.

Evaluation and treatment of metabolic syndrome and cardiovascular disease in adult patients with psoriasis.

Psoriasis is strongly associated with cardiovascular disease (CVD) and metabolic syndrome, with patients having an approximately twofold increased risk of each compared to the general population. This increased risk is based on shared underlying genetic and cytokine profiles, as well as similar environmental risks. Many screening guidelines do not address the development of CVD and metabolic syndrome in these predisposed patients. These deficits are evidenced by the exclusion of psoriasis as a risk factor in validated 10-year CVD risk calculators for adult patients with chronic inflammatory diseases, as well as insufficient screening guidelines for insulin resistance in patients with psoriasis. This manuscript aims to discuss and propose allopathic and lifestyle recommendations for the screening and management of the aforementioned comorbidities in adult patients with psoriasis.

Meta-Analysis of Immune Induced Gene Expression Changes in Diverse Drosophila melanogaster Innate Immune Responses.

Organisms are commonly infected by a diverse array of pathogens and mount functionally distinct responses to each of these varied immune challenges. Host immune responses are characterized by the induction of gene expression, however, the extent to which expression changes are shared among responses to distinct pathogens is largely unknown. To examine this, we performed meta-analysis of gene expression data collected from Drosophila melanogaster following infection with a wide array of pathogens. We identified 62 genes that are significantly induced by infection. While many of these infection-induced genes encode known immune response factors, we also identified 21 genes that have not been previously associated with host immunity. Examination of the upstream flanking sequences of the infection-induced genes lead to the identification of two conserved enhancer sites. These sites correspond to conserved binding sites for GATA and nuclear factor κB (NFκB) family transcription factors and are associated with higher levels of transcript induction. We further identified 31 genes with predicted functions in metabolism and organismal development that are significantly downregulated following infection by diverse pathogens. Our study identifies conserved gene expression changes in Drosophila melanogaster following infection with varied pathogens, and transcription factor families that may regulate this immune induction.

Extracellular matrix protein N-glycosylation mediates immune self-tolerance in Drosophila melanogaster.

In order to respond to infection, hosts must distinguish pathogens from their own tissues. This allows for the precise targeting of immune responses against pathogens and also ensures self-tolerance, the ability of the host to protect self tissues from immune damage. One way to maintain self-tolerance is to evolve a self signal and suppress any immune response directed at tissues that carry this signal. Here, we characterize the Drosophila tuSz1 mutant strain, which mounts an aberrant immune response against its own fat body. We demonstrate that this autoimmunity is the result of two mutations: 1) a mutation in the GCS1 gene that disrupts N-glycosylation of extracellular matrix proteins covering the fat body, and 2) a mutation in the Drosophila Janus Kinase ortholog that causes precocious activation of hemocytes. Our data indicate that N-glycans attached to extracellular matrix proteins serve as a self signal and that activated hemocytes attack tissues lacking this signal. The simplicity of this invertebrate self-recognition system and the ubiquity of its constituent parts suggests it may have functional homologs across animals.

Fourteen Recommendations to Create a More Inclusive Environment for LGBTQ+ Individuals in Academic Biology.

Individuals who identify as lesbian, gay, bisexual, transgender, queer, and otherwise nonstraight and/or non-cisgender (LGBTQ+) have often not felt welcome or represented in the biology community. Additionally, biology can present unique challenges for LGBTQ+ students because of the relationship between certain biology topics and their LGBTQ+ identities. Currently, there is no centralized set of guidelines to make biology learning environments more inclusive for LGBTQ+ individuals. Rooted in prior literature and the collective expertise of the authors who identify as members and allies of the LGBTQ+ community, we present a set of actionable recommendations to help biologists, biology educators, and biology education researchers be more inclusive of individuals with LGBTQ+ identities. These recommendations are intended to increase awareness of LGBTQ+ identities and spark conversations about transforming biology learning spaces and the broader academic biology community to become more inclusive of LGBTQ+ individuals.

Bioinformatic analysis suggests potential mechanisms underlying parasitoid venom evolution and function.

Hymenopteran parasitoid wasps are a diverse collection of species that infect arthropod hosts and use factors found in their venoms to manipulate host immune responses, physiology, and behaviour. Whole parasitoid venoms have been profiled using proteomic approaches, and here we present a bioinformatic characterization of the venom protein content from Ganaspis sp. 1, a parasitoid that infects flies of the genus Drosophila. We find evidence that diverse evolutionary processes including multifunctionalization, co-option, gene duplication, and horizontal gene transfer may be acting in concert to drive venom gene evolution in Ganaspis sp.1. One major role of parasitoid wasp venom is host immune evasion. We previously demonstrated that Ganaspis sp. 1 venom inhibits immune cell activation in infected Drosophila melanogaster hosts, and our current analysis has uncovered additional predicted virulence functions. Overall, this analysis represents an important step towards understanding the composition and activity of parasitoid wasp venoms.

Buprenorphine compared with methadone in opioid-dependent pregnant women: How does it affect neonatal abstinence syndrome?

BACKGROUND: The growing opioid epidemic in the United States has led to increasingly high rates of neonatal abstinence syndrome (NAS). Preliminary studies have shown that buprenorphine maintenance treatment (BMT) may lead to better outcomes for infants than methadone maintenance treatment (MMT). OBJECTIVES: The authors gathered recent evidence to answer the following PICO (population, intervention, comparison, and outcome) question: In opioid-dependent pregnant women, how does buprenorphine compared with methadone administration affect NAS? DATA SOURCES: A literature search was completed in PubMed, Scopus, Embase, and Web of Science databases and limited to the past 5 years. The following parameters were analyzed in the articles: NAS occurrence, length of hospital stay in days, NAS treatment length, and amount of pharmacotherapy administered to treat NAS. CONCLUSIONS: In comparison to methadone, buprenorphine exposure in utero is associated with significantly shorter hospital stays for the infant after delivery, shorter length of NAS treatment, and decreased frequency/duration of pharmacotherapy for NAS symptoms in the infant. IMPLICATIONS FOR PRACTICE: Based on the findings, a weak recommendation can be made for the use of BMT over MMT in opioid-dependent pregnant women. However, further research is necessary to definitively recommend buprenorphine over methadone use in this population, especially regarding the effect of maternal severity of addiction on adherence to BMT, and long-term effects of in utero buprenorphine exposure.

Call a Spade a Spade: Missed Diagnosis of Apical Hypertrophic Cardiomyopathy.

Apical hypertrophic cardiomyopathy is a variant of hypertrophic cardiomyopathy characterized by apical hypertrophy, deep T-wave inversions in precordial electrocardiogram (EKG) leads, and a ventriculogram shaped like the "Ace of Spades." Patients are often asymptomatic but sometimes present with atypical chest pain, angina, or atrial fibrillation. The deep T-wave inversions on EKG often mimic acute coronary syndrome. Coronary angiogram in these patients is unrevealing, but the characteristic left ventriculogram establishes this diagnosis. The deep T-wave inversions can appear suddenly or deepen over years, making the diagnosis difficult to establish early in the disease. Transthoracic echocardiogram may miss the hypertrophied apex, but echo contrast imaging or cardiac magnetic resonance imaging can reliably confirm the diagnosis and detect apical aneurysms. We present a case of apical hypertrophic cardiomyopathy which was not evident despite many admissions, EKGs, cardiac catheterizations and echocardiograms until the diagnosis was confirmed with left ventriculogram and cardiac magnetic resonance imaging 20 years after initial presentation.

Impact of Renal Function on Survival After Cardiac Resynchronization Therapy.

Chronic kidney disease (CKD) is associated with worse survival in patients with heart disease including those with implantable devices. Cardiac resynchronization therapy (CRT) can potentially improve renal function. To assess the relation between the change in renal function and survival with CRT, 238 patients undergoing initial CRT with defibrillator implantation between 2002 and 2011 were followed. The primary end point was all-cause mortality. The estimated glomerular filtration rate (eGFR), before implantation and 6 ± 3 months after CRT was calculated. Patients were grouped at baseline into mild (stage I/II) or advanced (stage III/IV) CKD. Patients with end-stage renal disease were excluded. The mean follow-up time was 4.3 years. Multivariate analysis of baseline clinical characteristics showed that only renal function predicted the change in eGFR over the first 6 months of CRT. In the subgroup with mild CKD, eGFR decreased (78.5 ± 17.3 to 67.8 ± 26.8 p <0.001), whereas eGFR did not change in the subgroup with advanced CKD (45.6 ± 11.1 to 46.8 ± 17.0, p = 0.46). Patients with advanced CKD had higher mortality than those with mild CKD (p <0.002). In both subgroups, an increase in eGFR was associated with improved survival (hazard ratio = 0.79, p <0.001). In conclusion, baseline renal function and the subsequent change in eGFR are associated with long-term survival with CRT.

The Effect of Chronic Kidney Disease on Mortality with Cardiac Resynchronization Therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) improves functional status, reduces heart failure hospitalizations, and decreases mortality. Several comorbidities including renal function affect outcomes with CRT. However, moderate to severe chronic kidney disease (CKD) was an exclusion criterion in the large randomized control trials. OBJECTIVE: To evaluate the association of renal function on survival following CRT implantation. METHODS: This was a retrospective analysis of 432 consecutive patients implanted with an implantable cardioverter defibrillator with CRT (CRT-D). The primary end point was defined as death by any cause, and it was determined using hospital records and the U.S. Social Security Death Index. A Kaplan-Meier analysis was performed separating renal dysfunction into renal stage based on glomerular filtration rate. Multivariate analysis was performed to assess the clinical predictors of mortality. RESULTS: Patients were followed for up to 12 years with a mean follow-up time of 4.3 ± 3.2 years. A total of 164 patients (39.3%) died over the course of the study. Patients with normal and mild renal diseases (Stages 1 and 2) had improved survival compared with those with moderate-, severe-, or end-stage (Stages 3-5) renal disease. This effect remained statistically significant after multivariate analysis. The estimated 5-year mortality was 36.3% for stage 1, 33.4% for stage 2, 40.6% for stage 3, and 62.1% for stage 4/5 kidney disease (P = 0.004 by log-rank test). CONCLUSION: CKD is a strong and an independent predictor of long-term mortality among patients undergoing CRT-D implantation.