Left Common Iliac Vein Stenting in a Case of Postural Orthostatic Tachycardia Syndrome/Pelvic Pain Overlap.

Postural orthostatic tachycardia syndrome (POTS) is mainly characterized by orthostatic intolerance and positional tachycardia although it frequently involves a myriad of non-specific symptoms that seem to overlap with existing medical conditions. Recent efforts have been made to further classify subtypes of POTS and associated conditions to better delineate underlying pathophysiology in an effort to guide diagnosis and tailor treatment. Here, we present a 22-year-old female with debilitating symptoms of POTS who reported pelvic pain on review of systems and underwent vascular ultrasound of the inferior vena cava, iliac veins, and bilateral lower extremities which revealed the characteristic left common iliac vein compression of May-Thurner syndrome prompting venous stenting which provided systemic symptomatic relief.

Redefining the Roles of Aspirin across the Spectrum of Cardiovascular Disease Prevention.

Even before its role in platelet inhibition was fully characterized in the 1980s, aspirin had been incorporated into the cardiovascular disease care algorithm. Early trials examining its use in unstable angina and acute myocardial infarction revealed evidence of its protective role in the secondary prevention of atherosclerotic cardiovascular disease (ASCVD). Large trials assessing use in the primary prevention setting and optimal dosing regimens were studied in the late 1990s and early 2000s. As a cornerstone of cardiovascular care, aspirin was incorporated into primary and secondary ASCVD prevention guidelines in the United States and mechanical heart valve guidelines. However, in recent years, with significant advances in medical and interventional ASCVD therapies, scrutiny has been placed on the bleeding profile of aspirin, and guidelines have adapted to new evidence. Updates in primary prevention guidelines reserve aspirin only for patients at higher ASCVD risk and low bleeding risk - though questions remain in ASCVD risk assessment as risk-enhancing factors have proven difficult to incorporate on a population level. New thoughts regarding aspirin use in secondary prevention - especially with the concomitant use of anticoagulants - have altered recommendations as additional data accrued. Finally, a recommendation for aspirin and vitamin K antagonists with mechanical heart valves has been modified. Despite aspirin losing a foothold in cardiovascular care, new evidence has strengthened claims for its use in women at high risk for preeclampsia.

Heart transplantation in Val142Ile mutation in the modern era: A single center experience.

Little is known about the post heart transplantation management of extra cardiac manifestations in patients with hereditary transthyretin amyloid cardiomyopathy (hATTR-CM) in the new era of disease modifying treatment for ATTR amyloidosis. This is a retrospective study of all patients with hATTR-CM associated with the Val142Ile variant who underwent heart transplantation (HT) from January 2014 to February 2022. All 10 patients with the Val142Ile mutation were successfully transplanted, with a 1 year survival post heart transplantation (HT) of 90%, comparable to an age, sex, and race matched cohort of patients transplanted for non-amyloid indications. However, 4 (40%) of these patients developed progressive extracardiac manifestations requiring initiation of TTR silencer therapy with the small interfering RNA (siRNA) drug patisiran, which was well tolerated with no significant side effects in this population. We recommend formal neurologic evaluation and assessment of extracardiac manifestations annually as part of routine post-transplant care, and disease modifying therapy, aimed at TTR stabilization or silencing, should be initiated in the context of previously untreated extracardiac manifestations or evidence of subclinical neuropathy to prevent progression.

Ventricular arrhythmia burden and implantable cardioverter-defibrillator outcomes in transthyretin cardiac amyloidosis.

BACKGROUND: As targeted treatments for amyloid transthyretin cardiomyopathy (ATTR-CM) are becoming available, we aim to characterize the rates of ventricular arrhythmias (VAs), implantable cardioverter-defibrillator (ICD) utilization, and their impact on survival. METHODS: This is a retrospective cohort study of 130 patients with ATTR-CM diagnosed at Emory University's Cardiac Amyloidosis Center between April 2012 and September 2020. VAs were defined as nonsustained or sustained ventricular tachycardia and ventricular fibrillation. RESULTS: Of 130 patients, 42 had wild-type disease (wtATTR) and 88 had hereditary variants (hATTR), most commonly Val122Ile (89%). At ATTR-CM diagnosis, 80 (62%) patients had EF ≤ 40% consistent with systolic heart failure. Of the 69 (53%) patients with documented VAs significantly higher rates occurred among those with EF ≤ 40% compared with EF > 40% (67% vs. 28%, p = .001). Thirty-two patients (25 hATTR, 7 wtATTR) had primary prevention ICDs implanted. Eight (25%) of these patients received appropriate ICD therapy while two (6%) experienced inappropriate therapy. Comparing patients with EF ≤ 35% with and without ICDs did not reveal any survival difference (3.3 ± 0.5 vs. 2.8 ± 0.4 years, p = .699). CONCLUSIONS: High rates of VAs and appropriate ICD therapy were found among a unique cohort of largely hereditary ATTR-CM patients with a high rate of systolic heart failure.

Here's the rub: A case of constrictive pericarditis in an adult with cystic fibrosis.

We present a rare coexistence of constrictive pericarditis in a patient with cystic fibrosis. Careful attention to cardiac friction rub auscultated on initial examination prompted echocardiography revealing constrictive pericarditis further confirmed by cardiac magnetic resonance imaging that allowed for dedicated treatment in addition to management of his concurrent respiratory infection.

Flexor tendon injuries: Repair & Rehabilitation.

Flexor tendon injuries are common and occur mostly by penetrating trauma. Suspected flexor tendon injuries require a thorough clinical assessment and often are not isolated injuries. A detailed understanding of flexor tendon anatomy and spatial relationships is essential, especially when repairing multi-tendon injuries. Principles of flexor tendon repair include a strong suture construct, minimising gap formation between tendon ends, preserving tendon blood supply and providing a smooth repair interface. Moreover, adequate exposure of the zone of injury using full-thickness skin flaps and preservation of neurovascular and pulley structures is essential. In this article an overview of contemporary management strategies is presented. Today's hand surgeons and therapists can choose from a variety of treatment options when managing these important and potentially life-changing injuries.

Ablation of manifest septal accessory pathways: a single-center experience.

BACKGROUND: Ablation of septal accessory pathways (SAPs) is associated with an increased risk of heart block. Data on outcomes of SAP ablation in adults are limited. OBJECTIVES: To describe outcomes of SAP ablation in our center. METHODS: Patients with Wolff-Parkinson-White syndrome (WPW) undergoing an EP study at our center between January 2008 and August 2019 were identified from our institutional database. Location of the pathway was noted as anteroseptal (AS), midseptal (MS), or posteroseptal (PS). Outcomes of the ablation including success, complication rates, and recurrences were also recorded. RESULTS: Thirty-three patients with SAP underwent 35 EP studies: AS (n = 13), MS (n = 5), and PS (n = 15). Thirty pathways were targeted for ablation, two of which required a 2nd procedure resulting in 32 attempts at ablation in 30 patients. In the remaining 3 patients, SAP did not have malignant features and were not targeted for ablation. Single-procedure success rate was 28/30 (93.33%): 9/10 AS, 5/5 MS, and 14/15 PS ablations. One AS pathway was successfully ablated during a 2nd procedure. Two complications were observed: 1 pericardial effusion in a patient who underwent epicardial mapping and ablation of both PS and right free wall APs. Additionally, transient 2:1 AV block occurred during an MS pathway ablation that recovered during follow-up and did not require permanent pacing procedure. CONCLUSION: In this single-center experience, ablation of manifest SAP was associated with high success rates and low complication rates. No instances of permanent heart block requiring pacing occurred.

Training in Implementation Practice Leadership (TRIPLE): evaluation of a novel practice change strategy in behavioral health organizations.

BACKGROUND: Effective leadership for organizational change is critical to the implementation of evidence-based practices (EBPs). As organizational leaders in behavioral health organizations often are promoted from within the agency for their long-standing, effective work as counselors, they may lack formal training in leadership, management, or practice change. This study assesses a novel implementation leadership training designed to promote leadership skills and successful organizational change specific to EBP implementation. METHODS: We conducted a pre-post outcome evaluation of the Training in Implementation Practice Leadership (TRIPLE), delivered via three in-person, half-day training sessions, with interim coaching and technical support. Sixteen mid-level leaders (75% female, 94% Caucasian, mean age 37 years) from 8 substance abuse treatment agencies participated. Professional roles included clinical managers, quality improvement coordinators, and program directors. Participants completed surveys prior to the first and following the final session. At both time points, measures included the Implementation Leadership Scale, Implementation Climate Scale, and Organizational Readiness for Implementing Change Scale. At post-test, we added the Training Acceptability and Appropriateness Scale (TAAS), assessing participant satisfaction with the training. Qualitative interviews were conducted 6 to 8 months after the training. RESULTS: Most participants (86% and 79%, respectively) reported increased implementation leadership skills and implementation climate; paired samples t tests indicated these pre-post increases were statistically significant. Implementation leadership scores improved most markedly on the Proactive and Knowledgeable subscales. For implementation climate, participants reported the greatest increases in educational support and recognition for using EBP. Post-test scores on the TAAS also indicated that participants found the training program to be highly acceptable and appropriate for their needs. Qualitative results supported positive outcomes of training that resulted in both increased organizational implementation as well as leadership skills of participants. CONCLUSIONS: This training program represents an innovative, effective, and well-received implementation strategy for emerging behavioral healthcare leaders seeking to adopt or improve the delivery of EBPs. Reported implementation leadership skills and implementation climate improved following the training program, suggesting that TRIPLE may have helped fulfill a critical need for emerging behavioral healthcare leaders.

Transfacet and Transpedicular Posterior Approaches to Thoracic Disc Herniations: Consecutive Case Series of 24 Patients.

OBJECTIVE: Various approaches are advocated for symptomatic thoracic disc herniation (TDH). The aim of this series is to demonstrate the feasibility, safety, and results of posterior transfacet or transpedicular approaches for excision of all types of extradural TDH. We report a consecutive series of patients undergoing posterior approach surgery for TDH. METHODS: Twenty-four patients (17 women, 7 men) underwent surgery at 25 disc levels. Mean age was 56.3 years (range, 23-79 years). A posterior transfacet or transpedicular approach was used. Patients presented with myelopathy (n = 21, 88%), radiculopathy (n = 8, 33%), sphincter dysfunction (n = 16, 67%), and axial back pain (n = 10, 43%). Preoperative imaging revealed 7 (30%) central, 14 (61%) calcified, and 10 (43%) large disc herniations. The mean follow-up period was 6.0 months (range, 2-36 months). RESULTS: Eighteen patients underwent unilateral approach surgery (5 transfacet and 13 transfacet plus transpedicular), and 7 patients required bilateral approach laminectomy for unilateral (n = 4) or bilateral (n = 3) discectomy. One patient required unplanned reoperation for resection of residual disc. Average operative time was 95 minutes (range, 40-175 minutes). Mean hospital stay was 4.9 days (range, 2-35 days). There were no major complications. Postoperative Frankel scores were maintained or improved in all patients at last review. CONCLUSIONS: TDH including large central calcified discs can be safely removed through posterior transfacet or transpedicular approaches with reduced morbidity in comparison with more invasive anterior approaches. Careful microsurgical technique and use of specialized instruments are important for successful excision of TDH from a posterior approach.

Morphological and Biophysical Determinants of the Intracellular and Extracellular Waveforms in Nigral Dopaminergic Neurons: A Computational Study.

Action potentials (APs) in nigral dopaminergic neurons often exhibit two separate components: the first reflecting spike initiation in the dendritically located axon initial segment (AIS) and the second the subsequent dendro-somatic spike. These components are separated by a notch in the ascending phase of the somatic extracellular waveform and in the temporal derivative of the somatic intracellular waveform. Still, considerable variability exists in the presence and magnitude of the notch across neurons. To systematically address the contribution of AIS, dendritic and somatic compartments to shaping the two-component APs, we modeled APs of previously in vivo electrophysiologically characterized and 3D-reconstructed male mouse and rat dopaminergic neurons. A parsimonious two-domain model, with high (AIS) and lower (dendro-somatic) Na+ conductance, reproduced the notch in the temporal derivatives, but not in the extracellular APs, regardless of morphology. The notch was only revealed when somatic active currents were reduced, constraining the model to three domains. Thus, an initial AIS spike is followed by an actively generated spike by the axon-bearing dendrite (ABD), in turn followed mostly passively by the soma. The transition from being a source compartment for the AIS spike to a source compartment for the ABD spike satisfactorily explains the extracellular somatic notch. Larger AISs and thinner ABD (but not soma-to-AIS distance) accentuate the AIS component. We conclude that variability in AIS size and ABD caliber explains variability in AP extracellular waveform and separation of AIS and dendro-somatic components, given the presence of at least three functional domains with distinct excitability characteristics.SIGNIFICANCE STATEMENT Midbrain dopamine neurons make an important contribution to circuits mediating motivation and movement. Understanding the basic rules that govern the electrical activity of single dopaminergic neurons is therefore essential to reveal how they ultimately contribute to movement and motivation as well as what goes wrong in associated disorders. Our computational study focuses on the generation and propagation of action potentials and shows that different morphologies and excitability characteristics of the cell body, dendrites and proximal axon can explain the diversity of action potentials shapes in this population. These compartments likely make differential contributions both to normal dopaminergic signaling and could potentially underlie pathological dopaminergic signaling implicated in addiction, schizophrenia, Parkinson's disease, and other disorders.

Combining mGRASP and Optogenetics Enables High-Resolution Functional Mapping of Descending Cortical Projections.

We have applied optogenetics and mGRASP, a light microscopy technique that labels synaptic contacts, to map the number and strength of defined corticocollicular (CC) connections. Using mGRASP, we show that CC projections form small, medium, and large synapses, and both the number and the distribution of synapse size vary among the IC regions. Using optogenetics, we show that low-frequency stimulation of CC axons expressing channelrhodopsin produces prolonged elevations of the CC miniature EPSC (mEPSC) rate. Functional analysis of CC mEPSCs reveals small-, medium-, and large-amplitude events that mirror the synaptic distributions observed with mGRASP. Our results reveal that descending ipsilateral projections dominate CC feedback via an increased number of large synaptic contacts, especially onto the soma of IC neurons. This study highlights the feasibility of combining microscopy (i.e., mGRASP) and optogenetics to reveal synaptic weighting of defined projections at the level of single neurons, enabling functional connectomic mapping in diverse neural circuits.

Building capacity for dissemination and implementation research: one university's experience.

BACKGROUND: While dissemination and implementation (D&I) science has grown rapidly, there is an ongoing need to understand how to build and sustain capacity in individuals and institutions conducting research. There are three inter-related domains for capacity building: people, settings, and activities. Since 2008, Washington University in St. Louis has dedicated significant attention and resources toward building D&I research capacity. This paper describes our process, challenges, and lessons with the goal of informing others who may have similar aims at their own institution. ACTIVITIES: An informal collaborative, the Washington University Network for Dissemination and Implementation Research (WUNDIR), began with a small group and now has 49 regular members. Attendees represent a wide variety of settings and content areas and meet every 6 weeks for half-day sessions. A logic model organizes WUNDIR inputs, activities, and outcomes. A mixed-methods evaluation showed that the network has led to new professional connections and enhanced skills (e.g., grant and publication development). As one of four, ongoing, formal programs, the Dissemination and Implementation Research Core (DIRC) was our first major component of D&I infrastructure. DIRC's mission is to accelerate the public health impact of clinical and health services research by increasing the engagement of investigators in later stages of translational research. The aims of DIRC are to advance D&I science and to develop and equip researchers with tools for D&I research. As a second formal component, the Washington University Institute for Public Health has provided significant support for D&I research through pilot projects and a small grants program. In a third set of formal programs, two R25 training grants (one in mental health and one in cancer) support post-doctoral scholars for intensive training and mentoring in D&I science. Finally, our team coordinates closely with D&I functions within research centers across the university. We share a series of challenges and potential solutions. CONCLUSION: Our experience in developing D&I research at Washington University in St. Louis shows how significant capacity can be built in a relatively short period of time. Many of our ideas and ingredients for success can be replicated, tailored, and improved upon by others.

Tubular microdiscectomy: techniques, complication avoidance, and review of the literature.

OBJECTIVE Microendoscopic discectomy is a minimally invasive surgery technique that was initially described in 1997. It allows surgeons to work with 2 hands through a small-diameter, operating table-mounted tubular retractor, and to apply standard microsurgical techniques in which a small skin incision and minimal muscle dissection are used. Whether the surgeon chooses to use an endoscope or a microscope for visualization, the technique uses the same type of retractor and is thus called tubular microdiscectomy. The goal in this study was to review the current literature, examine the level of evidence supporting tubular microdiscectomy, and describe surgical techniques for complication avoidance. METHODS The authors performed a systematic PubMed review using the terms "microdiscectomy trial," "tubular and open microdiscectomy," "microendoscopic open discectomy," and "minimally invasive open microdiscectomy OR microdiskectomy." Of 317 references, 10 manuscripts were included for analysis based on study design, relevance, and appropriate comparison of open to tubular discectomy. RESULTS Similar and very favorable clinical outcomes can be expected from tubular and standard microdiscectomy. Studies have demonstrated equivalent operating times for both procedures, with lower blood loss and shorter hospital stays associated with tubular microdiscectomy. Furthermore, postoperative analgesic usage has been shown to be significantly lower after tubular microdiscectomy. Overall rates of complications are no different for tubular and standard microdiscectomy. CONCLUSIONS Prospective randomized trials have been used to evaluate outcomes of common minimally invasive lumbar spine procedures. For lumbar discectomy, Level I evidence supports equivalently good outcomes for tubular microdiscectomy compared with standard microdiscectomy. Likewise, Level I data indicate similar safety profiles and may indicate lower blood loss for tubular microdiscectomy. Future studies should examine the comparative value of these procedures.

Epilepsy surgery for pediatric low-grade gliomas of the cerebral hemispheres: neurosurgical considerations and outcomes.

INTRODUCTION: Pediatric low-grade tumors are found in roughly 1-3 % of patients with childhood epilepsy; seizures associated with these tumors are often medically refractory and often present a significant morbidity, greater than the presence of the tumor itself. DISCUSSION: The unique morbidity of the seizures often requires an epilepsy surgical approach over a standard oncologic resection to achieve a reduction in morbidity for the child. Multiple quality-of-life studies have shown that unless a patient is seizure-free, they remain disabled throughout their life; the best way to achieve this in our patient population is with a multidisciplinary team approach with treatment goals focusing primarily on the epilepsy. CONCLUSION: In those patients treated with gross total resection, roughly 80 % will have an Engel class I outcome and 90 % will achieve some reduction in seizure frequency with a significant improvement in quality of life.

Trans-spliced Cas9 allows cleavage of HBB and CCR5 genes in human cells using compact expression cassettes.

CRISPR/Cas9 systems have been used in a wide variety of biological studies; however, the large size of CRISPR/Cas9 presents challenges in packaging it within adeno-associated viruses (AAVs) for clinical applications. We identified a two-cassette system expressing pieces of the S. pyogenes Cas9 (SpCas9) protein which splice together in cellula to form a functional protein capable of site-specific DNA cleavage. With specific CRISPR guide strands, we demonstrated the efficacy of this system in cleaving the HBB and CCR5 genes in human HEK-293T cells as a single Cas9 and as a pair of Cas9 nickases. The trans-spliced SpCas9 (tsSpCas9) displayed ~35% of the nuclease activity compared with the wild-type SpCas9 (wtSpCas9) at standard transfection doses, but had substantially decreased activity at lower dosing levels. The greatly reduced open reading frame length of the tsSpCas9 relative to wtSpCas9 potentially allows for more complex and longer genetic elements to be packaged into an AAV vector including tissue-specific promoters, multiplexed guide RNA expression, and effector domain fusions to SpCas9. For unknown reasons, the tsSpCas9 system did not work in all cell types tested. The use of protein trans-splicing may help facilitate exciting new avenues of research and therapeutic applications through AAV-based delivery of CRISPR/Cas9 systems.