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Context: Perioperative red blood cell transfusion is commonly used to address anemia, an independent risk factor for morbidity and mortality after cardiac operations; however, evidence regarding optimal blood transfusion practice in patients undergoing cardiac surgery is lacking.Objective: To define whether a restrictive perioperative red blood cell transfusion strategy is as safe as a liberal strategy in patients undergoing elective cardiac surgery.Design, Setting, and Patients: The Transfusion Requirements After Cardiac Surgery (TRACS) study, a prospective, randomized, controlled clinical noninferiority trial conducted between February 2009 and February 2010 in an intensive care unit at a university hospital cardiac surgery referral center in Brazil. Consecutive adult patients (n = 502) who underwent cardiac surgery with cardiopulmonary bypass were eligible; analysis was by intention-to-treat.Intervention: Patients were randomly assigned to a liberal strategy of blood transfusion (to maintain a hematocrit ≥30%) or to a restrictive strategy (hematocrit ≥24%).Main Outcome Measure: Composite end point of 30-day all-cause mortality and severe morbidity (cardiogenic shock, acute respiratory distress syndrome, or acute renal injury requiring dialysis or hemofiltration) occurring during the hospital stay. The noninferiority margin was predefined at -8% (ie, 8% minimal clinically important increase in occurrence of the composite end point).Results: Hemoglobin concentrations were maintained at a mean of 10.5 g/dL (95% confidence interval [CI], 10.4-10.6) in the liberal-strategy group and 9.1 g/dL (95% CI, 9.0-9.2) in the restrictive-strategy group (P < .001). A total of 198 of 253 patients (78%) in the liberal-strategy group and 118 of 249 (47%) in the restrictive-strategy group received a blood transfusion (P < .001). Occurrence of the primary end point was similar between groups (10% liberal vs 11% restrictive; between-group difference, 1% [95% CI, -6% to 4%]; P = .85). Independent of transfusion strategy, the number of transfused red blood cell units was an independent risk factor for clinical complications or death at 30 days (hazard ratio for each additional unit transfused, 1.2 [95% CI, 1.1-1.4]; P = .002).Conclusion: Among patients undergoing cardiac surgery, the use of a restrictive perioperative transfusion strategy compared with a more liberal strategy resulted in noninferior rates of the combined outcome of 30-day all-cause mortality and severe morbidity.Trial Registration: clinicaltrials.gov Identifier: NCT01021631. [ABSTRACT FROM AUTHOR]

Introduction: Surgery is a cost-effective public health intervention. Access to safe surgery is a basic human right. However, there are still significant disparities in the access to and safety of surgical and anaesthesia care between low-income and middle-income countries and high-income countries. The Latin American Surgical Outcomes Study in Paediatrics (LASOS-Peds) is an international, observational, 14-day cohort study to investigate the incidence of 30-day in-hospital complications following elective or emergency paediatric surgery in Latin American countries., Methods and Analysis: LASOS-Peds is a prospective, international, multicentre observational study of paediatric patients undergoing both elective and non-elective surgeries and procedures, inpatient and outpatient, including those performed outside the operating room. The primary outcome is the incidence of in-hospital postoperative complications up to 30 days after surgery. Secondary outcomes include intraoperative complications and the need for intensive care unit admission., Ethics and Dissemination: This study received approval from the Institutional Review Board of the coordinating centre (Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo) as well as from all the participating centres. The study results are expected to be published in peer-reviewed journals and disseminated at international conferences., Trial Registration Number: NCT05934682., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: There are limited data on the physical effects of androgen deprivation therapy (ADT) for prostate cancer (PC), and on the relationships of such measures of adiposity and strength to cardiovascular outcomes., Objectives: The primary objective of this study was to evaluate the relationships of measures of adiposity and strength to cardiovascular outcomes (cardiovascular death, myocardial infarction, stroke, heart failure, arterial revascularization, peripheral arterial disease, and venous thromboembolism) in patients with PC. A secondary objective was to characterize the relationships between ADT use and 12-month changes in these physical measures., Methods: This international, prospective cohort study included 3,967 patients with PC diagnosed in the prior 12 months or being treated with ADT for the first time. Median follow-up duration was 2.3 years., Results: Participants' mean age was 68.5 years, and 1,731 (43.6%) were exposed to ADT. ADT was associated with a 1.6% increase in weight, a 2.2% increase in waist circumference, a 1.6% increase in hip circumference, a 0.1% increase in waist-to-hip ratio, a 27.4% reduction in handgrip strength, and a 0.1% decrease in gait speed. High waist circumference and low handgrip strength were associated with adverse cardiovascular outcomes. Adjusting for age, education, race, tobacco and alcohol use, physical activity, cardiovascular disease, glomerular filtration rate, and ADT use, waist circumference above the highest quartile (110 cm) and handgrip strength below the lowest quartile (29.5 kg) were associated with higher likelihoods of a future cardiovascular event, with respective HRs of 1.40 (95% CI: 1.03-1.90; P  = 0.029) and 1.59 (95% CI: 1.14-2.22; P  = 0.006)., Conclusions: ADT was associated with increased adiposity and reduced strength over 12-month follow-up. High waist circumference and low baseline strength were associated with future adverse cardiovascular outcomes., Competing Interests: Research support for this study was provided by the Movember Foundation, the Canadian Cancer Society, and Tolmar Pharmaceuticals. This study was presented in part at a Late-Breaking Science Session at the Scientific Sessions of the European Society of Cardiology, Amsterdam, the Netherlands, August 28, 2023. Dr Leong has received consultancy fees or honoraria from Abbvie, Ferring, Ipsen, Janssen, Jazz Pharmaceuticals, Myovant, Novartis, Pfizer, Sanofi, Antev, AstraZeneca, Bayer, Boston Scientific, and XFacto; and has received research support from Novartis and Tolmar. Dr Higano has received consultancy fees or honoraria from AstraZeneca, Astellas, Bayer, Genetech, Eli Lilly, Merck Sharp & Dohme, Myovant, Menarini, Tolmar, Vaccitech, and Verity; is a stockholder of CTI Biopharma; and is a data and safety monitoring board member or chair in trials sponsored by AstraZeneca, Advantagene, and Exelixis. Dr Lavallée is an advisory board member for Astellas, Knight, Bayer, and AAA; and has received a grant from Tolmar unrelated to the present work. Dr Gopaul is an advisory board member for and has received honoraria from TerSera, Bayer, Ferring, Abbvie, and Knight. Dr Duceppe has received grant funding from Roche Diagnostics and Abbott Laboratories. Dr Guha is an advisory board member for Pfizer, Myovant, and Novartis; and has received research grants from the American Heart Association (847740 and 863620) and the U.S. Department of Defense PC Research Program (HT94252310158). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Aims: Cardiogenic shock (CS) and cardiac arrest (CA) are serious complications in ST-elevation myocardial infarction (STEMI) patients, with lack of long-term data according to their timing of occurrence. This study sought to determine the incidence and relationship between the timing of occurrence and prognostic impact of CS and CA complicating STEMI in the long-term follow-up., Methods and Results: We conducted a retrospective analysis of consecutive STEMI patients treated between 2004 and 2017. Patients were divided into four groups based on the occurrence of neither CA nor CS, CA only, CS only, and both CA and CS (CA-CS-, CA+, CS+, and CA+CS+, respectively). Adjusted Cox regression analysis was used to assess the independent association between the CS and CA categories and mortality. A total of 1603 STEMI patients were followed for a median of 3.6 years. CA and CS occurred in the 12.2% and 15.9% of patients, and both impacted long-term mortality [adjusted hazard ratio (HR) = 2.59, 95% confidence interval (CI): 1.53-4.41, P < 0.001; HR = 3.16, 95% CI: 2.21-4.53, P < 0.001, respectively). CA+CS+ occurred in 7.3%, with the strongest association with higher mortality (adjusted HR = 5.36; 95% CI: 3.80-7.55, P < 0.001). Using flexible parametric models with B-splines, the increased mortality was restricted to the first ∼10 months. In addition, overall mortality rates were higher at all timings (all with P < 0.001), except for CA during initial cardiac catheterization ( P < 0.183)., Conclusion: CS and CA complicating patients presenting with STEMI were associated with higher long-term mortality rate, especially in the first 10 months. Both CS+ and CA+ at any timeframe impacted outcomes, except for CA+ during the initial cardiac catheterization, although this will have to be confirmed in larger future studies, given the relatively small number of patients., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Once a patient has been diagnosed with severe COVID-19 pneumonia, treatment options have limited effectiveness. Opaganib is an oral treatment under investigation being evaluated for treatment of hospitalized patients with severe COVID-19 pneumonia. A randomized, placebo-controlled, double-blind phase 2/3 trial was conducted in 57 sites worldwide from August 2020 to July 2021. Patients received either opaganib (n = 230; 500 mg twice daily) or matching placebo (n = 233) for 14 days. The primary outcome was the proportion of patients no longer requiring supplemental oxygen by day 14. Secondary outcomes included changes in the World Health Organization Ordinal Scale for Clinical Improvement, viral clearance, intubation, and mortality at 28 and 42 days. Pre-specified primary and secondary outcome analyses did not demonstrate statistically significant benefit (except nominally for time to viral clearance). Post-hoc analysis revealed the fraction of inspired oxygen (FIO 2 ) at baseline was prognostic for opaganib treatment responsiveness and corresponded to disease severity markers. Patients with FIO 2 levels at or below the median value (≤60%) had better outcomes after opaganib treatment (n = 117) compared to placebo (n = 134). The proportion of patients with ≤60% FIO 2 at baseline that no longer required supplemental oxygen (≥24 h) by day 14 of opaganib treatment increased (76.9% vs. 63.4%; nominal p -value = 0.033). There was a 62.6% reduction in intubation/mechanical ventilation (6.84% vs. 17.91%; nominal p -value = 0.012) and a clinically meaningful 62% reduction in mortality (5.98% vs. 16.7%; nominal p -value = 0.019) by day 42. No new safety concerns were observed. While the primary analyses were not statistically significant, post-hoc analysis suggests opaganib benefit for patients with severe COVID-19 requiring supplemental oxygen with an FIO 2 of ≤60%. Further studies are warranted to prospectively confirm opaganib benefit in this subpopulation.

Background: Trimodulin (human polyvalent immunoglobulin [Ig] M ~ 23%, IgA ~ 21%, IgG ~ 56% preparation) has previously been associated with a lower mortality rate in a subpopulation of patients with severe community-acquired pneumonia on invasive mechanical ventilation (IMV) and with clear signs of inflammation. The hypothesis for the ESsCOVID trial was that trimodulin may prevent inflammation-driven progression of severe coronavirus disease 2019 (COVID-19) to critical disease or even death., Methods: Adults with severe COVID-19 were randomised to receive intravenous infusions of trimodulin or placebo for 5 consecutive days in addition to standard of care. The primary efficacy endpoint was a composite of clinical deterioration (Days 6-29) and 28-day all-cause mortality (Days 1-29)., Results: One-hundred-and-sixty-six patients received trimodulin (n = 84) or placebo (n = 82). Thirty-three patients died, nine during the treatment phase. Overall, 84.9% and 76.5% of patients completed treatment and follow-up, respectively. The primary efficacy endpoint was reported in 33.3% of patients on trimodulin and 34.1% of patients on placebo (P = 0.912). No differences were observed in the proportion of patients recovered on Day 29, days of invasive mechanical ventilation, or intensive care unit-free days. Rates of treatment-emergent adverse events were comparable. A post hoc analysis was conducted in patients with early systemic inflammation by excluding those with high CRP (> 150 mg/L) and/or D-dimer (≥ 3 mg/L) and/or low platelet counts (< 130 × 10 9 /L) at baseline. Forty-seven patients in the trimodulin group and 49 in the placebo group met these criteria. A difference of 15.5 percentage points in clinical deterioration and mortality was observed in favour of trimodulin (95% confidence interval: -4.46, 34.78; P = 0.096)., Conclusion: Although there was no difference in the primary outcome in the overall population, observations in a subgroup of patients with early systemic inflammation suggest that trimodulin may have potential in this setting that warrants further investigation. ESSCOVID WAS REGISTERED PROSPECTIVELY AT CLINICALTRIALS.GOV ON OCTOBER 6, 2020.: NCT04576728., (© 2024. The Author(s).)

It is unclear whether muscle blood flow (MBF) is altered in long-term Hodgkin lymphoma (HL) survivors. We tested the hypothesis that 1 ) MBF response during mental stress (MS) is impaired in long-term HL survivors and 2 ) aerobic exercise training combined with local strength exercise (ET) restores MBF responses during MS in these survivors. Eighteen 5-year HL survivors and 10 aged-paired healthy subjects (HC) were studied. Twenty HL survivors were randomly divided into two groups: exercise-trained (HLT, n = 10) and untrained (HLUT, n = 10). Maximal aerobic capacity was evaluated by a cardiopulmonary exercise test and forearm blood flow (FBF) by venous occlusion plethysmography. MS was elicited by Stroop color and word test. ET was conducted for 4 mo, 3/wk for 60 min each session. The aerobic exercise intensity corresponded to anaerobic threshold up to 10% below the respiratory compensation point. The strength exercises consisted of two to three sets of chest press, pulley and squat exercises, 12-15 repetitions each exercise at 30-50% of the maximal voluntary contraction. Baseline was similar in HL survivors and HC, except peak oxygen consumption (peak V̇o 2 , P = 0.013) and FBF ( P = 0.006) that were lower in the HL survivors. FBF responses during MS were lower in HL survivors ( P < 0.001). ET increased peak V̇o 2 (11.59 ± 3.07%, P = 0.002) and FBF at rest (33.74 ± 5.13%, P < 0.001) and during MS (24 ± 5.31%, P = 0.001). Further analysis showed correlation between the changes in peak V̇o 2 and the changes in FBF during MS (r = 0.711, P = 0.001). In conclusion, long-term HL survivors have impaired MBF responses during MS. ET restores MBF responses during MS. NEW & NOTEWORTHY Long-term Hodgkin lymphoma (HL) survivors have impaired muscle blood flow responses during mental stress and decreased maximal aerobic capacity. Supervised aerobic exercise training combined with local strength exercises restores muscle blood flow responses during mental stress and maximal aerobic capacity in these survivors. These findings provide evidence of safety and effectiveness of exercise training in HL survivors. Moreover, they highlight the importance of exercise training in the treatment of this set of patients.

Background: Oncological patients with coronary artery disease face an elevated risk of hemorrhagic and ischemic events following percutaneous coronary intervention. Despite medical guidelines recommending minimal dual antiplatelet therapy (DAPT) duration for patients with cancer, dedicated data on abbreviated DAPT in this population is lacking. This study aims to evaluate the occurrence of ischemic and hemorrhagic events in patients with cancer compared with other high-bleeding risk individuals., Methods: Patient-level data from 4 high-bleeding risk coronary drug-eluting stent studies (ONYX One, LEADERS FREE, LEADERS FREE II, and SENIOR trials) treated with short DAPT were analyzed. The comparison focused on patients with high-bleeding risk with and without cancer, assessing 1-year rates of net adverse clinical events (all-cause death, myocardial infarction, stroke, revascularization, and Bleeding Academic Research Consortium [BARC] types 3 to 5 bleeding) and major adverse clinical events (all-cause death, myocardial infarction, stroke)., Results: A total of 5232 patients were included, of whom 574 individuals had cancer, and 4658 were at high-bleeding risk without previous cancer. Despite being younger with fewer risk factors, patients with cancer had higher net adverse clinical event (HR, 1.25; P =0.01) and major adverse clinical event (HR, 1.26; P =0.02), primarily driven by all-cause mortality and major bleeding (BARC 3-5), but not myocardial infarction, stroke, stent thrombosis, or repeat revascularization. Cancer was an independent predictor of net adverse clinical event ( P =0.005), major adverse clinical event ( P =0.01), and major bleeding ( P =0.03)., Conclusions: The present work is the first report on abbreviated DAPT dedicated to patients with cancer. Cancer is a major marker of adverse outcomes and these events had high lethality. Despite short DAPT, patients with cancer experienced higher rates of major bleeding compared with patients without cancer with high-bleeding risk, which occurred mainly after DAPT discontinuation. These findings reinforce the need for a more detailed and individualized stratification of those patients., Registration: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT03344653, NCT01623180, NCT02843633, NCT0284., Competing Interests: Disclosures Dr Urban is senior advisor at European Cardiovascular Research Center (CERC), a contract research organization based in Massy, France; Consultant to MedAlliance, Nyon, Switzerland and Consultant to Biosensors, Morges Switzerland. Dr Varenne received research grants from Abbott Vascular and Boston Scientific, lecture fees from Boston Scientific, Servier and Abbott Vascular; and congress support from Astra Zeneca. Dr Mehran reports institutional research payments from Abbott, Abiomed, Alleviant Medical, AM-Pharma, Amgen, Applied Therapeutics, Arena, AstraZeneca, AtriCure, Bayer, Biosensors, Biotronik, Boston Scientific, Bristol-Myers Squibb, CardiaWave, CeloNova, Chiesi, Concept Medical, CSL Behring, Cytosorbents, Daiichi Sankyo, Element Science, Faraday, Humacyte, Idorsia, Janssen, Magenta, Medtronic, Novartis, OrbusNeich, PhaseBio, Philips, Pi-Cardia, RenalPro, RM Global, Shockwave, Vivasure, Zoll; personal fees from Cine-Med Research, WebMD; Equity <1% in Applied Therapeutics, Elixir Medical, Stel, ControlRad (spouse); Scientific Advisory Board for American Medical Association, American College of Cardiology (BOT Member), Society for Cardiovascular Angiography and Interventions (Women in Innovations Committee Member), JAMA Associate Editor; Faculty Cardiovascular Research Foundation (no fee). Dr Stone has received speaker honoraria from Medtronic, Pulnovo, Infraredx; has served as a consultant to Valfix, TherOx, Robocath, HeartFlow, Ablative Solutions, Vectorious, Miracor, Neovasc, Abiomed, Ancora, Elucid Bio, Occlutech, CorFlow, Apollo Therapeutics, Impulse Dynamics, Cardiomech, Gore, Amgen, Adona Medical, Millennia Biopharma; and has equity/options from Ancora, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, Xenter. Dr Stone’s daughter is an employee at IQVIA. Institutional disclosure: Dr Stone’s employer, Mount Sinai Hospital, receives research support from Abbott, Abiomed, Bioventrix, Cardiovascular Systems Inc, Phillips, Biosense-Webster, Shockwave, Vascular Dynamics, Pulnovo and V-wave. Dr Campos has received honoraria from Abbott Vascular, Teleflex, and Terumo. Dr Oldroyd is chief medical officer of Biosensors International. Dr Capodanno received spaker’s fee and honoraria from Daiichi Sankyo, AstraZeneca, Sanofi, Terumo. The other authors report no conflicts.

Introduction: COVID-19 pandemic changed the way medical research is published, possibly forever. As the need for rapidity led to the rise of preprint servers, the undeniable drop in the overall quality of scientific publications requires an in-depth review of all available evidence. The present manuscript aims to identify and summarize all treatments which have been reported to reduce mortality in randomized trials in hospitalized COVID-19 patients., Evidence Acquisition: Independent investigators searched MEDLINE/PubMed, Scopus, and Embase databases to identify all randomized trials of any intervention influencing mortality in hospitalized COVID-19 patients up to August 18 th , 2022. Articles were selected only when they fulfilled all the following: randomized trial design; dealing with any kind of interventions in adult hospitalized COVID-19 patients; and statistically significant reduction in mortality., Evidence Synthesis: We identified 28 interventions (42 manuscripts) reducing mortality in hospitalized COVID-19 patients. About 60% of the studies (26/42) were multicentric, for a total of 1140 centers involved worldwide. Several of these studies were published in high-ranked, peer-reviewed journals. Interventions with randomized evidence of mortality reduction in hospitalized COVID-19 patients belonged to 5 domains: corticosteroids, immunomodulators, antimicrobials, supportive therapies, and other drugs., Conclusions: Many interventions have the potential to reduce mortality in COVID-19 hospitalized patients. The correct treatment of future pandemics relies on large, multicentric randomized clinical trials for further evaluation of these promising strategies.

Background: SARS-CoV-2 binding to ACE2 is potentially associated with severe pneumonia due to COVID-19. The aim of the study was to test whether Mas-receptor activation by 20-hydroxyecdysone (BIO101) could restore the Renin-Angiotensin System equilibrium and limit the frequency of respiratory failure and mortality in adults hospitalized with severe COVID-19., Methods: Double-blind, randomized, placebo-controlled phase 2/3 trial. Randomization: 1:1 oral BIO101 (350 mg BID) or placebo, up to 28 days or until an endpoint was reached. Primary endpoint: mortality or respiratory failure requiring high-flow oxygen, mechanical ventilation, or extra-corporeal membrane oxygenation. Key secondary endpoint: hospital discharge following recovery (ClinicalTrials.gov Number, NCT04472728)., Findings: Due to low recruitment the planned sample size of 310 was not reached and 238 patients were randomized between August 26, 2020 and March 8, 2022. In the modified ITT population (233 patients; 126 BIO101 and 107 placebo), respiratory failure or early death by day 28 was 11.4% lower in the BIO101 (13.5%) than in the placebo (24.3%) group, (p = 0.0426). At day 28, proportions of patients discharged following recovery were 80.1%, and 70.9% in the BIO101 and placebo group respectively, (adjusted difference 11.0%, 95% CI [-0.4%, 22.4%], p = 0.0586). Hazard Ratio for time to death over 90 days: 0.554 (95% CI [0.285, 1.077]), a 44.6% mortality reduction in the BIO101 group (not statistically significant). Treatment emergent adverse events of respiratory failure were more frequent in the placebo group., Interpretation: BIO101 significantly reduced the risk of death or respiratory failure supporting its use in adults hospitalized with severe respiratory symptoms due to COVID-19., Funding: Biophytis., Competing Interests: Biophytis declares that potential commercial interests had no impact on the scientific conduct of the study nor on the analysis/interpretation of data. Cendrine Tourette, Luis Esmeraldino, Pierre Jean Dilda, René Lafont, Serge Camelo, Sandrine Rabut, Waly Dioh, Rob van Maanen and Stanislas veillet are Biophytis company employees, Anait Azbekyan Samuel Agus and Mounia Chabane are former Biophytis company employees. Jean Mariani is emeritus professor at Sorbonne University and consultant for Biophytis, Richard Kay is a consultant for Biophytis. Alpesh Amin, MD declares that as principal investigator or co-investigator of clinical trials sponsored by NIH/NIAID, NeuroRx Pharma, Pulmotect, Blade Therapeutics, Novartis, Takeda, Humanigen, Eli Lilly, PTC Therapeutics, OctaPharma, Fulcrum Therapeutics, Alexion, BioPhysitis its institution received payments and that he personnally received consultant fees from BMS, Pfizer, BI, Portola, Sunovion, Mylan, Salix, Alexion, AstraZeneca, Novartis, Nabriva, Paratek, Bayer, Tetraphase, Achogen LaJolla, Ferring, Seres, Spero, Eli Lilly, Gilead, Millenium, HeartRite, Aseptiscope, and Sprightly; but that these relationships were unrelated to the current work. Shaheen Islam, MD declares that he received grants or was in contract as a principal or sub investigator from the following companies:–Pliant therapeutics: INTEGRIS-ARDS, drug (PLN74809) Covid -trial 2021 (PI).—CytoDyn, Inc.: CD12-COVID 19 Drug: Leronlimab COVID trial 2020 (PI). -Pluristem Ltd.: PLX-COV-01. Drug PLX-PAD, COVID Trial 2020 (Sub-I).—Edesa Biotech Inc.: EB05-04-2020. Drug: EB05 COVID Trial 2020 (Sub-I). Fabiano Ramos, MD declares that its institution: Hospital São Lucas da Pontíficia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Rio Grande do Sul, Brazil received financial resources to conduct the study from Biophytis. Brian Snyder, MD declares that he receives research funding from Biophytis as part of the present clinical trial. Moreover, he declares that he received grants or has contracts with Behring, and Rheonix as part of COVID research studies. None of the other investigators declare any relationship related to the current work., (© 2023 The Author(s).)

Cardiotoxicity is the most worrying cardiovascular alteration in patients treated with chemotherapy. To improve the understanding regarding the cardiotoxicity, we studied whether 1 ) patients with cardiac dysfunction related to anthracycline-based chemotherapy have augmented sympathetic nerve activity and decreased exercise capacity and 2 ) these responses are similar to those observed in patients with heart failure caused by other etiologies. Sixteen patients with heart failure with reduced ejection fraction related to anthracycline-based chemotherapy with or without chest radiation (HFrEFCA), 10 patients with heart failure with reduced ejection not related to cancer therapy (HFrEF), and 16 age- and body mass index (BMI)-matched healthy control subjects were studied. Left ventricular ejection fraction (LVEF, echocardiography), peak oxygen consumption (peak V̇o 2 , cardiopulmonary exercise test), muscle sympathetic nerve activity (MSNA, microneurography), and forearm blood flow (FBF, venous occlusion plethysmography) were measured. We found that peak oxygen consumption peak V̇o 2 and LVEF were significantly reduced in patients with HFrEFCA compared with that of control subjects ( P < 0.0001) but similar to those found in patients with HFrEFCA. The sympathetic nerve activity burst frequency and incidence were significantly higher in patients with HFrEFCA than that in control subjects ( P < 0.0001). No differences were found between patients with HFrEF and HFrEFCA. Peak V̇o 2 was inversely associated with MSNA burst frequency ( r = -0.53, P = 0.002) and burst incidence ( r = -0.38, P = 0.01) and directly associated with LVEF ( r = 0.71, P < 0.0001). Taken together, we conclude that patients who develop heart failure due to anthracycline-based chemotherapy have sympathetic neural overdrive and reduced exercise capacity. In addition, these physiological changes are similar to those observed in patients with HFrEF. NEW & NOTEWORTHY Patients with heart failure with reduced ejection fraction related to anthracycline-based chemotherapy have increased sympathetic nerve activity and decreased exercise capacity. These alterations in autonomic control and physical capacity are similar to those observed in patients with heart failure due to other etiologies. These findings highlight the importance of special care of oncological patients treated with chemotherapy.

Purpose of Review: The aim of this study was to review the role of haemodynamic monitoring in the perioperative setting, highlighting who are the patients who most benefit, to describe the type of devices, to analyse the scientific evidence and to suggest algorithms of haemodynamic care in high-risk surgical patients., Recent Findings: In the last 50 years, many advances have contributed to better understand cardiovascular physiology at bedside, and haemodynamic monitoring has moved from invasive methods to minimally invasive and noninvasive devices. Randomized clinical trials have shown benefits of perioperative haemodynamic therapy to improve outcomes in high-risk surgical patients. A multimodal approach is purposed in the perioperative setting to optimize haemodynamic parameters, involving clinical analysis at bedside, the use of dynamic tests for fluid responsiveness and integration of variables, including cardiac output, systolic volume, tissue oxygen markers and echocardiographic measures., Summary: In this review, we summarize the benefits of haemodynamic monitoring, the type of devices with advantages and disadvantages, the scientific evidence supporting perioperative haemodynamic therapy, and we suggest a multimodal approach to improve patients' care., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

BACKGROUND: Glucocorticoids reduce mortality in hospitalized patients with severe and critical coronavirus disease 2019 (Covid-19), although a possible harm was documented in patients with Covid-19 not requiring oxygen. METHODS: We searched Embase, BioMed Central, medRxiv, bioRxiv, PubMed, and the Cochrane Central Register of Controlled Trials for any randomized trial or matched study ever performed on adult patients with Covid-19 not receiving oxygen therapy treated with intravenous or oral glucocorticoids versus any comparator (standard therapy or placebo); there were no restrictions on dose or time of administration. The primary end point was all-cause mortality at the longest available follow-up. RESULTS: Five randomized trials and one propensity-matched study involving 6634 hospitalized patients not on oxygen were finally included (3704 received glucocorticoids and 2930 received standard treatment). The overall mortality of patients treated with glucocorticoids was significantly higher than the mortality of patients in the control group (509 of 3704 [14%] in the glucocorticoid group vs. 294 of 2930 [10%] in the control group; odds ratio, 1.56 [95% confidence interval, 1.27 to 1.92], with three articles reporting mortality events and contributing to the combined odds ratio; P<0.001; number needed to harm=27). CONCLUSIONS: Glucocorticoid use likely increases mortality in hospitalized patients with Covid-19 not receiving oxygen, with a number needed to harm of 27. (PROSPERO number CRD42022342996.)

Background: Exercise training improves physical capacity in patients with heart failure with reduced ejection fraction (HFrEF), but the mechanisms involved in this response is not fully understood. The aim of this study was to determine if physical capacity increase in patients HFrEF is associated with muscle sympathetic nerve activity (MSNA) reduction and muscle blood flow (MBF) increase., Methods: The study included 124 patients from a 17-year database, divided according to exercise training status: 1) exercise-trained (ET, n = 83) and 2) untrained (UNT, n = 41). MSNA and MBF were obtained using microneurography and venous occlusion plethysmography, respectively. Physical capacity was evaluated by cardiopulmonary exercise test. Moderate aerobic exercise was performed 3 times/wk. for 4 months., Results: Exercise training increased peak oxygen consumption (V̇O 2 , 16.1 ± 0.4 vs 18.9 ± 0.5 mL·kg -1 ·min -1 , P < 0.001), LVEF (28 ± 1 vs 30 ± 1%, P = 0.027), MBF (1.57 ± 0.06 vs 2.05 ± 0.09 mL.min -1 .100 ml -1 , P < 0.001) and muscle vascular conductance (MVC, 1.82 ± 0.07 vs 2.45 ± 0.11 units, P < 0.001). Exercise training significantly decreased MSNA (45 ± 1 vs 32 ± 1 bursts/min, P < 0.001). The logistic regression analyses showed that MSNA [(OR) 0.921, 95% CI 0.883-0.962, P < 0.001] was independently associated with peak V̇O 2 ., Conclusions: The increase in physical capacity provoked by aerobic exercise in patients with HFrEF is associated with the improvement in MSNA., Competing Interests: Declaration of Competing Interest All authors have reported that there is no relationship with industry or financial associations, which might pose a conflict of interest in connection to this article., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Microvascular lung vessels obstructive thromboinflammatory syndrome has been proposed as a possible mechanism of respiratory failure in COVID-19 patients. However, it has only been observed in post-mortem studies and has never been documented in vivo , probably because of a lack of CT scan sensitivity in small pulmonary arteries. The aim of the present study was to assess the safety, tolerability, and diagnostic value of optical coherence tomography (OCT) for the assessment of patients with COVID-19 pneumonia for pulmonary microvascular thromboinflammatory syndrome., Methods: The COVID-OCT trial was a multicenter, open-label, prospective, interventional clinical study. Two cohorts of patients were included in the study and underwent pulmonary OCT evaluation. Cohort A consisted of patients with COVID-19 with a negative CT scan for pulmonary thrombosis and elevated thromboinflammatory markers (D-dimer > 10,000 ng/mL or 5,000 < D-dimer < 10,000 ng/mL and one of: C-reactive Protein > 100 mg/dL, IL-6 > 6 pg/mL, or ferritin > 900 ng/L). Cohort B consisted of patients with COVID-19 and a CT scan positive for pulmonary thrombosis. The primary endpoints of the study were: (i) to evaluate the overall safety of OCT investigation in patients with COVID-19 pneumonia, and (ii) to report on the potential value of OCT as a novel diagnostic tool for the diagnosis of microvascular pulmonary thrombosis in COVID-19 patients., Results: A total of 13 patients were enrolled. The mean number of OCT runs performed in each patient was 6.1 ± 2.0, both in ground glass and healthy lung areas, achieving a good evaluation of the distal pulmonary arteries. Overall, OCT runs identified microvascular thrombosis in 8 patients (61.5%): 5 cases of red thrombus, 1 case of white thrombus, and 2 cases of mixed thrombus. In Cohort A, the minimal lumen area was 3.5 ± 4.6 mm 2 , with stenosis of 60.9 ± 35.9% of the area, and the mean length of thrombus-containing lesions was 5.4 ± 3.0 mm. In Cohort B, the percentage area obstruction was 92.6 ± 2.6, and the mean thrombus-containing lesion length was 14.1 ± 13.9 mm. No peri-procedural complications occurred in any of the 13 patients., Conclusion: OCT appears to be a safe and accurate method of evaluating the distal pulmonary arteries in hospitalized COVID-19 patients. Here, it enabled the first in vivo documentation of distal pulmonary arterial thrombosis in patients with elevated thromboinflammatory markers, even when their CT angiogram was negative for pulmonary thrombosis., Clinical Trial Registration: ClinicalTrial.gov, identifier NCT04410549., Competing Interests: MM was a proctor for Abbott. MA received consultant fees from Abbott. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hajjar, Ancona, Filho, Tresoldi, Caldas, Monti, Carnevale, De Cobelli, Moreira de Assis, Ciceri, Landoni, Dijkstra, Moroni, Abizaid, Willemann Ungaretti, Carvalho Carmona, De Backer, Pompilio, Britto, Campos, Zangrillo and Montorfano.)

Background: Cardiovascular disease (CVD) incidence is higher in men with prostate cancer (PC) than without., Objectives: We describe the rate and correlates of poor cardiovascular risk factor control among men with PC., Methods: We prospectively characterized 2,811 consecutive men (mean age 68 ± 8 years) with PC from 24 sites in Canada, Israel, Brazil, and Australia. We defined poor overall risk factor control as ≥3 of the following: suboptimal low-density lipoprotein cholesterol (>2 mmol/L if Framingham Risk Score [FRS] ≥15 and ≥3.5 mmol/L if FRS <15), current smoker, physical inactivity (<600 MET min/wk), suboptimal blood pressure (BP) (≥140/90 mm Hg if no other risk factors, systolic BP ≥ 120 mm Hg if known CVD or FRS ≥15, and ≥130/80 mm Hg if diabetic), and waist:hip ratio >0.9., Results: Among participants (9% with metastatic PC and 23% with pre-existing CVD), 99% had ≥1 uncontrolled cardiovascular risk factor, and 51% had poor overall risk factor control. Not taking a statin (odds ratio [OR]: 2.55; 95% CI: 2.00-3.26), physical frailty (OR: 2.37; 95% CI: 1.51-3.71), need for BP drugs (OR: 2.36; 95% CI: 1.84-3.03), and age (OR per 10-year increase: 1.34; 95% CI: 1.14-1.59) were associated with poor overall risk factor control after adjustment for education, PC characteristics, androgen deprivation therapy, depression, and Eastern Cooperative Oncology Group functional status., Conclusions: Poor control of modifiable cardiovascular risk factors is common in men with PC, highlighting the large gap in care and the need for improved interventions to optimize cardiovascular risk management in this population., Competing Interests: RADICAL-PC is an investigator-initiated study that is funded by Prostate Cancer Canada (grant CT2015-01); the Movember Foundation, Hamilton Health Sciences (Research Strategic Initiative Program); and the Canadian Cancer Society (grant 706677). The funders of the study had no role in design of the study, analysis, interpretation, writing of the manuscript, and in the decision to publish the results. Dr Klimis is supported by an AFP Fellowship Award, Department of Cardiology, McMaster University. Dr Pinthus has served on advisory boards for Ferring Pharmaceuticals and Myovant Sciences; and has received research grant from Ferring Pharmaceuticals. Dr Duceppe has received investigator-initiated research grants from Roche Diagnostics and Abbott Laboratories; and has received lecture fees and honoraria for participation in advisory board meetings with Roche Diagnostics. Dr Siemens has been involved in clinical trials with Merck, Pfizer, Astellas, and Bayer. Dr Lavallee is on the advisory board for Sanofi, Astellas, Janssen, and Knight. Dr Gopaul has received personal fees outside the submitted manuscript from AstraZeneca, TerSera, Bayer, Ferring, and Abvie. Dr Hanna is on the advisory board for and has received honorarium and research support from Astellas, Bayer, Merck, Tolmar, Sanofi, and Abbvie. Dr Iakobishvili consults and lectures for Bayer, Pfizer, Boehringer Ingelheim, Novo Nordisk, Medtronic, Sanofi Adventist, and AstraZeneca. Dr Selvanayagam has received research grant support from Biotronik, Bayer, Sanofi, Actelion, and Novartis; is on the advisory board for Sanofi, Faraday, and Recardio; and is on the speaker bureau for AstraZeneca, Boehringer-Ingelheim, Novartis, Abbot, Bayer, Sanofi, Biotronik, Circle CVI, and Takeda. Dr Leong has served on advisory boards for Ferring Pharmaceuticals, Myovant Sciences, and Tolmar; reports speaker’s honoraria from Abbvie; and is supported by the Clive Kearon Career Award, Department of Medicine, McMaster University. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2023 The Authors.)

Competing Interests: The authors declare that they have no conflict of interest.

Objective: To investigate the effect of volatile anesthetics on the rates of postoperative myocardial infarction (MI) and cardiac death after coronary artery bypass graft (CABG)., Design: A post hoc analysis of a randomized trial., Setting: Cardiac surgical operating rooms., Participants: Patients undergoing elective, isolated CABG., Interventions: Patients were randomized to receive a volatile anesthetic (desflurane, isoflurane, or sevoflurane) or total intravenous anesthesia (TIVA). The primary outcome was hemodynamically relevant MI (MI requiring high-dose inotropic support or prolonged intensive care unit stay) occurring within 48 hours from surgery. The secondary outcome was 1-year death due to cardiac causes., Measurements and Main Results: A total of 5,400 patients were enrolled between April 2014 and September 2017 (2,709 patients randomized to the volatile anesthetics group and 2,691 to TIVA). The mean age was 62 ± 8.4 years, and the median baseline ejection fraction was 57% (50-67), without differences between the 2 groups. Patients in the volatile group had a lower incidence of MI with hemodynamic complications both in the per-protocol (14 of 2,530 [0.6%] v 27 of 2,501 [1.1%] in the TIVA group; p = 0.038) and as-treated analyses (16 of 2,708 [0.6%] v 29 of 2,617 [1.1%] in the TIVA group; p = 0.039), but not in the intention-to-treat analysis (17 of 2,663 [0.6%] v 28 of 2,667 [1.0%] in the TIVA group; p = 0.10). Overall, deaths due to cardiac causes were lower in the volatile group (23 of 2,685 [0.9%] v 40 of 2,668 [1.5%] than in the TIVA group; p = 0.03)., Conclusions: An anesthetic regimen, including volatile agents, may be associated with a lower rate of postoperative MI with hemodynamic complication in patients undergoing CABG. Furthermore, it may reduce long-term cardiac mortality., Competing Interests: Declaration of Competing Interest V.V.L. received a speaking honorarium from Baxter., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Zika virus infection is commonly described as a mild and self-limiting illness. However, cardiac complications were associated with acute Zika virus infection., Case Presentation: A 46-year-old woman without previous comorbidities with a 1-day history of symptoms tested positive for ZIKV by real time reverse transcriptase polymerase chain reaction (rRT-PCR). She was admitted two days after with clinical worsening, cardiac enzymes elevated, and cardiac imaging findings, and the diagnosis of myopericarditis was made. The patient was treated and presented significant clinical improvement after one year., Conclusions: Cardiac complication following ZIKV infection appears to be infrequent. Here, we report a rare case of viral myopericarditis caused by ZIKV infection., (© 2022. The Author(s).)