Rates of Reproductive Counseling and Contraception Use in Patients with Heart Failure at a Tertiary Care Center.

BACKGROUND: Increasing numbers of women of childbearing age have cardiac disease, including heart failure (HF). In these women, pregnancy can cause significant morbidity and mortality. Contraceptive use and pregnancy counseling in women with HF is an essential part of their medical care. Here, we assess contraceptive use and pregnancy counseling of patients with HF at a single tertiary care center. METHODS AND RESULTS: This was a retrospective, single-center cohort study of female patients with HF with reduced ejection fraction, left ventricular assist devices (LVADs), and heart transplants who were seen in the adult advanced HF outpatient clinics. Patients were identified in the electronic health care record system, and records were reviewed to assess for documentation of contraception and pregnancy counseling. We identified 156 women of childbearing age (aged >18 to <45), seen in the HF clinics between 2018 and 2023. Patients were subdivided by their most recent diagnosis and therapy: HF with reduced ejection fraction (83 [53.2%]), LVAD (18 [11.5%]), and heart transplant (55 [35.3%]). Contraception was documented for 74% of women with HF, 56% of women with LVAD, and 85% of women with heart transplants. Pregnancy counseling was documented for 18.00% of women with HF, 0.06% of women with LVAD, and 29.00% of women with heart transplants. CONCLUSIONS: In our study, many women with HF, LVAD, or transplant have documented contraceptive therapy; however, pregnancy counseling seems to be limited. This vital aspect of medical care should be available for all patients given potential pregnancy-associated risks.

Loss of LDAH associated with prostate cancer and hearing loss.

Great strides in gene discovery have been made using a multitude of methods to associate phenotypes with genetic variants, but there still remains a substantial gap between observed symptoms and identified genetic defects. Herein, we use the convergence of various genetic and genomic techniques to investigate the underpinnings of a constellation of phenotypes that include prostate cancer (PCa) and sensorineural hearing loss (SNHL) in a human subject. Through interrogation of the subject's de novo, germline, balanced chromosomal translocation, we first identify a correlation between his disorders and a poorly annotated gene known as lipid droplet associated hydrolase (LDAH). Using data repositories of both germline and somatic variants, we identify convergent genomic evidence that substantiates a correlation between loss of LDAH and PCa. This correlation is validated through both in vitro and in vivo models that show loss of LDAH results in increased risk of PCa and, to a lesser extent, SNHL. By leveraging convergent evidence in emerging genomic data, we hypothesize that loss of LDAH is involved in PCa and other phenotypes observed in support of a genotype-phenotype association in an n-of-one human subject.

Describing sequencing results of structural chromosome rearrangements with a suggested next-generation cytogenetic nomenclature.

With recent rapid advances in genomic technologies, precise delineation of structural chromosome rearrangements at the nucleotide level is becoming increasingly feasible. In this era of "next-generation cytogenetics" (i.e., an integration of traditional cytogenetic techniques and next-generation sequencing), a consensus nomenclature is essential for accurate communication and data sharing. Currently, nomenclature for describing the sequencing data of these aberrations is lacking. Herein, we present a system called Next-Gen Cytogenetic Nomenclature, which is concordant with the International System for Human Cytogenetic Nomenclature (2013). This system starts with the alignment of rearrangement sequences by BLAT or BLAST (alignment tools) and arrives at a concise and detailed description of chromosomal changes. To facilitate usage and implementation of this nomenclature, we are developing a program designated BLA(S)T Output Sequence Tool of Nomenclature (BOSToN), a demonstrative version of which is accessible online. A standardized characterization of structural chromosomal rearrangements is essential both for research analyses and for application in the clinical setting.

Stepwise Multimodality Imaging Assists in Atrial Myxoma Diagnosis and Management.

The case of a 67-year-old man who presented for elective gastroenterology procedures and was in atrial fibrillation is discussed. Transthoracic echocardiography revealed a large atrial mass. Preoperative coronary angiography revealed a heavily vascularized mass. Use of cardiac magnetic resonance identified the cardiac mass as likely an atrial myxoma. (Level of Difficulty: Beginner.).

Preconception Counseling in a Patient With a Mechanical Aortic Valve and Recent Ischemic Stroke.

A 31-year-old woman with a mechanical aortic valve for congenital aortic stenosis presented to the cardiology clinic for preconception counseling. After experiencing an acute stroke 4 weeks prior, she was subsequently discovered to have prosthetic valve thrombosis requiring replacement of the aortic valve. We discuss her clinical course and preconception considerations.

Simulation-Based Education in US Undergraduate Medical Education: A Descriptive Study.

PURPOSE: Simulation-based education (SBE) provides experiential learning, improvement in quality of care, and reduction in errors. In 2011, the Association of American Medical Colleges described adoption of SBE in 68.0% of medical schools and 25.0% of teaching hospitals. We sought to examine current trends of SBE integration in American undergraduate medical education since previous publications. METHODS: From 2016 to 2019, University of Texas Southwestern Medical Center postgraduate year 1 residents were invited to participate in a survey assessing medical school simulation experience with 26 clinical tasks from three categories: procedural, communication, and other. Deidentified results were analyzed to assess demographics including sex, specialty, residency program type, allopathic versus osteopathic medical school, and medical school region. RESULTS: Nine hundred sixty-seven of 1047 (92.3%) responses were obtained, representing 139 US medical schools, 91% from allopathic training. Of procedural tasks, most simulated was suturing (n = 848, 89.6%) and least simulated was thoracentesis (n = 737, 80.9%). Of communication tasks, most simulated was taking a history (n = 475, 51.1% reporting simulation >30) and least simulated (never or ≤1) were obtaining a consent (n = 669, 73.2%) and disclosing a medical error (n = 666, 72.4%). Of other tasks, most simulated was chest compressions (n = 898, 96.0%) and least simulated was operating a defibrillator (n = 206, 22.1%). Results were similar regardless of procedural or nonprocedural program. There was no significant difference in SBE exposure between allopathic and osteopathic students ( P = 0.89). Two participants (0.002%) reported no simulation exposure. CONCLUSIONS: Our study is the first to describe a high prevalence of SBE adoption in medical schools nationwide since the Association of American Medical Colleges' 2011 publication, with overall equal exposure for students regardless of residency type and allopathic or osteopathic medical school. Despite widespread adoption of simulation, opportunities remain to expand SBE use to teach critically important communication skills.

The pseudophosphatase MK-STYX induces neurite-like outgrowths in PC12 cells.

The rat pheochromocytoma PC12 cell line is a widely used system to study neuronal differentiation for which sustained activation of the extracellular signaling related kinase (ERK) pathway is required. Here, we investigate the function of MK-STYX [MAPK (mitogen-activated protein kinase) phosphoserine/threonine/tyrosine-binding protein] in neuronal differentiation. MK-STYX is a member of the MAPK phosphatase (MKP) family, which is generally responsible for dephosphorylating the ERKs. However, MK-STYX lacks catalytic activity due to the absence of the nucleophilic cysteine in the active site signature motif HC(X5)R that is essential for phosphatase activity. Despite being catalytically inactive, MK-STYX has been shown to play a role in important cellular pathways, including stress responses. Here we show that PC12 cells endogenously express MK-STYX. In addition, MK-STYX, but not its catalytically active mutant, induced neurite-like outgrowths in PC12 cells. Furthermore, MK-STYX dramatically increased the number of cells with neurite extensions in response to nerve growth factor (NGF), whereas the catalytically active mutant did not. MK-STYX continued to induce neurites in the presence of a MEK (MAP kinase kinase) inhibitor suggesting that MK-STYX does not act through the Ras-ERK/MAPK pathway but is involved in another pathway whose inactivation leads to neuronal differentiation. RhoA activity assays indicated that MK-STYX induced extensions through the Rho signaling pathway. MK-STYX decreased RhoA activation, whereas RhoA activation increased when MK-STYX was down-regulated. Furthermore, MK-STYX affected downstream players of RhoA such as the actin binding protein cofilin. The presence of MK-STYX decreased the phosphorylation of cofilin in non NGF stimulated cells, but increased its phosphorylation in NGF stimulated cells, whereas knocking down MK-STYX caused an opposite effect. Taken together our data suggest that MK-STYX may be a regulator of RhoA signaling, and implicate this pseudophosphatase as a regulator of neuronal differentiation.