The potential toxicity, safety and anti-drug antibody production of the novel IL-2 "no-alpha" mutein is in need of investigation as it may be a critical candidate for cancer therapy. The design of this mutein is meant to reduce toxicity compared to the IL-2 wildtype by disrupting interactions with the alpha receptor (CD25) and increasing the efficacy of the treatment. This was assessed following administration to Sprague-Dawley rats intravenously (IV), and it occurred over three cycles of five days each with daily dosing, with a 9-day washout period between each cycle. For the mutein dose groups, animals were dosed via IV at dose levels of 600, 6000, 18,000 U/kg. This dosing regimen is equivalent to 1x, 10x, and 30x the proposed first human dose, respectively. This study also assessed the progression or regression of any effects following a 14-day treatment-free recovery period for the control and high dose groups. Rats that were administered the "no-alpha" mutein at 600 and 6000 U/kg were well-tolerated with no apparent abnormal observations in general health, behaviour and autonomic function. There was no evidence of systemic toxicity based on evaluations in clinical pathology, gross necropsy and histopathology. At 18,000 U/kg (30x), abnormal clinical signs were observed at the injection sites consisting of localized swelling, discoloration, scabbing and necrosis. These animals showed a significant recovery in abnormal localized clinical signs following the treatment free period. Additionally other parameters did not indicate any significantly detrimental effects at this dose level. Therefore, the IL-2 mutein "no-alpha" seems to hold promise as a valuable addition to the current array of cancer therapy strategies, especially at the proposed dose level.

Hypoalbuminemia in septic patients is a known prognostic factor for poor outcomes, yet the optimal therapeutic interventions remain unclear. This study aimed to evaluate the effect of the co-administration of albumin and loop diuretics on in-hospital mortality among septic patients with hypoalbuminemia.

This retrospective cohort study utilized data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database, analyzing 3373 adult septic patients diagnosed with hypoalbuminemia. To control for potential confounding factors, Cox proportional hazard models and propensity score matching (PSM) were employed. The primary outcome was in-hospital mortality, and secondary outcomes included the effects of different dosages of loop diuretics.

The results demonstrated that septic patients with hypoalbuminemia who received a combination of albumin and loop diuretics had a significantly lower in-hospital mortality rate compared to those treated with albumin alone (25.5 % vs. 36.5 %, p < 0.001). The timing of diuretic administration, specifically after albumin infusion, was linked to further reductions in mortality. Notably, the administration of furosemide at dosages between 10 mg and 40 mg per day was associated with the lowest mortality rates.

In septic patients with hypoalbuminemia, co-administration of albumin and loop diuretics is associated with a substantial reduction in in-hospital mortality, especially when loop diuretics are administered following albumin infusion. These findings suggest a potential treatment strategy that merits validation through future prospective randomized controlled trials.

A 29-year-old Japanese woman was admitted to our hospital with fever, cardiogenic shock, and cardiac arrest and died 18 h after admission. The patient was diagnosed with systemic capillary leak syndrome associated with coronavirus disease 2019. Electron microscopy of the biopsied right-ventricular myocardium revealed extensive interstitial leakage of blood cells and plasma, damaged capillaries, and reticular vessel drainage into the Thebesian vein. These findings indicate that severe capillary leak and lumen occlusion due to damaged capillaries are the main features of systemic capillary leak syndrome.

Capillary leak syndrome (CLS) is a rare, often idiopathic condition, typically characterized by edema, hypotension, hypovolemic shock, and hypoalbuminemia. The progression of CLS is rapid, with a complex clinical course. If left undiagnosed or untreated, CLS can cause multiorgan failure and significantly increase the risk of mortality. Although CLS is generally associated with conditions such as infections, trauma, or autoimmune disorders, the occurrence of the condition following a cesarean section in patients with severe preeclampsia is exceedingly uncommon.

A 37-year-old pregnant woman at 37 weeks of gestation underwent a cesarean section due to severe preeclampsia. Postoperatively, the patient developed sudden hypoxemia, massive ascites, oliguria, hypotension, and hypoalbuminemia. Following prompt identification and diagnosis, treatment was initiated with blood pressure management, magnesium sulfate to alleviate spasms, and supplementation with hydroxyethyl starch, albumin, and crystalloids. Additionally, corticosteroids were administered to improve capillary permeability. The condition was rapidly managed, with subsequent follow-up revealing no recurrence of similar issues.

To the best of our knowledge, this is the first documented case of CLS occurring following a cesarean delivery in a patient with severe preeclampsia. The successful management of this patient offers valuable insights into early diagnosis, prompt treatment, and the potential to improve the prognosis of similar cases.

Identifying new early predictive markers for the development of severe forms in acute pancreatitis remains a major challenge. The aim of this study was to evaluate the performance of inferior vena cava (IVC) measurement to predict severe acute pancreatitis.

We conducted a single-center retrospective study including patients consecutively hospitalized for acute pancreatitis between 2014 and 2019 who had an abdominal scan within 24 h after admission, before any significant fluid resuscitation. We calculated the ratio of inferior vena cava diameters (IVCR) by dividing the transverse diameter by the anteroposterior. Admission parameters associated with the occurrence of severe acute pancreatitis (persistent organ failure or necrosis infection) were identified by multivariate logistic regression.

Of the 404 included patients, 64 (15.8%) progressed to severe pancreatitis. IVCR in these patients was significantly higher (2.2 ± 0.6 vs. 1.7 ± 0.9, p < .001). In multivariate analysis, IVCR was independently associated with severe pancreatitis (OR = 2.27 95% CI [1.38-3.72], p = .001), as well as visual analog scale, creatinine, albumin, and bicarbonates. The areas under the Receiver Operating Characteristic (ROC) curve of IVCR was 0.67, inferior to systemic inflammatory response syndrome (0.76; p = .03) and Bedside Index for Severe Acute Pancreatitis (BISAP) (0.80; p = .002) in predicting severe acute pancreatitis.

IVCR is associated with the development of severe acute pancreatitis.

Hyperlactatemia is intimately correlated with severity and poor prognosis of patients with sepsis. However, little experimental evidence on this process is known. We report here that lactate dehydrogenase B (LDHB), the glycolytic enzyme that catalyzes conversion of lactate to pyruvate, is transcriptionally downregulated in blood samples of hyperlactatemic patients, while mice receiving lactate injection have reduced LDHB activity in liver and kidney. LDHB knockout (Ldhb-/-) mice with hyperlactatemia are vulnerable to lethality, hypotension and vascular leakage. The hyperlactatemic Ldhb-/- mice develop severe liver and kidney injuries accompanied by increased hepatic and renal SLC16A1 abundance but unaltered morphology. Pharmacological targeting of SLC16A1 with AZD3965 in Ldhb-/- mice rescues the hyperlactatemia-induced lethality, liver and kidney injuries. Loss of LDHB renders hyperlactatemia, lethality, vascular leakage, liver and kidney injuries in response to abdominal sepsis. AZD3965 treatment partially abrogates liver and kidney injuries of septic Ldhb-/- mice without affecting necrosis. Blockade of necroptosis significantly protects Ldhb-/- mice against septic liver and kidney injuries, enabling a compensation towards the therapeutic efficacy of AZD3965. Our study together unearth the coordination of hyperlactatemia and necroptosis in septic liver and kidney injuries in the context of LDHB deficiency, and support further investigation of combined targeting SLC16A1 and necroptosis for clinical treatment of sepsis with low LDHB activity.

Ariel Dynamic Acute Pancreatitis Tracker (ADAPT) is an artificial intelligence tool using mathematical algorithms to predict severity and manage fluid resuscitation needs based on the physiologic parameters of individual patients. Our aim was to assess whether adherence to ADAPT fluid recommendations vs standard management impacted clinical outcomes in a large prospective cohort.

We analyzed patients consecutively admitted to the Los Angeles General Medical Center between June 2015 and November 2022 whose course was richly characterized by capturing more than 100 clinical variables. We inputted these data into the ADAPT system to generate resuscitation fluid recommendations and compared with the actual fluid resuscitation within the first 24 hours from presentation. The primary outcome was the difference in organ failure in those who were over-resuscitated (>500 mL) vs adequately resuscitated (within 500 mL) with respect to the ADAPT fluid recommendation. Additional outcomes included intensive care unit admission, systemic inflammatory response syndrome (SIRS) at 48 hours, local complications, and pancreatitis severity.

Among the 1,083 patients evaluated using ADAPT, 700 were over-resuscitated, 196 were adequately resuscitated, and 187 were under-resuscitated. Adjusting for pancreatitis etiology, gender, and SIRS at admission, over-resuscitation was associated with increased respiratory failure (odd ratio [OR] 2.73, 95% confidence interval [CI] 1.06-7.03) as well as intensive care unit admission (OR 2.40, 1.41-4.11), more than 48 hours of hospital length of stay (OR 1.87, 95% CI 1.19-2.94), SIRS at 48 hours (OR 1.73, 95% CI 1.08-2.77), and local pancreatitis complications (OR 2.93, 95% CI 1.23-6.96).

Adherence to ADAPT fluid recommendations reduces respiratory failure and other adverse outcomes compared with conventional fluid resuscitation strategies for acute pancreatitis. This validation study demonstrates the potential role of dynamic machine learning tools in acute pancreatitis management.

Capillary leak syndrome (CLS) is an urgent problem in postoperative patients, is challenging to diagnose early, and has a poor prognosis. We investigated a quick and convenient diagnostic indicator of secondary CLS in children after cardiopulmonary bypass (CPB).

We conducted this single-center, observational, prospective study in the Department of Critical Care Medicine at the Children's Hospital of Chongqing Medical University. All the data were collected within 24 h after cardiopulmonary bypass (CPB). The secondary CLS risk factors were determined using univariate and multivariate logistic regression analysis, and the cut-off point of secondary CLS was found by receiver operating characteristic (ROC) analysis.

Our study included two hundred four pediatric patients in the PICU after cardiopulmonary bypass (CPB). 42.65% (87/204) of patients were diagnosed with secondary CLS. The incidence of acute kidney injury (AKI) was 36.76% (75/204), and the mortality was 5.39% (11/204). Logistic analysis indicated that a pulmonary exudation on chest radiograph, a high thoracic fluid content (TFC) and a higher vasoactive inotropic score (VIS) were independent risk factors for secondary CLS [odds ratio [OR] 23.62, 95% confidence interval [CI] 7.20-90.41, p < 0.001; OR 1.08, 95% CI 1.02-1.16, p = 0.010; OR 1.06, 95% CI 1.01-1.14, p = 0.049; respectively]. According to the ROC analysis, the cut-off point for the TFC was 52 (Ω-1).

The TFC plays a key role in the early prediction of secondary CLS in children after CPB, and this novel indicator may help clinicians initiate intensive treatment as early as possible.

Capillary leak syndrome occurs when plasma leaks out of capillaries into muscles, tissues, organs and body cavities. There are two major types of capillary leak syndrome: 1. secondary capillary leak syndrome: it is a single episode triggered by another disease, condition or drug; 2. idiopathic systemic capillary leak syndrome: it is a rare disease characterized by recurrent episodes of acute life-threatening episodes of shock, hemoconcentration, and hypoalbuminemia. An increase in capillary permeability results in reversible plasma movement into the interstitial spaces followed by the appearance of related symptoms or complications, including acute kidney injury. Cytokines are likely to be important in the pathophysiology of systemic capillary leak syndrome. Fluid management is a critical part of the treatment of systemic capillary leak syndrome: hypovolemia and hypotension can cause organ injury, whereas capillary leakage of administered fluid can worsen organ edema leading to progressive organ injury.Although systemic capillary leak syndrome is a rare entity, it can be life-threatening. The nephrologist must be aware of the potential and serious complications linked to this pathology, including the need for kidney replacement therapy. This review aims to increase awareness of systemic capillary leak syndrome in the nephrology community.

Query fever (Q fever), a zoonotic disease, caused by Coxiella burnetii, is an infectious disease that has long been considered a rare and regionally restricted disease. It can be responsible for endocarditis and endovascular infections. Systemic capillary leak syndrome (SCLS), a rare disease of unknown etiology that most commonly develops in adults 50-70 years of age, is diagnosed clinically based on a characteristic symptomatic triad of hypotension, hemoconcentration (elevated hemoglobin or hematocrit), and serum hypoalbuminemia resulting from fluid extravasation. Although Q fever has increasingly been recognized and reported in recent years, the treatment of Q fever complicated by SCLS, with an etiological diagnosis aided by metagenomic next-generation sequencing (mNGS), remains uncommon.

This report describes a case of acute Q fever with concurrent SCLS in a 54-year-old male who worked in a slaughterhouse. The patient presented with fever, chest tightness, and shortness of breath, accompanied by severe headache. His condition rapidly deteriorated, leading to acute fever, generalized weakness, and hypotension. Due to respiratory failure and shock, he was admitted to the intensive care unit (ICU) for treatment. Despite empirical antibiotic therapy along with fluid resuscitation, his blood pressure continued to decline, and metabolic acidosis and respiratory distress worsened. As his condition failed to improve, tracheal intubation was performed. mNGS detected both Coxiella burnetii in his BALF and blood samples. Based on the mNGS results, he was started on doxycycline, alongside penicillin antibiotics, vasopressors, and continuous renal replacement therapy (CRRT). The patient's condition gradually improved, and he was discharged home after 12 days of treatment. At his 90-day follow-up, he had nearly fully recovered to his pre-illness status.

mNGS plays a crucial role in assisting the diagnosis of Q fever, which enables the timely treatment of the underlying disease triggering SCLS. This, combined with restrictive fluid resuscitation strategies, is essential for improving patient outcomes.

Neonatal capillary leak syndrome (CLS) is a rare, but life-threatening condition following neonatal sepsis or inflammatory injury. The objective of this study was to describe a standardized treatment approach for CLS that improves mortality and neonatal outcomes. A retrospective cohort study of 10 infants born at 22 to 26 weeks of gestation who developed CLS following a significant inflammatory insult was performed. Time to diagnosis and treatment approaches over 2 epochs were recorded and described. In epoch 2, with increased clinical awareness of CLS and implementation of a standardized treatment approach, there was a non-statistically significant decrease in the time to treatment with a significant decrease in mortality. An early targeted treatment approach for neonatal CLS can decrease mortality rates in this highly morbid condition.

Background: Fluid overload (FO) in critically ill children correlates with higher morbidity and mortality rates. Continuous renal replacement therapy (CRRT) is commonly employed to manage FO. In adults, both FO and CRRT adversely affect myocardial function. It remains unclear if children experience similar cardiovascular effects. Methods: Observational single-center study on children (<18 years) receiving CRRT at Texas Children's Hospital from 11/2019 to 3/2021. Excluded were those with end-stage renal disease, pacemakers, extracorporeal membrane oxygenation, ventricular assist devices, apheresis, or without an arterial line. Electrocardiometry (ICON Osypka Medical GmbH, Berlin, Germany) which is noninvasive and utilizes bioimpedance, was applied to obtain hemodynamic data over the first 48 h of CRRT. Our aim was to identify how FO >15% affects hemodynamics in children receiving CRRT. Results: Seventeen children, median age 43 months (interquartile range [IQR] 12-124), were included. The median FO at CRRT initiation was 14.4% (2.4%-25.6%), with 9 (53%) patients having FO >15%. Differences were noted in systemic vascular resistance index (1,277 [IQR 1088-1,666] vs. 1,030 [IQR 868-1,181] dynes/s/cm 5 /m 2 , P < 0.01), and cardiac index (3.90 [IQR 3.23-4.75] vs. 5.68 [IQR 4.65-6.32] L/min/m 2 , P < 0.01), with no differences in heart rate or mean arterial pressure between children with and without FO. Conclusion: FO affects the hemodynamic profile of children on CRRT, with those having FO >15% showing higher systemic vascular resistance index and lower cardiac index, despite heart rate and mean arterial pressure remaining unchanged. Our study illustrates the feasibility and utility of electrocardiometry in these patients, suggesting future research employ this technology to further explore the hemodynamic effects of dialysis in children.

Capillary leak syndrome is a unique complication characterized by extravasation of liquids in the interstitial space due to protein loss caused by snakebite envenoming. We describe the case of a 12-year-old boy from the district of Napo in the city of Iquitos in the Peruvian Amazon, who had edema and increased face volume due to the bite of a snake of the Bothrops genus in the lateral aspect of the right leg; he was the hospitalized and diagnosed with severe ophidism complicated with face edema. The patient received eight vials of antivenin, antibiotics and analgesics. Finally, the patient was discharged from the hospital after eight days of hospitalization, with favorable evolution and recovery.

Effective cancer therapies must address the tumor microenvironment (TME), a complex network of tumor cells and stromal components, including endothelial, immune, and mesenchymal cells. Durable outcomes require targeting both tumor cells and the TME while minimizing systemic toxicity. Interleukin-2 (IL-2)-based therapies have shown efficacy in cancers such as metastatic melanoma and renal cell carcinoma but are limited by severe side effects. Innovative IL-2-based immunotherapeutic approaches include immunotoxins, such as antibody-drug conjugates, immunocytokines, and antibody-cytokine fusion proteins that enhance tumor-specific delivery. These strategies activate cytotoxic CD8+ T lymphocytes and natural killer (NK) cells, eliciting a potent Th1-mediated anti-tumor response. Modified IL-2 variants with reduced Treg cell activity further improve specificity and reduce immunosuppression. Additionally, IL-2 conjugates with peptides or anti-angiogenic agents offer improved therapeutic profiles. Combining IL-2-based therapies with immune checkpoint inhibitors (ICIs), anti-angiogenic agents, or radiotherapy has demonstrated synergistic potential. Preclinical and clinical studies highlight reduced toxicity and enhanced anti-tumor efficacy, overcoming TME-driven immune suppression. These approaches mitigate the limitations of high-dose soluble IL-2 therapy, promoting immune activation and minimizing adverse effects. This review critically explores advances in IL-2-based therapies, focusing on immunotoxins, immunocytokines, and IL-2 derivatives. Emphasis is placed on their role in combination strategies, showcasing their potential to target the TME and improve clinical outcomes effectively. Also, the use of IL-2 immunocytokines in "in situ" vaccination to relieve the immunosuppression of the TME is discussed.

Accurate assessment of a patient's volume status is crucial in many conditions, informing decisions on fluid prescribing, vasoactive agents, and decongestive therapies. Determining a patient's volume status is challenging because of limitations in examination and investigations and the complexities of fluid homeostasis in disease states. Point-of-care ultrasound (POCUS) is useful in assessing hemodynamic parameters related to volume status, fluid responsiveness, and fluid tolerance. It requires understanding several physiologic concepts to interpret and integrate POCUS findings accurately into volume-related clinical decision-making.

The following concepts serve as a scaffold for a comprehensive volume status assessment: central venous pressure, right-sided heart function, left-sided heart assessment, extravascular volume, and venous congestion. POCUS allows us access to these hemodynamic and structural data points as an extension and refinement of the physical examination. Often, multiple POCUS applications are used, and findings must be integrated with the rest of the clinical evaluation. We illustrate this using 3 common scenarios: hypotension, hypoxia, and acute kidney injury. Clinicians must be aware of the strengths and weaknesses of findings in different physiologic states and the potential pitfalls of image acquisition and interpretation. Further studies are necessary to determine the benefits and clinical outcomes of a POCUS-directed volume status assessment.

Volume status assessment is ubiquitous, yet is challenging to perform. This review summarizes foundational physiologic concepts relevant to volume status evaluation and highlights how multiorgan POCUS elucidates hemodynamic parameters that can be combined with the conventional clinical assessment to make fluid-related decisions.

The short-term efficacy of red blood cell (RBC) transfusion among general traumatic brain injury (TBI) patients is unclear.

We used the MIMIC database to compare the efficacy of liberal (10 g/dL) versus conservative (7 g/dL) transfusion strategy in TBI patients. The outcomes were neurological progression (decrease of Glasgow coma scale (GCS) of at least 2 points) and death within 28 days of ICU admission. Each eligible individual was cloned and assigned each of the replicates to one of the treatment arm. The imbalance induced by informative censoring was adjusted by inverse probability weighting. The standardized, weighted pooled logistic regression with 500 bootstrap resampling was used to estimate the cumulative risk difference and 95% confidence interval (CI).

Of the 1141 eligible individuals, 29.0% received RBC transfusion. Compared with the restrictive group, the liberal strategy reduced early death (3 days: 5%, 95% CI: 2%-7%; 7 days: 6%, 95% CI: 3%-11%); however, no significant difference of mortality risk at 28-day or neurological progression risk at any time points was observed. The risk of coagulopathy at 3 days was increased by 7% (95% CI: 1%-19%) in the liberal group. The subgroup analysis indicated a beneficial effect of liberal transfusion on mortality in hemodynamically unstable patients.

Compared with the restrictive strategy, the liberal strategy does not improve the short-term neurological prognosis and death among patients with TBI in a real-world situation. The liberal strategy may be beneficial to survival at very early stage or in hemodynamically unstable subgroup.

Systemic capillary leak syndrome (SCLS) constitutes a rare clinical entity. It is characterized by spontaneous, recurrent episodes of increased capillary permeability, leading to a double clinico-biological paradox: diffuse pitting edema with hypovolemia or hypovolemic shock, and hemoconcentration with hypoalbuminemia, in the absence of secondary causes for such abnormalities. Even though several theories have been proposed, the exact pathophysiology of SCLS remains unclear. We report herein a case of idiopathic SCLS in a 38-year-old male patient with a history of previous immunization, following COVID-19 infection, who was also diagnosed with a myeloproliferative neoplasm (MPN). To our knowledge, this is the first case where SCLS coexists with an MPN, leading to a legitimate question: Who pulls the trigger?

The COVID-19 outbreak has been declared the sixth Public Health Emergency of International Concern certified by the World Health Organization. With the extensive application of COVID-19 vaccines, rare but serious adverse reactions have gradually emerged, among which systemic capillary leak syndrome (SCLS) deserves our attention. SCLS is difficult to diagnose. Not only can it exacerbate various diseases, but also can lead to pulmonary edema, kidney failure, and even death. We summarized and discussed case reports of SCLS induced by COVID-19 vaccines to raise awareness of COVID-19 vaccine-associated rare diseases. We conducted a comprehensive search in Web of Science, PubMed and Embase and collected case reports of SCLS induced by COVID-19 vaccine before February 19, 2024. We identified and analyzed 12 articles, encompassing 15 cases. We synthesized the data to summerize possible mechanisms of SCLS, clinical manifestations, differential diagnoses, and therapeutic approaches. Most SCLS occurred after vaccination with the Pfe-Biontech mRNA vaccine (9/15) and following the second vaccination (10/15). Almost all patients experienced hypotension (13/15) and tachycardia (11/15). Most patients received intravenous fluids (9/15) and corticosteroids (9/15). 11 patients were recovered and were discharged, while 4 patients died. Inflammation and endothelial cell damage may be linked to SCLS and COVID-19 vaccines. These findings highlight the necessity of focusing on serious adverse reactions of COVID-19 vaccines and the urgency to reconsider the safety of COVID-19 vaccines.

Inflammatory cytokines cooperate to maintain normal immune homeostasis, performing both a protective and a pro-inflammatory action in different body districts. However, their excessive persistence or deregulated expression may degenerate into tissue chronic inflammatory status. Advanced therapies should be designed to deploy selective cytokine neutralizers in the affected tissues. Magnetoelectric nanoparticles (MENPs) possess unexploited potentialities, conjugating their ferromagnetic nature, which enables confinement in a specific tissue by directed positioning when subjected to low-intensity magnetic fields, with the capability to generate high electric fields with elevated spatial resolution when subjected to higher magnetic fields. This work proposes to exploit the extremely localized heat generated by Joule's effect around MENPs under an external magnetic field to denature a harmful cytokine in a hypothetical tissue site. An interdisciplinary and multiphysics in silico study was conducted to provide comprehensive modeling of the temperature distribution generated by MENPs decorated with a membrane-derived microvesicle (MV) coating designed to allocate a specific antibody to bind a target cytokine. A damage model was also implemented to provide an estimation of the influence of several design parameters on the cytokine denaturation efficacy, with the final goal of guiding the future development of effective MENPs-based therapeutic applications and strategies.

Sepsis is a critical condition characterized by a systemic inflammatory response to infection, often leading to severe vascular dysfunction and high mortality. One of the hallmarks of vascular dysfunction in sepsis is increased vascular permeability and the loss of pericytes, which are essential for maintaining vascular integrity. Despite the significance of pericyte loss in sepsis, the primary type of cell death responsible and the underlying molecular mechanisms remain incompletely understood. This study aims to elucidate these mechanisms by focusing on ferroptosis, a form of programmed cell death, and its regulation through the Hippo/ACSL4 axis. Our research confirmed significant pericyte loss in patients with sepsis. Through advanced single-cell analysis and proteomics, ferroptosis was identified as a key differentiating cell death type between sepsis and sham samples. Further metabolomics analysis revealed that Acyl-CoA Synthetase Long-Chain Family Member 4 (ACSL4) plays a pivotal role in the ferroptosis of pericytes during sepsis. In vitro experiments demonstrated that downregulation of ACSL4 effectively reduced lipopolysaccharide (LPS)-induced lipid peroxidation, restored pericyte viability, and improved endothelial permeability. In vivo studies with pericyte-specific ACSL4 knockout mice showed a marked decrease in pericyte loss and enhanced vascular barrier function following sepsis induction. To translate these findings into potential therapeutic strategies, we developed pericyte-targeting liposomes encapsulating ACSL4 shRNA adenovirus. These liposomes successfully restored pulmonary vascular barrier function and significantly reduced pericyte loss in septic conditions. The results of this study underscore the crucial role of ACSL4 in mediating ferroptosis in pericytes and highlight the therapeutic potential of targeting ACSL4 to mitigate vascular dysfunction in sepsis.

Chimeric antigen receptor T-cell (CAR-T) therapy has shown promise in treating hematologic malignancies, yet its potential cardiotoxic effects require thorough investigation.

We aim to conduct a systematic review and meta-analysis to examine the cardiotoxic effects of CAR-T therapy in adults with hematologic malignancies.

We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for studies reporting cardiovascular outcomes, such as arrhythmias, heart failure, and reduced left ventricle ejection fraction (LVEF).

Our analysis of 20 studies involving 4789 patients revealed a 19.68% incidence rate of cardiovascular events, with arrhythmias (7.70%), heart failure (5.73%), and reduced LVEF (3.86%) being the most prevalent. Troponin elevation was observed in 23.61% of patients, while NT-Pro-BNP elevation was observed in 9.4. Subgroup analysis showed higher risks in patients with pre-existing conditions, such as atrial arrhythmia (OR 3.12; p < .001), hypertension (OR 1.85; p = .002), previous heart failure (OR 3.38; p = .003), and coronary artery disease (OR 2.80; p = .003).

Vigilant cardiovascular monitoring is crucial for patients undergoing CAR-T therapy to enhance safety and treatment efficacy.Novelty Statements.

Dynamic monitoring of the blood-brain barrier (BBB) functional status in septic mice can help to explore the pathological mechanisms. Therefore, we proposed a new method for monitoring BBB permeability and applied it to the detection of sepsis models.

The new method involves the construction of an optical cranial window and in vivo imaging. We performed dynamic monitoring of BBB permeability and cerebral blood flow (CBF) in cecal ligation puncture (CLP) and endotoxemia (lipopolysaccharide [LPS]) mice.

The sensitivity and accuracy of this method were higher than those of Evans blue evaluation. The increase of BBB permeability in the group of CLP mice was relatively mild and correlated with overall survival, and the damage was irreversible. Contrarily, BBB damage in the LPS group was more acute and severe, unrelated to overall survival, but recoverable. The CBF decreased significantly in both model mouse groups 24 h after modeling, but only the CBF proportion decrease in the LPS group was significantly correlated with an increase in BBB permeability. Within 24 h after both models were established, the decrease in blood flow in the digestive organs occurred earlier than in the brain and kidneys, and the decrease in small intestine blood flow in the LPS group progressed faster.

We have successfully demonstrated the feasibility of our novel method to detect BBB permeability in mice. Our results revealed a significant difference in the BBB permeability change trend between the CLP and LPS model mice when survival curves were consistent. Notably, the CLP-model mice demonstrated a closer resemblance to clinical patients. Our findings suggest that early-stage brain tissue hypoperfusion has a greater impact on BBB function damage in endotoxemia mice, which is related to the faster progression of blood flow redistribution.

Trigonelline (TRIG) is a natural compound in an alkaloid family found in diverse plants. This compound exerts anti-inflammatory, anti-allergic, anti-oxidative and anti-fibrotic activities in several disease models. However, its beneficial role in endothelial injury, especially induced by diabetes, is unclear. We, therefore, evaluated the effects of TRIG on the cellular proteome of human endothelial (EA.hy926) cells followed by functional validation in high-glucose (HG)-induced endothelial deteriorations. Label-free quantification using nanoLC-ESI-Qq-TOF MS/MS revealed 40 downregulated and 29 upregulated proteins induced by TRIG. Functional enrichment analysis using DAVID and REVIGO tools suggested the involvement of these altered proteins in several biological processes and molecular functions, particularly cell-cell adhesion, ATP metabolic process, cell redox homeostasis, cadherin binding, and ATP hydrolysis activity. Experimental validation showed that HG triggered endothelial-to-mesenchymal transition (EndMT) (as demonstrated by increased spindle index and mesenchymal markers, i.e., fibronectin and vimentin, and decreased endothelial markers, i.e., PECAM-1 and VE-cadherin), increased oxidized proteins, and reduced intracellular ATP, active mitochondria, endothelial tube/mesh formation and VEGF secretion. However, TRIG successfully abolished all these defects induced by HG. These data indicate that TRIG prevents HG-induced EndMT, oxidative stress, mitochondrial dysfunction, and impaired angiogenic activity in human endothelial cells.

Total cavo-pulmonary connection (TCPC) is a palliative treatment for single ventricular malformations. For high-risk patients (preoperative mean pulmonary arterial pressure, mPAP > 15 mmHg), between the inhaled and oral targeted medications, the application of intravenous treprostinil as a bridge therapy to achieve "seamless" management is core postoperative treatment. This study intends to explore the effect of different administration regimens on early postoperative recovery.

This was a retrospective cohort study. High-risk pediatric patients (age ≤ 14 years) who underwent TCPC procedure in Fu Wai Hospital from 2015 to 2022 were included. Since the regimen of treprostinil was standardized in our center in 2021, the patients in 2020 and before were included in group 1, patients in 2021 and 2022 were included in group 2. The hemodynamic parameters were compared before and after the maintenance dose of treprostinil. The differences of demographic characteristics, surgical data and postoperative recovery were compared between the two groups.

A total of 51 pediatric patients were included. Group 1 included 35 patients who received treprostinil at 1-3 postoperative days and an average dose of 12 ± 4 ng/(kg·min). Group 2 included 16 patients who received treprostinil within postoperative 1 day and an average dose of 22 ± 7 ng/(kg·min). There were no significant differences between the two groups in terms of age, weight, preoperative percutaneous oxygen saturation and mPAP,  heterotaxy syndrome, TCPC procedure type, other concurrent procedure, cardiopulmonary bypass time and aortic cross-clamp proportion (p > 0.05). After 24 h of treprostinil treatment, the mPAP in group 1 reduced from 17 ± 3 mmHg to 15 ± 2 mmHg (p < 0.001), and in group 2 from 17 ± 2 mmHg to 14 ± 2 mmHg (p < 0.001), with no difference between groups. In the postoperative recovery, patients in Group 2 exhibited a reduced duration of mechanical ventilation, 19 (11, 25) hours vs 69 (23, 189) hours, p = 0.001; a shorter stay in the ICU, 8 (6, 12) days vs 16 (9,26) days, p = 0.006; and a shorter postoperative length of stay, 27 (17,55) days vs 39 (29,58) days, p = 0.032. Patients in Group 2 also exhibited a lower incidence of thromboembolic events, 0 (0/26) vs 26% (9/35), p = 0.043; and the need for renal replacement therapy, 0 (0/26) vs 31% (11/35), p = 0.011.

Treprostinil reduces pulmonary artery pressure after TCPC procedure. The standardized application of treprostinil may improve the postoperative recovery which should be proven by randomized controlled trials or matched cohort studies in the future.

Microcirculation abnormality in septic shock is closely associated with organ dysfunction and mortality rate. It was hypothesized that the arterial blood glucose and interstitial fluid (ISF) glucose difference (GA-I) as a marker for assessing the microcirculation status can effectively evaluate the severity of microcirculation disturbance in patients with septic shock.

The present observational study enrolled patients with septic shock admitted to and treated in the intensive care unit (ICU) of a tertiary teaching hospital. The parameters reflecting organ and tissue perfusion, including lactic acid (Lac), skin mottling score, capillary refill time (CRT), venous-to-arterial carbon dioxide difference (Pv-aCO2), urine volume, central venous oxygen saturation (ScvO2) and GA-I of each enrolled patient were recorded at the time of enrollment (H0), H2, H4, H6, and H8. With ICU mortality as the primary outcome measure, the ICU mortality rate at any GA-I interval was analyzed.

A total of 43 septic shock patients were included, with median sequential organ failure assessment (SOFA) scores of 10.5 (6-16), and median Acute Physiology and Chronic Health Evaluation (APACHAE) II scores of 25.7 (9-40), of whom 18 died during ICU stay. The GA-I levels were negative correlation with CRT (r = 0.369, P < 0.001), Lac (r = -0.269, P < 0.001), skin mottling score (r=-0.223, P < 0.001), and were positively associated with urine volume (r = 0.135, P < 0.05). The ICU mortality rate of patients with septic shock presenting GA-I ≤ 0.30 mmol/L and ≥ 2.14 mmol/L was significantly higher than that of patients with GA-I at 0.30-2.14 mmol/L [65.2% vs. 15.0%, odds ratio (OR) = 10.625, 95% confidence interval (CI): 2.355-47.503].

GA-I was correlated with microcirculation parameters, and with differences in survival. Future studies are needed to further explore the potential impact of GA-I on microcirculation and clinical prognosis of septic shock, and the bedside monitoring of GA-I may be beneficial for clinicians to identify high-risk patients.

The release of pro-inflammatory cytokines in critically ill patients with sepsis leads to endothelial dysfunction resulting in cardiocirculatory insufficiency. Their extracorporeal elimination using the cytokine adsorber CytoSorb® (CS) (adsorption of especially hydrophobic molecules < 60 kDa) might be promising, but data about the adsorption capacity as well as a potential harmful adsorption of anti-inflammatory cytokines are missing so far.

The prospective Cyto-SOLVE-study included 15 patients with sepsis or other hyperinflammatory conditions (interleukin 6 > 500 pg/ml), continuous kidney replacement therapy, and the application of CS. Various cytokines and chemokines were measured pre- and post-CS as well as in patients' blood at predefined timepoints. Significant changes in the concentrations were detected with the Wilcoxon test with associated samples. Clearance of the adsorber (ml/min) was calculated with: b l o o d f l o w ∗ c o n c e n t r a t i o n p r e - p o s t c o n c e n t r a t i o n pre . RESULTS: Most of the inflammatory mediators showed a high initial extracorporeal clearance of 70-100 ml/min after CS installation, which dropped quickly to 10-30 ml/min after 6 h of treatment. No difference in clearance was observed between pro- and anti-inflammatory cytokines. Despite extracorporeal adsorption, a significant (p < 0.05) decrease in the blood concentration after 6 h was only observed for the pro-inflammatory cytokines tumor necrosis factorα (TNF-α) (median 284 vs. 230 pg/ml), vascular endothelial growth factor (VEGF) (median 294 vs. 252 pg/ml), macrophage inflammatory protein 1a (MIP-1a) (median 11.1 vs. 9.0 pg/ml), and regulated upon activation, normal T cell expressed and secreted (RANTES) (median 811 vs. 487 pg/ml) as well as the anti-inflammatory cytokines interleukin 4 (median 9.3 vs. 6.4 pg/ml), interleukin 10 (median 88 vs. 56 pg/ml), and platelet-derived growth factor (PDGF) (median 177 vs. 104 pg/ml). A significant (p < 0.05) decrease in patients' blood after 12 h was only detected for interleukin 10.

CS can adsorb pro- as well as anti-inflammatory mediators with no relevant difference regarding the adsorption rate. A fast saturation of the adsorber resulted in a rapid decrease of the clearance. The potential clinical benefit or harm of this unspecific cytokine adsorption needs to be evaluated in the future.

ClinicalTrials.gov NCT04913298, registration date June 4, 2021.

Chimeric antigen receptor T cell (CAR-T) therapy is a promising treatment for hematologic tumors, and adverse events of acute kidney injury (AKI) have been reported. However, its incidence, clinical characteristics, and prognosis remained unclear. We searched PubMed, EMBASE, and Web of Science for study about AKI after CAR-T therapy, a total of 15 studies, comprising 694 patients, were included. Among the 694 patients, 154 (22%) developed AKI, of which 89 (57.8%) were in stage 1, 59 (38.3%) were in stage 2 or 3, and 6 (3.9%) were not reported. Cytokine release syndrome is considered to be the most common cause of AKI. Of the 154 AKI patients, only 16 (10.4%) received renal replacement therapy, most AKI recovered renal function after symptomatic treatment. Although the occurrence of AKI after CAR-T therapy is rare and mostly mild, active knowledge of its pathogenesis, timely diagnosis and treatment are necessary for clinicians.

Precise assessment of postoperative volume status is important to administrate optimal fluid management. Bioelectrical impedance analysis (BIA) which measures the body composition using electric character. Extracellular water (ECW) ratio by BIA represented as the ratio of ECW to total body water (TBW) and is known to reflect the hydration status. Based on this, we aimed to determine whether aggressive fluid control using ECW ratio could improve clinical outcomes through a single blind, randomized controlled trial.

From November 2021 to December 2022, intensive care unit (ICU) patients admitted after surgery were randomly assigned to an intervention group or a control group whether postoperative fluid management was controlled via BIA. Among patients in the intervention group, dehydrated patients received a bolus infusion with crystalloid fluid whereas diuretics were administrated to overhydrated patients until the value of ECW ratio fell within its normal setting range (0.390-0.406). Contrarily, BIA was performed once a day for the control group. Patients in the control group received traditional fluid treatment regardless of BIA results. Primary outcome was in-hospital mortality in two groups. The secondary outcomes were postoperative morbidities, 28-day mortality.

77 patients of the intervention group and 90 patients of the control group were finally analyzed. The in-hospital mortality (0 in intervention, 4.4% in control, p = 0.125) and 28-day mortality (1.3% in intervention, 14.4% in control, p = 0.002) showed lower incidence in the intervention group than in the control group. In multivariate analysis, the overhydrated status whose ECW ratio exceeding 0.406 [odds ratio (OR): 2.731, 95% confidence interval (CI): 1.001-7.663, p = 0.049] and high capillary leak index (CLI) value at ICU admission (OR: 1.024, 95% CI: 1.008-1.039, p = 0.002) were risk factors of postoperative morbidities. Regarding the 28-day mortality, high CLI value (OR: 1.025, 95% CI: 1.002-1.050, p = 0.037) and traditional strategy without BIA monitoring (OR: 9.903, 95% CI: 1.095-89.566, p = 0.041) were the significant predisposing factors.

Our results revealed the rigorous fluid treatment with volume control based on ECW ratio by BIA failed to achieve significant improvement in in-hospital mortality, but it could reduce 28-day mortality of ICU patients. Monitoring of ECW ratio may help establish optimal fluid treatment strategies for postoperative ICU patients who are susceptible to fluid imbalances with fluid overload.

ClinicalTrials.gov, NCT06097923, retrospectively registered on October 16, 2023, https://clinicaltrials.gov/study/NCT06097923?term=NCT06097923&rank=1.

Capillary leak syndrome is a rare complication of cancer, particularly of hematologic malignancies. The syndrome was first described as an idiopathic entity; however, increasingly, more cases are being reported in association with cancers and other conditions. Diagnosis stems from the recognition of the double paradox, consisting of severe generalized oedema and hypotension, accompanied by hallmark laboratory modifications. Concurrent conditions in patients with malignancies can alter laboratory findings and make the diagnosis a challenge. This report presents the case of a patient with capillary leak syndrome and an atypical presentation, with generalized skin rash and transcutaneous exudation occurring concurrently with anaplastic large T cell lymphoma, macrophage activation syndrome, and cytopenias. Symptom-specific treatment with diuretics and albumin was ineffective in the case of our patient; however, the CLS remitted promptly with cancer-specific therapy. No treatment has proved to be generally effective against CLS up to date, as is the case for this patient. Thus, the rapid recognition of cancer-associated capillary leak syndrome and the initiation of cancer-specific treatment proves to be the better approach and is key to avoiding unnecessary delays and ineffective treatments targeted specifically at CLS.

Intravesical chemotherapy and immunotherapy are common adjuvant treatments for non-muscle invasive bladder cancer post-surgery. Analyzing adverse events linked to these therapies, can assist in clinical decision-making and risk assessment.

Disproportionality analysis was conducted to analyze data from the Food and Drug Administration Adverse Event Reporting System database from the first quarter of 2004 to the first quarter of 2024, exploring potential positive signals between Bacillus Calmette-Guérin, mitomycin-C, epirubicin, gemcitabine, and adverse events.

The database retrieved 2018, 140, 31, and 85 adverse event reports associated with Bacillus Calmette-Guérin, mitomycin-C, epirubicin, and gemcitabine, respectively. Adverse reactions not mentioned in the label, such as aortic aneurysm and ocular congestion, were observed in preferred term level related to Bacillus Calmette-Guérin. Mitomycin-C exhibited specificity in skin and subcutaneous tissue diseases not reflected in the package insert. Gemcitabine-induced adverse drug reactions showed signals in vascular and lymphatic diseases meeting the screening criteria of all 4 indicators, with capillary leakage syndrome being the preferred term with the highest signal intensity.

This study observed new adverse event signals, providing important assistance for drug selection in adjuvant therapy for non-muscle invasive bladder cancer postoperatively.

Sepsis is a leading cause of mortality in intensive care units and vasoactive drugs are widely used in septic patients. The cardiovascular response of septic shock patients during resuscitation therapies and the relationship of the cardiovascular response and clinical outcome has not been clearly described.

We included adult patients admitted to the ICU with sepsis from Peking Union Medical College Hospital (internal), Medical Information Mart for Intensive Care IV (MIMIC-IV) and eICU Collaborative Research Database (eICU-CRD). The Blood Pressure Response Index (BPRI) was defined as the ratio between the mean arterial pressure and the vasoactive-inotropic score. BRRI was compared with existing risk scores on predicting in-hospital death. The relationship between BPRI and in-hospital mortality was calculated. A XGBoost's machine learning model identified the features that influence short-term changes in BPRI.

There were 2139, 9455, and 4202 patients in the internal, MIMIC-IV and eICU-CRD cohorts, respectively. BPRI had a better AUROC for predicting in-hospital mortality than SOFA (0.78 vs. 0.73, p = 0.01) and APS (0.78 vs. 0.74, p = 0.03) in the internal cohort. The estimated odds ratio for death per unit decrease in BPRI was 1.32 (95% CI 1.20-1.45) when BPRI was below 7.1 vs. 0.99 (95% CI 0.97-1.01) when BPRI was above 7.1 in the internal cohort; similar relationships were found in MIMIC-IV and eICU-CRD. Respiratory support and latest cumulative 12-h fluid balance were intervention-related features influencing BPRI.

BPRI is an easy, rapid, precise indicator of the response of patients with septic shock to vasoactive drugs. It is a comparable and even better predictor of prognosis than SOFA and APS in sepsis and it is simpler and more convenient in use. The application of BPRI could help clinicians identify potentially at-risk patients and provide clues for treatment.

Fundings for the Beijing Municipal Natural Science Foundation; the National High Level Hospital Clinical Research Funding; the CAMS Innovation Fund for Medical Sciences (CIFMS) from Chinese Academy of Medical Sciences and the National Key R&D Program of China, Ministry of Science and Technology of the People's Republic of China.

The landscape of cancer therapeutics is continually evolving, with successes in improved survivorship and reduced disease progression for many patients with cancer. Improved cancer outcomes expose competing comorbidities, some of which may be exacerbated by cancer therapies. The leading cause of disability and death for many early-stage cancers is cardiovascular disease (CVD), which is often attributed to direct or indirect cardiac injury from cancer therapy. In this review, the authors propose that toxicities related to conventional and novel cancer therapeutics should be considered beyond the heart. The authors provide a framework using the oxygen pathway to understand the impact of cancer treatment on peak oxygen uptake, a marker of integrative cardiopulmonary function and CVD risk. Peripheral toxicities and the impact on oxygen transport are discussed. Consideration for the broad effects of cancer therapies will improve the prediction and identification of cancer survivors at risk for CVD, functional disability, and premature mortality and those who would benefit from therapeutic intervention, ultimately improving patient outcomes.

Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of non-Hodgkin lymphoma. Patients with hemophagocytic lymphohistiocytosis (HLH)-associated IVLBCL variants exhibit significantly poor survival. Cytokines play pivotal roles in malignancy-associated HLH as well as in capillary leak syndrome (CLS). The pathogenesis of CLS involves hyperpermeability and transient endothelial dysfunction. Here, we report the first case of HLH-associated IVLBCL variant complicated with CLS. The patient presented with fever, refractory hypoproteinemia, hypotension and severe edema, followed by telangiectasias. Treatment with etoposide and dexamethasone and hydroxyethyl starch-based artificial colloid led to transient improvement. The diagnosis of IVLBCL was confirmed after the sixth bone marrow biopsy. Subsequently, the R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisolone) regimen was administered and resulted in prompt alleviation of CLS and HLH symptoms. The patient has survived for more than 6 years after combination of immunochemotherapy and autologous peripheral stem-cell transplantation. This case provides some insights into the mechanism and clinical management of IVLBCL complicated with HLH and CLS. Similar cases concerning lymphoma-associated CLSs were also reviewed.

A 29-year-old Japanese woman was admitted to our hospital with a fever, cardiogenic shock, and cardiac arrest. Laboratory data indicated multiple organ failure in addition to hemoconcentration, hypoalbuminemia, and myocardial damage. The coronary angiography findings were normal, and fulminant myocarditis was suspected. Venoarterial peripheral extracorporeal membrane oxygenation and an Impella CP left ventricular assist device were initiated, along with the administration of positive inotropic agents. However, hypovolemic shock and hypoalbuminemia progressed along with severe anemia, and the patient died 18 hours after admission. The patient was diagnosed with systemic capillary leak syndrome associated with coronavirus disease 2019.

Although the medical field has made significant progress, there has been little improvement in the survival rate of patients with ruptured abdominal aortic aneurysms (rAAAs). We implemented a protocol consisting of five strategies in the management of rAAA patients who underwent open repair surgery.

The protocol comprised the following strategies: intentional hypotension <70 mmHg, lung first and kidney last policy (restricted fluid resuscitation and permissive oligoanuria), immediate postoperative extubation, free-water intake with active ambulation, and open abdomen with the routine second-look operation. The study included 13 patients (11 male) with a mean age of 75.5 ± 7.4 (range: 58-87) years who underwent the procedure from 2016 to 2018, with a mean follow-up of 40.1 ± 9.04 months. Five deteriorating to hemodynamic shock and decreased consciousness requiring intubation and ventilation prior to surgery were observed. Two of these patients required preoperative cardiopulmonary resuscitation (CPR).

All patients regained consciousness after surgery, including the two patients who required cardiopulmonary resuscitation. Immediate postoperative extubation was performed in nine patients, but two (22.2%) of them needed re-intubation due to ventilation/perfusion mismatch. Four patients underwent continuous renal replacement therapy, with three of them having anuria for up to 48 h after surgery. Two of these patients made a full recovery. Daily ambulation was carried out for a mean of 4.77 ± 3.5 (range 1-13) days with an open abdomen, during which no significant events were reported. Four cases of colon ischemia/necrosis were identified in the second-look operation, with two patients requiring Hartman's procedure and the other two undergoing left colon partial resection. There were two in-hospital mortalities (15.4%).

A protocol-based approach, through multidisciplinary team consensus and the development of optimal surgical strategies, could improve clinical outcomes for patients undergoing emergency surgery for rAAA. Further studies with larger sample sizes are needed to refine the protocols.

Vascular pathologies are prevalent in a broad spectrum of diseases, necessitating a deeper understanding of vascular biology, particularly in overcoming the oxygen and nutrient diffusion limit in tissue constructs. The evolution of vascularized tissues signifies a convergence of multiple scientific disciplines, encompassing the differentiation of human pluripotent stem cells (hPSCs) into vascular cells, the development of advanced three-dimensional (3D) bioprinting techniques, and the refinement of bioinks. These technologies are instrumental in creating intricate vascular networks essential for tissue viability, especially in thick, complex constructs. This review provides broad perspectives on the past, current state, and advancements in key areas, including the differentiation of hPSCs into specific vascular lineages, the potential and challenges of 3D bioprinting methods, and the role of innovative bioinks mimicking the native extracellular matrix. We also explore the integration of biophysical cues in vascularized tissues in vitro, highlighting their importance in stimulating vessel maturation and functionality. In this review, we aim to synthesize these diverse yet interconnected domains, offering a broad, multidisciplinary perspective on tissue vascularization. Advancements in this field will help address the global organ shortage and transform patient care.

This population-based study investigated the occurrence of capillary leak syndrome (CLS) in children with multisystem inflammatory syndrome in children (MIS-C), associated with COVID-19. We also examined associations between CLS and MIS-C disease severity.

All eligible individuals aged 0-18 years, who were diagnosed with MIS-C in Skåne, southern Sweden, from 1 April 2020 to 31 July 2021, were studied. They were all included in the Pediatric Rheumatology Quality Register and clinical and laboratory data were compared between patients with and without CLS.

We included 31 patients (61% male) with MIS-C in the study. The median age at diagnosis was 10.6 years (range 1.99-17.15) and 45% developed CLS. All six patients who required intensive care had CLS. Patients with CLS also had a higher incidence of reduced cardiac function, measured as low ejection fraction. The CLS group exhibited significantly higher C-reactive protein values (p < 0.001) and N-terminal pro-B-type natriuretic peptide levels (p < 0.001), as well as lower platelet counts (p = 0.03), during the first week of treatment. Individuals with CLS also received more intense immunosuppression.

CLS was a common complication of MIS-C in our study and these patients had a more severe disease course that required more intensive treatment.

Lymphatic leakage is one of the postoperative complications of neuroblastoma. The purpose of this study is to summarize the clinical characteristics and risk factors of lymphatic leakage and try to find effective prevention and treatment measures.

A retrospective study included 186 children with abdominal neuroblastoma, including 32 children of lymphatic leakage and 154 children of non-lymphatic leakage. The clinical information, surgical data, postoperative abdominal drainage, treatment of lymphatic leakage and prognosis of the two groups were collected and analyzed.

The incidence of lymphatic leakage in this cohort was 14% (32 children). Through univariate analysis of lymphatic leakage group and non-lymphatic leakage group, we found that lymphatic leakage increased the complications, prolonged the time of abdominal drainage and hospitalization, and delayed postoperative chemotherapy (p < 0.05). In this cohort, the median follow-up time was 46 (95% CI: 44-48) months. The follow-up data of 7 children were partially missing. 147 children survived, of which 23 had tumor recurrence (5 children recurred in the surgical area). 37 children died, of which 32 had tumor recurrence (9 children recurred in the operation area). In univariate analysis, there was no statistical difference in overall survival (p = 0.21) and event-free survival (p = 0.057) between lymphatic leakage group and non-lymphatic leakage group, while 3-year cumulative incidence of local progression was higher in lymphatic leakage group (p = 0.015). However, through multivariate analysis, we found that lymphatic leakage did not affect event-free survival, overall survival and cumulative incidence of local progression in children with neuroblastoma. Resection of 5 or more lymphatic regions was an independent risk factor for lymphatic leakage after neuroblastoma surgery. All 32 children with lymphatic leakage were cured by conservative treatment without surgery. Of these, 75% (24/32) children were cured by fat-free diet or observation, 25% (8/32) children were cured by total parenteral nutrition. The median drain output at diagnosis in total parenteral nutrition group was higher than that in non-total parenteral nutrition group (p < 0.001). The cut-off value was 17.2 ml/kg/day.

Lymphatic leakage does not affect the prognosis of children with neuroblastoma, but long-term drain output caused by lymphatic leakage will still adversely affect postoperative complications and follow-up treatment, which requires attention and active treatment measures. More attention should be paid to the children with 5 or more lymphatic regions resection, and the injured lymphatic vessels should be actively found and ligated after tumor resection to reduce the postoperative lymphatic leakage. Early application of total parenteral nutrition is recommended for those who have drain output at diagnosis of greater than 17.2 ml/kg/day.