Non-inferiority study assessing the utility of postcervical and lumbar radiofrequency ablation steroid use.

INTRODUCTION: Many physicians administer steroids after radiofrequency ablation (RFA) to mitigate postprocedural inflammation and decrease postprocedural pain. However, robust evidence supporting the benefits of steroids after RFA is lacking and steroids have risks. METHODS: This study was a single-center, prospective, observational study designed to assess whether RFA alone is inferior to RFA with steroids for postprocedure pain. Eligible patients were at least 18 years of age and scheduled to undergo cervical or lumbar RFA. The primary outcome measure was the average pain score on the numeric rating scale (NRS) 7 days after the RFA. The secondary outcome measures included anxiety, depression and physical function, measured via the Patient-Reported Outcomes Measurement Information System short forms. All outcome measures were completed prior to the procedure and at 7 and 60 days postprocedure. RESULTS: Out of the 365 participants who completed baseline assessments, 175 received steroids and 190 did not receive steroids. The pain intensity at 7 days postprocedure was similar between the steroid and non-steroid groups (mean difference (steroid-non-steroid): -0.23). The 95% CI of the estimate (-0.76 to 0.30) was within the prespecified non-inferiority margin of 1.5 NRS points. Similar results were obtained for pain at 60 days (mean difference: 0.09; 95% CI -0.48 to 0.65). No significant differences between groups were observed for anxiety, depression or physical function at either 7 or 60 days. CONCLUSION: This study suggests that the addition of steroids to the RFA procedure does not provide added benefits and is therefore not worth the additional risks that they pose.

Implementing Screening, Brief Interventions, and Referral to Treatment at Pediatric Trauma Centers: A Step Wedge Cluster Randomized Trial.

BACKGROUND: Pediatric trauma centers have had challenges meeting the American College of Surgeons criteria for screening and intervening for alcohol with adolescent trauma patients. The study objective was to conduct an implementation trial to evaluate the effectiveness of the Science to Service Laboratory (SSL) implementation strategy in improving alcohol and other drugs (AOD) screening, brief intervention, and referral to treatment (SBIRT) delivery at pediatric trauma centers. METHODS: Using a stepped wedge cross-over cluster randomized design, 10 US pediatric trauma centers received the SSL implementation strategy to deliver SBIRT with admitted adolescent (12-17 years old) trauma patients. The strategy adapted three core SSL elements: didactic training, performance feedback, and facilitation. The main outcome measured was SBIRT reach. Data were collected from each center's electronic health record (EHR) during pre- and post-implementation wedges (2018-2022). RESULTS: EHR data from 8461 adolescent patients were extracted. Aggregated across all sites, the reach of screening with a validated AOD screening tool increased significantly from 25.2% (95% CI: 23.9, 26.5%) of adolescents during pre-implementation to 47.7% (95% CI: 46.3%, 49.2%) post-implementation. There was variability of change across centers. Brief interventions continued to be delivered at high levels to identified adolescents. Referral to primary care providers for further AOD discussion or referral to specialty service for adolescents with high risk use did not improve post-implementation and remained low. CONCLUSIONS: The SSL implementation strategy can be successfully utilized by pediatric trauma centers to improve AOD screening, but challenges exist in connecting adolescents for continuation of AOD discussions after discharge. LEVEL OF EVIDENCE: Level II, Therapeutic.

Ethical and Legal Perspectives on the Treatment of Hypoxic Ischemic Encephalopathy in the Newborn.

Hypoxic ischemic encephalopathy (HIE) in neonates can cause severe, life-long functional impairments or death. Treatment of these neonates can involve ethically challenging questions about if, when, and how it may be appropriate to limit life-sustaining medical therapy. Further, parents whose infants suffer severe neurologic damage may seek recourse in the form of a medical malpractice lawsuit. This study uses several hypothetical cases to highlight important ethical and legal considerations in the care of infants with HIE.

Impact of Age on Pharmacogenomics and Treatment Outcomes of B-Cell Acute Lymphoblastic Leukemia.

PURPOSE: Acute lymphoblastic leukemia (ALL) can occur across all age groups, with a strikingly higher cure rate in children compared with adults. However, the pharmacological basis of age-related differences in ALL treatment response remains unclear. METHODS: Studying 767 children and 309 adults with newly diagnosed B-cell ALL enrolled on frontline trials at St Jude Children's Research Hospital, MD Anderson Cancer Center, the Alliance for Clinical Trials in Oncology, and the ECOG-ACRIN Cancer Research Group, we determined the ex vivo sensitivity of leukemia cells to 21 drugs. Twenty-three ALL molecular subtypes were identified using RNA sequencing. We systematically characterized the associations between drug response and ALL genomics in children, adolescents and young adults, and elderly adults. We evaluated the effect of age-related gene expression signature on ALL treatment outcomes. RESULTS: Seven ALL drugs (asparaginase, prednisolone, mercaptopurine, dasatinib, nelarabine, daunorubicin, and inotuzumab ozogamicin) showed differential activity between children and adults, of which six were explained by age-related differences in leukemia molecular subtypes. Adolescents and young adults showed similar patterns of drug resistance as older adults, relative to young children. Mercaptopurine exhibited subtype-independent greater sensitivity in children. Transcriptomic profiling uncovered subclusters within CRLF2-, DUX4-, and KMT2A-rearranged ALL that were linked to age and cytotoxic drug resistance. In particular, a subset of children had adult-like ALL on the basis of leukemia gene expression patterns across subtypes, despite their chronological age. Resistant to cytotoxic drugs, children with adult-like ALL exhibited poor prognosis in pediatric ALL trials, even after adjusting for age and minimal residual diseases. CONCLUSION: Our results provide pharmacogenomic insights into age-related disparities in ALL cure rates and identify leukemia prognostic features for treatment individualization across age groups.

Identifying associations between sample characteristics, symptoms, and self-efficacy differences in adult patients with rare tumors of the central nervous system who participated in a novel web-based natural history study.

OBJECTIVE: High self-efficacy is associated with improved self-care and reduced symptoms in cancer patients but has not been fully interrogated in adults with central nervous system (CNS) cancers. We aimed to identify the relationship between self-efficacy levels in managing emotions (SEMEM) and social interactions (SEMSI) by examining sample characteristics and symptom burden. METHODS: Sample characteristics and patient-reported outcome (PRO) measures addressing self-efficacy (PROMIS SEMEM & SEMSI) and symptom burden (MDASI BT or SP) were collected in a novel web-based study of 158 adult patients diagnosed with rare CNS tumors. RESULTS: The sample was predominantly female (73%), diagnosed with an ependymoma (66%), and had a median age of 45 (19-75). Low SEMEM was associated with a longer duration of symptoms before surgery (r = -0.26) and female gender (92%) among brain tumor (BT) participants and in spinal cord tumors (SCT), those with lower education (r = 0.29). Reporting low SEMSI was associated with being married (42%), lower education (r = 0.22), and a prolonged time with symptoms before surgery (r = 0.29) in those with BTs, with no associations identified in SCT. More severe mood-related interference (including mood, enjoyment of life, and relationship with others) was associated with lower SEMEM among both locations (r = -0.61 brain, r = -0.28 spine) and SEMSI in BT participants (r = -0.54). CONCLUSIONS: Low self-efficacy was linked to a prolonged time between symptom onset and initial surgery, education, gender, and marital status and was associated with higher mood-related interference. Understanding characteristics associated with low self-efficacy underscores a need for future studies to tailor interventions that enhance self-efficacy.

Oculometric biomarkers of visuomotor deficits in clinically asymptomatic patients with systemic lupus erythematosus undergoing long-term hydroxychloroquine treatment.

Introduction: This study examines a set of oculomotor measurements, or "oculometric" biomarkers, as potential early indicators of visual and visuomotor deficits due to retinal toxicity in asymptomatic Systemic Lupus Erythematosus (SLE) patients on long-term hydroxychloroquine (HCQ) treatment. The aim is to identify subclinical functional impairments that are otherwise undetectable by standard clinical tests and to link them to structural retinal changes. Methods: We measured oculomotor responses in a cohort of SLE patients on chronic HCQ therapy using a previously established behavioral task and analysis technique. We also examined the relationship between oculometrics, OCT measures of retinal thickness, and standard clinical perimetry measures of visual function in our patient group using Bivariate Pearson Correlation and a Linear Mixed-Effects Model (LMM). Results: Significant visual and visuomotor deficits were found in 12 asymptomatic SLE patients on long-term HCQ therapy compared to a cohort of 17 age-matched healthy controls. Notably, six oculometrics were significantly different. The median initial pursuit acceleration was 22%, steady-state pursuit gain 16%, proportion smooth 7%, and target speed responsiveness 31% lower, while catch-up saccade amplitude was 46% and fixation error 46% larger. Excluding the two patients with diagnosed mild toxicity, four oculometrics, all but fixation error and proportion smooth, remained significantly impaired compared to controls. Across our population of 12 patients (24 retinae), we found that pursuit latency, initial acceleration, steady-state gain, and fixation error were linearly related to retinal thickness even when age was accounted for, while standard measures of clinical function (Mean Deviation and Pattern Standard Deviation) were not. Discussion: Our data show that specific oculometrics are sensitive early biomarkers of functional deficits in SLE patients on HCQ that could be harnessed to assist in the early detection of HCQ-induced retinal toxicity and other visual pathologies, potentially providing early diagnostic value beyond standard visual field and OCT evaluations.

Effects of mixed land use on urban stormwater quality under different rainfall event types.

The joint effect of mixed land uses and rainfall event types was studied using a two-year field monitoring program in four urban catchments in Calgary, Alberta, Canada. Event mean concentration (EMC) and event pollutant load (EPL) were employed to evaluate the total suspended sediment (TSS), nitrogen and phosphorus. The correlation analysis showed that most nitrogen and phosphorus components (except for NO2-/NO3- and TDP) predominantly exist in particulate form in the study areas. The correlation for EPL was notably stronger than EMC, which can be attributed to varying rainfall characteristics. The differences in EMCs and EPLs of TSS, nitrogen and phosphorus across catchments indicated that the complexity and spatial distribution of mixed land use can influence the generation and transportation of pollutants in urban runoff. The impacts of rainfall characteristics on stormwater quality are integrated rather than driven by a single rainfall characteristic. Brief but intense events tended to elevate TSS, nitrogen and phosphorus concentrations, especially in complex land-use catchments. Events with long antecedent dry days and short duration also resulted in increased pollutant concentrations, while events with long duration and low intensity could result in higher EPLs. The effect of mixed land use on water quality can vary depending on rainfall event types. Seasonal variations were found in EMC and EPL of TSS, nitrogen and phosphorus, with higher values in the spring and summer than the fall. Seasonal variations are mainly influenced by rainfall conditions, temperature and anthropogenic activities (e.g. lawn fertilization and de-icing with sands). MLR considering rainfall characteristics is an effective method for predicting stormwater quality within a single catchment. Considering complexity and spatial distribution of mixed land use can improve the accuracy of the harmonized MLR model. This research provided insights into understanding the complexities introduced by mixed land use and rainfall event types in urban stormwater quality.

Cross-coupling of CO and an isocyanide mediated by a tetrameric magnesium hydride cluster.

Sequential addition of CNXyl (Xyl = 2,6-dimethylphenyl) and CO to a tetrametallic magnesium hydride cluster results in stepwise reduction and cross-coupling of these substrates. Cross-coupling results in the formation of an ethene amidolate ligand [OC1(H1)[double bond, length as m-dash]C2(H2)NAr]2- a previously unknown entity which contains a 1,2-difunctionalised carbon chain reminiscent of those found in aminoalcohols and amino acids. To the best of our knowledge, this is the first example of such reactivity with metal hydride precursors. DFT calculations support a mechanism that parallels that established for coupling of CO to form ethenediolate ligands, with the key carbon-carbon bond step occurring by nucleophilic attack of a putative azamethylene intermediate on CO. The cluster plays a key role in templating the synthesis, providing kinetic control over each of the steps. The ethene amidolate ligand can be transferred to other metals (Al) and semi-metals (B) through onwards metathesis reactions.

Hip Arthroscopy Versus Physical Therapy for the Treatment of Symptomatic Acetabular Labral Tears in Patients Older Than 40 Years: 24-Month Results From a Randomized Controlled Trial.

BACKGROUND: The indications for hip arthroscopy in patients aged ≥40 years remain controversial, as observational studies have suggested that advanced age portends poor functional outcomes, poor durability of improvement, and high rates of conversion to total hip arthroplasty. PURPOSE: To compare hip arthroscopy versus nonoperative management for symptomatic labral tears in patients aged ≥40 years with limited radiographic osteoarthritis. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: This single-surgeon, parallel randomized controlled trial included patients aged ≥40 years with limited osteoarthritis (Tönnis grades 0-2) who were randomized 1:1 to arthroscopic surgery with postoperative physical therapy (SPT) or physical therapy alone (PTA). Patients who received PTA and achieved unsatisfactory improvement were permitted to cross over to SPT after completing ≥14 weeks of physical therapy (CO). The primary outcomes were the International Hip Outcome Tool-33 score and modified Harris Hip Score at 24 months after surgery, and secondary outcomes included other patient-reported outcome measures and the visual analog scale for pain. The primary analysis was performed on an intention-to-treat basis using linear mixed-effects models. Sensitivity analyses included modified as-treated and treatment-failure analyses. RESULTS: A total of 97 patients were included, with 52 (53.6%) patients in the SPT group and 45 (46.4%) patients in the PTA group. Of the patients who underwent PTA, 32 (71.1%) patients crossed over to arthroscopy at a mean of 5.10 months (SD, 3.3 months) after physical therapy initiation. In both intention-to-treat and modified as-treated analyses, the SPT group displayed superior mean patient-reported outcome measure and pain scores across the study period for nearly all metrics relative to the PTA group. In the treatment-failure analysis, the SPT and CO groups showed greater improvement across all metrics compared with PTA; however, post hoc analyses revealed no significant differences in improvement between the SPT and CO groups. No significant differences were observed between groups in rates of total hip arthroplasty conversion. CONCLUSION: In patients ≥40 years of age with limited osteoarthritis, hip arthroscopy with postoperative physical therapy led to better outcomes than PTA at a 24-month follow-up. However, additional preoperative physical therapy did not compromise surgical outcomes and allowed some patients to avoid surgery. When surgery is indicated, age ≥40 years should not be considered an independent contraindication to arthroscopic acetabular labral repair. REGISTRATION: NCT03909178 (ClinicalTrials.gov identifier).

A Scaled Proteomic Discovery Study for Prostate Cancer Diagnostic Markers Using ProteographTM and Trapped Ion Mobility Mass Spectrometry.

There is a significant unmet need for clinical reflex tests that increase the specificity of prostate-specific antigen blood testing, the longstanding but imperfect tool for prostate cancer diagnosis. Towards this endpoint, we present the results from a discovery study that identifies new prostate-specific antigen reflex markers in a large-scale patient serum cohort using differentiating technologies for deep proteomic interrogation. We detect known prostate cancer blood markers as well as novel candidates. Through bioinformatic pathway enrichment and network analysis, we reveal associations of differentially abundant proteins with cytoskeletal, metabolic, and ribosomal activities, all of which have been previously associated with prostate cancer progression. Additionally, optimized machine learning classifier analysis reveals proteomic signatures capable of detecting the disease prior to biopsy, performing on par with an accepted clinical risk calculator benchmark.

A growth-differentiation factor 15 receptor agonist in randomized placebo-controlled trials in healthy or obese persons.

BACKGROUND: Growth Differentiation Factor 15 (GDF15), a divergent member of the TGF-ß superfamily, signals via the hindbrain glial-derived neurotrophic factor receptor alpha-like and rearranged during transfection receptor co-receptor (GFRAL-RET) complex. In nonclinical species, GDF15 is a potent anorexigen leading to substantial weight loss. MBL949 is a half-life extended recombinant human GDF15 dimer. METHODS: MBL949 was evaluated in multiple nonclinical species and then in humans in two randomized and placebo-controlled clinical trials. In the Phase 1 first-in-human, single ascending dose trial MBL949 or placebo was injected subcutaneously to overweight and obese healthy volunteers (n=65) at doses ranging from 0.03 to 20 mg. In Phase 2, MBL949 or placebo was administered subcutaneously every other week for a total of 8 doses to obese participants (n=126) in five different dose regimens predicted to be efficacious based on data from the Phase 1 trial. RESULTS: In nonclinical species, MBL949 was generally safe and effective with reduced food intake and body weight in mice, rats, dogs, and monkeys. Weight loss was primarily from reduced fat, and metabolic endpoints improved. A single ascending dose study in overweight or obese healthy adults demonstrated mean terminal half-life of 18-22 days, and evidence of weight loss at the higher doses. In the Phase 2, weight loss was minimal following biweekly dosing of MBL949 for 14 weeks. MBL949 was safe and generally tolerated in humans over the dose range tested, adverse events of the gastrointestinal system were the most frequent observed. CONCLUSION: The prolonged half-life of MBL949 supports biweekly dosing in patients. MBL949 had an acceptable safety profile. The robust weight loss observed in nonclinical species did not translate to weight loss efficacy in humans. TRIAL REGISTRATION: ClinicalTrials.gov NCT05199090.

An engineered lactate oxidase based electrochemical sensor for continuous detection of biomarker lactic acid in human sweat and serum.

Lactate levels in humans reveal intensity and duration of exertion and provide a critical readout for the severity of life-threatening illnesses such as pediatric sepsis. Using the lactate oxidase enzyme (Lox) from Aerococcus viridians, we demonstrated its functionality for lactate electrochemical sensing in physiological fluids in a lab setting. The structure and dynamics of LOx were validated by crystallography, X-ray scattering, and hydroxyl radical protein footprinting. This provided a validated protein template for understanding and designing an enzyme-based electrochemical sensing elements. Using this template, LOx enzyme variants were generated and compared. Comparison of the variants demonstrates that one exhibits effective lactate sensing at significantly reduced operating voltages. Additionally, we demonstrate that the four hexahistidine-tags on each enzyme tetramer are sufficient for immobilization to create a durable, functional sensor, with no need for a covalent attachment, enabling self-immobilization and eliminating the need for additional immobilization steps. The functionality of the LOx enzyme variants was verified at physiological lactate concentrations in both human serum (0-4 mM) and artificial sweat (0-100 mM) using 3-electrode setups for analysis of the three variants in parallel. Accuracy of measurement in both artificial sweat and human serum were high. Employing a microfluidic flow cell, we successfully monitored varying lactate levels in physiological fluids continuously over a 2h period. Overall, this optimized LOx enzyme, which self-immobilizes onto gold sensing electrodes, facilitates efficient and reliable lactate detection and continuous monitoring at reduced operating voltages suitable for further development towards commercial use.

Alterations of the skeletal muscle nuclear proteome after acute exercise reveals a post-transcriptional influence.

Exercise is firmly established as a key contributor to overall well-being and is frequently employed as a therapeutic approach to mitigate various health conditions. One pivotal aspect of the impact of exercise lies in the systemic transcriptional response, which underpins its beneficial adaptations. While extensive research has been devoted to understanding the transcriptional response to exercise, our knowledge of the protein constituents of nuclear processes that accompany gene expression in skeletal muscle remains largely elusive. We hypothesize that alterations in the nuclear proteome following exercise hold vital clues for comprehending the transcriptional regulation and other related nuclear functions. We isolated skeletal muscle nuclei from C57BL/6 mice both sedentary control and one-hour post 30-minute treadmill running, to gain insights into the nuclear proteome after exercise. A substantial number of the 2,323 proteins identified, were related to nuclear functions. For instance, we found 59 proteins linked to nucleocytoplasmic transport were higher in sedentary mice compared to exercise, hinting at an exercise-induced modulation to nuclear trafficking. Furthermore, 135 proteins exhibited increased abundance after exercise (FDR < 0.1) while 89 proteins decreased, with the most prominent changes in proteins linked to mRNA processing and splicing. Super resolution microscopy further highlights potential localization change in mRNA processing proteins post-exercise, further suggesting changes in nuclear transport dynamics. Nonetheless, our data provide important considerations for the study of the nuclear proteome and supports a paradigm through which exercise downregulated mRNA processing and splicing, offering valuable insights into the broader landscape of the impact from acute exercise. New & Noteworthy: Exercise plays a crucial role in promoting muscle health, but our understanding of nuclear proteins orchestrating exercise responses is limited. Isolation of skeletal muscle nuclei coupled with mass spectrometry enhanced the identification of nuclear proteins. This approach was used to investigate the effects of acute exercise, revealing changes in the muscle nuclear proteome 1-hour post-exercise, including proteins linked to post-transcriptional processing and splicing. Our findings offer insights into the exercise-induced changes within muscle nuclear proteins.

Pregnancy in women with a Fontan circulation: Short and long-term outcomes.

BACKGROUND: The Fontan circulation procedure is the palliative surgery of choice for patients with single ventricle physiology, many of whom are now reaching childbearing age due to advances in care. Our study examines the impact of pregnancy on women with Fontan circulation, assessing both short and long-term outcomes. METHODS: We retrospectively analysed pregnancies in women with Fontan circulation at our centre from 2005 to 2023, including a matched non-pregnant, nulliparous cohort for comparison. Pregnancies lost before 18 weeks were analysed separately. RESULTS: Among 26 pregnancies in 18 women, preterm births were common (73.1%), with 3 fetal losses and no maternal deaths. Neonatal complications included a 50% incidence of babies small for gestational age (SGA). Cardiac events occurred in 19.2% of pregnancies, primarily supraventricular arrhythmias, and 23% experienced postpartum haemorrhage. Over a median 6.1 [5.2-10.6]-year follow-up, no deaths, heart failure (HF), or Fontan-associated liver disease (FALD) developed, and functional status remained stable. CONCLUSIONS: Women with a Fontan-type circulation undergoing pregnancy had a few serious maternal cardiac events, though there was a high rate of post-partum haemorrhage. The rates of neonatal complications, particularly related to restricted growth and pre-term birth, were also high. Our findings indicate a generally positive medium-term outlook for these patients, though the impact of pregnancy on long-term survival remains unclear. Careful selection of patients with Fontan circulation during pre-pregnancy counselling may help to reduce complications during and after pregnancy.

Acute sleep deprivation in mice generates protein pathology consistent with neurodegenerative diseases.

Introduction: Insufficient or disturbed sleep is strongly associated with adverse health conditions, including various neurodegenerative disorders. While the relationship between sleep and neurodegenerative disease is likely bidirectional, sleep disturbances often predate the onset of other hallmark clinical symptoms. Neuronal waste clearance is significantly more efficient during sleep; thus, disturbed sleep may lead to the accumulation of neuronal proteins that underlie neurodegenerative diseases. Key pathological features of neurodegenerative diseases include an accumulation of misfolded or misprocessed variants of amyloid beta (Aß), tau, alpha synuclein (α-syn), and TarDNA binding protein 43 (TDP-43). While the presence of fibrillar protein aggregates of these neuronal proteins are characteristic of neurodegenerative diseases, the presence of small soluble toxic oligomeric variants of these different proteins likely precedes the formation of the hallmark aggregates. Methods: We hypothesized that sleep deprivation would lead to accumulation of toxic oligomeric variants of Aß, tau, α-syn, and TDP-43 in brain tissue of wild-type mice. Adult mice were subjected to 6 h of sleep deprivation (zeitgeber 0-6) for 5 consecutive days or were left undisturbed as controls. Following sleep deprivation, brains were collected, and protein pathology was assessed in multiple brain regions using an immunostain panel of reagents selectively targeting neurodegenerative disease-related variants of Aß, tau, α-syn, and TDP-43. Results: Overall, sleep deprivation elevated levels of all protein variants in at least one of the brain regions of interest. The reagent PDTDP, targeting a TDP-43 variant present in Parkinson's disease, was elevated throughout the brain. The cortex, caudoputamen, and corpus callosum brain regions showed the highest accumulation of pathology following sleep deprivation. Discussion: These data provide a direct mechanistic link between sleep deprivation, and the hallmark protein pathologies of neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases.

Resolution of the Aleiodesseriatus (Herrich-Schäffer, 1838)-aggregate in the western Palaearctic (Hymenoptera, Braconidae, Rogadinae), with description of a new species.

Two European species are recognised and characterised within the traditional Aleiodesseriatus species concept, based initially on DNA barcoding but with supporting, although slight and sometimes unreliable, morphological differences. Aleiodespseudoseriatus sp. nov. is described and a neotype is designated for Rogasseriatus Herrich-Schäffer, 1838. Specimens from the Russian Far East were also DNA barcoded and were found to belong to a new species distinct from the two European taxa. The two European species were found to use different lithosiine hosts.

Outcomes and quality of life in patients receiving durable left ventricular assist device with biventricular support.

BACKGROUND: Patients requiring biventricular support (BIVAD) face higher morbidity than those undergoing durable left ventricular assist device (LVAD) implantation alone. The goal of the current study was to evaluate quality of life (QOL) of patients with LVAD therapy in the modern era, stratified by use of biventricular support. METHODS: All patients undergoing LVAD at our center were reviewed between October 2017 and September 2021. Patients were stratified by perioperative use of BIVAD. Patients were administered a telephone survey consisting of the Kansas City Cardiomyopathy Questionnaire (KCCQ-12) as well as free-responses regarding satisfaction surrounding their operation. Outcomes included survival, KCCQ-12 metrics, and thematic analysis of free response questions. RESULTS: 92 patients were identified, of whom 26 (28%) received BIVAD support. BIVAD patients had more preoperative ECMO use (54% vs. 12%, p < 0.001) and lower INTERMACS scores (Category 1: 46% vs. 14%, p = 0.001). Three-year survival was 73.8% among LVAD-alone patients and 50.1% among BIVAD patients (log-rank p = 0.022). Median composite KCCQ-12 score was 78 (57-88). No differences in composite or any component scores were noted between groups. 76% of patients report they would be moderately or extremely like to go through surgery again if given repeat choice. The most common themes expressed were overall gratitude (24%) and disappointment with device-related restrictions (20%). CONCLUSIONS: Patients requiring BIVAD therapy have more advanced shock, longer associated hospital courses, and lower long-term survival. However, those that survive enjoy similar overall quality of life, and many endorse positive outlooks on their surgical course. Continued assessments of quality of life are important in providing patient-centered LVAD care.

ACE Inhibitor and Angiotensin Receptor Blocker use during Pregnancy: data from the ESC Registry Of Pregnancy And Cardiac disease (ROPAC).

Angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) are not recommended during the second and third trimester due to the significant risk of congenital anomalies associated with their use. However, data are scarce, especially regarding their use in the first trimester and about the impact of stopping just before pregnancy. Our study illustrates the profile of the women who used ACE-Is or ARBs during pregnancy and evaluates the impact on perinatal outcomes. The Registry of Pregnancy and Cardiac disease (ROPAC) is a prospective, global registry of pregnancies in women with structural heart disease. Outcomes were compared between women who used ACE-Is or ARBs and those who did not. Multivariable regression analysis was performed to assess the effect of ACE-I or ARB use on the occurrence of congenital anomalies. ACE-I (n=35) and/or ARB (n=8) were used in 42 (0.7%) of the 5739 ROPAC pregnancies. Women who used ACE-Is or ARBs more often came from a low-or-middle-income country (57% vs 40%, p=0.021), had chronic hypertension (31% vs 6%, p<0.001), or a left ventricular ejection fraction <40% (33% vs 4%, p<0.001). In the multivariable analysis, ACE-I use during the first trimester was associated with an increased risk of congenital anomaly (OR 3.2; 95% CI 1.0-9.6). Therefore, ACE-Is should be avoided during pregnancy, also in the first trimester, due to a higher risk of congenital anomalies. However, there is no need to stop long before pregnancy. Preconception counseling is crucial to discuss the potential risks of these medications, to evaluate the clinical condition and, if possible, change or stop the medication.