Expanding the Paradigm for Cardiovascular Palliative Care.

Cardiovascular disease (CVD) is the leading cause of death worldwide. Despite medical advances, patients with CVD experience high morbidity and mortality rates, affecting their quality of life and death. Among CVD conditions, palliative care has been studied mostly in patients with heart failure, where palliative care interventions have been associated with improvements in patient-centered outcomes, including quality of life, end-of-life care, and health care use. Although palliative care is now incorporated into the American Heart Association/American College of Cardiology/Heart Failure Society of America guidelines for heart failure, the role of palliative care for non-heart failure CVD remains uncertain. Across all causes of CVD, palliative care can play an important role in all domains of CVD care from initial diagnosis to terminal care. In addition to general cardiovascular palliative care practices applicable to all areas, disease-specific palliative care needs may warrant individualized palliative care models. In this review, we discuss the role of cardiovascular palliative care for ischemic heart disease, valvular disease, arrhythmias, peripheral artery disease, and adult congenital heart disease. Although there are multiple barriers to cardiovascular palliative care, we recommend a framework for studying and developing cardiovascular palliative care models to improve patient-centered goal-concordant care for this underserved patient population.

MRI Assessment of Myocardial Deformation for Risk Stratification of Major Arrhythmic Events in Patients With Non-Ischemic Cardiomyopathy Eligible for Primary Prevention Implantable Cardioverter Defibrillators.

BACKGROUND: Implantable cardioverter-defibrillator (ICD) intervention is an established prophylactic measure. Identifying high-benefit patients poses challenges. PURPOSE: To assess the prognostic value of cardiac magnetic resonance imaging (MRI) parameters including myocardial deformation for risk stratification of ICD intervention in non-ischemic cardiomyopathy (NICM) while accounting for competing mortality risk. STUDY TYPE: Retrospective and prospective. POPULATION: One hundred and fifty-nine NICM patients eligible for primary ICD (117 male, 54 ± 13 years) and 49 control subjects (38 male, 53 ± 5 years). FIELD STRENGTH/SEQUENCE: Balanced steady state free precession (bSSFP) and three-dimensional phase-sensitive inversion-recovery late gadolinium enhancement (LGE) sequences at 1.5 T or 3 T. ASSESSMENT: Patients underwent MRI before ICD implantation and were followed up. Functional parameters, left ventricular global radial, circumferential and longitudinal strain, right ventricular free wall longitudinal strain (RV FWLS) and left atrial strain were measured (Circle, cvi42). LGE presence was assessed visually. The primary endpoint was appropriate ICD intervention. Models were developed to determine outcome, with and without accounting for competing risk (non-sudden cardiac death), and compared to a baseline model including LGE and clinical features. STATISTICAL TESTS: Wilcoxon non-parametric test, Cox's proportional hazards regression, Fine-Gray competing risk model, and cumulative incidence functions. Harrell's c statistic was used for model selection. A P value <0.05 was considered statistically significant. RESULTS: Follow-up duration was 1176 ± 960 days (median: 896). Twenty-six patients (16%) met the primary endpoint. RV FWLS demonstrated a significant difference between patients with and without events (-12.5% ± 5 vs. -16.4% ± 5.5). Univariable analyses showed LGE and RV FWLS were significantly associated with outcome (LGE: hazard ratio [HR] = 3.69, 95% CI = 1.28-10.62; RV FWLS: HR = 2.04, 95% CI = 1.30-3.22). RV FWLS significantly improved the prognostic value of baseline model and remained significant in multivariable analysis, accounting for competing risk (HR = 1.73, 95% CI = 1.12-2.66). DATA CONCLUSIONS: In NICM, RV FWLS may provide additional predictive value for predicting appropriate ICD intervention. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 5.

Pharmacokinetic similarity of switching SAR341402 insulin aspart biosimilar and NovoLog insulin aspart versus continuous use of NovoLog in adults with type 1 diabetes: The GEMELLI X trial.

AIM: To assess whether multiple switches between SAR341402 biosimilar insulin aspart (SAR-Asp) and the insulin aspart reference product (NovoLog; NN-Asp) leads to equivalent pharmacokinetic (PK) exposure compared with continuous use of NN-Asp in adults with type 1 diabetes (T1D). MATERIALS AND METHODS: This multicentre, open-label, phase 3 study randomized (1:1) 210 subjects with T1D treated with once-daily insulin glargine U100 as basal insulin to four 4-week periods of alternating multiple daily injections of SAR-Asp and NN-Asp (NN-Asp for the first 4 weeks, SAR-Asp in the last 4 weeks; switching group) versus 16 weeks of continuous NN-Asp (non-switching group). At week 16, a single dose (0.15 U/kg) of SAR-Asp in the switching group (n = 95) or NN-Asp in the non-switching group (n = 105) was given in the morning before breakfast. Primary PK endpoints were area under the plasma concentration curve (AUC) and maximum plasma concentration (Cmax ) of SAR-Asp versus NN-Asp after the single dose at week 16. RESULTS: The extent of PK exposure was similar between the two treatments (SAR-Asp in the switching group and NN-Asp in the non-switching group) at week 16, with point estimates of treatment ratios close to 1. The 90% confidence intervals for AUC treatment ratios were contained within 0.8-1.25. For Cmax in the primary analysis set, the upper confidence limit was 1.32. This was because of the profiles of three participants with implausible high values. A prespecified sensitivity analysis excluding implausible values showed results contained within 0.8-1.25. CONCLUSIONS: PK exposure of SAR-Asp (switching group) and reference NN-Asp (non-switching group) were similar, supporting interchangeability between these two insulin aspart products.

Brain Shift during Staged Deep Brain Stimulation for Movement Disorders.

INTRODUCTION: Deep brain stimulation (DBS) is a routine neurosurgical procedure utilized to treat various movement disorders including Parkinson's disease (PD), essential tremor (ET), and dystonia. Treatment efficacy is dependent on stereotactic accuracy of lead placement into the deep brain target of interest. However, brain shift attributed to pneumocephalus can introduce unpredictable inaccuracies during DBS lead placement. This study aimed to determine whether intracranial air is associated with brain shift in patients undergoing staged DBS surgery. METHODS: We retrospectively evaluated 46 patients who underwent staged DBS surgery for PD, ET, and dystonia. Due to the staged nature of DBS surgery at our institution, the first electrode placement is used as a concrete fiducial marker for movement in the target location. Postoperative computed tomography (CT) images after the first electrode implantation, as well as preoperative, and postoperative CT images after the second electrode implantation were collected. Images were analyzed in stereotactic targeting software (BrainLab); intracranial air was manually segmented, and electrode shift was measured in the x, y, and z plane, as well as a Euclidian distance on each set of merged CT scans. A Pearson correlation analysis was used to determine the relationship between intracranial air and brain shift, and student's t test was used to compare means between patients with and without radiographic evidence of intracranial air. RESULTS: Thirty-six patients had pneumocephalus after the first electrode implantation, while 35 had pneumocephalus after the second electrode implantation. Accumulation of intracranial air following the first electrode implantation (4.49 ± 6.05 cm3) was significantly correlated with brain shift along the y axis (0.04 ± 0.35 mm; r (34) = 0.36; p = 0.03), as well as the Euclidean distance of deviation (0.57 ± 0.33 mm; r (34) = 0.33; p = 0.05) indicating statistically significant shift on the ipsilateral side. However, there was no significant correlation between intracranial air and brain shift following the second electrode implantation, suggesting contralateral shift is minimal. Furthermore, there was no significant difference in brain shift between patients with and without radiographic evidence of intracranial air following both electrode implantation surgeries. CONCLUSION: Despite observing volumes as high as 22.0 cm3 in patients with radiographic evidence of pneumocephalus, there was no significant difference in brain shift when compared to patients without pneumocephalus. Furthermore, the mean magnitude of brain shift was <1.0 mm regardless of whether pneumocephalus was presenting, suggesting that intracranial air accumulation may not produce clinical significant brain shift in our patients.

Pilot Study to Investigate the Use of In-Clinic Sensing to Identify Optimal Stimulation Parameters for Deep Brain Stimulation Therapy in Parkinson's Disease.

BACKGROUND: Deep brain stimulation (DBS) programming is time intensive. Recent advances in sensing technology of local field potentials (LFPs) may enable improvements. Few studies have compared the use of this technology with standard of care. OBJECTIVE/HYPOTHESIS: Sensing technology of subthalamic nucleus (STN) DBS leads in Parkinson's disease (PD) is reliable and predicts the optimal contacts and settings as predicted by clinical assessment. MATERIALS AND METHODS: Five subjects with PD (n = 9 hemispheres) with bilateral STN DBS and sensing capable battery replacement were recruited. An LFP sensing review of all bipolar contact pairs was performed three times. Contact with the maximal beta peak power (MBP) was then clinically assessed in a double-blinded fashion, and five conditions were tested: 1) entry settings, 2) off stimulation, 3) MBP at 30 µs, 4) MBP at 60 µs, and 5) MBP at 90 µs. RESULTS: Contact and frequency of the MBP power in all hemispheres did not differ across sessions. The entry settings matched with the contact with the MBP power in 5 of 9 hemispheres. No clinical difference was evident in the stimulation conditions. The clinician and subject preferred settings determined by MBP power in 7 of 9 and 5 of 7 hemispheres, respectively. CONCLUSIONS: This study indicates that STN LFPs in PD recorded directly from contacts of the DBS lead provide consistent recordings across the frequency range and a reliably detected beta peak. Furthermore, programming based on the MBP power provides at least clinical equivalence to standard of care programming with STN DBS.

Oscillatory beta dynamics inform biomarker-driven treatment optimization for Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by loss of dopaminergic neurons and dysregulation of the basal ganglia. Cardinal motor symptoms include bradykinesia, rigidity, and tremor. Deep brain stimulation (DBS) of select subcortical nuclei is standard of care for medication-refractory PD. Conventional open-loop DBS delivers continuous stimulation with fixed parameters that do not account for a patient's dynamic activity state or medication cycle. In comparison, closed-loop DBS, or adaptive DBS (aDBS), adjusts stimulation based on biomarker feedback that correlates with clinical state. Recent work has identified several neurophysiological biomarkers in local field potential recordings from PD patients, the most promising of which are 1) elevated beta (∼13-30 Hz) power in the subthalamic nucleus (STN), 2) increased beta synchrony throughout basal ganglia-thalamocortical circuits, notably observed as coupling between the STN beta phase and cortical broadband gamma (∼50-200 Hz) amplitude, and 3) prolonged beta bursts in the STN and cortex. In this review, we highlight relevant frequency and time domain features of STN beta measured in PD patients and summarize how spectral beta power, oscillatory beta synchrony, phase-amplitude coupling, and temporal beta bursting inform PD pathology, neurosurgical targeting, and DBS therapy. We then review how STN beta dynamics inform predictive, biomarker-driven aDBS approaches for optimizing PD treatment. We therefore provide clinically useful and actionable insight that can be applied toward aDBS implementation for PD.

Limits of the spatial ventricular gradient and QRST angles in patients with normal electrocardiograms and no known cardiovascular disease stratified by age, sex, and race.

INTRODUCTION: Measurement of the spatial ventricular gradient (SVG), spatial QRST angles, and other vectorcardiographic measures of myocardial electrical heterogeneity have emerged as novel risk stratification methods for sudden cardiac death and other adverse cardiovascular events. Prior studies of normal limits of these measurements included primarily young, healthy, White volunteers, but normal limits in older patients are unknown. The influence of race and body mass index (BMI) on these measurements is also unclear. METHODS: Normal 12-lead electrocardiograms (ECGs) from a single center were identified. Patients with abnormal cardiovascular, pulmonary, or renal history (assessed by International Classification of Disease [ICD-9/ICD-10] codes) or abnormal cardiovascular imaging were excluded. The SVG and QRST angles were measured and stratified by age, sex, and race. Multivariable linear regression was used to assess the influence of age, BMI, and heart rate (HR) on these measurements. RESULTS: Among 3292 patients, observed ranges of SVG and QRST angles (peak and mean) differed significantly based on sex, age, and race. Sex differences attenuated with increasing age. Men tended to have larger SVG magnitude (60.4 [46.1-77.8] vs. 52.5 [41.3-65.8] mv*ms, p < .0001) and elevation, and more anterior/negative SVG azimuth (-14.8 [-25.1 to -4.3] vs. 1.3 [-9.8 to 10.5] deg, p < .0001) compared to women. Men also had wider QRST angles. Observed ranges varied significantly with BMI and HR. SVG and QRST angle measurements were robust to different filtering bandwidths and moderate fiducial point annotation errors, but were heavily affected by changes in baseline correction. CONCLUSIONS: Age, sex, race, BMI, and HR significantly affect the range of SVG and QRST angles in patients with normal ECGs and no known cardiovascular disease, and should be accounted for in future studies. An online calculator for prediction of these "normal limits" given demographics is provided at https://bivectors.github.io/gehcalc/.

Anatomic, histologic, and mechanical features of the right atrium: implications for leadless atrial pacemaker implantation.

BACKGROUND: Leadless pacemakers (LPs) may mitigate the risk of lead failure and pocket infection related to conventional transvenous pacemakers. Atrial LPs are currently being investigated. However, the optimal and safest implant site is not known. OBJECTIVES: We aimed to evaluate the right atrial (RA) anatomy and the adjacent structures using complementary analytic models [gross anatomy, cardiac magnetic resonance imaging (MRI), and computer simulation], to identify the optimal safest location to implant an atrial LP human. METHODS AND RESULTS: Wall thickness and anatomic relationships of the RA were studied in 45 formalin-preserved human hearts. In vivo RA anatomy was assessed in 100 cardiac MRI scans. Finally, 3D collision modelling was undertaken assessing for mechanical device interaction. Three potential locations for an atrial LP were identified; the right atrial appendage (RAA) base, apex, and RA lateral wall. The RAA base had a wall thickness of 2.7 ± 1.6 mm, with a low incidence of collision in virtual implants. The anteromedial recess of the RAA apex had a wall thickness of only 1.3 ± 0.4 mm and minimal interaction in the collision modelling. The RA lateral wall thickness was 2.6 ± 0.9 mm but is in close proximity to the phrenic nerve and sinoatrial artery. CONCLUSIONS: Based on anatomical review and 3D modelling, the best compromise for an atrial LP implantation may be the RAA base (low incidence of collision, relatively thick myocardial tissue, and without proximity to relevant epicardial structures); the anteromedial recess of the RAA apex and lateral wall are alternate sites. The mid-RAA, RA/superior vena cava junction, and septum appear to be sub-optimal fixation locations.

2023 HRS/EHRA/APHRS/LAHRS Expert Consensus Statement on Practical Management of the Remote Device Clinic.

Remote monitoring is beneficial for the management of patients with cardiovascular implantable electronic devices by impacting morbidity and mortality. With increasing numbers of patients using remote monitoring, keeping up with higher volume of remote monitoring transmissions creates challenges for device clinic staff. This international multidisciplinary document is intended to guide cardiac electrophysiologists, allied professionals, and hospital administrators in managing remote monitoring clinics. This includes guidance for remote monitoring clinic staffing, appropriate clinic workflows, patient education, and alert management. This expert consensus statement also addresses other topics such as communication of transmission results, use of third-party resources, manufacturer responsibilities, and programming concerns. The goal is to provide evidence-based recommendations impacting all aspects of remote monitoring services. Gaps in current knowledge and guidance for future research directions are also identified.

Comparative performance of distinct frailty measures among patients undergoing percutaneous left atrial appendage closure.

AIMS: Frailty is associated with increased morbidity and mortality in patients undergoing left atrial appendage closure (LAAC). This study aimed to compare the performance of two claims-based frailty measures in predicting adverse outcomes following LAAC. METHODS: We identified patients 66 years and older who underwent LAAC between October 1, 2016, and December 31, 2019, in Medicare fee-for-service claims. Frailty was assessed using the previously validated Hospital Frailty Risk Score (HFRS) and Kim Claims-based Frailty Index (CFI). Patients were identified as frail based on HFRS ≥5 and CFI ≥0.25. RESULTS: Of the 21,787 patients who underwent LAAC, frailty was identified in 45.6% by HFRS and 15.4% by CFI. There was modest agreement between the two frailty measures (kappa 0.25, Pearson's correlation 0.62). After adjusting for age, sex, and comorbidities, frailty was associated with higher risk of 30-day mortality, 1-year mortality, 30-day readmission, long hospital stay, and reduced days at home (p < .01 for all) regardless of the frailty measure used. The addition of frailty to standard comorbidities significantly improved model performance to predict 1-year mortality, long hospital stay, and reduced days at home (Delong p-value < .001). CONCLUSION: Despite significant variation in frailty detection and modest agreement between the two frailty measures, frailty status remained highly predictive of mortality, readmissions, long hospital stay, and reduced days at home among patients undergoing LAAC. Measuring frailty in clinical practice, regardless of the method used, may provide prognostic information useful for patients being considered for LAAC, and may inform shared decision-making in this population.

Racial and ethnic disparities in antifibrotic therapy in idiopathic pulmonary fibrosis.

BACKGROUND AND OBJECTIVE: Racial disparities have been documented in care of many respiratory diseases but little is known about the impact of race on the treatment of interstitial lung diseases. The purpose of this study was to determine how race and ethnicity influence treatment of idiopathic pulmonary fibrosis. METHODS: Adults with idiopathic pulmonary fibrosis (>18 years) were identified using TriNetX database and paired-wised comparisons were performed for antifibrotic treatment among White, Black, Hispanic and Asian patients. Mortality of treated and untreated IPF patients was compared after propensity score matching for age, sex, nicotine dependence, oxygen dependence and predicted FVC. Additional comparisons were performed in subgroups of IPF patients older than 65 years of age and with lower lung function. RESULTS: Of 47,184 IPF patients identified, the majority were White (35,082), followed by Hispanic (6079), Black (5245) and Asian (1221). When subgroups were submitted to matched cohort pair-wise comparisons, anti-fibrotic usage was lower among Black patients compared to White (6.2% vs. 11.4%, p-value <0.0001), Hispanic (10.8% vs. 20.2%, p-value <0.0001) and Asian patients (9.6% vs. 14.7%, p-value = 0.0006). Similar treatment differences were noted in Black individuals older than 65 years and those with lower lung function. Mortality among White patients, but not Hispanic, Black, or Asian patients, was lower in patients on antifibrotic therapy versus not on therapy. CONCLUSION: This study demonstrated that Black IPF patients had lower antifibrotic use compared to White, Hispanic and Asian patients. Our findings suggest that urgent action is needed to understand the reason why racial disparities exist in the treatment of IPF.

Frailty and Cardiovascular Mortality: A Narrative Review.

PURPOSE OF REVIEW: The goal of the narrative review is to provide an overview of the epidemiology of frailty in cardiovascular disease and cardiovascular mortality and discuss applications of frailty in cardiovascular care of older adults. RECENT FINDINGS: Frailty is highly prevalent in older adults with cardiovascular disease and is a robust, independent predictor of cardiovascular death. There is a growing interest in using frailty to inform management of cardiovascular disease either through pre- or post-treatment prognostication or by delineating treatment heterogeneity in which frailty serves to distinguish patients with differential harms or benefits from a given therapy. Frailty can enable more individualized treatment in older adults with cardiovascular disease. Future studies are needed to standardize frailty assessment across cardiovascular trials and enable implementation of frailty assessment in cardiovascular clinical practice.

The Neurophysiological Representation of Imagined Somatosensory Percepts in Human Cortex.

Intracortical microstimulation (ICMS) in human primary somatosensory cortex (S1) has been used to successfully evoke naturalistic sensations. However, the neurophysiological mechanisms underlying the evoked sensations remain unknown. To understand how specific stimulation parameters elicit certain sensations we must first understand the representation of those sensations in the brain. In this study we record from intracortical microelectrode arrays implanted in S1, premotor cortex, and posterior parietal cortex of a male human participant performing a somatosensory imagery task. The sensations imagined were those previously elicited by ICMS of S1, in the same array of the same participant. In both spike and local field potential recordings, features of the neural signal can be used to classify different imagined sensations. These features are shown to be stable over time. The sensorimotor cortices only encode the imagined sensation during the imagery task, while posterior parietal cortex encodes the sensations starting with cue presentation. These findings demonstrate that different aspects of the sensory experience can be individually decoded from intracortically recorded human neural signals across the cortical sensory network. Activity underlying these unique sensory representations may inform the stimulation parameters for precisely eliciting specific sensations via ICMS in future work.SIGNIFICANCE STATEMENT Electrical stimulation of human cortex is increasingly more common for providing feedback in neural devices. Understanding the relationship between naturally evoked and artificially evoked neurophysiology for the same sensations will be important in advancing such devices. Here, we investigate the neural activity in human primary somatosensory, premotor, and parietal cortices during somatosensory imagery. The sensations imagined were those previously elicited during intracortical microstimulation (ICMS) of the same somatosensory electrode array. We elucidate the neural features during somatosensory imagery that significantly encode different aspects of individual sensations and demonstrate feature stability over almost a year. The correspondence between neurophysiology elicited with or without stimulation for the same sensations will inform methods to deliver more precise feedback through stimulation in the future.

Large area ion beam sputtered dielectric ultrafast mirrors for petawatt laser beamlines.

The latest advances in petawatt laser technology within the ELI Beamlines project have stimulated the development of large surface area dielectrically coated mirrors meeting all demanding requirements for guiding the compressed 30 J, 25 fs HAPLS laser beam at 10 Hz repetition rate and a center wavelength of 810 nm entirely in vacuum. We describe the production and evaluation of Ta2O5/HfO2/SiO2 ion beam sputtered coated (440 × 290 × 75) mm3 beam transport mirrors. No crazing was observed after thirty vacuum-air cycles. A laser induced damage threshold of 0.76 J/cm2 (fluence on mirror surface) was achieved and maintained at high shot rates.

Three-Dimensional Imaging Provides Detailed Atherosclerotic Plaque Morphology and Reveals Angiogenesis After Carotid Artery Ligation.

RATIONALE: Remodeling of the vessel wall and the formation of vascular networks are dynamic processes that occur during mammalian embryonic development and in adulthood. Plaque development and excessive neointima formation are hallmarks of atherosclerosis and vascular injury. As our understanding of these complex processes evolves, there is a need to develop new imaging techniques to study underlying mechanisms. OBJECTIVE: We used tissue clearing and light-sheet microscopy for 3-dimensional (3D) profiling of the vascular response to carotid artery ligation and induction of atherosclerosis in mouse models. METHODS AND RESULTS: Adipo-Clear and immunolabeling in combination with light-sheet microscopy were applied to image carotid arteries and brachiocephalic arteries, allowing for 3D reconstruction of vessel architecture. Entire 3D neointima formations with different geometries were observed within the carotid artery and scored by volumetric analysis. Additionally, we identified a CD31-positive adventitial plexus after ligation of the carotid artery that evolved and matured over time. We also used this method to characterize plaque extent and composition in the brachiocephalic arteries of ApoE-deficient mice on high-fat diet. The plaques exhibited inter-animal differences in terms of plaque volume, geometry, and ratio of acellular core to plaque volume. A 3D reconstruction of the endothelium overlying the plaque was also generated. CONCLUSIONS: We present a novel approach to characterize vascular remodeling in adult mice using Adipo-Clear in combination with light-sheet microscopy. Our method reconstructs 3D neointima formation after arterial injury and allows for volumetric analysis of remodeling, in addition to revealing angiogenesis and maturation of a plexus surrounding the carotid artery. This method generates complete 3D reconstructions of atherosclerotic plaques and uncovers their volume, geometry, acellular component, surface, and spatial position within the brachiocephalic arteries. Our approach may be used in a number of mouse models of cardiovascular disease to assess vessel geometry and volume. Visual Overview: An online visual overview is available for this article.

Resource users as land-sea links in coastal and marine socioecological systems.

Coastal zones, which connect terrestrial and aquatic ecosystems, are among the most resource-rich regions globally and home to nearly 40% of the global human population. Because human land-based activities can alter natural processes in ways that affect adjacent aquatic ecosystems, land-sea interactions are increasingly recognized as critical to coastal conservation planning and governance. However, the complex socioeconomic dynamics inherent in coastal and marine socioecological systems (SESs) have received little consideration. Drawing on knowledge generalized from long-term studies in Caribbean Nicaragua, we devised a conceptual framework that clarifies the multiple ways socioeconomically driven behavior can link the land and sea. In addition to other ecosystem effects, the framework illustrates how feedbacks resulting from changes to aquatic resources can influence terrestrial resource management decisions and land uses. We assessed the framework by applying it to empirical studies from a variety of coastal SESs. The results suggest its broad applicability and highlighted the paucity of research that explicitly investigates the effects of human behavior on coastal SES dynamics. We encourage researchers and policy makers to consider direct, indirect, and bidirectional cross-ecosystem links that move beyond traditionally recognized land-to-sea processes.

Los Usuarios de Recursos como Conexiones entre la Tierra y el Mar dentro de los Sistemas Socioecológicos Marinos y Costeros Resumen Las zonas costeras, que conectan los ecosistemas terrestres y acuáticos, se encuentran entre las regiones más ricas en recursos a nivel mundial y además albergan a casi el 40% de la población humana de todo el mundo. Ya que las actividades humanas terrestres pueden alterar los procesos naturales de manera que terminan por afectar a los ecosistemas acuáticos adyacentes, cada vez se reconoce más a las interacciones tierra-mar como críticas para la planeación de la conservación y la gestión costera. Sin embargo, las complejas dinámicas socioeconómicas inherentes a los sistemas socioecológicos (SES) marinos y costeros han recibido poca atención. Con el conocimiento generalizado a partir de los estudios a largo plazo realizados en el Caribe de Nicaragua como punto de partida, diseñamos un marco conceptual que clarifica las múltiples formas en las que el comportamiento con origen socioeconómico puede conectar a la tierra y al mar. Sumado a otros efectos de los ecosistemas, el marco conceptual ilustró cómo los comentarios resultantes de los cambios ocurridos en los recursos acuáticos pueden influir sobre las decisiones de manejo de recursos terrestres y de uso de suelo. Evaluamos el marco conceptual mediante su aplicación a los estudios empíricos de una variedad de SES costeros. Los resultados sugirieron su aplicabilidad generalizada y resaltaron la escasez de investigaciones busquen específicamente los efectos del comportamiento humano sobre las dinámicas de los SES costeros. Alentamos a los investigadores y a los formuladores de políticas a considerar las conexiones directas, indirectas y bidireccionales entre ecosistemas que van más allá de los procesos de tierra a mar reconocidos tradicionalmente.

The long-term outcomes of cardiac implantable electronic devices implanted via the femoral route.

BACKGROUND: Conventional superior access for cardiac implantable electronic devices (CIEDs) is not always possible and femoral CIEDs (F-CIED) are an alternative option when leadless systems are not suitable. The long-term outcomes and extraction experiences with F-CIEDs, in particular complex F-CIED (ICD/CRT devices), remain poorly understood. METHODS: Patients referred for F-CIEDs implantation between 2002 and 2019 at two tertiary centers were included. Early complications were defined as ≤30 days following implant and late complications >30 days. RESULTS: Thirty-one patients (66% male; age 56 ± 20 years; 35% [11] patients with congenital heart disease) were implanted with F-CIEDs (10 ICD/CRT and 21 pacemakers). Early complications were observed in 6.5% of patients: two lead displacements. Late complications at 6.8 ± 4.4 years occurred in 29.0% of patients. This was higher with complex F-CIED compared to simple F-CIED (60.0% vs. 14.3%, p = .02). Late complications were predominantly generator site related (n = 8, 25.8%) including seven infections/erosions and one generator migration. Eight femoral generators and 14 leads (median duration in situ seven [range 6-11] years) were extracted without complication. CONCLUSIONS: Procedural success with F-CIEDs is high with clinically acceptable early complication rates. There is a notable risk of late complications, particularly involving the generator site of complex devices following repeat femoral procedures. Extraction of chronic F-CIED in experienced centers is feasible and safe.

Informed consent and compulsory medical device registries: ethics and opportunities.

Many high-risk medical devices earn US marketing approval based on limited premarket clinical evaluation that leaves important questions unanswered. Rigorous postmarket surveillance includes registries that actively collect and maintain information defined by individual patient exposures to particular devices. Several prominent registries for cardiovascular devices require enrolment as a condition of reimbursement for the implant procedure, without informed consent. In this article, we focus on whether these registries, separate from their legal requirements, have an ethical obligation to obtain informed consent from enrolees, what is lost in not doing so, and the ways in which seeking and obtaining consent might strengthen postmarket surveillance in the USA.

68-year old man with progressive weakness and ventilator dependent respiratory failure: a case report of sporadic late onset nemaline myopathy.

BACKGROUND: Neuromuscular pathologies must be considered when caring for patients with persistent or progressive respiratory failure. Pertinent disease states may involve skeletal muscles of respiration or associated neurologic structures including motor neurons, peripheral neurons and the neuromuscular junction. Diagnosis may require pulmonary function testing, neurophysiologic studies, imaging, and/or muscle biopsy. CASE PRESENTATION: A 68-year-old male was transferred to our intensive care unit (ICU) for management of ventilator dependent respiratory failure. Upon further historical review, he described gradually worsening gait instability and muscle weakness, which was previously attributed to vascular Parkinsonism in the setting of known cerebrovascular disease. Upon arrival to our hospital, he was found to have elevated muscle specific enzymes, prompting evaluation for neuromuscular causes of respiratory failure. He was also found to have elevated HMG-CoA Reductase (HMGCR) antibodies. Ultimately, a right quadriceps muscle biopsy was performed and electron microscopy identified nemaline bodies within skeletal myofibers. Given the clinical course and other histopathologic findings, he was diagnosed with Sporadic late-onset nemaline myopathy (SLONM). CONCLUSION: The diagnosis of neuromuscular disease in patients with ventilator dependent respiratory failure is challenging. A detailed history of a patient's clinical course prior to hospitalization is key and may raise suspicion for underlying neuromuscular pathology. Further evaluation in non-critically ill patients may include pulmonary function, electromyography and confirmatory muscle biopsy. Sporadic late onset nemaline myopathy remains a rare disease entity which rarely presents with respiratory failure and lacks effective treatment.