A prospective observational cohort study comparing the treatment effectiveness and safety of ciclosporin, dupilumab and methotrexate in adult and paediatric patients with atopic dermatitis: results from the UK-Irish A-STAR register.

BACKGROUND: The main conventional systemic atopic dermatitis (AD) treatments are methotrexate (MTX) and ciclosporin (CyA). Dupilumab was the first novel systemic agent to enter routine clinical practice. There are no head-to-head randomised controlled trials or real-world studies comparing these agents directly. Network meta-analyses provide indirect comparative efficacy and safety data and have shown strong evidence for dupilumab and CyA. OBJECTIVES: The aim of this study was to compare the real-world clinical effectiveness and safety of CyA, dupilumab and MTX in AD. METHODS: We compared the effectiveness and safety of these systemic agents in a prospective observational cohort study of adult and paediatric patients recruited into the UK-Irish Atopic eczema Systemic TherApy Register (A-STAR). Treatment effectiveness measures included Eczema Area and Severity Index (EASI), Patient-Oriented Eczema Measure (POEM), Peak Pruritus Numerical Rating Scale (PP-NRS), Dermatology Life Quality Index (DLQI) and children's DLQI (cDLQI). Minimum duration of treatment was 28 days and follow-up was 12 months. Adjusted Cox-regression was used to compare the hazards of achieving EASI-50, EASI-75 and EASI-90 over time, and linear mixed-effects models were used to estimate changes in efficacy scores. Treatment safety was assessed by examining adverse events (AEs) at follow-up visits. RESULTS: 488 patients (n=311 adults and n=177 children/adolescents) on dupilumab (n=282), methotrexate (n=149), or CyA (n=57) were included. CyA and MTX were primarily used first line, while dupilumab was mainly a second line systemic as per UK National Institute of Clinical and Care Excellence (NICE) recommendations. EASI-50, EASI-75 and EASI-90 were achieved more rapidly in the dupilumab and CyA groups compared to MTX. After adjustment for previous severity, the reduction in EASI, POEM, PP-NRS and DLQI was greater for patients treated with dupilumab compared to MTX. In severe patients the reduction in EASI, POEM, and PP-NRS was even greater with CyA. The incidence of AEs was similar across groups (734, 654 and 594 per 10,000 person-month on CyA, dupilumab and MTX respectively). CONCLUSIONS: This real-world comparison of CyA, dupilumab and MTX in AD suggests that dupilumab is consistently more effective than MTX and that CyA is most effective in very severe disease within one follow-up year.

Update on Applications and Limitations of Perioperative Tranexamic Acid.

Tranexamic acid (TXA) is a potent antifibrinolytic with documented efficacy in reducing blood loss and allogeneic red blood cell transfusion in several clinical settings. With a growing emphasis on patient blood management, TXA has become an integral aspect of perioperative blood conservation strategies. While clinical applications of TXA in the perioperative period are expanding, routine use in select clinical scenarios should be supported by evidence for efficacy. Furthermore, questions regarding optimal dosing without increased risk of adverse events such as thrombosis or seizures should be answered. Therefore, ongoing investigations into TXA utilization in cardiac surgery, obstetrics, acute trauma, orthopedic surgery, neurosurgery, pediatric surgery, and other perioperative settings continue. The aim of this review is to provide an update on the current applications and limitations of TXA use in the perioperative period.

Coagulation and Transfusion Updates From 2021.

2021 and the COVID 19 pandemic have brought unprecedented blood shortages worldwide. These deficits have propelled national efforts to reduce blood usage, including limiting elective services and accelerating Patient Blood Management (PBM) initiatives. A host of research dedicated to blood usage and management within cardiac surgery has continued to emerge. The intent of this review is to highlight this past year's research pertaining to PBM and COVID-19-related coagulation changes.

The Year in Graduate Medical Education: Selected Highlights From 2021.

This special article is the first in a planned annual series for the Journal of Cardiothoracic and Vascular Anesthesia that will highlight significant literature from the world of graduate medical education (GME) that was published over the past year. The major themes selected for this inaugural review are the educational value of simulation and training workshops, the expanding role of social media and other information technologies in GME and recruitment, the state of residency and fellowship training before the COVID-19 pandemic, and the inevitable effects COVID-19 has had on graduate medical education. The authors would like to thank the editorial board for allowing us to shine a light on a small subset of the writing and research produced in this field, so that educators may understand how best to educate and train the next generation of anesthesiologists.

Direct relationship between transvalvular velocity and cardiac dysfunction, morbidity, and mortality in patients with aortic stenosis.

OBJECTIVE: Current guidelines recommend intervention in subjects with severe symptomatic aortic stenosis (AS), even though any degree of AS is associated with a higher risk of mortality. We investigated the association between the degree of AS, delineated by transvalvular flow velocity, and patient morbidity and mortality. METHODS: Medically managed patients aged 40-95 years with maximum flow velocity (Vmax ) by echocardiography between 2013 and 2018 were stratified into five groups (A-E) based on the 75th, 90th, 97.5th, and the 99th percentiles of Vmax distribution. Patient characteristics, cardiac structural changes, and end-organ disease were compared using Kruskal-Wallis and Cochran-Armitage tests. Mortality over a median of 2.8 (1.52-4.8) years was compared using Kaplan-Meier curves and risk estimates were derived from the Cox model. RESULTS: The Vmax was reported in 37,131 patients. There was a steady increase (from Group A towards E) in age, Caucasian race, structural cardiac changes, end-organ morbidities, and all-cause mortality. In reference to Group A, there as an increased risk of mortality in Groups B (hazard ratio [HR] = 1.3; confidence interval [CI]: 1.2-1.35; p < .0001), C (HR = 1.5; CI: 1.4-1.6; p < .0001), and D (HR = 1.8; CI: 1.6-2; p < .0001), with an exponential increase in Group E (HR = 2.5; CI: 2.2-2.8; p < .0001). CONCLUSIONS: A direct, strong correlation exists between the degree of AS and cardiac structural changes and mortality. Patients with Vmax ≥ 97.5th percentile (≥3.2 m/s) might benefit from early intervention.

Correction to: Callus culture and plantlet regeneration in date palm (Phoenix dactylifera L.): an important horticultural cash crop for arid and semi-arid horticulture.

[This corrects the article DOI: 10.1007/s12298-019-00733-w.].

The Year in Coagulation: Selected Highlights from 2020.

This is the second annual review in the Journal of Cardiothoracic and Vascular Anesthesia to cover highlights in coagulation for cardiac surgery. The goal of this article is to provide readers with a focused summary from the literature of the prior year's most important coagulation topics. In 2020, this included a discussion covering allogeneic transfusion, antiplatelet and anticoagulant therapy, factor concentrates, coagulation testing, mechanical circulatory support, and the effects of coronavirus disease 2019.

Skeletal Muscle Characteristics May Inform Preprocedural Risk Stratification in Transcatheter Aortic Valve Replacement Patients.

OBJECTIVES: Low psoas muscle mass previously has been associated with mortality after transcatheter aortic valve replacement (TAVR). Evidence from other clinical disciplines suggests that psoas density (PD) may be a better predictor than psoas muscle cross-sectional area indexed to body surface area (PI). The authors hypothesized that PD would be more strongly correlated with patient discharge disposition and survival after TAVR than PI. DESIGN: The authors performed a single-center, retrospective study of TAVR patients from 2013 to 2016. PI and PD were assessed at the third lumbar spine level using computed tomography imaging. Propensity-score matching was used to investigate the association of PI and PD with discharge disposition and mortality. SETTING: Tertiary university hospital PARTICIPANTS: Cohort of 245 TAVR patients. INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: A total of 245 patients met inclusion criteria. Following propensity score matching, patients with PI <4 cm2/m2 and PD <25 Hounsfield units (HU) were less likely to survive and to be discharged home compared with patients with PI ≥4 cm2/m2 or PD >25 HU. After repeating the propensity score matching with PI as a covariable, PD remained associated with mortality (90 days: odds ratio [OR] 4.59; 95% confidence interval [CI] 2.96-10.31, p < 0.001, 1 year: OR 6.14; 95% CI 3.45-28.57, p = 0.01, 3 years: OR 4.55; 95% CI 2.41-40.00, p = 0.03). CONCLUSIONS: PD may be more relevant than PI in risk stratification for TAVR patients.

The Year in Coagulation: Selected Highlights From 2019.

This is the first annual highlights in coagulation article to be published in the Journal of Cardiothoracic and Vascular Anesthesia. Its purpose is to review the most important coagulation literature from 2019. In the review, the authors discuss the recent Society of Cardiovascular Anesthesiologists clinical practice advisory on the management of perioperative bleeding and hemostasis, heparin monitoring, protamine dosing, antiplatelet therapy, factor concentrate therapy, and coagulopathy during mechanical circulatory support.

The Program Evaluation Committee in the Adult Cardiothoracic Anesthesiology Fellowship - Harnessing Opportunities for Program Improvement.

The Program Evaluation Committee has an essential role in the quality improvement process of the adult cardiothoracic anesthesiology fellowship. The annual program evaluation presents all stakeholders with an opportunity to evolve with the changing needs and opportunities of the fellowship milieu. The active engagement of the program in this process is a high-quality approach to successful planning, preparation and conduct of the self-study and site visit that are important extensions of the annual program evaluation and the program evaluation committee.

Contemporary Challenges for Fellowship Training in Adult Cardiothoracic Anesthesiology: Perspectives From Program Directors Around the United States.

The fellowship in adult cardiothoracic anesthesiology has matured as an accredited program. This special article addresses current challenges in this educational milieu. The first challenge relates to serving as a program director in the contemporary era. The second challenge deals with the accreditation process, including the site visit. The third challenge discusses the integration of structural heart disease and interventional echocardiography into daily practice. The fourth challenge deals with the issues that face fellowship education in the near future. Taken together, these perspectives provide a review of the contemporary challenges facing fellowship education in adult cardiothoracic anesthesiology.

Mentoring Fellows in Adult Cardiothoracic Anesthesiology for Academic Practice in the Contemporary Era-Perspectives From Mentors Around the United States.

This special article presents perspectives on the mentoring of fellows for academic practice in adult cardiothoracic anesthesiology. A comprehensive mentoring model should address the areas of clinical care, educational expertise and exposure to scholarly activity. The additional value of educational exposure to patient safety, quality improvement and critical care medicine in this model is also explored.

The Year in Cardiothoracic and Vascular Anesthesia: Selected Highlights from 2019.

This highlights in our specialty for 2019 begin with the ongoing major developments in transcatheter valve interventions. Thereafter, the advances in left ventricular assist devices are reviewed. The recent focus on conduit selection and robotic options in coronary artery bypass surgery are then explored. Finally, this special articles closes with a discussion of pulmonary hypertension in noncardiac surgery, anesthetic technique in cardiac surgery, as well as postoperative pneumonia and its outcome consequences.

Successful in vitro fertilization in women with Fontan physiology.

PURPOSE: Patients with single ventricle anatomy palliated with Fontan operation are at risk for thromboembolism, arrhythmia, and heart failure rendering pregnancy high risk or even contraindicated. Infertility and high rates of first trimester miscarriage are not uncommon. In vitro fertilization (IVF) with or without gestational surrogacy can be an option, but poses risks during ovarian stimulation, oocyte retrieval, and the post-procedural period. We present six cases of women with complex congenital heart disease status post Fontan operation who underwent successful IVF. METHODS: Case series from a single-center tertiary care setting. RESULTS: Indications for referral were cardiac or fertility concerns for pregnancy of the congenital cardiologist. One woman had mild volume overload after oocyte retrieval requiring furosemide and one experienced post-operative colitis. There were no thrombotic complications. CONCLUSIONS: A multidisciplinary team-based approach can result in successful oocyte retrieval and IVF in women with complex congenital heart disease and Fontan physiology.

Callus culture and plantlet regeneration in date palm (Phoneix dactylifera L.): an important horticultural cash crop for arid and semi-arid horticulture.

Phoneix dactylifera L. commonly called date palm is a highly valuable horticultural cash crop for arid and semi-arid regions. The availability of offshoots and their survival during plantation are major concern. Being dioecious tree, seed propagation in date palm do not produce true-to-type offspring and tissue culture propagation is the only viable option to supply quality-planting propagules. Hereby, we report callus culture and plantlet regeneration in female date palm using in vitro-derived adventitious shoot bud tissues as explants. Explants (89.33 ± 2.67%) produced callus culture on 0.8% agar-gelled Murashige and Skoog's basal medium containing 100.0 mg l-1 each polyvinylpyrrolidone, ascorbic acid and glutamine, 50.0 mg l-1 each citric acid, adenine sulphate and l-arginine as additives, 0.1% activated charcoal (AC), 100 mg l-1 2,4-dichlorophenoxyacetic acid (2,4-D) and 3.0 mg l-1 2-isopentenyladenine (2-iP). Callus culture were amplified on medium containing 3.0 mg l-1 2-iP along with 50 mg l-1 2,4-D for 2 passages and 10 mg l-1 2,4-D for 2 passages. Cultures grew moderately, organized and subsequently regenerated into shoot bud like structures during gradual transfer from medium containing higher concentration of 2,4-D to lower concentration. Plantlets were developed by sub-culturing of differentiated buds on (1) hormone free medium supplied with 10.0% sucrose and (2) medium containing 100.0 mg l-1 each ascorbic acid and glutamine, 50.0 mg l-1 each citric acid, adenine sulphate and l-arginine as additives, 1.0 mg l-1 each 6-benzylaminopurine, kinetin, 2-iP and α-naphthaleneacetic acid. Plantlets were developed on medium containing 0.1% AC, 1.0 mg l-1 each indole-3-acetic acid and indole-3-butyric acid. Rooted plantlets were soil-transplanted and acclimatized through gradual exposure from in vitro to in vivo conditions. Simple adoption, higher culture regeneration and simultaneous production of rooted plantlets in a cyclic manner render the protocol useful for mass scale propagation of elite genotype of female date palm.

Society of Cardiovascular Anesthesiologists Clinical Practice Improvement Advisory for Management of Perioperative Bleeding and Hemostasis in Cardiac Surgery Patients.

Bleeding after cardiac surgery is a common and serious complication leading to transfusion of multiple blood products and resulting in increased morbidity and mortality. Despite the publication of numerous guidelines and consensus statements for patient blood management in cardiac surgery, research has revealed that adherence to these guidelines is poor, and as a result, a significant variability in patient transfusion practices among practitioners still remains. In addition, although utilization of point-of-care (POC) coagulation monitors and the use of novel therapeutic strategies for perioperative hemostasis, such as the use of coagulation factor concentrates, have increased significantly over the last decade, they are still not widely available in every institution. Therefore, despite continuous efforts, blood transfusion in cardiac surgery has only modestly declined over the last decade, remaining at ≥50% in high-risk patients. Given these limitations, and in response to new regulatory and legislature requirements, the Society of Cardiovascular Anesthesiologists (SCA) has formed the Blood Conservation in Cardiac Surgery Working Group to organize, summarize, and disseminate the available best-practice knowledge in patient blood management in cardiac surgery. The current publication includes the summary statements and algorithms designed by the working group, after collection and review of the existing guidelines, consensus statements, and recommendations for patient blood management practices in cardiac surgery patients. The overall goal is creating a dynamic resource of easily accessible educational material that will help to increase and improve compliance with the existing evidence-based best practices of patient blood management by cardiac surgery care teams.

Differential pharmacokinetic drug-drug interaction potential of eletriptan between oral and subcutaneous routes.

1. Pharmacokinetic drug-drug interaction (DDI) data is important from a label claim either in combination drug usage or in polypharmacy situation. 2. Eletriptan undergoes first pass related metabolism through CYP3A4 enzyme to form pharmacologically active N-desmethyl metabolite. 3. Differential DDI interaction of the concomitant oral dosing of ketoconazole (20.1 mg/kg), a CYP3A4 inhibitor, with oral (4.2 mg/kg) or subcutaneous dose (2.1 mg/kg) of eletriptan was evaluated in male Sprague Dawley rats. Serial pharmacokinetic samples were collected and simultaneously analysed for eletriptan/N-desmethyl eletriptan using validated assay. Non-compartmentally derived pharmacokinetic parameters for various treatments were analysed statistically. 4. After oral eletriptan in presence of ketoconazole, Cmax (40 vs. 32 ng/mL alone) and AUCinf (81 vs. 24 ng.h/mL alone) of eletriptan increased; the formation of N-desmethyl eletriptan decreased (Cmax=1.1 ng/mL, 3.9%) with ketoconazole as compared to without treatment (Cmax=3.7 ng/mL, 11.2%). After subcutaneous eletriptan in presence of ketoconazole, there was no change in Cmax (153 vs.152 ng/mL) or AUCinf (267 vs. 266 ng.h/mL) of eletriptan. Formation of N-desmethyl eletriptan after the subcutaneous dose was determined at few intermittent time points with/without ketoconazole. 5. Preclinical data support differential DDI of eletriptan when dosed oral vs. subcutaneous, which need to be evaluated in a clinical setting.

Rats and rabbits as pharmacokinetic screening tools for long acting intramuscular depots: case study with paliperidone palmitate suspension.

Development of prodrug of 9-hydroxyrisperidone (paliperidone) long-acting intramuscular injection has enabled delivery over four-week time period with improved compliance. The key aim of this work was to establish a reliable preclinical model which may potentially serve as a screening tool for judging the pharmacokinetics of paliperidone formulation(s) prior to human clinical work. Sparse sampling composite study was used in rats, (Wistar/Sprague-Dawley (SD; n = 10)) and a serial blood sampling study design was used in rabbits (n = 4). Animals received intramuscular injection of paliperidone palmitate in the thigh muscle at dose of 16 (rats) and 4.5 mg/kg (rabbits). Samples were drawn in rats (retro-orbital sinus) and rabbits (central ear artery) and were analysed for paliperidone using liquid chromatography-mass spectrometry/ mass spectrometry (LC-MS/MS) assay. The plasma data was subjected to pharmacokinetic analysis. Following intramuscular injection of depot formulation in Wistar/SD rats and rabbits, absorption of paliperidone was slow and gradual with median value of time to reach maximum concentration (Tmax) occurring on day 7. The exposures (i.e. area under the curve (AUC; 0-28) days) were 18,597, 21,865 and 18,120 ng.h/mL, in Wistar, SD and rabbits, respectively. The clearance was slow and supported long half-life (8-10 days). Either one of the two models can serve as a research tool for establishing pharmacokinetics of paliperidone formulation(s).

Operational and Institutional Recommendations and Requirements for TAVR: A Review of Expert Consensus and the Impact on Health Care Policy.

When transcatheter aortic valve replacement (TAVR) was first approved for use in the United States in 2012, multiple leading surgical and cardiology societies were tasked with creating recommendations and requirements for operators and institutions starting and maintaining TAVR programs. Creation of this consensus document was challenging due to limited experience with this new technology, and a lack of robust centralized data that could be used to validate outcome measures and create benchmarks for self-assessment and improvement. Despite these limitations, this document provided government agencies a framework for regulation that ultimately determined requirements for Medicare payment for TAVR and therefore greatly determined how and where care was delivered for patients with aortic stenosis. After the proliferation of TAVR institutions throughout the US and with data from more than 100,000 cases in the STS/ACC Transcatheter Valve Therapies TM Registry, leaders of the same societies reconvened in 2018 to update their consensus document. The new recommendations include suggested personnel, facilities, training, and assessment of outcomes and competencies required to run a safe and efficient TAVR program. This article seeks to detail the changes from the original consensus document with a particular focus on issues relevant to cardiac anesthesiologists as well as important healthcare policy ramifications for patients and providers in the United States.

Practice Pattern Variation in the Use of Transesophageal Echocardiography for Open Valve Cardiac Surgery.

OBJECTIVE: The authors sought to assess for the presence of practice variation in the use of intraoperative transesophageal echocardiography (TEE) for open cardiac valve surgery. DESIGN: This study was a retrospective cohort analysis. SETTING: The administrative claims data used for this investigation were multi-institutional and a representative sample of commercially insured patients in the United States between 2010 and 2015. PARTICIPANTS: The cohort consisted of adult patients, aged 18 years or older, undergoing open mitral valve (MV) or aortic valve (AV) surgery. INTERVENTIONS: This was an observational analysis without interventions. MEASUREMENTS AND MAIN RESULTS: Of 19,386 valve surgeries, 12,313 (64%) underwent AV replacement, 6,192 (32%) underwent MV repair or replacement, and 881 (<5%) underwent both MV and AV surgery. The overall rate of intraoperative TEE was 82% (95% confidence interval [CI]: 81%-82%), less frequently observed in AV procedures compared to MV or combined MV-AV procedures (80% v 85%, p < 0.001). Rates of intraoperative TEE claims varied markedly across U.S. states. After adjustment, the relative odds of an intraoperative TEE claim ranged across states from 0.26 (Louisiana, 95% CI: 0.18-0.36; p < 0.001) to 2.10 (North Carolina, 95% CI: 1.57-2.82; p < 0.001). CONCLUSION: Among adult patients undergoing open AV or MV surgery in the United States, 82% had a claim for an intraoperative TEE with marked variability across U.S. states. Increasing adherence to intraoperative TEE guidelines for valve surgery may represent an unrecognized opportunity to improve the quality of cardiac surgical care.