A Novel Subcutaneous Furosemide Formulation for Outpatient Management of Heart Failure.

In patients with fluid overload and congestion, parenteral diuretic therapy is frequently utilized. However, administration of parenteral diuretic therapy commonly requires hospital admission or outpatient clinic visits. Furoscix (scPharmaceuticals, Burlington, MA), a subcutaneous formulation of furosemide designed for home use, offers new treatment possibilities with the potential for profound cost savings for patients and health systems. Currently, subcutaneous furosemide formulations have been studied in palliative care populations and outpatient clinics, however, new literature has evaluated utility in prescribing on discharge from the emergency department. This review aims to describe the pharmacokinetic profile and utilization of subcutaneous furosemide for treatment of congestion in patients with heart failure.

Myocarditis Presenting as ST-Elevation Myocardial Infarction.

When evaluating a patient with ST-segment elevation on ECG and acute chest pain, providers often rapidly arrive at the diagnosis of ST-elevation myocardial infarction (STEMI). As myocardial infarction is deadly and time is of the essence in establishing reperfusion, it is reasonable to place it at the top of the differential. However, doing so should not come at the expense of conducting a thorough clinical evaluation, considering all causes of ST-segment elevation, and creating a comprehensive differential. Myocarditis, in particular, can present similarly to myocardial infarction and misdiagnosis can lead to unnecessary and sometimes harmful interventions such as thrombolytic therapy, vasodilator therapy, or coronary angiography. We present a case of myocarditis mimicking STEMI and discuss diagnosis and treatment of myocarditis.

A Case of Concurrent Tricuspid Valve, Mitral Valve, and Device Endocarditis.

Endocarditis involving multiple valves is a relatively rare phenomenon, and much about its etiology, prognosis, and best practices for treatment remains uncharacterized. Currently, the treatment of multiple-valve endocarditis is similar to that of single-valve endocarditis. However, limited data suggest that patients may potentially benefit from different treatment approaches not yet clearly defined. Here, we present a unique case of a 22-year-old female with a history of aortic coarctation repair and a ventricular septal defect (VSD) patch repair who presented to the emergency department (ED) after acute onset of fever, chills, nausea, vomiting, and diarrhea. The patient was admitted to the ICU with septic shock and was found to have concurrent mitral valve, tricuspid valve, and VSD patch endocarditis. We discussed her hospital course and treatment as well as current treatment approaches to multiple-valve endocarditis.

Fake-news-free evidence-based communication for proper vein-lymphatic disease management.

Published scientific evidence demonstrate the current spread of healthcare misinformation in the most popular social networks and unofficial communication channels. Up to 40% of the medical websites were identified reporting inappropriate information, moreover being shared more than 450,000 times in a 5-year-time frame. The phenomenon is particularly spread in infective diseases medicine, oncology and cardiovascular medicine. The present document is the result of a scientific and educational endeavor by a worldwide group of top experts who selected and analyzed the major issues and related evidence-based facts on vein and lymphatic management. A section of this work is entirely dedicated to the patients and therefore written in layman terms, with the aim of improving public vein-lymphatic awareness. The part dedicated to the medical professionals includes a revision of the current literature, summing up the statements that are fully evidence-based in venous and lymphatic disease management, and suggesting future lines of research to fulfill the still unmet needs. The document has been written following an intense digital interaction among dedicated working groups, leading to an institutional project presentation during the Universal Expo in Dubai, in the occasion of the v-WINter 2022 meeting.

Outcome and technical evolution of type 2 endoleak embolization with ethylene-vinyl-alcohol copolymer.

PURPOSE: This study aims to evaluate the safety and efficacy of novel approaches to type 2 endoleak access for the purpose of embolization using ethylene-vinyl-alcohol copolymer (EVOH) in patients with abdominal aortic aneurysm (AAA) sac expansion post endovascular abdominal aortic repair (EVAR). METHODS: A retrospective review of 43 consecutive patients (mean age = 80.2 ± 6.7 years) who underwent 52 embolization procedures for type 2 endoleaks using EVOH was performed at a single institution. Catheterization of the endoleaks was achieved using the transarterial (TA) and direct translumbar approaches (DTL), in addition to the novel direct transabdominal (DTA) and perigraft (PG) approaches. Endpoints included technical success of endoleak catheterization, technical success of endoleak embolization, endoleak persistence, endoleak recurrence, AAA sac area change, and adverse events. RESULTS: The TA, DTL, DTA, and PG approaches were used 25, 2, 14, and 19 times respectively, including nine procedures where a combination of approaches was used. The technical success rate of endoleak embolization was 98%. Five patients developed recurrent type 2 endoleaks, while five patients developed a type 1 endoleak. The persistent endoleak rate at a mean initial follow-up of 3 months was 34%. At a mean follow-up of 18 months, 58% of patients demonstrated absence of an endoleak, and 71% showed freedom from AAA sac enlargement. No major adverse events were recorded. CONCLUSION: The DTA and PG approaches were safe and effective in this cohort of patients undergoing embolization of type 2 endoleaks with EVOH.

Safety and Success Rates of Excimer Laser Sheath-Assisted Retrieval of Embedded Inferior Vena Cava Filters.

Importance: Despite historically high rates of use, most inferior vena cava (IVC) filters are not retrieved. The US Food and Drug Administration safety communications recommended retrieval when the IVC filter is no longer indicated out of concern for filter-related complications. However, failure rates are high when using standard techniques for retrieval of long-dwelling filters, and until recently, there have been no devices approved for retrieval of embedded IVC filters. Objective: To evaluate the safety and success of excimer laser sheath-assisted retrieval of embedded IVC filters. Design, Setting, and Participants: A retrospective, multicenter, clinical cohort study of excimer laser sheath-assisted IVC filter retrievals from 7 US sites was conducted between March 1, 2012, and February 28, 2021, among 265 patients who underwent IVC filter retrieval using the laser. Patients were substratified between a high-volume single center and a multicenter data set. A blinded physician committee adjudicated reported complications and their association with use of the laser. Exposures: Retrieval of IVC filters using excimer laser sheath. Main Outcomes and Measures: The primary safety end point was device-related major complication rate (Society of Interventional Radiology categories C to F, which included any adverse event associated with morbidity or disability that increases the level of care, results in hospital admission, or substantially lengthens the hospital stay). The primary success end point was technical success of IVC filter retrieval. The primary end points were compared with literature-derived, meta-analysis-suggested target performance goals. Results: The single-center experience included 139 participants (mean [SD] age, 52 [16] years; 78 female participants [56.1%]), and the multicenter experience included 126 participants (mean [SD] age, 52 [16] years; 75 female participants [59.5%]). The device-related major complication rate was 2.9% (4 of 139; 95% CI, 0.8%-7.2%; P = .001) for the single-center experience and 4.0% (5 of 126; 95% CI, 1.3%-9.0%; P = .01) for the multicenter experience, both of which were significantly lower than the primary safety performance goal (10%). No major complications were considered to be definitively associated with use of the laser. The technical success rate was 95.7% (133 of 139; 95% CI, 90.8%-98.4%; P = .007) for the single-center experience and 95.2% (120 of 126; 95% CI, 89.9%-98.2%; P = .02) for the multicenter experience, both of which were significantly higher than the primary performance goal (89.4%). Conclusions and Relevance: This cohort study demonstrated high technical success and low complication rates of excimer laser sheath-assisted retrieval of embedded IVC filters in centers with variable case volume and experience, which suggests a wide applicability of the technique with proper training. The excimer laser sheath offers physicians a valuable tool for retrieval of challenging embedded IVC filters.

Clinical Risk Factors for Infective Endocarditis Patients With Staphylococcus Aureus Bacteremia and the Diagnostic Utility of Transesophageal Echocardiogram.

Approximately 25% of patients with staphylococcus aureus bacteremia (SAB) develop infective endocarditis (IE), which has a consequent mortality of 25-46%. Current guidelines recommend routine transthoracic echocardiography (TTE) for patients with SAB; transesophageal echocardiogram (TEE) is reserved for those in whom initial TTE is negative and clinical suspicion for IE remains high. We sought to elucidate high risk features of SAB associated with the development of IE that warrant a TEE after a negative TTE. This retrospective study included 213 patients who were diagnosed with SAB at the University of New Mexico Hospital between 2010-2020. A pre-determined list of clinical risk factors along with TTE and TEE status was extracted from the electronic medical record. The primary outcome was development of IE in patients with SAB. Multivariate logistic regression analysis was used to identify clinical risk factors for IE. Moreover, sensitivity and specificity of TTE and TEE was calculated. Out of 213 patients with SAB, 68 patients met diagnostic criteria for IE. Most patients (n = 209) underwent TTE and 171 patients underwent subsequent TEE. The overall sensitivity of TTE was 63% and overall sensitivity of TEE was 88%. Multivariate analysis showed significantly increased risk of IE in patients who had implanted permanent pacemaker (aOR 32.3, CI 5.23 - 281, p < 0.001) and persistent fever (aOR 6.97, CI 2.42 - 21.0 P < 0.001). Based on our analysis, we recommend that TEE should be strongly considered after negative TTE in SAB patients with intracardiac prosthetics or persistent fever despite appropriate antibiotic therapy.

Multiple Biventricular Thrombi Associated With Methamphetamine-Associated Cardiomyopathy.

Background: As methamphetamine use has increased around the world, cardiovascular mortality has also increased. Methamphetamine-associated cardiomyopathy (MACM) is one of the serious cardiovascular complications of methamphetamine use. Limited evidence has been published regarding the increased risk of thrombogenicity in the setting of methamphetamine use. We propose that increased thrombogenicity presents a risk factor for intracardiac thrombi. Case Report: A 48-year-old female with a history of MACM was admitted to the hospital with acute decompensated heart failure. Transthoracic echocardiogram revealed multiple biventricular masses requiring further workup, but the patient left against medical advice on warfarin. The patient presented again 2.5 months later with decompensated heart failure. During the second admission, cardiac magnetic resonance imaging (CMR) characterized the masses in the left ventricle as thrombi, and computed tomography of the chest with contrast showed pulmonary embolism. Although the right ventricle mass was not seen on CMR, we believe the mass was a thrombus that either had migrated into the lungs or had resolved with warfarin use. Conclusion: MACM and biventricular thrombi are associated, but the association is rare and not well studied. Although the exact mechanism of this association is unknown, the increased circulating catecholamines are believed to be a contributing factor for increased thrombogenicity in the setting of active methamphetamine use. We suggest keeping a low threshold for surveillance echocardiography to screen for intracardiac thrombi in MACM patients with active methamphetamine use when they present with even mild symptoms of decompensated heart failure.

Laboratory diet influences cold tolerance in a genotype-dependent manner in Drosophila melanogaster.

Cold stress can reduce insect fitness and is an important determinant of species distributions and responses to climate change. Cold tolerance is influenced by genotype and environmental conditions, with factors such as day length and temperature having a particularly strong influence. Recent studies also indicate that diet impacts cold tolerance, but it is unclear whether diet-mediated shifts in cold tolerance are consistent across distinct genotypes. The goal of this study was to determine the extent to which commonly used artificial diets influence cold tolerance in Drosophila melanogaster, and whether these effects are consistent across genetically distinct lines. Specifically, we tested the impact of different fly diets on 1) ability to survive cold stress, 2) critical thermal minimum (CTmin), and 3) the ability to maintain reproduction after cold stress. Experiments were conducted across six isogenic lines from the Drosophila Genetic Reference Panel, and these lines were reared on different fly diets. Cold shock survival, CTmin, and reproductive output pre- and post-cold exposure varied considerably across diet and genotype combinations, suggesting strong genotype by environment interactions shape nutritionally mediated changes in cold tolerance. For example, in some lines cold shock survival remained consistently high or low across diets, while in others cold shock survival ranged from 5% to 75% depending on diet. Ultimately, these results add to a growing literature that cold tolerance is shaped by complex interactions between genotype and environment and inform practical considerations when selecting a laboratory diet for thermal tolerance experiments in Drosophila.

The Protégé Nitinol Self-Expanding Stent for the Treatment of Iliofemoral Veno-Occlusive Disease.

PURPOSE: To evaluate the safety and effectiveness of the Protégé nitinol self-expanding stent for the treatment of iliofemoral veno-occlusive disease. MATERIALS AND METHODS: A retrospective review was performed of 376 (284 left, 92 right) Protégé stents in 212 limbs of 183 patients (mean age: 53 ± 17 years, 52% female) treated for iliofemoral veno-occlusive disease between 2011 and 2018. Binary patency was assessed with duplex ultrasound and calculated by Kaplan Meier analysis. Clinical outcomes were evaluated by clinical-etiology-anatomy-pathophysiology (CEAP) classification and Villalta scores. Adverse events were recorded and categorized per Society of Interventional Radiology reporting standards. RESULTS: Of the 212 limbs, 125 presented with acute thrombosis and 28 with chronic thrombosis requiring thrombectomy (n = 44), catheter directed thrombolysis (n = 32), or both (n = 77). Fifty-nine limbs were non-thrombotic. Mean follow-up time was 11.44 ± 11.37 months. Kaplan Meier analysis revealed a primary limb-level patency of 92.3%, 88.6%, 86.9% and 86.9% at 6, 12, 24 and 36 months, respectively. CEAP and Villalta scores improved from a median of C3 (range: 0-6) to C1 (0-5) (p < 0.001) and from a mean of 13.4 ± 7.5 to 5.3 ± 4.9 (p < 0.001), respectively. Nine minor and 2 major adverse events were recorded. CONCLUSIONS: Endovascular treatment of iliofemoral veno-occlusive disease with the Protégé self-expanding stent appears to have good mid-term patency. LEVEL OF EVIDENCE: Level 4, Case Series.

High-Throughput Assays of Critical Thermal Limits in Insects.

Upper and lower thermal limits of plants and animals are important predictors of their performance, survival, and geographic distributions, and are essential for predicting responses to climate change. This work describes two high-throughput protocols for measuring insect thermal limits: one for assessing critical thermal minima (CTmin), and the other for assessing heat knock down time (KDT) in response to a static heat stressor. In the CTmin assay, individuals are placed in an acrylic-jacketed column, subjected to a decreasing temperature ramp, and counted as they fall from their perches using an infrared sensor. In the heat KDT assay, individuals are contained in a 96 well plate, placed in an incubator set to a stressful, hot temperature, and video recorded to determine the time at which they can no longer remain upright and move. These protocols offer advantages over commonly used techniques. Both assays are low cost and can be completed relatively quickly (~2 h). The CTmin assay reduces experimenter error and can measure a large number of individuals at once. The heat KDT protocol generates a video record of each assay and thus removes experimenter bias and the need to continuously monitor individuals in real time.

Distinct cold tolerance traits independently vary across genotypes in Drosophila melanogaster.

Cold tolerance, the ability to cope with low temperature stress, is a critical adaptation in thermally variable environments. An individual's cold tolerance comprises several traits including minimum temperatures for growth and activity, ability to survive severe cold, and ability to resume normal function after cold subsides. Across species, these traits are correlated, suggesting they were shaped by shared evolutionary processes or possibly share physiological mechanisms. However, the extent to which cold tolerance traits and their associated mechanisms covary within populations has not been assessed. We measured five cold tolerance traits-critical thermal minimum, chill coma recovery, short- and long-term cold tolerance, and cold-induced changes in locomotor behavior-along with cold-induced expression of two genes with possible roles in cold tolerance (heat shock protein 70 and frost)-across 12 lines of Drosophila melanogaster derived from a single population. We observed significant genetic variation in all traits, but few were correlated across genotypes, and these correlations were sex-specific. Further, cold-induced gene expression varied by genotype, but there was no evidence supporting our hypothesis that cold-hardy lines would have either higher baseline expression or induction of stress genes. These results suggest cold tolerance traits possess unique mechanisms and have the capacity to evolve independently.

Ultrasound-Accelerated Thrombolysis and Venoplasty for the Treatment of the Postthrombotic Syndrome: Results of the ACCESS PTS Study.

Background Postthrombotic syndrome is a common complication of deep vein thrombosis, with limited treatment options. Methods and Results ACCESS PTS (Accelerated Thrombolysis for Post-Thrombotic Syndrome Using the Acoustic Pulse Thrombolysis Ekosonic Endovascular System) is a multicenter, single-arm, prospective study evaluating patients with chronic deep vein thrombosis and postthrombotic syndrome (Villalta score ≥8) who received minimum 3 months of anticoagulation. Patients underwent percutaneous transluminal venoplasty and ultrasound-accelerated thrombolysis, with data collected on clinical characteristics, postthrombotic syndrome, imaging, and quality of life to 1 year. The primary efficacy outcome was a reduction of ≥4 points in the Villalta score 30 days after procedure. The primary safety outcomes were major bleeding episodes within 72 hours and symptomatic pulmonary embolism during the index hospitalization. A total of 82 limbs (78 patients) were treated (age, 54.6±12.7 years; 32.1% women; mean Villalta score, 15.5±5.2). The primary end point was met in 64.6% (51/79). At 1 year, 77.3% (51/66) of limbs continued with a Villalta reduction ≥4. At 365 days, >90% of segments had patency with ultrasound flow present. Baseline to 1-year Physical Component Summary mean score of the Short Form-36 increased from 38.9±9.5 to 45.2±9.8 (P≤0.0001), and mean VEINES-QOL (Venous Insufficiency Epidemiological and Economic Study-Quality of Life) increased from 61.9±19.7 to 82.6±20.8 at 1 year (P<0.0001). Iliofemoral venous stenting was performed in 42 patients, with similar improvements seen in all outcomes, regardless of stenting status. One patient developed severe bleeding within 72 hours of the intervention and died at 32 days after procedure (1.3% mortality rate). Conclusions Percutaneous transluminal venoplasty and ultrasound-accelerated thrombolysis resulted in successful recanalization of chronic venous obstruction with improved postthrombotic syndrome severity and quality of life. Results were sustained at 1-year after procedure. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT02159521.

Cold stress results in sustained locomotor and behavioral deficits in Drosophila melanogaster.

Tolerance of climatic stressors is an important predictor of the current distribution of insect species, their potential to invade new environments, and their responses to rapid climate change. Cold stress causes acute injury to nerves and muscles, and here we tested the hypothesis that low temperature causes sublethal deficits in locomotor behaviors that are dependent on neuromuscular function. To do so, we applied a previously developed assay, the rapid iterative negative geotaxis (RING) assay, to investigate behavioral consequences of cold stress in Drosophila melanogaster. The RING assay allows for rapid assessment of negative geotaxis behavior by quantifying climbing height and willingness to climb after cold stress. We exposed flies to cold stress at 0°C and assessed the extent to which duration of cold stress, recovery time, and cold acclimation influenced climbing performance. There was a clear dose-response relationship between cold exposure and performance deficits, with climbing height and willingness decreasing as cold exposure increased from 2 to 24 hr. Following cold exposure of an intermediate duration (12 hr), climbing height and willingness gradually improved as recovery time increased from 4 to 72 hr but flies never fully recovered. Finally, cold acclimation improved overall climbing height and willingness in both untreated and cold-stressed flies but did not prevent a reduction in climbing performance. Thus, cold stress causes deficits in locomotor and behavior that are dependent on the dose of cold exposure and persist long after the stress subsides. These results likely have implications for the ecological and evolutionary responses of insect populations to thermally variable environments.

Sexual phenotype drives variation in endocrine responses to social challenge in a quasi-clonal animal.

In many species, males tend to behave more aggressively than females and female aggression often occurs during particular life stages such as maternal defence of offspring. Though many studies have revealed differences in aggression between the sexes, few studies have compared the sexes in terms of their neuroendocrine responses to contest experience. We investigated sex differences in the endocrine response to social challenge using mangrove rivulus fish, Kryptolebias marmoratus. In this species, sex is determined environmentally, allowing us to produce males and hermaphrodites with identical genotypes. We hypothesized that males would show elevated androgen levels (testosterone and 11-ketotestosterone) following social challenge but that hermaphrodite responses might be constrained by having to maintain both testicular and ovarian tissue. To test this hypothesis, we staged fights between males and between hermaphrodites, and then compared contest behaviour and hormone responses between the sexes. Hermaphrodites had significantly higher oestradiol but lower 11-ketotestosterone than males before contests. Males took longer to initiate contests but tended to fight more aggressively and sustain longer fights than hermaphrodites. Males showed a dramatic post-fight increase in 11-ketotestosterone but hermaphrodites did not. Thus, despite being genetically identical, males and hermaphrodites exhibit dramatically different fighting strategies and endocrine responses to contests.

Pharmacomechanical Catheter-Directed Thrombolysis for Deep-Vein Thrombosis.

BACKGROUND: The post-thrombotic syndrome frequently develops in patients with proximal deep-vein thrombosis despite treatment with anticoagulant therapy. Pharmacomechanical catheter-directed thrombolysis (hereafter "pharmacomechanical thrombolysis") rapidly removes thrombus and is hypothesized to reduce the risk of the post-thrombotic syndrome. METHODS: We randomly assigned 692 patients with acute proximal deep-vein thrombosis to receive either anticoagulation alone (control group) or anticoagulation plus pharmacomechanical thrombolysis (catheter-mediated or device-mediated intrathrombus delivery of recombinant tissue plasminogen activator and thrombus aspiration or maceration, with or without stenting). The primary outcome was development of the post-thrombotic syndrome between 6 and 24 months of follow-up. RESULTS: Between 6 and 24 months, there was no significant between-group difference in the percentage of patients with the post-thrombotic syndrome (47% in the pharmacomechanical-thrombolysis group and 48% in the control group; risk ratio, 0.96; 95% confidence interval [CI], 0.82 to 1.11; P=0.56). Pharmacomechanical thrombolysis led to more major bleeding events within 10 days (1.7% vs. 0.3% of patients, P=0.049), but no significant difference in recurrent venous thromboembolism was seen over the 24-month follow-up period (12% in the pharmacomechanical-thrombolysis group and 8% in the control group, P=0.09). Moderate-to-severe post-thrombotic syndrome occurred in 18% of patients in the pharmacomechanical-thrombolysis group versus 24% of those in the control group (risk ratio, 0.73; 95% CI, 0.54 to 0.98; P=0.04). Severity scores for the post-thrombotic syndrome were lower in the pharmacomechanical-thrombolysis group than in the control group at 6, 12, 18, and 24 months of follow-up (P<0.01 for the comparison of the Villalta scores at each time point), but the improvement in quality of life from baseline to 24 months did not differ significantly between the treatment groups. CONCLUSIONS: Among patients with acute proximal deep-vein thrombosis, the addition of pharmacomechanical catheter-directed thrombolysis to anticoagulation did not result in a lower risk of the post-thrombotic syndrome but did result in a higher risk of major bleeding. (Funded by the National Heart, Lung, and Blood Institute and others; ATTRACT ClinicalTrials.gov number, NCT00790335 .).

Transcatheter Embolization of Type I Endoleaks Associated With Endovascular Abdominal Aortic Aneurysm Repair Using Ethylene Vinyl Alcohol Copolymer.

PURPOSE: To evaluate the feasibility, safety, and outcome of transcatheter embolization using ethylene vinyl alcohol copolymer (EVOH) of type I endoleaks associated with endovascular abdominal aortic aneurysm repair. PATIENT POPULATION AND METHODS: Retrospective chart review was performed to identify 8 consecutive patients who had undergone EVOH embolization for type I endoleaks between 2012 and 2015. The primary approach used to access the endoleak was the perigraft technique, where the endoleak itself is catheterized at the anastomotic site. RESULTS: Six type Ia and 2 type Ib endoleaks were treated. In 2 patients, a direct transabdominal approach was used to access the endoleak because it was inaccessible via the perigraft approach. Coils were used in addition to EVOH in 5 cases. Residual endoleak was noted in 1 case, whereas 2 patients developed a recurrent type I endoleak during follow-up. No EVOH complications were observed. The 5 remaining patients demonstrated freedom from endoleak and reintervention at a mean follow-up of 6.9 months. CONCLUSION: Type I endoleaks can be safely and effectively treated by embolotherapy with EVOH. Larger endoleaks resulting from grossly undersized endografts appear to be unsuitable for EVOH embolization.

Phenotypic differences between the sexes in the sexually plastic mangrove rivulus fish (Kryptolebias marmoratus).

To maximize reproductive success, many animal species have evolved functional sex change. Theory predicts that transitions between sexes should occur when the fitness payoff of the current sex is exceeded by the fitness payoff of the opposite sex. We examined phenotypic differences between the sexes in a sex-changing vertebrate, the mangrove rivulus fish (Kryptolebias marmoratus), to elucidate potential factors that might drive the 'decision' to switch sex. Rivulus populations consist of self-fertilizing hermaphrodites and males. Hermaphrodites transition into males under certain environmental conditions, affording us the opportunity to generate 40 hermaphrodite-male pairs where, within a pair, individuals possessed identical genotypes despite being different sexes. We quantified steroid hormone levels, behavior (aggression and risk taking), metabolism and morphology (organ masses). We found that hermaphrodites were more aggressive and risk averse, and had higher maximum metabolic rates and larger gonadosomatic indices. Males had higher steroid hormone levels and showed correlations among hormones that hermaphrodites lacked. Males also had greater total mass and somatic body mass and possessed considerable fat stores. Our findings suggest that there are major differences between the sexes in energy allocation, with hermaphrodites exhibiting elevated maximum metabolic rates, and showing evidence of favoring investments in reproductive tissues over somatic growth. Our study serves as the foundation for future research investigating how environmental challenges affect both physiology and reproductive investment and, ultimately, how these changes dictate the transition between sexes.

Endovascular Management of Acute Pulmonary Embolism Using the Ultrasound-Enhanced EkoSonic System.

Acute, symptomatic pulmonary embolism (PE) in the massive and submassive categories continues to be a healthcare concern with significant risk for increased morbidity and mortality. Despite increased awareness and venous thromboembolism prophylaxis, endovascular treatment is still an important option for many of these patients. There are a variety of techniques and devices used for treating PE, but none have been evaluated as extensively as the EkoSonic endovascular system that is also currently the only FDA-approved device for the treatment of pulmonary embolism. This article describes the use of the EkoSonic device for this patient population.

A Prospective, Single-Arm, Multicenter Trial of Ultrasound-Facilitated, Catheter-Directed, Low-Dose Fibrinolysis for Acute Massive and Submassive Pulmonary Embolism: The SEATTLE II Study.

OBJECTIVES: This study conducted a prospective, single-arm, multicenter trial to evaluate the safety and efficacy of ultrasound-facilitated, catheter-directed, low-dose fibrinolysis, using the EkoSonic Endovascular System (EKOS, Bothell, Washington). BACKGROUND: Systemic fibrinolysis for acute pulmonary embolism (PE) reduces cardiovascular collapse but causes hemorrhagic stroke at a rate exceeding 2%. METHODS: Eligible patients had a proximal PE and a right ventricular (RV)-to-left ventricular (LV) diameter ratio ≥0.9 on chest computed tomography (CT). We included 150 patients with acute massive (n = 31) or submassive (n = 119) PE. We used 24 mg of tissue-plasminogen activator (t-PA) administered either as 1 mg/h for 24 h with a unilateral catheter or 1 mg/h/catheter for 12 h with bilateral catheters. The primary safety outcome was major bleeding within 72 h of procedure initiation. The primary efficacy outcome was the change in the chest CT-measured RV/LV diameter ratio within 48 h of procedure initiation. RESULTS: Mean RV/LV diameter ratio decreased from baseline to 48 h post-procedure (1.55 vs. 1.13; mean difference, -0.42; p < 0.0001). Mean pulmonary artery systolic pressure (51.4 mm Hg vs. 36.9 mm Hg; p < 0.0001) and modified Miller Index score (22.5 vs. 15.8; p < 0.0001) also decreased post-procedure. One GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries)-defined severe bleed (groin hematoma with transient hypotension) and 16 GUSTO-defined moderate bleeding events occurred in 15 patients (10%). No patient experienced intracranial hemorrhage. CONCLUSIONS: Ultrasound-facilitated, catheter-directed, low-dose fibrinolysis decreased RV dilation, reduced pulmonary hypertension, decreased anatomic thrombus burden, and minimized intracranial hemorrhage in patients with acute massive and submassive PE. (A Prospective, Single-arm, Multi-center Trial of EkoSonic® Endovascular System and Activase for Treatment of Acute Pulmonary Embolism (PE) [SEATTLE II]; NCT01513759).