Engineered tumor-specific T cells using immunostimulatory photothermal nanoparticles.

BACKGROUND: Adoptive T cell therapy (ATCT) has been successful in treating hematological malignancies and is currently under investigation for solid-tumor therapy. In contrast to existing chimeric antigen receptor (CAR) T cell and/or antigen-specific T cell approaches, which require known targets, and responsive to the need for targeting a broad repertoire of antigens in solid tumors, we describe the first use of immunostimulatory photothermal nanoparticles to generate tumor-specific T cells. METHODS: Specifically, we subject whole tumor cells to Prussian blue nanoparticle-based photothermal therapy (PBNP-PTT) before culturing with dendritic cells (DCs), and subsequent stimulation of T cells. This strategy differs from previous approaches using tumor cell lysates because we use nanoparticles to mediate thermal and immunogenic cell death in tumor cells, rendering them enhanced antigen sources. RESULTS: In proof-of-concept studies using two glioblastoma (GBM) tumor cell lines, we first demonstrated that when PBNP-PTT was administered at a "thermal dose" targeted to induce the immunogenicity of U87 GBM cells, we effectively expanded U87-specific T cells. Further, we found that DCs cultured ex vivo with PBNP-PTT-treated U87 cells enabled 9- to 30-fold expansion of CD4+ and CD8+ T cells. Upon co-culture with target U87 cells, these T cells secreted interferon-É£ in a tumor-specific and dose-dependent manner (up to 647-fold over controls). Furthermore, T cells manufactured using PBNP-PTT ex vivo expansion elicited specific cytolytic activity against target U87 cells (donor-dependent 32-93% killing at an effector to target cell (E:T) ratio of 20:1) while sparing normal human astrocytes and peripheral blood mononuclear cells from the same donors. In contrast, T cells generated using U87 cell lysates expanded only 6- to 24-fold and killed 2- to 3-fold less U87 target cells at matched E:T ratios compared with T cell products expanded using the PBNP-PTT approach. These results were reproducible even when a different GBM cell line (SNB19) was used, wherein the PBNP-PTT-mediated approach resulted in a 7- to 39-fold expansion of T cells, which elicited 25-66% killing of the SNB19 cells at an E:T ratio of 20:1, depending on the donor. CONCLUSIONS: These findings provide proof-of-concept data supporting the use of PBNP-PTT to stimulate and expand tumor-specific T cells ex vivo for potential use as an adoptive T cell therapy approach for the treatment of patients with solid tumors.

Comparable transforming growth factor beta-mediated immune suppression in ex vivo-expanded natural killer cells from cord blood and peripheral blood: implications for adoptive immunotherapy.

T cell-based therapies like genetically modified immune cells expressing chimeric antigen receptors have shown robust anti-cancer activity in vivo, especially in patients with blood cancers. However, extending this approach to an "off-the-shelf" setting can be challenging, as allogeneic T cells carry a significant risk of graft-versus-host disease (GVHD). By contrast, allogeneic natural killer (NK) cells recognize malignant cells without the need for prior antigen exposure and have been used safely in multiple cancer settings without the risk of GVHD. However, similar to T cells, NK cell function is negatively impacted by tumor-induced transforming growth factor beta (TGF-ß) secretion, which is a ubiquitous and potent immunosuppressive mechanism employed by most malignancies. Allogeneic NK cells for adoptive immunotherapy can be sourced from peripheral blood (PB) or cord blood (CB), and the authors' group and others have previously shown that ex vivo expansion and gene engineering can overcome CB-derived NK cells' functional immaturity and poor cytolytic activity, including in the presence of exogenous TGF-ß.  However, a direct comparison of the effects of TGF-ß-mediated immune suppression on ex vivo-expanded CB- versus PB-derived NK cell therapy products has not previously been performed. Here the authors show that PB- and CB-derived NK cells have distinctive gene signatures that can be overcome by ex vivo expansion. Additionally, exposure to exogenous TGF-ß results in an upregulation of inhibitory receptors on NK cells, a novel immunosuppressive mechanism not previously described. Finally, the authors provide functional and genetic evidence that both PB- and CB-derived NK cells are equivalently susceptible to TGF-ß-mediated immune suppression. The authors believe these results provide important mechanistic insights to consider when using ex vivo-expanded, TGF-ß-resistant PB- or CB-derived NK cells as novel immunotherapy agents for cancer.

Long-term outcomes for children with an incidentally discovered Chiari malformation type 1: what is the clinical significance?

OBJECTIVES: Chiari malformation type 1 (CM1) is an increasingly common incidental finding on magnetic resonance imaging (MRI). The proportion of children with an incidentally discovered CM1 who upon further evaluation require operative intervention for previously unrecognized signs and symptoms of neurological compromise or significant radiographic findings (syringomyelia) is unclear. An extensive long-term single-institution patient series was evaluated to better clarify the likelihood of surgery in patients who present with an incidentally discovered CM1. METHODS: This study was conducted using prospective data for patients up to 18 years old that were evaluated for a CM1 at a large tertiary pediatric neurosurgery clinic between February 2009 and June 2019. Patients were excluded if they did not have an incidentally discovered CM1 and at least 12 months of clinical follow-up. RESULTS: A total of 218 consecutive patients were included in this study. The mean age at the initial neurosurgical evaluation was 6.5 years (range 5 months to 18.4 years), and the mean duration of clinical follow-up was 40.6 months (range 12 to 114 months). Initial MR imaging was most commonly obtained for the evaluation of seizures (15.1%), nonspecific headaches (not occipital or tussive) (14.7%), trauma (9.6%), and developmental delay (7.8%). Of the patients studied that eventually required surgery, we identified two groups: those operated before 6 months since presentation and those operated after 6 months. A total of 36 patients (16.5%) underwent a decompression with 22 patients (61.1%) receiving surgery within 6 months and the remaining 14 patients (38.9%) beyond 6 months. Patients undergoing early surgery (10.1%) initially presented with a significant syrinx or were noted to have an occult neurological dysfunction, whereas a smaller subset of patients (6.4%) eventually required surgery over time due to the development of new symptoms or a de novo syrinx. Only the presence of syringomyelia was statistically significant for the need of a surgical intervention, while age, sex and degree of tonsillar herniation were not. CONCLUSION: Evaluation of a large group of patients with an incidentally discovered Chiari malformation demonstrated that most patients may be managed conservatively, especially in the absence of syringomyelia. However, there is a subset of patients who will go on to develop a de novo syrinx or neurological symptoms that are new or progressive during follow-up, which should be evaluated by imaging of the brain and spinal cord. The presence of syringomyelia was associated with need for early surgical intervention. However, for patients without syringomyelia, surgical intervention is uncommon but may be delayed up to several years after presentation; therefore, long-term clinical follow-up is recommended.

The influence of body mass index on the survival of patients with melanoma. A cross-sectional study of 707 patients.

INTRODUCTION: Obesity has been linked with an increased incidence of melanoma; however, there are few data about its impact on melanoma prognosis. We aimed to determine if there is an association between body mass index (BMI) and overall survival (OS) in 707 patients with melanoma. MATERIAL AND METHODS: A retrospective study of 707 patients with melanoma collected consecutively from 2005 to 2015 with a diagnosis of melanoma, who were been diagnosed and treated in our institution and who had clinical follow-up was carried out. Survival analysis was performed comparing patients according to their BMI. RESULTS: In a multivariate analysis, factors influencing the 5-year OS were a positive margin (HR = 3.475, 95% CI: 1.829-6.600), the clinical-stage (HR = 2.565, 95% CI: 2.020-3.257, per switch to the upper stage), ulceration (HR = 3.475, 95% CI: 1.829-6.600), and BMI (HR .905, p = 0.018 for the overweight group; HR = 0.663, p = 0.021 for obesity grade I). CONCLUSIONS: Patients who had a BMI between 25 and 34.9 kg/m2 had better survival.

The initial U.S. experience with the Tempo active fixation temporary pacing lead in structural heart interventions.

OBJECTIVES: This multicenter retrospective study of the initial U.S. experience evaluated the safety and efficacy of temporary cardiac pacing with the Tempo® Temporary Pacing Lead. BACKGROUND: Despite increasing use of temporary cardiac pacing with the rapid growth of structural heart procedures, temporary pacing leads have not significantly improved. The Tempo lead is a new temporary pacing lead with a soft tip intended to minimize the risk of perforation and a novel active fixation mechanism designed to enhance lead stability. METHODS: Data from 269 consecutive structural heart procedures were collected. Outcomes included device safety (absence of clinically significant cardiac perforation, new pericardial effusion, or sustained ventricular arrhythmia) and efficacy (clinically acceptable pacing thresholds with successful pace capture throughout the index procedure). Postprocedure practices and sustained lead performance were also analyzed. RESULTS: The Tempo lead was successfully positioned in the right ventricle and achieved pacing in 264 of 269 patients (98.1%). Two patients (0.8%) experienced loss of pace capture. Procedural mean pace capture threshold (PCT) was 0.7 ± 0.8 mA. There were no clinically significant perforations, pericardial effusions, or sustained device-related arrhythmias. The Tempo lead was left in place postprocedure in 189 patients (71.6%) for mean duration of 43.3 ± 0.7 hr (range 2.5-221.3 hr) with final PCT of 0.84 ± 1.04 mA (n = 80). Of these patients, 84.1% mobilized out of bed with no lead dislodgment. CONCLUSION: The Tempo lead is safe and effective for temporary cardiac pacing for structural heart procedures, provides stable peri and postprocedural pacing and allows mobilization of patients who require temporary pacing leads.

Coronary and peripheral stenting in aorto-ostial protruding stents: The balloon assisted access to protruding stent technique.

Treatment of aorto-ostial in-stent restenosis lesions represents a challenge for interventional cardiologists. Excessive protrusion of the stent into the aorta may lead to multiple technical problems, such as difficult catheter reengagement of the vessel ostium or inability to re-wire through the stent lumen in repeat interventions. We describe a balloon assisted access to protruding stent technique in cases where conventional coaxial engagement of an aorto-ostial protruding stent with the guide catheter or passage of the guide wire through the true lumen is not feasible. This technique is applicable both in coronary and peripheral arteries.

Revascularization heart team recommendations as an adjunct to appropriate use criteria for coronary revascularization in patients with complex coronary artery disease.

OBJECTIVES: To evaluate how a comprehensive evidence-based clinical review by a multidisciplinary revascularization heart team on treatment decisions for revascularization in patients with complex coronary artery disease using SYNTAX scores combined with Society of Thoracic Surgeons-derived clinical variables can be additive to the utilization of Appropriate Use Criteria for coronary revascularization. BACKGROUND: Decision-making regarding the use of revascularization for coronary artery disease has come under major scrutiny due to inappropriate overuse of revascularization. There is little data in routine clinical practice evaluating how a structured, multidisciplinary heart team approach may be used in combination with the Appropriate Use Criteria for revascularization. METHODS: From May 1, 2012 to January 1, 2015, multidisciplinary revascularization heart team meetings were convened to discuss evidence-based management of 301 patients with complex coronary artery disease. Heart team recommendations were adjudicated with the Appropriate Use Criteria for coronary revascularization for each clinical scenario using the Society for Cardiovascular Angiography and Interventions' Quality Improvement Toolkit (SCAI-QIT) Appropriate Use Criteria App. RESULTS: Concordance of the Heart Team to Appropriate Use Criteria had a 99.3% appropriate primary indication for coronary revascularization. Among patients who underwent percutaneous revascularization, 34.9% had an inappropriate or uncertain indication as recommended by the Heart Team. Patients with uncertain or inappropriate percutaneous coronary interventions had significantly higher SYNTAX score (27.3 ± 6.6; 28.5 ± 5.5; 19.2 ± 6; P < 0.0001) and Society of Thoracic Surgeons-Predicted Risk of Mortality (6.1% ± 4.7%; 8.1% ± 6.3%; 3.7% ± 4.1%; P < 0.0081) compared to appropriate indications, frequently had concomitant forms of advanced comorbidities and frailty in the setting of symptomatic coronary artery disease. CONCLUSIONS: A formal, multidisciplinary revascularization heart team can provide proper validation for clinical decisions and should be considered in combination with the Appropriate Use Criteria for coronary revascularization to formulate revascularization strategies for individuals in a patient-centered fashion. © 2015 Wiley Periodicals, Inc.

Simplifying Transcatheter Tricuspid Valve Replacement With 3-Dimensional Intracardiac Echocardiography.

Transcatheter tricuspid valve replacement (TTVR) offers the potential for improved outcomes for the significant number of patients with severe tricuspid valve regurgitation relative to current treatment options. Imaging is a critical component of the success of this procedure. Here we describe strategies and techniques for the use of 3-dimensional intracardiac echocardiography as an adjunct to standard transesophageal echocardiography during TTVR procedure.

Socioeconomic Disparities Affecting the Presentation and Outcomes in Pediatric Subdural Empyema Patients.

BACKGROUND AND OBJECTIVES: Pediatric subdural empyemas (SDE) carry significant morbidity and mortality, and prompt diagnosis and treatment are essential to ensure optimal outcomes. Nonclinical factors affect presentation, time to diagnosis, and outcomes in several neurosurgical conditions and are potential causes of delay in presentation and treatment for patients with SDE. To evaluate whether socioeconomic status, race, and insurance status affect presentation, time to diagnosis, and outcomes for children with subdural empyema. METHODS: We conducted a retrospective cohort study with patients diagnosed with SDE between 2005 and 2020 at our institution. Information regarding demographics (age, sex, zip code, insurance status, race/ethnicity) and presentation (symptoms, number of prior visits, duration of symptoms) was collected. Outcome measures included mortality, postoperative complications, length of stay, and discharge disposition. RESULTS: 42 patients were diagnosed with SDE with a mean age of 9.5 years. Most (85.7%) (n = 36) were male ( P = .0004), and a majority, 28/42 (66.7%), were African American ( P < .0001). There was no significant difference in socioeconomic status based on zip codes, although a significantly higher number of patients were on public insurance ( P = .015). African American patients had a significantly longer duration of symptoms than their Caucasian counterparts (8.4 days vs 1.8 days P = .0316). In total, 41/42 underwent surgery for the SDE, most within 24 hours of initial neurosurgical evaluation. There were no significant differences in the average length of stay. The average length of antibiotic duration was 57.2 days and was similar for all patients. There were no significant differences in discharge disposition based on any of the factors identified with most of the patients (52.4%) being discharged to home. There was 1 mortality (2.4%). CONCLUSION: Although there were no differences in outcomes based on nonclinical factors, African American men on public insurance bear a disproportionately high burden of SDE. Further investigation into the causes of this is warranted.

Temporal Trends, Outcomes, and Predictors of Next-Day Discharge and Readmission Following Uncomplicated Evolut Transcatheter Aortic Valve Replacement: A Propensity Score-Matched Analysis.

BACKGROUND: Next-day discharge (NDD) outcomes following uncomplicated self-expanding transcatheter aortic valve replacement have not been studied. Here, we compare readmission rates and clinical outcomes in NDD versus non-NDD transcatheter aortic valve replacement with Evolut. METHODS AND RESULTS: Society of Thoracic Surgeons/American College of Cardiology TVT (Transcatheter Valve Therapy) Registry patients (n=29 597) undergoing elective transcatheter aortic valve replacement with self-expanding supra-annular valves (Evolut R, PRO, and PRO+) from July 2019 to June 2021 were stratified by postprocedure length of stay: ≤1 day (NDD) versus >1 day (non-NDD). Propensity score matching was used to compare risk adjusted 30-day readmission rates and 1-year outcomes in NDD versus non-NDD, and multivariable regression to determine predictors of NDD and readmission. Between the first and last calendar quarter, the rate of NDD increased from 45.4% to 62.1% and median length of stay decreased from 2 days to 1. Propensity score matching produced relatively well-matched NDD and non-NDD cohorts (n=10 549 each). After matching, NDD was associated with lower 30-day readmission rates (6.3% versus 8.4%; P<0.001) and 1-year adverse outcomes (death, 7.0% versus 9.3%; life threatening/major bleeding, 1.6% versus 3.4%; new permanent pacemaker implantation/implantable cardioverter-defibrillator, 3.6 versus 11.0%; [all P<0.001]). Predictors of NDD included non-Hispanic ethnicity, preexisting permanent pacemaker implantation/implantable cardioverter-defibrillator, and previous surgical aortic valve replacement. CONCLUSIONS: Most patients undergoing uncomplicated self-expanding Evolut transcatheter aortic valve replacement are discharged the next day. This study found that NDD can be predicted from baseline patient characteristics and was associated with favorable 30-day and 1-year outcomes, including low rates of permanent pacemaker implantation and readmission.

Structural Heart Imaging Using 3-Dimensional Intracardiac Echocardiography: JACC Cardiovascular Imaging Position Statement.

3-dimensional (3D) intracardiac echocardiography (ICE) is emerging as a promising complement and potential alternative to transesophageal echocardiography for imaging guidance in structural heart interventions. To establish standardized practices, our multidisciplinary expert position statement serves as a comprehensive guide for the appropriate indications and utilization of 3D-ICE in various structural heart procedures. The paper covers essential aspects such as the fundamentals of 3D-ICE imaging, basic views, and workflow recommendations specifically tailored for ICE-guided structural heart procedures, such as transeptal puncture, device closure of intracardiac structures, and transcatheter mitral and tricuspid valve interventions. Current challenges, future directions, and training requirements to ensure operator proficiency are also discussed, thereby promoting the safety and efficacy of this innovative imaging modality to support expanding its future clinical applications.

Percutaneous management of inferior epigastric artery injury after cardiac catheterization.

Inferior epigastric artery injury after cardiac catheterization and percutaneous coronary intervention is sporadically reported in the literature, yet it is a serious complication that can lead to life-threatening retroperitoneal hemorrhage and poor clinical outcomes after percutaneous coronary intervention. We present two cases of inferior epigastric artery injury from inadvertent puncture during cardiac catheterization and a discussion in the management and prevention of this potentially fatal complication.

NK Cell Adoptive Immunotherapy of Cancer: Evaluating Recognition Strategies and Overcoming Limitations.

Natural killer (NK) cells, the primary effector cells of the innate immune system, utilize multiple strategies to recognize tumor cells by (1) detecting the presence of activating receptor ligands, which are often upregulated in cancer; (2) targeting cells that have a loss of major histocompatibility complex (MHC); and (3) binding to antibodies that bind to tumor-specific antigens on the tumor cell surface. All these strategies have been successfully harnessed in adoptive NK cell immunotherapies targeting cancer. In this review, we review the applications of NK cell therapies across different tumor types. Similar to other forms of immunotherapy, tumor-induced immune escape and immune suppression can limit NK cell therapies' efficacy. Therefore, we also discuss how these limitations can be overcome by conferring NK cells with the ability to redirect their tumor-targeting capabilities and survive the immune-suppressive tumor microenvironment. Finally, we also discuss how future iterations can benefit from combination therapies with other immunotherapeutic agents.

Left Atrial Appendage Closure: Technical Considerations of Endocardial Closure.

Left atrial appendage closure (LAAC) is a safe and effective therapy for the prevention of stroke in patients with nonvalvular atrial fibrillation and high bleeding risk with oral anticoagulants. Multimodality imaging with transesophageal echocardiography and computed tomography angiography to define the anatomy and its implications on endocardial exclusion is becoming increasingly important. The only LAAC device currently approved for clinical use in the United States is the WATCHMAN device. Systematic assessment of the transseptal crossing site, left atrial appendage anatomy, adequate device size selection, and device postdeployment evaluation is essential for the safety and efficacy of the procedure.

Overcoming the transcatheter aortic valve replacement Achilles heel: coronary re-access.

Transcatheter aortic valve replacement (TAVR) is an alternative to surgical aortic valve replacement (SAVR) for the treatment of symptomatic severe aortic stenosis (AS). Coronary artery disease (CAD) is common in patients with severe AS. As the indications for TAVR extend to lower risk patients with longer life expectancy and as CAD is a progressive condition, coronary angiography will become increasingly common in patients who have had a previous TAVR. Coronary artery re-access after TAVR may be challenging but is possible in most cases. Commissural alignment of the prosthesis with the native coronary ostia plays an important role in successful coronary re-access. Coronary artery obstruction is a potentially devastating complication of TAVR, particularly in valve-in-valve procedures. In the present keynote lecture, we review techniques used to mitigate the risk of coronary obstruction, as well as catheter selection and strategies for selective coronary artery engagement for specific transcatheter aortic valve (TAV) bioprostheses.

Predictors and Risk Calculator of Early Unplanned Hospital Readmission Following Contemporary Self-Expanding Transcatheter Aortic Valve Replacement from the STS/ACC TVT Registry.

BACKGROUND: Predictors of hospital readmissions and tools to predict readmissions after TAVR are scarce. Our objective was to identify predictors of early hospital readmission following TAVR in contemporary clinical practice and develop a risk calculator. METHODS: Patients with a contemporary self-expanding TAVR between 2015 and 2017 in the STS/ACC/TVT Registry™ database were included. Patients were divided into a derivation and validation cohort (2:1). A risk score was calculated using the derivation cohort based on multivariable predictors of 30-day unplanned readmissions and applied to the validation cohort. RESULTS: A total of 10,345 TAVR patients at 350 centers were included. Unplanned 30-day hospital readmission was 9.2%. Patients with an early readmission had higher 30-day rates for mortality (2.3% vs. 0.8%, p ≪ 0.001), stroke (4.1% vs. 2.7% p = 0.009), major vascular complications (2.0% vs. 1.0%, p = 0.003) and new pacemaker implantation (25.7% vs. 18.6%, p ≪ 0.001). Multivariable predictors of 30-day readmission included diabetes, atrial fibrillation, advanced heart failure symptoms, home oxygen, decreased 5-m gait speed or the inability to walk, serum creatinine ≫1.6 mg/dL, index hospitalization length of stay ≫5 days, major vascular complication and ≥ moderate post-procedure aortic or mitral valve regurgitation. Based on these predictors, we stratified 30-day readmission risk into low-, moderate- and high-risk subsets. There was a 2.5× difference in readmission rates between the low- (5.8%) and high-risk subsets (14.6%). CONCLUSION: We stratified the risk of early hospital readmission after TAVR based on a simple scoring system. This score may improve discharge planning centered on the individual's readmission risk. SUMMARY: Unplanned readmissions in the United States are prevalent and costly accounting for $41.3 billion in annual hospital payments and are associated with adverse clinical outcomes. We found that diabetes, atrial fibrillation, advanced heart failure symptoms, home oxygen, frailty, acute kidney injury, prolonged hospitalization, major vascular complications, and moderate or worse post-procedure aortic or mitral valve regurgitation predicted of 30-day readmission following self-expanding TAVR. This information may improve discharge planning centered on each patient's readmission risk.

Robot-assisted stereotactic biopsy of pediatric brainstem and thalamic lesions.

OBJECTIVE: Biopsies of tumors located in deep midline structures require highly accurate stereotaxy to safely obtain lesional tissue suitable for molecular and histological analysis. Versatile platforms are needed to meet a broad range of technical requirements and surgeon preferences. The authors present their institutional experience with the robotic stereotactic assistance (ROSA) system in a series of robot-assisted biopsies of pediatric brainstem and thalamic tumors. METHODS: A retrospective analysis was performed of 22 consecutive patients who underwent 23 stereotactic biopsies of brainstem or thalamic lesions using the ROSA platform at Rady Children's Hospital in San Diego between December 2015 and January 2020. RESULTS: The ROSA platform enabled rapid acquisition of lesional tissue across various combinations of approaches, registration techniques, and positioning. No permanent deficits, major adverse outcomes, or deaths were encountered. One patient experienced temporary cranial neuropathy, and 3 developed small asymptomatic hematomas. The diagnostic success rate of the ROSA system was 91.3%. CONCLUSIONS: Robot-assisted stereotactic biopsy of these lesions may be safely performed using the ROSA platform. This experience comprises the largest clinical series to date dedicated to robot-assisted biopsies of brainstem and diencephalic tumors.

Occurrence of pharmaceuticals, hazard assessment and ecotoxicological evaluation of wastewater treatment plants in Costa Rica.

The continuous release of pharmaceuticals from WWTP effluents to freshwater is a matter of concern, due to their potential effects on non-target organisms. The occurrence of pharmaceuticals in WWTPs and their associated hazard have been scarcely studied in Latin American countries. This study aimed at monitoring for the first time the occurrence of 70 pharmaceutical active compounds (PhACs) in WWTPs across Costa Rica; the application of the hazard quotient (HQ) approach coupled to ecotoxicological determinations permitted to identify the hazard posed by specific pharmaceuticals and toxicity of the effluents, respectively. Thirty-three PhACs were found, with 1,7-dimethylxanthine, caffeine, acetaminophen, ibuprofen, naproxen, ketoprofen and gemfibrozil being the most frequently detected (influents/effluents). HQ for specific pharmaceuticals revealed 24 compounds with high/medium hazard in influents, while the amount only decreased to 21 in effluents. The top HQ values were obtained for risperidone, lovastatin, diphenhydramine and fluoxetine (influent/effluent samples), plus caffeine (influent) and trimethoprim (effluent). Likewise, the estimation of overall hazard in WWTP samples (sum of individual HQ, ∑HQ) demonstrated that every influent and 96% of the effluents presented high hazard towards aquatic organisms. Ecotoxicological analysis (Daphnia magna, Lactuca sativa and Microtox test) revealed that 16.7% of the effluents presented toxicity towards all benchmark organisms; the phytotoxicity was particularly frequent, as inhibition values ≥20% in the germination index for L. sativa were obtained for all the effluents. The ∑HQ approach estimated the highest hazard in urban wastewater, while the ecotoxicological results showed the highest toxicity in hospital and landfill wastewater. Likewise, ecotoxicological results and ∑HQ values showed a rather poor correlation; instead, better correlations were obtained between ecotoxicological parameters and HQ values for some individual pharmaceuticals such as cephalexin and diphenhydramine. Findings from this study provide novel information on the occurrence of pharmaceuticals and the performance of WWTPs in the tropical region of Central America.

Rate-controlled intraventricular endoscopic irrigation via bipolar foot pedal activation: technical note.

Irrigation during intraventricular endoscopic surgery is critical for visualization, with normal intracranial pressure maintained by balancing fluid ingress and egress. Although irrigation is typically achieved through manual manipulation of inexact stopcocks, the authors have developed a rate-controlled, foot pedal-activated system for precise intraventricular irrigation by using a standard irrigating bipolar electrocautery machine.This study is a retrospective review of patients who underwent endoscopic intraventricular surgery between January 1, 2018, and September 25, 2019, in which this irrigation system was used. Important components of this system include a bipolar module irrigation regulator that is set to a desired rate, a secure connection of the bipolar irrigation tubing to the endoscope, and one or more open egress ports on the endoscope for passive fluid drainage. Nineteen consecutive patients were identified on review (average age ± SD, 4.3 ± 4.1 years). Procedures performed included third ventriculostomies (n = 10); arachnoid/choroid cyst fenestrations/resections (n = 3); biopsy/tumor resection (n = 1); and combined procedures (n = 5). Foot pedal-controlled irrigation provided visualization of all intraventricular structures. A single operator was able to control the endoscope, endoscopic instruments, and irrigation, with assistance as indicated for more complex maneuvers. There were no perioperative complications. Because this setup is easily constructed from a standard irrigating bipolar machine, delivers precise irrigation flow rates, and facilitates a single-surgeon bimanual technique, these data support the utility of foot-controlled irrigation for endoscopic intraventricular surgery.

Innovations in Transcatheter Valve Technology: What the Next Five Years Hold.

Transcatheter aortic valve replacement is indicated for the treatment of symptomatic severe aortic stenosis in patients at intermediate or greater risk for surgery. Future indications may include low-risk patients, asymptomatic patients, bicuspid valves, moderate aortic stenosis, and pure native aortic valve regurgitation. Key hurdles to overcome include pacemaker risk, vascular injury, paravalvular regurgitation, coronary artery reaccess, durability, and embolic risk. New valve designs include synthetic polymeric valves that may allow for greater durability, in addition to advances in terms of precise positioning and repositioning to reduce the complication rate.