Practicality and Safety of Electrical Pulmonary Vein Isolation and Left Atrial Appendage Ligation in Lung Transplant Recipients With Pretransplant Atrial Fibrillation.

Background: Lung transplant surgery creates surgical pulmonary vein isolation (PVI) as a routine part of the procedure. However, many patients with pretransplant atrial fibrillation continue to have atrial fibrillation at 1 y. We hypothesized that the addition of electrical PVI and left atrial appendage isolation/ligation (LAL) to the lung transplant procedure restores sinus rhythm at 1 y in patients with pretransplant atrial fibrillation. Methods: We retrospectively reviewed all adult lung transplant recipients at the University of California Los Angeles from April 2006 to August 2021. All patients with pretransplant atrial fibrillation underwent concomitant PVI/LAL and were compared with lung transplant recipients without preoperative atrial fibrillation. In-hospital outcomes; 1-y survival; and the incidence of stroke, cardiac readmissions, repeat ablations, and sinus rhythm (composite endpoint) were examined at 1 y for the PVI/LAL cohort. Results: Sixty-one lung transplant recipients with pretransplant atrial fibrillation underwent concomitant PVI/LAL. No patient in the PVI/LAL cohort required cardiac-related readmission or catheter ablation for atrial fibrillation within 1 y of transplantation. Freedom from the composite endpoint of death, stroke, cardiac readmission, and repeat ablation for atrial fibrillation at 1 y was 85% (95% confidence interval, 73%-92%) for lung transplant recipients treated with PVI/LAL. Conclusions: The addition of PVI/LAI to the lung transplant operation in patients with pretransplant atrial fibrillation was safe and effective in maintaining sinus rhythm and baseline risk of stroke at 1 y.

Characteristics and outcomes of lung transplants performed with ex-situ lung perfusion.

BACKGROUND: Ex-situ lung perfusion (ESLP) can be used to assess and rehabilitate donor lungs, potentially expanding the donor pool. We examined the characteristics and outcomes of lung transplants performed with ESLP in the United States. METHODS: Retrospective review of the United Network for Organ Sharing registry of primary adult lung transplant recipients from February 28, 2018, to June 30, 2021, was performed, comparing baseline characteristics, in-hospital outcomes, and 1-year survival of ESLP vs no ESLP lung transplants. RESULTS: Of 8204 lung transplants, 426 (5.2%) were performed with ESLP. ESLP donors were older, more donation after circulatory death (DCD), and had lower PaO2:FiO2 (P:F) ratios. Recipients had lower lung allocation scores. ESLP lungs traveled further, had longer preservation times, and were more likely double lung transplants. Reintubation rates, extracorporeal membrane oxygenation at 72 hours, and hospital length of stay were greater in the ESLP group. On multivariable analysis, ESLP was not an independent predictor of 1-year survival. However, further analysis showed that DCD lungs managed on ESLP had worse 1-year survival compared to DCD lungs preserved with standard cold storage or with donation after brain death donor lungs. CONCLUSIONS: ESLP is used in a small percentage of lung transplants in the US and is not independently associated with 1-year survival. ESLP combined with DCD lungs, however, is associated with worse 1-year survival and warrants further investigation.

Aligning Semantic Interoperability Frameworks with the FOXS Stack for FAIR Health Data.

BACKGROUND: FAIR Guiding Principles present a synergy with the use cases for digital health records, in that clinical data need to be found, accessible within a range of environments, and data must interoperate between systems and subsequently reused. The use of HL7 FHIR, openEHR, IHE XDS, and SNOMED CT (FOXS) together represents a specification to create an open digital health platform for modern health care applications. OBJECTIVES: To describe where logical FOXS components align to the European Open Science Cloud Interoperability Framework (EOSC-IF) reference architecture for semantic interoperability. This should provide a means of defining if FOXS aligns to FAIR principles and to establish the data models and structures that support longitudinal care records as being fit to underpin scientific research. METHODS: The EOSC-IF Semantic View is a representation of semantic interoperability where meaning is preserved between systems and users. This was analyzed and cross-referenced with FOXS architectural components, mapping concepts, and objects that describe content such as catalogues and semantic artifacts. RESULTS: Majority of conceptual Semantic View components were featured within the FOXS architecture. Semantic Business Objects are composed of a range of elements such as openEHR archetypes and templates, FHIR resources and profiles, SNOMED CT concepts, and XDS document identifiers. Semantic Functional Content comprises catalogues of metadata that were also supported by openEHR and FHIR tools. CONCLUSIONS: Despite some elements of EOSC-IF being vague (e.g., FAIR Digital Object), there was a broad conformance to the framework concepts and the components of a FOXS platform. This work supports a health-domain-specific view of semantic interoperability and how this may be achieved to support FAIR data for health research via a standardized framework.

An Effective Approach for Extending Medical Data to the Cloud Through Synthetic Data Generation for Educational Environments.

When taking advantage of technology, healthcare is often met with considerably more barriers to entry than business. Cloud platforms can offer great benefits such as scalability, reduced cost and the ability to effortlessly collaborate across services, and indeed, across the world [6] yet healthcare has been slow to take advantage of these gains. This paper explores the challenges faced by healthcare, how using synthetic data can avoid the initial information governance barriers, provide the experience to effectively evaluate cloud platforms, enable effective research collaboration with education and industry, and support the digital transformation journey.

Sympathetic nervous system hyperactivity results in potent cerebral hypoperfusion in swine.

INTRODUCTION: Cerebral vasospasm is a complex disease resulting in reversible narrowing of blood vessels, stroke, and poor patient outcomes. Sympathetic perivascular nerve fibers originate from the superior cervical ganglion (SCG) to innervate the cerebral vasculature, with activation resulting in vasoconstriction. Sympathetic pathways are thought to be a significant contributor to cerebral vasospasm. OBJECTIVE: We sought to demonstrate that stimulation of SCG in swine can cause ipsilateral cerebral perfusion deficit similar to that of significant human cerebral vasospasm. Furthermore, we aimed to show that inhibition of SCG can block the effects of sympathetic-mediated cerebral hypoperfusion. METHODS: SCG were surgically identified in 15 swine and were electrically stimulated to achieve sympathetic activation. CT perfusion scans were performed to assess for changes in cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT) and time-to-maximum (TMax). Syngo.via software was used to determine regions of interest and quantify perfusion measures. RESULTS: SCG stimulation resulted in 20-30% reduction in mean ipsilateral CBF compared to its contralateral unaffected side (p < 0.001). Similar results of hypoperfusion were seen with CBV, MTT and TMax with SCG stimulation. Prior injection of lidocaine to SCG inhibited the effects of SCG stimulation and restored perfusion comparable to baseline (p > 0.05). CONCLUSION: In swine, SCG stimulation resulted in significant cerebral perfusion deficit, and this was inhibited by prior local anesthetic injection into the SCG. Inhibiting sympathetic activation by targeting the SCG may be an effective treatment for sympathetic mediated cerebral hypoperfusion.

Structural and function organization of intrathoracic extracardiac autonomic projections to the porcine heart: Implications for targeted neuromodulation therapy.

BACKGROUND: Mapping the structure/function organization of the cardiac nervous system is foundational for implementation of targeted neuromodulation-based therapeutics for the treatment of cardiac disease. OBJECTIVE: The purpose of this study was to define the spatial organization of intrathoracic parasympathetic and sympathetic efferent projections to the heart. METHODS: Yucatan mini-pigs (N = 11) were anesthetized and the thoracic cavity exposed. Electrical stimulation of the cervical vagi and stellate ganglia was performed individually, and hemodynamic responses were assessed in the intact state and after progressive debranching of each thoracic vagosympathetic trunk (VST). Subsequently, residual cardiac efferent projections arising from paravertebral chain ganglia (T1-T4) were evaluated by stimulation before and after individual ganglionic debranching. RESULTS: Stimulation of the cervical vagi decreased heart rate and contractility while prolonging the activation-recovery interval (ARI). Stimulation of the stellate ganglia increased heart rate and contractility and decreased ARI. The majority of parasympathetic and sympathetic cardiac-evoked responses were mitigated after debranching of the right VST rostral to heart, whereas the left VST demonstrated a distribution with greater dispersion and caudal intrathoracic shift compared to the right. After complete thoracic VST debranching, stimulation of the T4 paravertebral chain ganglia demonstrated residual cardiac sympathetic efferent innervation to the heart in ∼50% of animals. That response was mitigated by transecting medial ganglionic branches. CONCLUSION: The nexus point for optimum neuromodulation engagement of parasympathetic efferent projections to the heart is the cervical vagus and the T1-T2 paravertebral chain ganglia for sympathetic control. Removal of principal sympathetic efferent projections to heart requires targeting the T1-T4 regions of the paravertebral chain.

Utilising the FOXS Stack for FAIR Architected Data Access.

A FOXS stack assembles HL7 FHIR, openEHR, IHE XDS and SNOMED CT as an operational clinical data platform to build digital systems. This paper analyses its applicability for FAIR-enabled medical research based on a summary of key principles. It highlights the benefit of the blended approach to operational technology stacks for health systems, and a need for industry standard technologies to enable greater semantic coherence for primary/secondary data use.

openEHR Based Contextual Problem List.

The problem list is a key facet of the digital patient record that has historically been difficult to curate. This paper presents an implementation of a contextual problem list using openEHR. It describes the modelling approach, key model elements, and how these are assembled to underpin a Problem Oriented Medical Record. Finally, it discusses issues associated with how problem lists may be used.

Innervation and Neuronal Control of the Mammalian Sinoatrial Node a Comprehensive Atlas.

[Figure: see text].

Mechanism of ventricular premature beats elicited by left stellate ganglion stimulation during acute ischaemia of the anterior left ventricle.

AIMS: Enhanced sympathetic activity during acute ischaemia is arrhythmogenic, but the underlying mechanism is unknown. During ischaemia, a diastolic current flows from the ischaemic to the non-ischaemic myocardium. This 'injury' current can cause ventricular premature beats (VPBs) originating in the non-ischaemic myocardium, especially during a deeply negative T wave in the ischaemic zone. We reasoned that shortening of repolarization in myocardium adjacent to ischaemic myocardium increases the 'injury' current and causes earlier deeply negative T waves in the ischaemic zone, and re-excitation of the normal myocardium. We tested this hypothesis by activation and repolarization mapping during stimulation of the left stellate ganglion (LSG) during left anterior descending coronary artery (LAD) occlusion. METHODS AND RESULTS: In nine pigs, five subsequent episodes of acute ischaemia, separated by 20 min of reperfusion, were produced by occlusion of the LAD and 121 epicardial local unipolar electrograms were recorded. During the third occlusion, left stellate ganglion stimulation (LSGS) was initiated after 3 min for a 30-s period, causing a shortening of repolarization in the normal myocardium by about 100 ms. This resulted in more negative T waves in the ischaemic zone and more VPBs than during the second, control, occlusion. Following the decentralization of the LSG (including removal of the right stellate ganglion and bilateral cervical vagotomy), fewer VPBs occurred during ischaemia without LSGS. During LSGS, the number of VPBs was similar to that recorded before decentralization. CONCLUSION: LSGS, by virtue of shortening of repolarization in the non-ischaemic myocardium by about 100 ms, causes deeply negative T waves in the ischaemic tissue and VPBs originating from the normal tissue adjacent to the ischaemic border.

Rapid measurement of cardiac neuropeptide dynamics by capacitive immunoprobe in the porcine heart.

Sympathetic control of regional cardiac function occurs through postganglionic innervation from stellate ganglia and thoracic sympathetic chain. Whereas norepinephrine (NE) is their primary neurotransmitter, neuropeptide Y (NPY) is an abundant cardiac cotransmitter. NPY plays a vital role in homeostatic processes including angiogenesis, vasoconstriction, and cardiac remodeling. Elevated sympathetic stress, resulting in increased NE and NPY release, has been implicated in the pathogenesis of several cardiovascular disorders including hypertension, myocardial infarction, heart failure, and arrhythmias, which may result in sudden cardiac death. Current methods for the detection of NPY in myocardium are limited in their spatial and temporal resolution and take days to weeks to provide results [e.g., interstitial microdialysis with subsequent analysis by enzyme-linked immunosorbent assay (ELISA), high performance liquid chromatography (HPLC), or mass spectrometry]. In this study, we report a novel approach for measurement of interstitial and intravascular NPY using a minimally invasive capacitive immunoprobe (C.I. probe). The first high-spatial and temporal resolution, multichannel measurements of NPY release in vivo are provided in both myocardium and transcardiac vascular space in a beating porcine heart. We provide NPY responses evoked by sympathetic stimulation and ectopic ventricular pacing and compare these to NE release and hemodynamic responses. We extend this approach to measure both NPY and vasoactive intestinal peptide (VIP) and show differential release profiles under sympathetic stimulation. Our data demonstrate rapid and local changes in neurotransmitter profiles in response to sympathetic cardiac stressors. Future implementations include real-time intraoperative determination of cardiac neuropeptides and deployment as a minimally invasive catheter.NEW & NOTEWORTHY The sympathetic nervous system regulates cardiac function through release of neurotransmitters and neuropeptides within the myocardium. Neuropeptide Y (NPY) acts as an acute cardiac vasoconstrictor and chronically to regulate angiogenesis and cardiac remodeling. Current methodologies for the measure of NPY are not capable of providing rapid readouts on a single-sample basis. Here we provide the first in vivo methodology to report dynamic, localized NPY levels within both myocardium and vascular compartments in a beating heart.

Postoperative Physician Phone Calls as a Method to Decrease Urgent Care and Emergency Department Returns After Ambulatory General Surgery.

Unplanned returns after ambulatory surgery pose a burden to patients and health care providers alike. We hypothesized that a postoperative phone call by a physician would decrease avoidable returns to urgent care (UC) or the emergency department (ED) in the week after anorectal (AR), laparoscopic cholecystectomy (LC), inguinal hernia repair (IHR), and umbilical hernia repair (UHR) operations. A retrospective analysis from 1/2011 to 12/2015 across 14 Kaiser hospitals was conducted to determine baseline UC/ED return rates of patients pre-call. Between 10/2017 and 06/2019, physicians placed phone calls to patients within postoperative days (PODs) 1-4. The cohorts were compared using chi-squared analysis with significance determined at P < .05. In total, 276 patients received a call, with the majority placed on PODs 1-3. There were no statistically significant differences in return rates between the pre- and post-call groups. All of the AR, 50.0% of LC, 66.7% of IHR, and 50.0% of UHR patients returned prior to phone call placement. Our data indicate that a physician phone call does not help in decreasing UC/ED returns. However, it is noteworthy that many of the returns occurred pre-call placement. Future directions should be aimed at placing earlier postoperative phone calls.

Stellate ganglion stimulation causes spatiotemporal changes in ventricular repolarization in pig.

BACKGROUND: Dispersion in ventricular repolarization is relevant for arrhythmogenesis. OBJECTIVE: The purpose of this study was to determine the spatiotemporal effects of sympathetic stimulation on ventricular repolarization. METHODS: In 5 anesthetized female open-chest pigs, ventricular repolarization was measured from the anterior, lateral, and posterior walls of the left ventricle (LV) and right ventricle using up to 40 transmural plunge needles (4 electrodes each) before and after left stellate ganglion stimulation (LSGS) and right stellate ganglion stimulation. In addition, LSGS was performed in 3 pigs (2 male, 1 female) before and after verapamil (5-10 mg/h) administration. RESULTS: LSGS yielded a biphasic response in repolarization in the lateral and posterior walls of the LV, with prolongation at ∼5 seconds (10 ± 1.5 ms) and shortening at 20-30 seconds of stimulation (-28.9 ± 4.4 ms) during a monotonic pressure increase. While the initial prolongation was abolished by verapamil, late shortening was augmented. Sequential transections of the vagal nerve and stellate ganglia augmented repolarization dispersion responses to LSGS in 2 of 5 hearts. An equal pressure increase by aortic occlusion resulted in a homogeneous shortening of repolarization in the LV, and the effects were smaller than those during LSGS. Right stellate stimulation shortened repolarization mainly in the anterior LV wall, but the effects were smaller than those of LSGS. CONCLUSION: LSGS first prolongs (through the L-type calcium current) and then shortens repolarization. The effect of LSGS was prominent in the posterior and lateral, not the anterior, LV walls.

Evaluating the Relevance of the 2013 Tokyo Guidelines for the Diagnosis and Management of Cholecystitis.

BACKGROUND: The 2013 Tokyo Guidelines (TG13) are used to diagnose, grade severity, and guide management of acute cholecystitis (AC). The aim of our study was to verify the diagnostic criteria, severity assessment, and management protocols based on the TG13. STUDY DESIGN: Our prospectively maintained emergency general surgery registry was used to review patients who had a surgical consultation for right upper quadrant pain (from 2013 to 2015). Diagnosis and severity were graded based on TG13 and compared with pathology reports. Our institutional management protocols were compared with TG13. RESULTS: Nine hundred and fifty-two patients were analyzed, of which 857 had biliary diseases. Mean age was 42 ± 18 years and 67% were female. Seven hundred and seventy-nine had a cholecystectomy, 15 underwent cholecystostomy tube placement, and 63 patients were managed conservatively. Only 4% were febrile on presentation and 51% of patients had leukocytosis. Fifty-nine percent of patients did not have any signs of AC on ultrasonography. The TG13 criteria had a sensitivity of 53% for diagnosing AC (definitive 27%, suspected 26%, and undiagnosed 47%) when compared with the final pathology report; 92.5% of patients with grade I, 93% with grade II, and even 64% with grade III, underwent cholecystectomy safely at our institute. There were no differences in complication rates (3.7% vs 4.7%; p = 0.81), return to operating room rates (0.6% vs 0.7%; p = 0.95), or mortality rates (0.3% vs 0%; p = 0.96) between grade I and grade II patients who underwent early cholecystectomy. CONCLUSIONS: The TG13 diagnostic criteria lack sensitivity and missed more than half of the patients with AC, as many patients lack clinical signs (fever and leukocytosis). The TG13 recommendations for conservative management and delayed cholecystectomy in grade II and grade III disease are not warranted.

Quality of Life and Functional Outcomes after Multiligament Knee Reconstruction.

We aimed to determine factors that affect the quality of life of patients undergoing a standardized surgical and postoperative management protocol for knee dislocations. A total of 31 patients (33 knees) were included in this study. We contacted patients at a minimum of 12 months postoperatively (mean: 38 months; range, 12-111 months) and administered the previously validated Multiligament Quality of Life questionnaire (ML-QOL), 2000 International Knee Documentation Committee Subjective Knee Form (IKDC), and Lysholm Knee Scoring Scale. We performed independent two-sample t-tests and age-adjusted multivariable linear regression analysis to examine the difference in these scores. Patients who underwent previous knee ligament surgery had significantly worse mean ML-QOL scores relative to patients who did not undergo previous knee ligament surgery (114.3 versus 80.4; p = 0.004) (higher score indicates worse quality of life). All other differences in the ML-QOL scores were not statistically significant. IKDC and Lysholm scores did not differ significantly with regards to the studied variables. Among patients with no previous knee ligament surgery, patients undergoing surgery within 3 weeks of injury had significantly worse mean ML-QOL scores relative to patients undergoing surgery greater than 3 weeks after their injury (98.7 versus 74.7; p = 0.042) and patients with Schenck classification of III or IV had significantly worse mean ML-QOL scores relative to patient with a Schenck classification of I or II (88.7 versus 62.9; p = 0.015). We found that patients with a previous history of knee ligament surgery had a significantly worse quality of life relative to those with no history of knee ligament surgery. This is a level III, retrospective cohort study.

The effect of a rapid response team on major clinical outcome measures in a community hospital.

OBJECTIVE: To determine the effect of a rapid response system composed primarily of a rapid response team led by physician assistants on the rates of in-hospital cardiac arrests, total and unplanned intensive care unit admissions, and hospital mortality. DESIGN: Prospective, controlled, before and after trial. SETTING: A 350-bed nonteaching community hospital. PATIENTS: All adult patients admitted to the hospital from May 1, 2005, to October 1, 2006. INTERVENTIONS: We introduced a hospital-wide rapid response system that included a rapid response team (RRT) led by physician assistants with specialized critical care training. MEASUREMENTS AND MAIN RESULTS: We measured the incidence of cardiac arrests that occurred outside of the intensive care unit, total intensive care unit admissions, unplanned intensive care unit admissions, intensive care unit length of stay, and the total hospital mortality rate occurring over the study period. There were 344 RRT calls during the study period. In the 5 months before the rapid response system began, there were an average of 7.6 cardiac arrests per 1,000 discharges per month. In the subsequent 13 months, that figure decreased to 3.0 cardiac arrests per 1,000 discharges per month. Overall hospital mortality the year before the rapid response system was 2.82% and decreased to 2.35% by the end of the RRT year. The percentage of intensive care unit admissions that were unplanned decreased from 45% to 29%. Linear regression analysis of key outcome variables showed strong associations with the implementation of the rapid response system, as did analysis of variables over time. Physician assistants successfully managed emergency airway situations without assistance in the majority of cases. CONCLUSIONS: The deployment of an RRT led by physician assistants with specialized skills was associated with significant decreases in rates of in-hospital cardiac arrest and unplanned intensive care unit admissions.

Hydroxyurea-induced dermatomyositis-like eruption.

Hydroxyurea is a cytotoxic chemotherapeutic agent used for myelodysplasia. The adverse cutaneous effects due to hydroxyurea include leg ulcers, hyperpigmentation of the skin and nails, a lichen planus-like eruption, lupus erythematosus, and a dermatomyositis-like eruption. We present a case of hydroxyurea-induced dermatomyositis-like eruption and review the features of this entity as previously reported.