Postcardiac Surgery Euglycemic Diabetic Ketoacidosis in Patients on Sodium-Glucose Cotransporter 2 Inhibitors.

OBJECTIVES: To evaluate sodium-glucose cotransporter 2 inhibitors (SGLT2i) use and complications (euglycemic diabetic ketoacidosis [eDKA] rate, mortality, infection, hospital, and cardiovascular intensive care unit [CVICU] length of stay [LOS]) in patients undergoing cardiac surgery. DESIGN: A retrospective study. SETTING: At an academic university hospital. PARTICIPANTS: Adult patients undergoing cardiac surgery. INTERVENTIONS: SGLT2i use versus no SGLT2i use. MEASUREMENTS AND MAIN RESULTS: The authors evaluated patients undergoing cardiac surgery within 24 hours of hospital admission (between February 2, 2019 to May 26, 2022) for SGLT2i prevalence and eDKA frequency. The outcomes were compared using Wilcoxon rank sum and chi-square testing as appropriate. The cohort included 1,654 patients undergoing cardiac surgery, of whom 53 (3.2%) were prescribed an SGLT2i before surgery; 8 (15.1%) of 53 had eDKA. The authors found no differences between patients with and without SGLT2i use in hospital LOS (median [IQR]: 4.5 [3.5-6.3] v 4.4 [3.4-5.6] days, p = 0.46) or CVICU LOS (median [IQR]: 1.2 [1.0-2.2] v 1.1 [1.0-1.9] days, p = 0.22), 30-day mortality (1.9% v 0.7%, p = 0.31), or sternal infections (0.0% v 0.3%, p = 0.69). Among patients prescribed an SGLT2i, those with and without eDKA had similar hospital LOS (5.1 [4.0-5.8] v 4.4 [3.4-6.3], p = 0.76); however, CVICU LOS was longer in patients with eDKA (2.2 [1.5-2.9] v 1.2 [0.9-2.0], p = 0.042). Mortality (0.0% v 2.2%, p = 0.67) and wound infections (0.0% v 0.0%, p > 0.99) were similarly rare. CONCLUSIONS: Postoperative eDKA occurred in 15% of patients on an SGLT2i prior to cardiac surgery, and was associated with longer CVICU LOS. Future studies into SGLT2i management perioperatively are important.

Use of Point-of-Care Ultrasound to Confirm Central Venous Catheter Placement and Evaluate for Postprocedural Complications.

BACKGROUND: Central venous catheter (CVC) placement is commonly performed in the emergency department (ED), but traditional confirmation of placement includes chest radiograph. OBJECTIVE: This manuscript details the use of point-of-care ultrasound (POCUS) to confirm placement of a CVC and evaluate for postprocedural complications. DISCUSSION: CVC access in the ED setting is an important procedure. Traditional confirmation includes chest radiograph. POCUS is a rapid, inexpensive, and accurate modality to confirm CVC placement and evaluate for postprocedural complications. POCUS after CVC can evaluate lung sliding for pneumothorax and the internal jugular vein for misdirected CVC. A bubble study with POCUS visualizing agitated saline microbubbles within the right heart can confirm venous placement. CONCLUSIONS: POCUS can rapidly and reliably confirm CVC placement, as well as evaluate for postprocedural complications. Knowledge of this technique can assist emergency clinicians.

Fournier Gangrene: A Review for Emergency Clinicians.

BACKGROUND: Fournier gangrene (FG) is a rare, life-threatening infection that can result in significant morbidity and mortality, with many patients requiring emergency department (ED) management for complications and stabilization. OBJECTIVE: This narrative review provides an evidence-based summary of the current data for the emergency medicine evaluation and management of FG. DISCUSSION: Although originally thought to be an idiopathic process, FG has been shown to have a strong association for male patients with advanced age and comorbidities affecting microvascular circulation and immune system function, most commonly those with diabetes or alcohol use disorder. However, it can also affect patients without risk factors. The initial infectious nidus is usually located in the genitourinary tract, gastrointestinal tract, or perineum. FG is a mixed infection of aerobic and anaerobic bacterial flora. The development and progression of gangrene is often fulminant and can rapidly cause multiple organ failure and death, although patients may present subacutely with findings similar to cellulitis. Laboratory studies, as well as imaging including point-of-care ultrasound, conventional radiography, and computed tomography are important diagnostic adjuncts, though negative results cannot exclude diagnosis. Treatment includes emergent surgical debridement of all necrotic tissue, broad-spectrum antibiotics, and resuscitation with intravenous fluids and vasoactive medications. CONCLUSIONS: FG requires a high clinical level of suspicion, combined with knowledge of anatomy, risk factors, and etiology for an accurate diagnosis. Although FG remains a clinical diagnosis, relevant laboratory and radiography investigations can serve as useful adjuncts to expedite surgical management, hemodynamic resuscitation, and antibiotic administration.

Causal modeling in a multi-omic setting: insights from GAW20.

BACKGROUND: Increasingly available multilayered omics data on large populations has opened exciting analytic opportunities and posed unique challenges to robust estimation of causal effects in the setting of complex disease phenotypes. The GAW20 Causal Modeling Working Group has applied complementary approaches (eg, Mendelian randomization, structural equations modeling, Bayesian networks) to discover novel causal effects of genomic and epigenomic variation on lipid phenotypes, as well as to validate prior findings from observational studies. RESULTS: Two Mendelian randomization studies have applied novel approaches to instrumental variable selection in methylation data, identifying bidirectional causal effects of CPT1A and triglycerides, as well as of RNMT and C6orf42, on high-density lipoprotein cholesterol response to fenofibrate. The CPT1A finding also emerged in a Bayesian network study. The Mendelian randomization studies have implemented both existing and novel steps to account for pleiotropic effects, which were independently detected in the GAW20 data via a structural equation modeling approach. Two studies estimated indirect effects of genomic variation (via DNA methylation and/or correlated phenotypes) on lipid outcomes of interest. Finally, a novel weighted R2 measure was proposed to complement other causal inference efforts by controlling for the influence of outlying observations. CONCLUSIONS: The GAW20 contributions illustrate the diversity of possible approaches to causal inference in the multi-omic context, highlighting the promises and assumptions of each method and the benefits of integrating both across methods and across omics layers for the most robust and comprehensive insights into disease processes.

RNA-Generated and Gene-Edited Induced Pluripotent Stem Cells for Disease Modeling and Therapy.

Cellular reprogramming by epigenomic remodeling of chromatin holds great promise in the field of human regenerative medicine. As an example, human-induced Pluripotent Stem Cells (iPSCs) obtained by reprograming of patient somatic cells are sufficiently similar to embryonic stem cells (ESCs) and can generate all cell types of the human body. Clinical use of iPSCs is dependent on methods that do not utilize genome altering transgenic technologies that are potentially unsafe and ethically unacceptable. Transient delivery of exogenous RNA into cells provides a safer reprogramming system to transgenic approaches that rely on exogenous DNA or viral vectors. RNA reprogramming may prove to be more suitable for clinical applications and provide stable starting cell lines for gene-editing, isolation, and characterization of patient iPSC lines. The introduction and rapid evolution of CRISPR/Cas9 gene-editing systems has provided a readily accessible research tool to perform functional human genetic experiments. Similar to RNA reprogramming, transient delivery of mRNA encoding Cas9 in combination with guide RNA sequences to target specific points in the genome eliminates the risk of potential integration of Cas9 plasmid constructs. We present optimized RNA-based laboratory procedure for making and editing iPSCs. In the near-term these two powerful technologies are being harnessed to dissect mechanisms of human development and disease in vitro, supporting both basic, and translational research. J. Cell. Physiol. 232: 1262-1269, 2017. © 2016 Wiley Periodicals, Inc.

Machine learning and data mining in complex genomic data--a review on the lessons learned in Genetic Analysis Workshop 19.

In the analysis of current genomic data, application of machine learning and data mining techniques has become more attractive given the rising complexity of the projects. As part of the Genetic Analysis Workshop 19, approaches from this domain were explored, mostly motivated from two starting points. First, assuming an underlying structure in the genomic data, data mining might identify this and thus improve downstream association analyses. Second, computational methods for machine learning need to be developed further to efficiently deal with the current wealth of data.In the course of discussing results and experiences from the machine learning and data mining approaches, six common messages were extracted. These depict the current state of these approaches in the application to complex genomic data. Although some challenges remain for future studies, important forward steps were taken in the integration of different data types and the evaluation of the evidence. Mining the data for underlying genetic or phenotypic structure and using this information in subsequent analyses proved to be extremely helpful and is likely to become of even greater use with more complex data sets.

Fournier Gangrene in the Emergency Department: Diagnostic Dilemmas, Treatments and Current Perspectives.

Fournier gangrene (FG) is a rare and life-threatening urosurgical emergency characterized most often by a polymicrobial infection of the perineal, genital, or perianal region. FG has an increased incidence in male patients, patients with alcoholism, and patients with immunocompromise including human immunodeficiency virus (HIV) and uncontrolled diabetes. FG often begins as a simple abscess or cellulitis with progression to necrotizing soft tissue infection (NSTI). Delays in diagnosis and treatment confer high mortality. Early recognition and high clinical suspicion are important in making a timely diagnosis, as early manifestations are often subtle. The most significant modifiable risk factor associated with NSTI mortality is delay to surgical intervention. Coordination of both inpatient medical and surgical teams to implement appropriate therapy is vital to successful outcomes. The emergency medicine clinician must be vigilant for this condition and be aware of risk factors, prognostic indicators, and proper treatment protocols to recognize FG early and initiate appropriate management. The objective of this review is to provide updated and relevant information regarding recognition, diagnosis, and management of FG for the emergency medicine provider.

The High-Risk Airway.

The high-risk airway is a common presentation and a frequent cause of anxiety for emergency physicians. Preparation and planning are essential to ensure that these challenging situations are managed successfully. Difficult airways typically present as either physiologic or anatomic, each type requiring a specialized approach. Primary physiologic considerations are oxygenation, hemodynamics, and acid-base, whereas anatomic difficulty is overcome using proper positioning and skilled laryngoscopy to ensure success. It is essential to be comfortable performing alternative techniques to address varying presentations. Ultimately, competence in airway management hinges on consistent training, deliberate practice, and a dedication to excellence.

Spontaneous Splenic Artery Pseudoaneurysm Rupture Causing Hemorrhagic Shock.

Splenic artery pseudoaneurysm (SAP) is an uncommon etiology of acute abdominal pain, requiring a high degree of clinical suspicion to diagnose in a timely manner. There are currently no reports of spontaneous SAP ruptures in the emergency medicine literature. We report a case of a man who presented with acute abdominal pain secondary to an SAP. A computed tomography angiography scan of the abdomen revealed a ruptured SAP with hemoperitoneum. He successfully underwent emergency laparotomy and surgical ligation of his SAP with splenectomy. SAP rupture remains an under-recognized etiology of abdominal pain, even though it is the most frequent type of visceral pseudoaneurysm. Our case herein reinforces the importance of a broad list of differential diagnoses in the patient with acute abdominal pain, as well as the importance of the emergency physician in identifying an emergent condition and then directing the initial stabilization, resuscitation, and management.

CD30 is a survival factor and a biomarker for transformed human pluripotent stem cells.

The application of human embryonic stem (hES) cells in regenerative medicine will require rigorous quality control measures to ensure the safety of hES cell-derived grafts. During propagation in vitro, hES cells can acquire cytogenetic abnormalities as well as submicroscopic genetic lesions, such as small amplifications or deletions. Many of the genetic abnormalities that arise in hES cell cultures are also implicated in human cancer development. The causes of genetic instability of hES cells in culture are poorly understood, and commonly used cytogenetic methods for detection of abnormal cells are capable only of low-throughput analysis on small numbers of cells. The identification of biomarkers of genetic instability in hES cells would greatly facilitate the development of culture methods that preserve genomic integrity. Here we show that CD30, a member of the tumor necrosis factor receptor superfamily, is expressed on transformed but not normal hES cells, and that CD30 expression protects hES cells against apoptosis.

Coping with family structure in genome-wide association studies: a comparative evaluation.

In this paper, a fully statistical investigation of the control of family structure as random effects is analyzed and discussed, using both the genome-wide association studies (GWAS) data and simulated data. Three modeling strategies are proposed and the analysis results suggest the hybrid use of results from all possible models should be combined in practice.

Expressions of loss predict aggressive comments on Twitter among gang-involved youth in Chicago.

Recent studies suggest social media shapes the transmission of firearm violence in high-poverty, urban neighborhoods. However, the exact pathways by which content on social media becomes threatening has not been studied. We consider a dataset of tweets by gang-involved Chicago youth that are coded for expressions of aggression and/or loss. Using a permutation test and mixed-effects log linear regression, we find that aggression and loss tweets do not occur randomly, and furthermore that in a 2-day window after loss expressions we find an increase in aggressive tweets. We discuss implications for intervention.

A molecular scheme for improved characterization of human embryonic stem cell lines.

BACKGROUND: Human embryonic stem cells (hESC) offer a renewable source of a wide range of cell types for use in research and cell-based therapies to treat disease. Inspection of protein markers provides important information about the current state of the cells and data for subsequent manipulations. However, hESC must be routinely analyzed at the genomic level to guard against deleterious changes during extensive propagation, expansion, and manipulation in vitro. RESULTS: We found that short tandem repeat (STR) analysis, human leukocyte antigen (HLA) typing, single nucleotide polymorphism (SNP) genomic analysis, mitochondrial DNA sequencing, and gene expression analysis by microarray can be used to fully describe any hESC culture in terms of its identity, stability, and undifferentiated state. CONCLUSION: Here we describe, using molecular biology alone, a comprehensive characterization of 17 different hESC lines. The use of amplified nucleic acids means that for the first time full characterization of hESC lines can be performed with little time investment and a minimum of material. The information thus gained will facilitate comparison of lines and replication of results between laboratories.

Solid-Organ Graft-Versus-Host Disease After Liver Transplant: A Case Report.

Solid-organ transplant graft-versus-host disease (SOT-GVHD) is a rare complication of organ transplant that is associated with high mortality. The initial signs and symptoms are vague, so this disease is easily confused with other posttransplant complications. A case of SOT-GVHD occurred after orthotopic liver transplant for liver failure due to hepatitis C in a patient in a Veterans Affairs intensive care unit. The patient had dehydration, acute kidney injuries, rashes, diarrhea, and pancytopenia. Results of skin biopsy, bone marrow biopsy, and cytogenetic studies were consistent with SOT-GVHD. Despite supportive care including antibiotics, antiviral and antifungal therapy, high-dose steroids, antithymoglobulin and neupogen, the patient died of overwhelming sepsis. Owing to the rarity of SOT-GVHD, no evidence-based guidelines or recommendations for treatment exist. Treatment includes high-dose corticosteroids and antibiotic, antifungal, and antiviral prophylaxis. Treatment of liver transplant-related GVHD with anti-tumor necrosis factor a agents has been successful.

Identifying regions of disease-related variants in admixed populations with the summation partition approach.

We propose a new method for identifying disease-related regions of single nucleotide variants in recently admixed populations. We use principal component analysis to derive both global and local ancestry information. We then use the summation partition approach to search for disease-related regions based on both rare variants and the local ancestral information of each region. We demonstrate this method using individuals with high systolic blood pressure from a sample of unrelated Mexican American subjects provided in the 19th Genetic Analysis Workshop.

Network-guided interaction mining for the blood pressure phenotype of unrelated individuals in genetic analysis workshop 19.

Interactions between genes are an important part of the genetic architecture of complex diseases. In this paper, we use literature-guided individual genes known to be associated with type 2 diabetes (referred to as "seed genes") to create a larger list of genes that share implied or direct networks with these seed genes. This larger list of genes are known to interact with each other, but whether they interact in ways to influence hypertension in individuals presents an interesting question. Using Genetic Analysis Workshop data on individuals with diabetes, for which only case-control labels of hypertension are known, we offer a foray into identification of diabetes-related gene interactions that are associated with hypertension. We use the approach of Lo et al. (Proc Natl Acad Sci U S A 105: 12387-12392, 2008), which creates a score to identify pairwise significant gene associations. We find that the genes GCK and PAX4, formerly known to be found within similar coexpression and pathway networks but without specific direct interactions, do, in fact, show significant joint interaction effects for hypertension.

Acute onset of psychosis in a patient with a left temporal lobe arachnoid cyst.

Arachnoid cysts are considered a rare neurological tumor, few of which exhibit any symptomatology. A 38-year-old Haitian American female with no past psychiatric history presented with rapid onset of psychosis. Workup for medical etiology proved to be within normal limits, with the exception of a left temporal lobe arachnoid cyst. The purpose of this paper is to add to a number of existing case reports that suggest a relationship between such lesions and psychiatric illness.