Search Results (728)

Background: The landscape of paediatric oncology has undergone a remarkable transformation over recent decades. Advances in both oncological and supportive therapies have dramatically improved survival in children with haematological malignancies and solid tumours, with current survival rates exceeding 80% for many childhood cancers. However, this therapeutic success has brought with it an unexpected consequence: the intensification of treatment protocols has led to a parallel increase in life-threatening complications requiring intensive care support. Current evidence indicates that up to 40% of paediatric oncology patients will require admission to a Paediatric Intensive Care Unit (PICU) at some point during their disease trajectory. Objectives: This comprehensive review synthesises current evidence to provide an updated framework for PICU admission decision-making in oncology haematology patients. We have integrated the most recently published international guidelines, including the groundbreaking Phoenix 2024 sepsis criteria and the updated PALICC-2 2023 recommendations for paediatric acute respiratory distress syndrome. Beyond establishing admission criteria, we critically analyse the efficacy of advanced support strategies and examine emerging therapeutic approaches in this uniquely vulnerable population. Methods: Our methodology encompassed a systematic review of the literature published between 2011 and 2024, complemented by a detailed analysis of current international guidelines and expert consensus statements. We included randomised controlled trials, observational studies, meta-analyses, and consensus conference proceedings specifically addressing the intensive care management of paediatric patients with oncological or haematological conditions. Main Results: Several key findings emerge from our analysis. The Phoenix 2024 criteria represent a fundamental reconceptualisation of paediatric sepsis diagnosis, validated through an unprecedented dataset encompassing more than 3 million paediatric encounters. In the realm of respiratory support, early implementation of non-invasive ventilation (NIV) or continuous positive airway pressure (CPAP) has demonstrated remarkable efficacy, reducing the need for invasive mechanical ventilation by 45% (RR 0.45, 95% CI 0.26–0.78) when applied to appropriately selected patients. Extracorporeal membrane oxygenation (ECMO), whilst increasingly utilised, shows survival to decannulation ranging from 52% to 64%, though survival to hospital discharge remains less encouraging at 36–42%. Continuous renal replacement therapy (CRRT) has proven highly effective for tumour lysis syndrome, achieving metabolic correction in 90% of severe cases. Perhaps most promisingly, emerging biomarkers—particularly interleukin-6, interleukin-10, and procalcitonin—have substantially enhanced our ability to stratify infection risk, demonstrating sensitivity exceeding 85% for bacteraemia detection. Conclusions: The evidence unequivocally supports several core principles for optimising outcomes in this population. Early identification of deterioration through validated scoring systems enables timely intervention before irreversible organ failure develops. Prompt implementation of non-invasive respiratory support, when appropriately applied, can obviate the need for mechanical ventilation with its attendant complications. Perhaps most critically, centralisation of care in centres with dedicated expertise and comprehensive support capabilities fundamentally improves survival. These findings argue compellingly for the establishment of a formal national network of reference centres, implementing standardised protocols and structured care pathways specifically designed for critically ill paediatric oncology haematology patients. Full article

Background and Objectives: One of the two primary classes of drugs administered in ICUs for pharmacological sedation is benzodiazepines. Among these, anesthesiologists consider midazolam the most commonly used and clinically significant agent. Materials and Methods: A prospective, single-center investigation involving 25 patients was carried out in the ICU. The study population consisted of patients undergoing mechanical ventilation with an FiO₂ exceeding 60%, as well as ventilated individuals requiring additional support such as ECMO, NO, or ECCOR over 24 h before the study. Participants under 18 years of age or those not receiving continuous midazolam infusion were excluded. Measurements obtained from RASS and BIS were then compared with serum midazolam concentrations. On each day, when blood samples for midazolam measurements were taken, additional laboratory tests assessing renal and hepatic function were also carried out. Results: A negative correlation was shown between RASS and midazolam dosage (r = −0.44, p < 0.001), midazolam concentration (r = −0.33, p < 0.001), and α-OH-midazolam concentration (r = −0.24, p = 0.008). Similarly, a negative correlation was shown between BIS and midazolam concentration (r = −0.3, p = 0.016), as well as α-OH-midazolam (r = −0.3, p = 0.016). We observed that deceased patients received higher doses of midazolam to maintain the minimum level of required sedation compared to the others (135.5 ± 75.1 mg vs. 39.6 ± 59.2 mg; p = 0.002), indicating that these patients had higher concentrations of both midazolam and α-OH-midazolam (148.6 ± 83.5 µg/L vs. 27.2 ± 36.1 µg/L; p < 0.001, and 18 ± 15.9 vs. 5.3 ± 6.1 µg/L; p < 0.001). Conclusions: The results show that routine monitoring of midazolam does not provide additional clinical value. However, further studies are needed in high-risk groups. Despite the high mortality rate in the ICU for patients with severe respiratory failure, the six-month survival rate for discharged patients was high, exceeding 80%. Full article

Background: Heart failure (HF) is a major public health challenge. Management at or transfer to advanced therapy centers (ATCs) is linked to greater procedural use and better outcomes for HF, however there is little data on the impact of patient sex on access to ATCs and transfer patterns. We evaluated sex-based differences in HF management and outcomes during admissions across center types and transfer status. Method: Adult HF admissions were identified in the 2016–19 Nationwide Readmissions Database. Centers performing ≥1 heart transplant or LVAD were classified as ATCs. Patients were stratified by sex and center type: (A) non-ATC admission, (B) ATC admission, (C) transfer to ATC. Multivariable regression adjusted for comorbidities and HF decompensations. Results: Among 2,872,268 weighted HF admissions (51.3% male), females were older, while males had more HF decompensations (cardiogenic shock, ventricular arrhythmias, mechanical ventilation, AKI). Females comprised only 39.6% of all transfers to ATCs (0.4% vs. 0.6%, OR 0.69, p < 0.001) and had a lower unadjusted mortality (2.6% vs. 2.8%, p < 0.001); however, rates of transfer and mortality were similar between sexes when adjusted for comorbidities and HF decompensations. Female patients were significantly less likely to receive invasive procedures (CRT/ICD, PCI, right heart catheterization, CABG, temporary mechanical support, ECMO, LVAD or heart transplant) across all hospital types and transfers. This disparity in procedural utilization persisted after multivariable adjustment and in sensitivity analysis of patients with severe HF. Conclusions: Females had lower frequency of transfer to ATCs. In-hospital mortality and transfer rates to ATCs were similar across patient sex when adjusted for comorbidities and HF decompensations. Females consistently underwent fewer diagnostic and therapeutic interventions across all center types and transfers. Full article

Utilization of a blood pump to aid in circulating a patient’s blood, otherwise known as mechanical circulatory support, is an effective and often life-saving treatment for cardiac/pulmonary failure patients, yet adverse events remain a common complication often attributed to mechanical trauma inflicted on blood components. This work specifically focuses on erythrocyte-derived extracellular vesicles (ErEVs) as a marker of this mechanical trauma as they are elevated in patients with blood pumps and have been tied to adverse events. Despite this, ErEVs are typically neglected during device development which usually includes testing with animal blood, most commonly porcine and bovine. Flow cytometry was employed to monitor ErEVs generated during a 6 h perfusion of porcine or bovine red blood cells (RBCs) in a blood circulatory loop with the CentriMag blood pump. Successful measurement meant overcoming limitations in suitable stains for the RBCs and ErEVs of the two species. Between the two species, 12 different antibodies and dyes were evaluated, including multiple glycophorin A clones, the typical human erythrocyte antigen. Only CD46 and carboxyfluorescein succinimidyl ester (CFSE) were found to successfully and reliably label porcine and bovine RBCs, respectively. With these stains, statistically significant increases for both porcine and bovine ErEVs with perfusion time were observed. Bovine erythrocytes produced significantly more ErEVs than porcine, indicating they are more sensitive to mechanical trauma and could be useful in early-stage device development. The utility of CD46 and CFSE used for porcine and bovine ErEV detection was demonstrated for in vitro pump testing with implications for physiological and pathological research with these animals. Full article

Carbapenem-resistant Gram-negative infections have become one of the most formidable challenges in intensive care units (ICUs). Critically ill patients—often exposed to invasive procedures, prolonged hospitalization, and broad-spectrum antibiotics—are highly susceptible to infections by carbapenem-resistant Enterobacterales (CRE), Pseudomonas aeruginosa (CRPA), and Acinetobacter baumannii (CRAB). These pathogens are associated with mortality exceeding 40%, prolonged ICU stays, and increased healthcare costs. Therapeutic advances have reshaped management in recent years. New β-lactam/β-lactamase inhibitor combinations—ceftazidime–avibactam, meropenem–vaborbactam, imipenem–relebactam, and sulbactam–durlobactam—along with cefiderocol, have provided safer and more effective alternatives to previously used regimens. Yet, none are universally effective, particularly against carbapenemase-producing organisms, especially metallo-β-lactamase (MBL) producers, and resistance may still emerge during treatment. Rapid molecular and phenotypic diagnostics, when integrated into antimicrobial stewardship, have improved early therapy alignment and reduced unnecessary broad-spectrum use. Beyond antibiotics, colonization surveillance and infection control remain pivotal, as colonization often precedes invasive infection. Biofilm formation on devices such as endotracheal tubes and catheters further promotes persistence and relapse. Strategies targeting biofilm disruption, improved dosing guided by pharmacokinetic/pharmacodynamic optimization, and therapeutic drug monitoring are crucial in ICU practice. The future of managing these infections will depend on integrating precision tools—rapid diagnostics, mechanism-based therapy, and stewardship-guided decisions—with emerging treatments and adjunctive options such as immunomodulators, bacteriophages, and AI-driven decision support. Continued research in ICU-specific populations, especially regarding pharmacokinetics in patients on ECMO or CRRT, is urgently needed. In summary, while the therapeutic landscape for carbapenem-resistant Gram-negative infections has evolved substantially, sustained success will rely on a multifaceted strategy combining innovation, precision, and prevention to improve outcomes for the most vulnerable patients. Full article

Cardiogenic shock is a life-threatening condition caused by the heart’s sudden inability to pump sufficient blood to maintain adequate tissue perfusion, most commonly occurring following a myocardial infarction or acute decompensated heart failure. The resultant hypoperfusion can quickly progress to end-organ failure and ultimately death if not treated urgently. This review explores the management of cardiogenic shock, highlighting current treatments, their effectiveness, and the challenges faced by healthcare providers. It looks at both pharmacological therapies and devices used for cardiac support, including mechanical circulatory support and emergency revascularisation procedures to restore blood flow. We also examine how different stages of shock affect survival and how new technologies including artificial intelligence and wearable monitors could help detect and treat this condition earlier. In addition, this review discusses the significant pressure that cardiogenic shock places on healthcare provision, including the typical financial cost of treatment in the UK, resource utilisation and regional disparities. Finally, we outline future directions for trial design, better prevention, more rapid diagnosis and improved treatments that could improve morbidity and mortality. Full article

Background: Massive pulmonary hemorrhage is a life-threatening complication of pulmonary endarterectomy (PEA) with limited evidence to guide standardized management. Methods: We retrospectively evaluated consecutive PEA procedures performed at a high-volume center and analyzed the incidence, perioperative characteristics, management strategies, and early outcomes of patients who developed massive pulmonary hemorrhage. Results: Among 1123 patients who underwent PEA, massive pulmonary hemorrhage occurred in 51 (4.54%) and developed intraoperatively after completion of PEA and separation from total circulatory arrest. Primary suturing achieved hemostasis in 12 patients (23.5%), and bronchial isolation was applied in 18 (35.3%). Local adjuncts included intraoperative bronchial clamping in 1 patient (2.0%) and biological glue occlusion in 2 (3.9%). Extracorporeal membrane oxygenation (ECMO) was required in 25 patients (49.0%), initiated intraoperatively in 22 and postoperatively in 3. Overall in-hospital mortality was 41.2%, while 30 patients (58.8%) survived to hospital discharge; among survivors, mean hospital length of stay was 16.1 ± 6.8 days. Conclusions: Massive pulmonary hemorrhage after PEA remains associated with substantial early mortality and resource utilization; a stepwise institutional algorithm combining bronchoscopy-guided localization, targeted airway/surgical control, and timely ECMO support may help standardize management in this critical setting. Full article

Background: Extracorporeal membrane oxygenation (ECMO) is commonly used for temporary support in patients with severe cardiogenic shock and may serve as a bridge to heart transplantation. In recent years, outcomes have improved with better timing, patient management and advances in ECMO technology. Case presentation: We describe the case of a 61-year-old man who developed refractory cardiogenic shock after an extensive acute myocardial infarction complicated by recurrent ventricular arrhythmias. After an initial period of stabilization following complex percutaneous coronary intervention, the patient suddenly deteriorated with acute pulmonary edema and severe hypoxemia. A peripheral femoro-femoral veno-arterial ECMO with distal limb perfusion was promptly implanted using the ECMOLIFE system and the Landing Advance system (Eurosets s.r.l., Medolla, MO, Italy) to stabilize the patient and enable continuous monitoring. Due to severe left ventricular distension, surgical left ventricular venting was performed through a minimally invasive approach. ECMO support allowed rapid hemodynamic stabilization without major complications. During ECMO support, the patient remained stable and after less than 48 h a suitable donor heart became available. The patient was safely transferred to a transplant center while on ECMO and successfully underwent heart transplantation. Conclusions: This case shows that early ECMO implantation, combined with appropriate ventricular unloading and careful management with an advanced monitoring system, can be an optimal support as a bridge to heart transplantation. Limiting the duration of ECMO support and ensuring timely referral to a transplant center may improve outcomes in patients with refractory cardiogenic shock. Full article

Background: Determining the optimal duration of extracorporeal cardiopulmonary resuscitation (ECPR) remains challenging, as patient outcomes may vary significantly based on individual characteristics. We aimed to establish critical time thresholds for achieving favorable neurological outcomes with ECPR across different risk groups, potentially providing more tailored guidance for clinical decision-making. Methods: This single-center retrospective study screened 279 adult patients who received ECPR between 2013 and 2020. Through multivariate analysis of various clinical parameters, we developed a pragmatic bedside risk stratification framework to identify groups with different prognostic profiles. The primary outcome was neurological status at discharge, assessed by the Cerebral Performance Categories scale. Results: In multivariate analysis, age greater than 50 years with asystole (adjusted odds ratio [OR]: 4.89, 95% confidence interval [CI]: 1.41–17.00) or pulseless electrical activity (adjusted OR: 9.70, 95% CI: 2.80–33.60), aspartate transaminase (adjusted OR: 1.52, 95% CI: 1.15–1.99), creatinine (adjusted OR: 2.08, 95% CI: 1.30–3.34), initial lactate (adjusted OR: 1.88, 95% CI: 1.27–3.45), and low-flow time (adjusted OR: 3.50, 95% CI: 2.02–6.06) were associated with poor neurological outcomes. Based on these findings, we identified three distinct risk groups showing different acceptable low-flow time thresholds: low-risk (38 min), moderate-risk (27 min), and high-risk (20 min). Notably, no favorable neurological outcomes were observed beyond 70 min in the low-risk group and 90 min in moderate/high-risk groups. Risk group stratification effectively predicted neurological outcomes across different low-flow time intervals. Conclusions: Risk-stratified evaluation of low-flow time (cardiac arrest to ECMO pump-on) provides clinically relevant thresholds for different patient groups, suggesting that continuation of ECPR may be warranted in low-risk patients even with extended low-flow times. This approach may enable more personalized decision-making in ECPR implementation. Full article

Echocardiographic assessment is essential for evaluating patients with cardiogenic shock (CS) and determining their potential need for mechanical circulatory support (MCS) implantation. The use of Impella devices has increased significantly in recent years, paralleling the growing recognition of their hemodynamic benefits in selected patient populations. As the clinical experience with these devices has expanded, the need for a more standardized imaging approach has emerged. Both transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) play complementary roles in guiding the pre-implantation evaluation, placement procedure, and post-implantation management of Impella devices. Currently, no comprehensive guidelines exist concerning the echocardiographic evaluation of Impella devices throughout their entire clinical course, from initial patient selection and device implantation to ongoing monitoring and eventual weaning. This gap in standardized guidance has led to significant variability in clinical practice across different institutions and healthcare systems. This comprehensive review examines the role of transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) in managing patients on Impella support across five distinct phases: candidate identification and pre-implantation assessment, intraoperative procedural guidance and device positioning, postoperative monitoring and haemodynamic optimisation, complication detection and troubleshooting, and weaning strategies with post-explantation surveillance. Both left-sided devices (Impella CP, CP Smart Assist, and Impella 5.5) and right-sided support (Impella RP) are covered, including combined configurations with VA-ECMO (ECPella). For each phase, we detail the recommended echocardiographic views, essential measurements and their evidence-based thresholds, signs of device malposition, and practical corrective strategies. A level-of-evidence approach is adopted throughout, specifying whether proposed thresholds derive from randomised trials, observational studies, expert consensus, or manufacturer recommendations. Summary tables and a bedside workflow are provided to facilitate immediate clinical application. Full article

Background/Objectives: Acute hemodynamic collapse is a rare but deadly complication of transcatheter aortic valve replacement (TAVR) that can require temporary mechanical circulatory support (tMCS). Using a statewide collaborative, we conducted a focused analysis on the incidence and outcomes associated with the use of tMCS during TAVR as hemodynamic rescue. Methods: We identified adult patients who underwent TAVR between September 2012 and September 2024 within the statewide collaborative and stratified them based on if tMCS was needed. Baseline patient characteristics and risk factors associated with tMCS use were analyzed as well as the impact of tMCS on outcomes. Results: We identified 7735 patients who underwent TAVR. A total of 44 (0.57%) patients required tMCS. Patients requiring tMCS were more likely to have histories that included diabetes, concurrent mitral regurgitation, prior MI, or NYHA class III or IV. These patients also experienced more emergent procedures and were more likely to require inotropic support. Patients experienced significantly worse outcomes following tMCS rescue during TAVR, with 18% requiring conversion to surgical approach (vs. 1%, p < 0.001) and 37% of tMCS patients experiencing cardiac arrest, compared to 1% of those who did not need tMCS (p < 0.001). Thirty-day mortality was worse for patients requiring tMCS (p < 0.001). MCS usage was independently associated with the need for further procedures. Conclusions: Unplanned, emergent tMCS during TAVR as hemodynamic rescue represents significant risk of complications and should be utilized judiciously in cases of acute hemodynamic collapse. Full article

Background: Unfractionated heparin (UFH) remains the standard anticoagulant for extracorporeal membrane oxygenation (ECMO), despite complications, such as heparin resistance, heparin-induced thrombocytopenia, bleeding and variable pharmacokinetics. This has prompted the search for alternative and novel anticoagulation strategies, including pharmacologic agents, circuit modifications, and monitoring approaches. This scoping review aimed to map the breadth and characteristics of evidence on ECMO anticoagulation strategies beyond UFH. Methods: A comprehensive search of peer-reviewed and gray literature was conducted across PubMed, Cochrane, Clinical Trials, WHO Trials Registry, and conference abstracts through manual searches in key journals. Clinical, pre-clinical, and gray literature studies evaluating pharmacologic agents, anticoagulation-free or heparin-sparing, biocompatible circuits, and monitoring innovations were included. Data were charted and synthesized descriptively to identify trends, gaps, and emerging directions. Results: A total of 269 records were included. Evidence was highly heterogeneous among study designs, populations, ECMO modalities, and outcome definitions. Most clinical studies were retrospective cohorts and adult-centered, with limited multicenter randomized controlled trials and underrepresentation of neonatal and pediatric populations. Direct thrombin inhibitors were frequently studied and clinically implemented alternatives to UFH. Other agents, including nafamostat mesylate, prostaglandin E1, and factor pathway inhibitors remain early in clinical investigation. Anticoagulation-free strategies and biocompatible circuit technologies were mostly supported through pre-clinical and single-center studies. Monitoring and modeling innovations, like TEG, ROTEM, real-time imaging, and machine learning, are quickly emerging. Conclusions: ECMO anticoagulation is transitioning from UFH reliance toward diversified and personalized strategies. Future research should prioritize multicenter randomized controlled trials, standardize protocols, expand to neonatal and pediatric investigation, and integrate strategies. Full article

Background/Objectives: Heart rate variability (HRV) and cerebral autoregulation (CAR) reflect physiologic processes that may influence neurological injury in children supported with extracorporeal membrane oxygenation (ECMO). Although abnormalities in both have been associated with adverse neurological outcomes, their physiologic relationship during ECMO remains unclear. Methods: This retrospective single-center study evaluated the association between HRV and CAR during the first 24 h of ECMO support and assessed their independent relationships with neurological outcome. Patients with at least two hours of simultaneous HRV and CAR monitoring within 24 h of ECMO initiation were included. HRV metrics were derived from artifact-free NN intervals across time, frequency, and nonlinear domains, while CAR was quantified using the cerebral oximetry index (COx), with impaired CAR defined as COx > 0.3. Associations between HRV indices and COx were examined using Spearman correlations at hourly and 24 h resolutions. Unfavorable outcome was defined as death or a Pediatric Cerebral Performance Category (PCPC) score ≥3 at discharge with deterioration from baseline. Results: Eighty-nine patients met inclusion criteria, and 16% demonstrated impaired CAR. HRV measures were reduced relative to age-adjusted norms in both CAR groups without significant differences between groups. Correlations between HRV indices and COx were consistently weak. Overall, 50% experienced unfavorable neurological outcomes. In adjusted logistic regression models, NN skewness and COx were independently associated with outcome, although only NN skewness remained significant in interaction analyses. Conclusions: HRV and CAR exhibited limited physiological coupling during early ECMO support, while each measure provided independent prognostic information with respect to neurological outcome. Full article

Background/Objectives: While caregiver burden in Inflammatory Bowel Disease (IBD) is well documented, the association between informal support and patient-reported outcomes (PROs), particularly health-related quality of life (QoL) and psychological well-being, remains underexplored. This systematic review synthesizes evidence on the association of informal caregiving on patient-reported QoL and psychosocial outcomes and maps the available evidence on clinical outcomes. Methods: Following international reporting guidelines and prospective protocol registration, a systematic search was conducted across five electronic databases between May and October 2025. Observational studies in adults with IBD assessing informal support and patient-reported or psychosocial outcomes were included. Owing to substantial heterogeneity in constructs and outcome measures, results were synthesised using a structured Synthesis Without Meta-analysis (SWiM) approach. Methodological quality was assessed using standardised critical appraisal checklists. Results: Six cross-sectional studies involving 1036 patients and 417 informal caregivers met the inclusion criteria. All studies reported a positive direction of association between higher levels or better quality of informal caregiver support and improved patient-reported QoL. Several studies identified psychological and relational factors, such as lower patient psychological distress and caregiver-related positive feelings and caring ability, as mechanisms statistically associated with this relationship. Conclusions: Available cross-sectional evidence suggests a positive association between informal support and patient-reported QoL/psychological outcomes in IBD, but causality cannot be inferred. Priorities include longitudinal dyadic studies and caregiver-inclusive interventions, alongside standardised definitions and measures of support. Full article

Heparin remains a foundational parenteral anticoagulant across both acute and chronic care settings. This narrative review summarizes clinical indications and dosing of unfractionated (UFH) and low-molecular-weight heparin (LMWH). It also details laboratory monitoring using activated partial thromboplastin (APTT), anti-factor Xa (anti-Xa), activated clotting time (ACT) and viscoelastic testing (VET), including common pitfalls and interferences. We provide considerations for specific populations as well as complications including heparin resistance, heparin-induced thrombocytopenia (HIT) and heparin reversal strategies. Future research directions include harmonization of therapeutic ranges, mitigation of assay interference and prospective evaluation on monitoring, particular in extracorporeal membrane oxygenation (ECMO), pregnancy and cardiac surgical settings. Full article