The Women in Cardiothoracic Anesthesiology Special Interest Group: What Can the Lessons of One Anesthesiology Affinity Group Tell Us About How to Build Impactful Professional Communities?

The Women In Cardiothoracic Anesthesiology (WICTA), a special interest group of the Society of Cardiovascular Anesthesiologists, has been highly successful in mobilizing WICTA, a historically underrepresented and marginalized group in the subspecialty, and in supporting real and meaningful change in the professional community. The experience of WICTA as a professional affinity group in impacting a professional organization to diversify, evolve, and become more responsive to a wider professional audience has important lessons for other professional organizations. This article discusses the recent history of affinity organizations in anesthesiology, the benefits they offer professional organizations, and the strategies that have been used to effectively motivate change in professional communities. These strategies include engaging a strong advisory board, identifying the need of constituents, creating additional opportunities for networking and membership, addressing gaps in professional development, and aligning goals with those of the larger national organization. WICTA is just one example of the potential opportunities that affinity groups offer to professional societies and organizations for expanding their reach, enhancing their impact on physicians in their target audience, and achieving organizational missions.

Unexpected TEE Findings During Rheumatic Triple-Valve Surgery: Incidental, Yet Impactful.

This E-Challenge highlights an incidental prebypass transesophageal echocardiographic (TEE) finding of a right atrial membrane that impacted cardiac surgical management during triple-valve surgery. Two-dimensional and advanced 3-dimensional (3D) TEE were used in real-time to assist intraoperative decision-making. The findings, clinical course, discussion of the differential diagnosis, final diagnosis, and patient management are detailed here.

The Many Faces of the Interatrial Septum: A Diagnostic Dilemma and Considerations for Defect Closure Device Selection.

PATENT FORAMEN ovales (PFOs) and atrial septal defects (ASDs) are 2 examples of interatrial septal pathology.1 The presence of a PFO is a well-known risk factor for cryptogenic stroke.1,2 Newer evidence over the course of the last decade suggests percutaneous device closure of PFOs significantly reduces the subsequent risk of recurrent stroke.2 Among ASDs, the ostium secundum type is the most common pathology and, due to its anatomy, is most amenable to transcatheter closure.1 The tools that are available to percutaneously close these different pathologies vary, and choosing the correct device for the procedure can have significant impact on the clinical outcome. The authors here present a case that highlights how the differentiation of an ASD from a PFO using 2-dimensional (2D) and 3-dimensional (3D) echocardiography can affect the clinical decision-making and outcome in a challenging structural heart disease case.

Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease.

This evidence-based clinical practice guideline for the prevention, diagnosis, and treatment of Lyme disease was developed by a multidisciplinary panel representing the Infectious Diseases Society of America (IDSA), the American Academy of Neurology (AAN), and the American College of Rheumatology (ACR). The scope of this guideline includes prevention of Lyme disease, and the diagnosis and treatment of Lyme disease presenting as erythema migrans, Lyme disease complicated by neurologic, cardiac, and rheumatologic manifestations, Eurasian manifestations of Lyme disease, and Lyme disease complicated by coinfection with other tick-borne pathogens. This guideline does not include comprehensive recommendations for babesiosis and tick-borne rickettsial infections, which are published in separate guidelines. The target audience for this guideline includes primary care physicians and specialists caring for this condition such as infectious diseases specialists, emergency physicians, internists, pediatricians, family physicians, neurologists, rheumatologists, cardiologists and dermatologists in North America.

Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease.

This evidence-based clinical practice guideline for the prevention, diagnosis, and treatment of Lyme disease was developed by a multidisciplinary panel representing the Infectious Diseases Society of America (IDSA), the American Academy of Neurology (AAN), and the American College of Rheumatology (ACR). The scope of this guideline includes prevention of Lyme disease, and the diagnosis and treatment of Lyme disease presenting as erythema migrans, Lyme disease complicated by neurologic, cardiac, and rheumatologic manifestations, Eurasian manifestations of Lyme disease, and Lyme disease complicated by coinfection with other tick-borne pathogens. This guideline does not include comprehensive recommendations for babesiosis and tick-borne rickettsial infections, which are published in separate guidelines. The target audience for this guideline includes primary care physicians and specialists caring for this condition such as infectious diseases specialists, emergency physicians, internists, pediatricians, family physicians, neurologists, rheumatologists, cardiologists and dermatologists in North America.

Transcatheter mitral valve-in-valve-in-valve replacement with transseptal puncture in the presence of an atrial septal occluder device.

Quite often the iatrogenic atrial septal defect created after percutaneous transcatheter mitral valve replacement procedures is closed with an atrial septal occluder device thus precluding further transseptal interventions if required. In this case report, we describe a patient who previously underwent a valve-in-valve transcatheter mitral valve replacement and iatrogenic atrial septal defect closure with an Amplatzer device, who developed severe prosthetic mitral valve stenosis. This patient required a second percutaneous valve-in-valve in-valve procedure with a transseptal puncture in the presence of an atrial septal occluder device.

Transapical ProtekDuo Rapid Deployment Cannula as Temporary Left Ventricular Assist Device in a Jehovah's Witness Patient.

Temporary left ventricular support aims to decompress the left ventricle and provide adequate forward flow into the arterial circulation. This can be accomplished with endovascular devices such as the Impella with an internal motor, or with the implementation of cannulae to drain the left ventricle or left atrium and then return to the arterial circulation using an external pump. In this report, the authors describe the transesophageal echocardiography-guided placement of a single-cannula system with the Protek Duo RD (TandemLife, LivaNova) via a left ventricular apical approach to provide minimally invasive left ventricular support in a high-risk Jehovah's Witness patient.

Artificial Intelligence for Dynamic Echocardiographic Tricuspid Valve Analysis: A New Tool in Echocardiography.

There has been a resurgence of interest in the structure and function of the tricuspid valve (TV) with the established prognostic impact of functional tricuspid regurgitation. Current 3-dimensional transesophageal echocardiography prototype software is limited to exploration of the mitral and aortic valves exclusively. Thus, newer analytical software is required for dynamic geometric analysis of the TV morphology for remodeling. This article presents a preliminary experience with novel artificial intelligence-based semiautomated software for TV analysis. The software offers high correlation to surgical inspection by its ability to analyze morphology and dynamics of the valve throughout the cardiac cycle. In addition, it allows higher reproducibility of data analysis and reduces interobserver variability with minimal need for manual intervention. Integration of interactivity through preprocedural placement of specific devices of different sizes and shapes in the mitral and aortic positions facilitates prognostic evaluation of surgical and interventional procedures.

New mechanism of X-linked anhidrotic ectodermal dysplasia with immunodeficiency: impairment of ubiquitin binding despite normal folding of NEMO protein.

Nuclear factor-κB essential modulator (NEMO), the regulatory subunit of the IκB kinase complex, is a critical component of the NF-κB pathway. Hypomorphic mutations in the X-linked human NEMO gene cause various forms of anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID). All known X-linked EDA-ID-causing mutations impair NEMO protein expression, folding, or both. We describe here 2 EDA-ID-causing missense mutations that affect the same residue in the CC2-LZ domain (D311N and D311G) that do not impair NEMO production or folding. Structural studies based on pull-down experiments showed a defect in noncovalent interaction with K63-linked and linear polyubiquitin chains for these mutant proteins. Functional studies on the patients' cells showed an impairment of the classic NF-κB signaling pathways after activation of 2 NEMO ubiquitin-binding-dependent receptors, the TNF and IL-1ß receptors, and in the CD40-dependent NF-κB pathway. We report the first human NEMO mutations responsible for X-linked EDA-ID found to affect the polyubiquitin binding of NEMO rather than its expression and folding. These experiments demonstrate that the binding of human NEMO to polyubiquitin is essential for NF-κB activation. They also demonstrate that the normal expression and folding of NEMO do not exclude a pathogenic role for NEMO mutations in patients with EDA-ID.

Adjunctive Diagnostic Studies Completed Following Detection of Candidemia in Children: Secondary Analysis of Observed Practice From a Multicenter Cohort Study Conducted by the Pediatric Fungal Network.

BACKGROUND: Adjunctive diagnostic studies (aDS) are recommended to identify occult dissemination in patients with candidemia. Patterns of evaluation with aDS across pediatric settings are unknown. METHODS: Candidemia episodes were included in a secondary analysis of a multicenter comparative effectiveness study that prospectively enrolled participants age 120 days to 17 years with invasive candidiasis (predominantly candidemia) from 2014 to 2017. Ophthalmologic examination (OE), abdominal imaging (AbdImg), echocardiogram, neuroimaging, and lumbar puncture (LP) were performed per clinician discretion. Adjunctive diagnostic studies performance and positive results were determined per episode, within 30 days from candidemia onset. Associations of aDS performance with episode characteristics were evaluated via mixed-effects logistic regression. RESULTS: In 662 pediatric candidemia episodes, 490 (74%) underwent AbdImg, 450 (68%) OE, 426 (64%) echocardiogram, 160 (24%) neuroimaging, and 76 (11%) LP; performance of each aDS per episode varied across sites up to 16-fold. Longer durations of candidemia were associated with undergoing OE, AbdImg, and echocardiogram. Immunocompromised status (58% of episodes) was associated with undergoing AbdImg (adjusted odds ratio [aOR] 2.38; 95% confidence intervals [95% CI] 1.51-3.74). Intensive care at candidemia onset (30% of episodes) was associated with undergoing echocardiogram (aOR 2.42; 95% CI 1.51-3.88). Among evaluated episodes, positive OE was reported in 15 (3%), AbdImg in 30 (6%), echocardiogram in 14 (3%), neuroimaging in 9 (6%), and LP in 3 (4%). CONCLUSIONS: Our findings show heterogeneity in practice, with some clinicians performing aDS selectively, potentially influenced by clinical factors. The low frequency of positive results suggests that targeted application of aDS is warranted.

Primary and acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer: an update.

Epidermal growth factor receptor (EGFR) is a critical target in the treatment of nonsmall cell lung cancer (NSCLC). The mutations involving EGFR are more prevalent in patients of Asian ancestry, women, never smokers, and those with adenocarcinoma histology. Primary mechanism of resistance to EGFR-TKIs includes in frame insertion mutation in exon 20, de novo T790M mutation also on exon 20, activating mutations in KRAS, loss of PTEN, and amplification of c-MET whereas acquired resistance results from development of secondary alteration in ATP domain of T790M. There are many novel targeting agents in development to overcome resistance to EGFR TKIs.

Regulation of mature ADAM17 by redox agents for L-selectin shedding.

L-selectin is constitutively expressed by neutrophils and plays a key role in directing these cells to sites of inflammation. Upon neutrophil activation, L-selectin is rapidly and efficiently down-regulated from the cell surface by ectodomain shedding. We have directly shown that A disintegrin and metalloprotease 17 (ADAM17) is a primary and nonredundant sheddase of L-selection by activated neutrophils in vivo. Following cell activation, intracellular signals lead to the induction of ADAM17's enzymatic activity; however, the target of this inducer mechanism remains unclear. Our study provides evidence of an activation mechanism that involves the extracellular region of the mature form of cell surface ADAM17 and not its intracellular region. We demonstrate that the catalytic activity of purified ADAM17 lacking a prodomain and its intracellular region is diminished under mild reducing conditions by DTT and enhanced by H(2)O(2) oxidation. Moreover, H(2)O(2) reversed ADAM17 inhibition by DTT. The treatment of neutrophils with H(2)O(2) also induced L-selectin shedding in an ADAM17-dependent manner. These findings suggest that thiol-disulfide conversion occurring in the extracellular region of ADAM17 may be involved in its activation. An analysis of ADAM17 revealed that within its disintegrin/cysteine-rich region are two highly conserved, vicinal cysteine sulfhydryl motifs (cysteine-X-X-cysteine), which are well-characterized targets for thiol-disulfide exchange in various other proteins. Using a cell-based ADAM17 reconstitution assay, we demonstrate that the cysteine-X-X-cysteine motifs are critical for L-selectin cleavage. Taken together, our findings suggest that reduction-oxidation modifications of cysteinyl sulfhydryl groups in mature ADAM17 may serve as a mechanism for regulating the shedding of L-selectin following neutrophil stimulation.

Heterotopic caval valve implantation for the management of severe tricuspid regurgitation: a case series.

BACKGROUND: Severe tricuspid regurgitation (TR) is a complex condition that can be difficult to treat medically, and often surgical intervention is prohibited due to the high morbidity and mortality associated with this intervention. In patients who have failed maximal medical therapy and have progressive symptoms related to their severe TR, heterotopic caval valve implantation (CAVI) offers potential for symptom relief for these patients. CASE SUMMARY: We present two cases of patients with severe TR with symptoms of heart failure that were refractory to medical therapy. Due to extensive comorbidities in these patient's surgical intervention was deemed unsuitable and the decision was made to proceed with heterotopic CAVI in order to try and control their symptoms. Both patients successfully underwent the procedure and had an Edwards SAPIEN 3 valve (Edwards Lifesciences, Irvine, CA, USA) implanted in the inferior vena cava/right atrium junction. In both patients, there was improvement in the postoperative haemodynamics as measured by invasive and non-invasive methods. Successful discharge was achieved in both patients with improvement in their symptoms. DISCUSSION: Selective use of heterotopic CAVI to treat symptomatic severe TR that is refractory to medical therapy may be a viable option to improve symptoms in those patients that are unsuitable for surgical intervention.

Comparative Effectiveness of Echinocandins vs Triazoles or Amphotericin B Formulations as Initial Directed Therapy for Invasive Candidiasis in Children and Adolescents.

BACKGROUND: Invasive candidiasis is the most common invasive fungal disease in children and adolescents, but there are limited pediatric-specific antifungal effectiveness data. We compared the effectiveness of echinocandins to triazoles or amphotericin B formulations (triazole/amphotericin B) as initial directed therapy for invasive candidiasis. METHODS: This multinational observational cohort study enrolled patients aged >120 days and <18 years with proven invasive candidiasis from January 1, 2014, to November 28, 2017, at 43 International Pediatric Fungal Network sites. Primary exposure was initial directed therapy administered at the time qualifying culture became positive for yeast. Exposure groups were categorized by receipt of an echinocandin vs receipt of triazole/amphotericin B. Primary outcome was global response at 14 days following invasive candidiasis onset, adjudicated by a centralized data review committee. Stratified Mantel-Haenszel analyses estimated risk difference between exposure groups. RESULTS: Seven-hundred and fifty invasive candidiasis episodes were identified. After exclusions, 541 participants (235 in the echinocandin group and 306 in the triazole/amphotericin B group) remained. Crude failure rates at 14 days for echinocandin and triazole/amphotericin B groups were 9.8% (95% confidence intervals [CI]: 6.0% to 13.6%) and 13.1% (95% CI: 9.3% to 16.8%), respectively. The adjusted 14-day risk difference between echinocandin and triazole/amphotericin B groups was -7.1% points (95% CI: -13.1% to -2.4%), favoring echinocandins. The risk difference was -0.4% (95% CI: -7.5% to 6.7%) at 30 days. CONCLUSIONS: In children with invasive candidiasis, initial directed therapy with an echinocandin was associated with reduced failure rate at 14 days but not 30 days. These results may support echinocandins as initial directed therapy for invasive candidiasis in children and adolescents. CLINICAL TRIALS REGISTRATION: NCT01869829.

Clinical Practice Guidelines by the Infectious Diseases Society of America, American Academy of Neurology, and American College of Rheumatology: 2020 Guidelines for the Prevention, Diagnosis, and Treatment of Lyme Disease.

This evidence-based clinical practice guideline for the prevention, diagnosis, and treatment of Lyme disease was developed by a multidisciplinary panel representing the Infectious Diseases Society of America (IDSA), the American Academy of Neurology (AAN), and the American College of Rheumatology (ACR). The scope of this guideline includes prevention of Lyme disease, and the diagnosis and treatment of Lyme disease presenting as erythema migrans, Lyme disease complicated by neurologic, cardiac, and rheumatologic manifestations, Eurasian manifestations of Lyme disease, and Lyme disease complicated by coinfection with other tick-borne pathogens. This guideline does not include comprehensive recommendations for babesiosis and tick-borne rickettsial infections, which are published in separate guidelines. The target audience for this guideline includes primary care physicians and specialists caring for this condition such as infectious diseases specialists, emergency physicians, internists, pediatricians, family physicians, neurologists, rheumatologists, cardiologists and dermatologists in North America.