Search Results (649)

Vilobelimab, a first-in-class, human–mouse chimeric immunoglobulin G4 (IgG4) kappa monoclonal antibody, targets human complement component 5a (C5a) in plasma. Unlike upstream complement inhibitors, vilobelimab does not inhibit the generation of the membrane attack complex (C5b-9), necessary to mitigate certain infections. C5a is a strong anaphylatoxin and chemotactic agent that plays an essential role in both innate and adaptive immunity. Elevated levels of C5a have been associated with pathologic processes, including sepsis and inflammatory respiratory disorders such as acute respiratory distress syndrome (ARDS). Blocking C5a with vilobelimab has shown therapeutic promise. A randomized, multicenter placebo-controlled Phase III study of vilobelimab in patients with severe COVID-19 (PANAMO) found that patients treated with vilobelimab had a significantly lower risk of death by day 28 and 60. Based on this study, the United States Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for Gohibic^® (vilobelimab) injection for the treatment of COVID-19 in hospitalized adults when initiated within 48 h of receiving invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO). In January 2025, the European Commission (EC) granted marketing authorization for Gohibic^® (vilobelimab) for the treatment of adult patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced ARDS who are receiving systemic corticosteroids as part of standard of care and receiving IMV with or without ECMO. Herein, we review the mechanism of action of vilobelimab in selectively inhibiting C5a-induced inflammation, outlining its bench-to-bedside development from the fundamental biology of the complement system and preclinical evidence through to the clinical data demonstrating its life-saving potential in the management of COVID-19–induced ARDS. Full article

Background: Outcome prediction in patients undergoing lung transplantation (LUTX) for end-stage pulmonary disease can be challenging. We examined the prognostic value for mortality of respiratory system compliance (C_RS) and mechanical power of ventilation (MP) at end of surgery in patients undergoing LUTX for end-stage pulmonary disease. Methods: In this single-center retrospective study, we included 755 patients undergoing LUTX between 2014 and 2023. The primary endpoint of this study was 1-year mortality, with 30-day mortality serving as a secondary endpoint. We conducted both univariate and multivariate analyses and constructed Receiver Operating Characteristic curves. Results: Of 755 patients, 1.9% and 12.2% patients died within 30 days and 1 year after LUTX. Fifteen-point four percent of all patients required extracorporeal membrane oxygenation (ECMO) prolongation into the early postoperative period. C_RS, but not MP was higher in 1-year survivors compared to non-survivors [median 25.8 mL/cmH₂O (20.1, 32.1) and 22.5 mL/cmH₂O (15.2, 28.4); p < 0.001] and [median 10.0 J/min (7.8, 12.0) and 9.3 J/min (6.2, 13.1); p = 0.329]. Moreover, low C_RS < 25.1 mL/cmH₂O remained an independent factor for increased 1-year mortality after LUTX. Additionally, increased MP and C_RS were predictive for 30-day survival with an acceptable area under the curve of 0.758 (95% CI: 0.6–0.8; p < 0.001) and 0.735 (95% CI: 0.5–0.9; p = 0.003), and a sensitivity and specificity of 51% and 75.5% for MP and 50% and 85% for C_RS, respectively. Conclusions: Postoperative C_RS serves as a significant independent predictor for short and long-term outcome in patients undergoing LUTX with and without ECMO prolongation into the early postoperative period. Full article

Background/Objectives: Mechanical circulatory support (MCS) is increasingly utilized for the management of acute decompensated heart failure (HF) and cardiogenic shock (CS). The primary goals of MCS are to restore systemic perfusion, reduce cardiac workload, and support end-organ function. A thorough understanding of cardiovascular physiology in patients supported by MCS is essential for clinical decision-making. This review summarizes current evidence on the physiological effects of various MCS devices, key monitoring techniques, patient management, and explores the emerging role of artificial intelligence (AI) in this field. Main Text: Short-term MCS devices include intra-aortic balloon pumps (IABP), percutaneous left-sided devices such as Impella (Abiomed, Danvers, MA, USA) and TandemHeart (LivaNova, London, UK), percutaneous right-sided support devices like Protek Duo (LivaNova, London, UK) and Impella RP Flex (Abiomed, Danvers, MA, USA), and veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Long-term support is mainly provided by left ventricular assist devices (LVADs), including the HeartMate 3 (Abbott Laboratories, Chicago, IL, USA). Optimal MCS application requires an understanding of device-specific cardiovascular interactions and expertise in appropriate monitoring tools to assess device performance and patient response. The choice of device, timing of initiation, and patient selection must be individualized, with careful consideration of ethical implications. The integration of AI offers significant potential to advance clinical care by improving complication prediction, enabling real-time optimization of device settings, and refining patient selection criteria. Conclusions: MCS is a rapidly evolving field that requires a comprehensive understanding of cardiovascular interactions, careful selection of monitoring strategies, and individualized clinical management. Future research should address current device limitations, clarify device-specific clinical applications, and assess the validity of AI-driven technologies. Full article

Right heart failure (RHF) remains an under-recognized yet devastating condition in critically ill and chronic patients, frequently complicating cardiac surgery, pulmonary embolism, advanced heart failure, sepsis and left ventricular assist device (LVAD) implantation. Despite growing awareness, clinical decision making is still hampered by the complex pathophysiology, limitations in diagnosis and a fragmented therapeutic landscape. In recent years, progress in hemodynamic phenotyping, advanced echocardiographic and biomarker-based assessment, and the development of mechanical circulatory support (MCS) systems, including percutaneous and surgical right ventricle assist devices (RVAD), veno-arterial extracorporeal membrane oxygenation (V-A ECMO), Impella RP (right percutaneous) or BiPella (Impella CP/5.0/5.5 + Impella RP) has expanded the armamentarium for managing RHF. This review synthetizes current evidences on the anatomical, physiological and molecular underpinnings of RHF, delineates the distinction and continuum between acute and chronic forms and provides a comparative analysis of diagnostic tools and MCS strategies. By integrating mechanistic insights with emerging clinical frameworks, the review aims to support earlier recognition, tailored management and innovative therapeutic approaches for this high-risk population. Full article

Background/Objectives: Eosinophilic myocarditis (EM) is a rare, life-threatening inflammatory cardiomyopathy driven by eosinophil cytotoxicity and extracellular trap formation. Interleukin-5 (IL-5) inhibition may disrupt this pathogenic cascade. We reviewed contemporary evidence on IL-5 blockade in EM and contextualized it with an illustrative case. Methods: We searched PubMed through May 2025 for reports of EM treated with mepolizumab or benralizumab. Inclusion criteria were consistent with prior cohorts: acute cardiac symptoms with biomarker elevation plus abnormalities on transthoracic echocardiography and/or cardiac magnetic resonance imaging (CMR), along with documented IL-5-targeted therapy. We extracted clinical, imaging, biopsy, treatment-timing, and outcome data and included one institutional case. Results: Twenty-one episodes were analyzed (median age, 45 years; 10 men). Underlying conditions included eosinophilic granulomatosis with polyangiitis (10 cases; 48%), hypereosinophilic syndrome (5 cases; 24%), drug reaction with eosinophilia and systemic symptoms (DRESS, 3 cases; 14%), and eosinophilic asthma (3 cases; 14%). Treatments involved mepolizumab in 17 cases (81%) and benralizumab in 4 (19%); 4 patients received “early-start” therapy within 14 days of EM diagnosis. Among the 11 episodes with reported left ventricular ejection fraction (LVEF) at baseline and follow-up, the median baseline LVEF was 40% (range, 30–62), with 10 of 11 (91%) <50%. On follow-up, all 11 patients improved: 4 normalized (≥50%) and 7 improved to 40–49%. CMR (n = 18) demonstrated late gadolinium enhancement in 14 cases (78%), edema in 9 (50%), and intracardiac thrombus in 4 (22%). Endomyocardial biopsy confirmed eosinophilic infiltration in 13 of 15 cases (87%). Outcomes included one death (fulminant DRESS), one recovery following veno-arterial extracorporeal membrane oxygenation, and one successful heart transplantation. Illustrative case: A 24-year-old man on a steroid taper received mepolizumab 300 mg on Day 4. His LVEF improved from 47% to 59% by Day 15, accompanied by biomarker decline and successful steroid tapering. Conclusions: Across published cases and our institutional experience, IL-5–targeted therapy appears safe, steroid-sparing, and associated with rapid ventricular recovery, particularly when initiated early. Although limited, these findings support the need for prospective trials to define the optimal agent, dosing, timing, and integration with standard immunosuppression and anticoagulation. Full article

Pneumocystis jirovecii pneumonia (PCP) remains a frequent cause of intensive care unit (ICU) admission among people living with HIV (PLWH), despite widespread antiretroviral therapy (ART) use. We conducted a retrospective cohort study of 39 PLWH with PCP admitted to the ICU at the Croatian national HIV referral center between 2002 and 2023. Patients were grouped by calendar period (pre-2015 vs. post-2015, reflecting the adoption of the “test and treat” strategy in 2015). Primary outcomes included ICU, 30-day, and 1-year mortality. We also evaluated the association between in-ICU ART initiation and survival. There were 37 (94.9%) males with a median age of 49 years (Q1–Q3, 37.5–54.5). Thirty-three (84.6%) were newly diagnosed with HIV. There were no differences between the observed periods regarding demographic characteristics. ART was initiated in the ICU in 21 (53.8%) patients, more frequently after 2015 (p < 0.001). ICU, 30-day, and 1-year mortality rates were 53.9% (n = 21), 51.3% (n = 20), and 66.7% (n = 26), respectively. Survival significantly improved in the later period, with 1-year survival reaching 54.5% (12/22). In-ICU ART initiation was associated with improved survival in univariable analysis, but this effect attenuated after adjusting for APACHE II or calendar year. Early ART may offer benefit but remains confounded by disease severity and evolving care standards. Full article

Persistent pulmonary hypertension of the newborn (PPHN) results from disrupted fetal–neonatal circulatory transition, characterized by elevated pulmonary vascular resistance (PVR), right-to-left shunting, and refractory hypoxemia. Despite improved perinatal care, PPHN remains a major source of neonatal morbidity and mortality. This review details PPHN phenotypes, pathophysiology, etiology, diagnostics including echocardiography and biomarkers like B-type Natriuretic Peptide (BNP) or N-terminal pro-B-type Natriuretic Peptide (NT-proBNP), and current therapeutic modalities, from lung recruitment and surfactant to targeted vasodilator therapy (iNO, sildenafil, milrinone, bosentan) and extracorporeal membrane oxygenation (ECMO). We emphasize the role of endothelial and molecular mechanisms in precision therapy and outline guidelines for clinical decision-making in diverse care settings. Full article

Background: Sickle cell disease (SCD) is a hereditary hemoglobinopathy associated with life-threatening complications such as acute chest syndrome (ACS), which may necessitate extracorporeal membrane oxygenation (ECMO) in refractory cases. Despite growing use, ECMO in SCD remains challenging due to risks of hemolysis, thrombosis, and anticoagulation complications. This systematic review consolidates existing evidence on ECMO outcomes in SCD, focusing on indications, complications, and survival. Methods: A systematic search of MEDLINE, Cochrane CENTRAL, and Google Scholar was conducted up to January 2025, identifying case reports/series on ECMO use in SCD. Studies reporting venovenous (VV) or venoarterial (VA) ECMO for acute cardiopulmonary failure were included. Data on demographics, laboratory findings, management, and outcomes were extracted. Quality assessment was performed using the Joanna Briggs Institute checklist. Results: Sixteen case reports (23 patients) were included. Most patients were female (65.2%), with ACS (47.8%) and pulmonary embolism (13.0%) as common ECMO indications. VV-ECMO (69.6% of cases) was primarily used for respiratory failure, with a 69% survival rate, while VA-ECMO (30.4%) had a 29% survival rate, often due to cardiogenic shock or cardiac arrest. Complications included hemorrhage (26.1%), neurological injury (21.7%), and thrombosis (13.0%). Exchange transfusion was frequently employed (43.5%), with post-ECMO echocardiography showing improved right ventricular function in survivors. Conclusions: VV-ECMO demonstrates favorable outcomes in SCD-related respiratory failure, whereas VA-ECMO carries higher mortality risks. Careful patient selection, anticoagulation management, and multidisciplinary coordination are essential. Larger prospective studies are needed to refine ECMO utilization in this high-risk population. Full article

Background: Pulmonary hypertension (PH) in newborns is a rare but serious condition and potentially life-threatening disorder, often initially confused with congenital heart disease due to overlapping echocardiographic findings in the late third trimester. Evidence on prenatal predictors of postnatal PH is limited. We aimed to describe detailed third-trimester echocardiographic findings associated with postnatal PH in infants with prenatally suspected CoA based on a retrospective case series. Methods: We reviewed 18 years of fetal echocardiography (2004–2022) in a tertiary maternal–fetal–neonatal center. We identified fetuses with suspected coarctation of the aorta (CoA) in late gestation who were delivered at term (≥37 weeks) and had prolonged neonatal hospitalization (>10 days) without cardiac surgery or catheterization. Z-scores for cardiac dimensions were calculated. All examinations were performed by experienced fetal cardiologists. Postnatal evaluations confirmed PH based on echocardiographic and clinical findings. Results: Among 19,836 fetuses examined, 138 were prenatally suspected of CoA. In 70 cases, this diagnosis was not confirmed postnatally (false positives). Of these, eight infants (0.04% of the total cohort) developed postnatal PH. Postnatally, all eight neonates required intensive care. Prenatal features included ventricular/atrial disproportion (7/8), cardiomegaly (8/8), main pulmonary artery dilatation (10.2 ± 2.2 mm; Z-score +2.7 ± 1.3), tricuspid regurgitation (8/8), pulmonary regurgitation (4/8), and interventricular septal hypertrophy (>4.5 mm in 5/8). Postnatal evaluations confirmed PH based on echocardiographic criteria (elevated right ventricular pressure, septal flattening/bowing, right ventricular dilation or dysfunction, and abnormal shunt direction) combined with clinical compromise. All infants received prostaglandin E1 (PGE1) initially; none required extracorporeal membrane oxygenation-ECMO. Three died, while five survived with medical management (oxygen, inhaled nitric oxide, sildenafil). Conclusions: Specific functional abnormalities on late third-trimester echocardiography may indicate impaired pulmonary vascular adaptation and predict postnatal PH, particularly in cases initially suspected of CoA. Recognition and awareness of these findings can guide delivery planning, neonatal surveillance, and timely intervention. Prospective multicenter studies are needed to validate these associations and refine prenatal screening protocols. Full article

Background: Contact between blood and the large artificial surfaces within membrane lungs (MLs) is one reason for device-induced thrombus formation during extracorporeal membrane oxygenation (ECMO). Methods: Hemocompatibility testing of gas-exchange fibers (GFs) and heat-exchange fibers (HEs) from commercially available/non-used MLs (ML-type, coating: PLS, Bioline^®; Hilite7000LT, X.ELLENCE^®; Nautilus, Balance^®; EOS, PH.I.S.I.O^®) included static hemolysis and platelet adhesion/activation assays. Platelet activation of non-adherent platelets was identified after antibody (CD62P, PAC-1, CD61) and fibrinogen staining (flow cytometry). The surface coverage (%) of adherent platelets was quantified after F-actin filament-staining. Results: All materials were non-hemolytic and did not induce platelet activation. However, platelet adhesion (median (IQR)) depended on the type of surface coating of GFs made entirely of polymethylpentene. Both uncoated GFs (12 (7–19)%) and X.ELLENCE-coated GFs (Hilite-ML, 13 (8–19)%) showed a significantly higher surface coverage compared to Balance-coated GFs (Nautilus-ML, 3 (1–6)%), PH.I.S.I.O-coated GFs (EOS-ML, 2 (2–5)%) and Bioline-coated GFs (PLS-ML, 4 (1–8)%) (p < 0.001). HEs made of polyethyleneterephthalate (Hilite-ML, Nautilus-ML) that were coated with X.ELLENCE were covered with more platelets (5 (3–7)%) compared to Balance-coated HEs (3 (1–6)%), respectively (p = 0.029). Conclusions: In vitro testing disclosed fourfold higher platelet adhesion on X.ELLENCE-coated GFs (and HEs) from the Hilite-ML compared to other ECMO-materials. Additional hemocompatibility tests are necessary to assess the increased platelet adhesion on the materials from the Hilite-ML. Full article

Background: Burn patients with severe inhalation injury and refractory hypoxemia are at high risk for cardiorespiratory failure and mortality. Extracorporeal membrane oxygenation (ECMO) has emerged as a potential rescue therapy, but its survival benefits in this population remain uncertain. This study aimed to evaluate the impact of ECMO on mortality in burn patients with severe lung injury, to identify risk factors associated with death, and to analyze causes of rehospitalization among survivors. Methods: We conducted a population-based, retrospective cohort study using the Taiwan National Health Insurance Research Database (NHIRD). Burn patients with severe hypoxia requiring mechanical ventilation between 2000 and 2015 were identified. A 0.25-fold propensity score matching was applied based on age, gender, and burn severity. Mortality rates, survival risk factors, and rehospitalization causes were analyzed between ECMO and non-ECMO groups. Results: Among 6493 eligible patients, ECMO-treated patients had a hospital mortality rate of 47.09%, compared to 38.71% in the non-ECMO group. Early-phase mortality was higher among ECMO patients (adjusted 1-year mortality HR: 3.19), but survivors demonstrated stable long-term outcomes. Pulmonary complications, cardiac dysfunction, and sepsis were the leading causes of death. Kidney failure and infections were the most common reasons for rehospitalization among survivors. Conclusions: This research offers a comprehensive real-world analysis of the effectiveness of ECMO in burn patients. While ECMO does not eliminate early mortality risk, it may provide critical support during acute phase in carefully selected burn patients with severe hypoxemia. Multidisciplinary care and early rehabilitation planning are essential to improve long-term outcomes. Further research is needed to refine patient selection and optimize ECMO strategies in this high-risk population. Full article

Cardiopulmonary bypass (CPB) is one of the most groundbreaking medical innovations in history, enabling safe and effective heart surgery by temporarily replacing the function of the heart and lungs. This review starts with ancient concepts of cardiopulmonary function and then traces the evolution of CPB through important physiological and anatomical discoveries, culminating in the development of the modern heart–lung machine. In addition to examining the contributions of significant figures like Galen, Ibn al-Nafis, William Harvey, and John Gibbon, we also examine the ethical and technical challenges faced in the early days of open heart surgery. Modern developments are also discussed, such as miniature extracorporeal systems, off-pump surgical techniques, and the increasing importance of extracorporeal membrane oxygenation (ECMO) and extracorporeal life support (ECLS), while the evolving role of perfusionists in diverse cardiac teams and the variations in global access to CPB technology are also given special attention. We look at recent advancements in CPB, including customized methods, nanotechnology, artificial intelligence-guided perfusion, and organ-on-chip testing, emphasizing CPB’s enduring significance as a technological milestone and a living example of the cooperation of science, medicine, and human inventiveness because it bridges the gap between the past and the future. Full article

Background/Objectives: Antibiotic pharmacokinetics (PK) and pharmacodynamics (PD) are altered during extracorporeal membrane oxygenation (ECMO). Meropenem and piperacillin are among the most commonly prescribed antibiotics for infections in this population. However, guidance on dosage adjustments in the ECMO setting remains limited. We aim to assess differences in meropenem and piperacillin concentrations achieved and identify the clinical, physiological, and mechanical factors influencing antibiotic exposure. Methods: This is a retrospective, single-centre, observational study comparing an ECMO cohort with a population control group from a prior study, without renal dysfunction. Demographic, clinical, PK/PD parameters, and ECMO-related data were analysed using univariate and generalised estimating equations. For both antimicrobials, the PK/PD target was set at 100%fT_>4xMIC. Results: A total of 130 critically ill patients were included: 18 in the ECMO group and 112 in the control group. The mean age was 65 years (23), 67% were male and 26.9% were classified as obese. For meropenem, renal function and ECMO support significantly influenced drug exposure, with PK/PD targets being achieved in 67% of measurements; in contrast, piperacillin exposure exhibited greater variability, primarily driven by renal function and mechanical ventilation. Notably, PK/PD targets for piperacillin were met in only 20% of measurements. Conclusions: Our findings highlight the considerable variability in β-lactam exposures and PK/PD target attainment in critically ill patients. This study underscores the importance of therapeutic drug monitoring and individualised dosing in attempts to improve antimicrobial efficacy and patient outcomes in this challenging setting. Full article

Background: Infections following cardiac surgery are a significant cause of morbidity and mortality, particularly in intensive care units (ICUs). The role of antibiotic prophylaxis (AP) in preventing surgical site infections (SSIs) and other nosocomial infections is crucial; however, the optimal approach to agent selection, dosing, and duration remains controversial. Objective: This narrative review aims to summarise the current evidence and expert recommendations regarding the use of perioperative antibiotic prophylaxis (AP) in adults undergoing cardiac surgery, with a particular focus on intensive care settings, transplant recipients, and adult patients on extracorporeal membrane oxygenation (ECMO). Methods: A comprehensive review of recent literature was conducted, focusing on pharmacokinetic/pharmacodynamic (PK/PD) principles, microbial epidemiology, antimicrobial resistance (AMR), and practical strategies for tailored prophylaxis in high-risk populations. Results: Cefazolin remains the first-line agent for most procedures, with vancomycin or clindamycin reserved for patients who are allergic to β-lactams or who are colonised with MRSA. Redosing is recommended in cases of prolonged surgery or cardiopulmonary bypass. Evidence supports limiting prophylaxis to ≤24 h, with a potential extension to 48 h in select high-risk cases; however, continuation beyond this is discouraged due to the risk of resistance. In heart transplantation, multimodal prophylaxis against bacteria, fungi, and viruses is essential but must be tailored to the individual patient. In the ECMO setting, the current evidence does not support the routine administration of prophylaxis (AP), and therapy should be tailored based on pharmacokinetics (PK)/pharmacodynamics (PD) changes and the clinical context. A multidisciplinary, evidence-based approach to AP in cardiac surgery is essential. Prophylaxis should be patient-specific, microbiologically guided, and limited in duration to reduce the emergence of multidrug-resistant organisms. Integrating antimicrobial stewardship, non-pharmacological measures, and rigorous surveillance is crucial for optimising the prevention of infections in this vulnerable population. Full article

Andes virus (ANDV) is the leading cause of hantavirus cardiopulmonary syndrome (HCPS) in South America, a severe zoonosis with high mortality. Advances in critical care and extracorporeal membrane oxygenation (ECMO) have significantly improved survival rates; however, data on recovery beyond survival remain limited. This multicenter cohort study enrolled laboratory-confirmed HCPS survivors in Chile between 2021 and 2024, with follow-up at 3–6 months post-symptom onset to assess physical and neuropsychological sequelae. Participants were stratified by ECMO requirement and the clinical severity of HCPS, and evaluated using self-reported recovery, standardized symptom questionnaires, and EQ-5D quality-of-life instruments. Among 21 survivors (11 ECMO, 10 non-ECMO), 61.9% reported incomplete recovery. While 60–70% of patients received general medical follow-up, only 30% of non-ECMO patients—compared to all ECMO patients—had contact with a rehabilitation provider. Motor dysfunction and palpitations were more frequent in ECMO survivors; however, Jaccard index analysis revealed clustering of physical and neuropsychological symptoms across both groups. EQ-5D assessments showed comparable quality-of-life impairment, though non-ECMO survivors more often reported pain/discomfort (90.0% vs. 63.6%) and higher rates of analgesic self-medication. These findings highlight the burden of persistent symptoms after HCPS and the need for multidisciplinary post-discharge care in endemic regions. Full article