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Introduction: Most patients on extracorporeal membrane oxygenation (ECMO) decease during therapy on the system. However, the actual causes of death have not been studied sufficiently. This study analyses the etiology, prevalence, and risk factors for the outcome variable death during ongoing ECMO for all patients and divided according to venoarterial (VA) or venovenous (VV) support. Methods: We retrospectively analysed all patients receiving ECMO support at our institution between March 2006 to January 2021. Only the patients deceased during ongoing support were included. Results: 2016 patients were placed on VA (n = 1168; 58%) or VV (n = 848; 42%) ECMO; 759 patients (37.7%) deceased on support. The causes of death differed between the support types: VA ECMO patients mostly died from cerebral ischemia (34%), low-cardiac output (LCO; 24.1%) and multi-organ failure (MOF; 21.6%), whereas in VV ECMO cases, refractory respiratory failure (28.2%), and sepsis (20.4%) dominated. Multivariate regression analysis revealed cardiopulmonary resuscitation (CPR) and acidosis prior to ECMO as risk factors for dying on VA ECMO, while high inotropic doses pre-ECMO, a high fraction of inspired oxygen on day 1, elevated lactate dehydrogenase, and international normalized ratio levels lead to an unfavourable outcome in VV ECMO patients. Conclusion: Even in highly experienced centers, ECMO mortality remains high and occurs mainly on support or 24 h after its termination. The causes of death differ between VV and VA ECMO, depending on the underlying diseases responsible for the need of extracorporeal support. [ABSTRACT FROM AUTHOR]

Clinical manifestations of congenital syphilis (CS) include liver disease with/without impaired liver function, identified as syphilitic hepatitis. Hepatic involvement may be dramatic; therefore, early diagnosis is crucial to provide treatment and prevent fatal outcomes. A new resurgence of CS cases has been described in recent years worldwide. We reported our experience with a case series of infants hospitalized for liver disease with a final diagnosis of CS, highlighting the wide spectrum of liver involvement, the rapid progression in cases with late diagnosis, and the pitfalls of the management of this forgotten but reemerging disease. A retrospective analysis of CS patients with hepatic presentation in the period 2008–2023 was conducted. We collected five cases (three female) with a median age of 13.8 days (range 1–84 days). In three cases, mothers were not screened for syphilis during pregnancy, and in two cases, they were seronegative in the first trimester screening. None practiced specific therapy during pregnancy. Hepatic involvement was characterized by hepatosplenomegaly, in four cases associated with cholestatic jaundice and in three cases with liver failure. Rapid plasma reagin (RPR) and Treponema pallidum hemagglutination assay (TPHA) were positive in all cases in mothers and infants. CS presented with multiorgan involvement and was fatal in one case. Conclusions: It is important to consider CS in infants with cholestasis and acute liver failure, but also in sick infants with isolated hepatomegaly. Early recognition of infants with CS is critical to identify missed cases during pregnancy and to start early treatment. What is known: • In recent years, it has been seen an increase of congenital syphilis cases in both low- and middle-income countries. • In most cases, infants born to mothers untreated for syphilis appear normal without signs of infection at birth but may develop manifestations of the disease after months or years if left untreated. • What is new: • Congenital syphilis is an emerging problem that may result in multiorgan involvement with liver disease predominant at onset. • It is important to consider congenital syphilis in infants with cholestasis and liver failure, but also in sick infants with isolated hepatomegaly. [ABSTRACT FROM AUTHOR]

We report a case of T‐B+NK+ severe combined immunodeficiency disease (SCID) caused by IL2RG gene mutation (NM_000206.3 [IL2RG]: c.925‐2A > G). The patient, a 2‐month‐old male, experienced multiple infections and decreased white blood cells in the early postnatal period. Antibiotic treatment was ineffective and ultimately resulted in multiple organ failure. The second‐generation gene sequencing of patient showed that the IL2RG gene had a hemizygous mutation NM_000206.3 (IL2RG): c.925‐2A > G, indicating a classical splice site mutation. According to the guidelines of the American College of Medical Genetics (ACMG), NM_00206.3 (IL2RG): c.925‐2A > G variants can be classified as pathogenic (PVS1&PM1&PM6). [ABSTRACT FROM AUTHOR]

Sepsis is a life-threatening syndrome of organ dysfunction, characterized by uncontrolled inflammatory response and immune dysregulation, often leading to multiple organ failure and even death. Specialized pro-resolving mediators (SPMs), which are typically thought to be formed via consecutive steps of oxidation of polyenoic fatty acids, have been shown to suppress inflammation and promote timely resolution of inflammation. They are mainly divided into four categories: lipoxins, resolvins, protectins, and maresins. The SPMs may improve the prognosis of sepsis by modulating the immune and inflammatory balance, thereby holding promise for clinical applications. However, their biosynthetic and pharmacological properties are very complex. Through a literature review, we aim to comprehensively elucidate the protective mechanisms of different SPMs in sepsis and its organ damage, in order to provide sufficient theoretical basis for the future clinical translation of SPMs. [ABSTRACT FROM AUTHOR]

Objective: To summarize the causes of death and clinical characteristics of systemic lupus erythematosus (SLE) hospitalized patients in the last 20 years to improve SLE survival rates by detecting critical SLE early. Methods: In this case-control study, 218 SLE death cases were retrospectively analyzed from January 2002 to December 2022, with 110 SLE inpatients chosen at random as controls. The clinical symptoms, causes of death, and risk factors in patients with SLE were investigated. Results: There were 218 deaths among 9538 patients with SLE, including 188 women and 30 men. The death rate fell steadily from 4.14% in 2002 to 1.96% in 2013 and remained at 1.84% from 2014 to 2022. The standardized mortality ratio (SMR) was 4.98 [95% CI (4.06-5.89)] from 2002 to 2012 and 3.39 [95% CI (2.74-4.04)] from 2013 to 2022. Infection, lupus-induced multiple organ failure syndrome (MODS), and neuropsychiatric lupus (NPLE) were the leading causes of death, accounting for 31.19%, 15.14%, and 11.47% of overall deaths. Age had a significant association with the major causes of death. Logistic regression analysis showed NPLE[OR = 10.772,95% CI (3.350,34.633), p < 0.001], lupus pulmonary involvement (LP)[OR = 3.844,95%CI (1.547,9.552), p = 0.004], pneumonia[OR = 3.439,95%CI(1.552,7.621), p = 0.002], thrombocytopenia[OR = 14.941,95%CI (4.088,54.604), p < 0.001], creatinine>177 μmol/L[OR = 8.644,95%CI (2.831,26.388), p < 0.001], glutamic transaminase(AST) > 60U/L[OR = 5.762,95%CI (2.200,15.088), p < 0.001], total bilirubin > 34 μmol/L[OR = 16.701,95%CI (3.349,83.294), p = 0.001], higher SLE Disease Activity Index (SLEDAI)[OR = 1.089,95%CI (1.032,1.149), p = 0.002] and SLE Damage Index (SDI)[OR = 3.690,95%CI (2.487,5.474), p < 0.001] correlated positively with death. Conclusion: From 2002 to 2013, the mortality rate among patients with SLE fell steadily but remained unchanged from 2014 to 2022. Patients with SLE had significantly higher SMR than the general population. Childhood-onset SLE had a poorer prognosis than adult-onset SLE. Infection, MODS, and NPLE were the three leading causes of death. Major organ involvement and high disease activity were risk factors for mortality. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Aims Methods Results Conclusions Acute‐on‐chronic liver failure (ACLF) is a syndrome of patients with chronic liver disease presenting with multiple organ failures. Recently, Sundaram‐ACLF‐LT Mortality (SALT‐M) score has been developed to predict 1‐year post‐liver transplantation mortality. We validated the SALT‐M score in a large‐volume, Asian single‐centre cohort.We validated the SALT‐M score in a large‐volume, Asian single‐centre cohort.We analysed 224 patients of ACLF grade 2–3. Area under the receiver operating characteristic curve (AUROC) and concordance index (c‐index) were used to assess and compare the predictability of posttransplant mortality of SALT‐M and other scores. Moreover, we compared the survivals of patients with high and low SALT‐M, in conjunction with MELD score and ACLF grade.The AUROC for prediction of 1‐year post‐LT survival was higher in SALT‐M (0.691) than in MELD, MELD‐Na, MELD 3.0 and delta‐MELD. Similarly, the c‐index of the SALT‐M (0.650) was higher than aforementioned MELD systems. When categorised by the cut‐off of SALT‐M ≥ 20 and MELD ≥ 30, patients with high SALT‐M exhibited lower post‐LT survival than those with low SALT‐M scores regardless of high or low MELD (40.0% for high SALT‐M/high MELD vs. 42.9% for high SALT‐M/low MELD vs. 73.8% for low SALT‐M/high MELD vs. 63.7% for low SALT‐M/low MELD, p < 0.001). In patients with ACLF grade 3, SALT‐M effectively stratified the posttransplant mortality (39.4% for high SALT‐M vs. 63.1% for low SALT‐M, p = 0.018).SALT‐M outperformed previous MELD systems for predicting posttransplant mortality in Asian LT cohort with severe ACLF. Transplantability for patients with severe ACLF could be determined based on SALT‐M. [ABSTRACT FROM AUTHOR]

Background: Peripheral veno-arterial extracorporeal membrane oxygenation (pECMO) has become the first-line device in refractory cardiogenic shock (rCS). Some pECMO complications can preclude any bridging strategies and a peripheral-to-central ECMO (cECMO) switch can be considered as a bridge-to-decision. We conducted this study to appraise the in-hospital survival and the bridging strategies in patients undergoing peripheral-to-central ECMO switch. Methods: This retrospective monocenter study included patients admitted to a ECMO-dedicated intensive care unit from February 2006 to January 2023. Patients with rCS requiring pECMO switched to cECMO were included. Patients were not included when the cECMO was the first mechanical circulatory support. Results: Eighty patients, with a median [IQR25-75] age of 44 [29–53] years at admission and a female-to-male sex ratio of 0.6 were included in the study. Refractory pulmonary edema was the main switching reason. Thirty patients (38%) were successfully bridged to: heart transplantation (n = 16/80, 20%), recovery (n = 10/80, 12%) and ventricle assist device (VAD, n = 4/30, 5%) while the others died on cECMO (n = 50/80, 62%). The most frequent complications were the need for renal replacement therapy (76%), hemothorax or tamponade (48%), need for surgical revision (34%), mediastinitis (28%), and stroke (28%). The in-hospital and one-year survival rates were 31% and 27% respectively. Myocardial infarction as the cause of the rCS was the only variable independently associated with in-hospital mortality (HR 2.5 [1.3–4.9], p = 0.009). Conclusions: The switch from a failing pECMO support to a cECMO as a bridge-to-decision is a possible strategy for a very selected population of young patients with a realistic chance of heart function recovery or heart transplantation. In this setting, cECMO allows patients triage preventing from wasting expensive and limited resources. [ABSTRACT FROM AUTHOR]

Although toxicity from excessive exogenous vitamin D supplementation is rare, a range of symptoms can occur, most of which result from hypercalcemia. We report a novel case of posterior reversible encephalopathy syndrome (PRES) in a young child who required intensive care after presenting with hypercalcemia, hypertensive emergency, acute kidney injury, and hypercarbic respiratory failure, which ultimately were attributed to vitamin D toxicity (VDT). We report a young child who developed PRES in association with VDT. Our report informs pediatric outpatient, hospitalist, and intensivist providers about rare but lifethreatening complications from hypervitaminosis D, adds VDT to the differential diagnosis for children with similar presentations, and highlights the importance of vitamin supplementation safety guidance for families. [ABSTRACT FROM AUTHOR]

Objectives Systemic lupus erythematosus (SLE) is a complex autoimmune disease with varying symptoms and multi-organ damage. Relapse-remission cycles often persist for many patients for years with the current treatment. Improved understanding of molecular changes caused by SLE flare and intensive treatment may result in more targeted therapies. Methods RNA sequencing was performed on peripheral blood mononuclear cells (PBMCs) from 65 SLE patients in flare, collected both before (SLE1) and after (SLE2) in-hospital treatment, along with 15 healthy controls (HC). Differentially expressed genes (DEGs) were identified among the three groups. Enriched functions and key molecular signatures of the DEGs were analysed and scored to elucidate the transcriptomic changes during treatment. Results Few upregulated genes in SLE1 vs HC were affected by treatment (SLE2 vs SLE1), mostly functional in interferon signalling (IFN), plasmablasts and neutrophils. IFN and plasmablast signatures were repressed, but the neutrophil signature remained unchanged or enhanced by treatment. The IFN and neutrophil scores together stratified the SLE samples. IFN scores correlated well with leukopenia, while neutrophil scores reflected relative cell compositions but not cell counts. Conclusions In-hospital treatment significantly relieved SLE symptoms with expression changes of a small subset of genes. Notably, IFN signature changes matched SLE flare and improvement, while enhanced neutrophil signature upon treatment suggested the involvement of low-density granulocytes (LDG) in disease development. [ABSTRACT FROM AUTHOR]

The article focuses on a teenage male who was admitted to the pediatric intensive care unit (PICU) after a mixed overdose, presenting with severe symptoms including low Glasgow Coma Scale (GCS), fixed dilated pupils, and metabolic and respiratory acidosis. Topics include the patient's clinical presentation and initial lab findings, the management of his overdose with intubation and supportive care, and the subsequent monitoring of his vital signs and neurological status in the PICU.

We describe a case of autochthonous human Babesia divergens infection in an immunocompetent woman in England. The patient had fever, hemolysis, multiorgan failure, and 18% parasitemia. We confirmed B. divergens by 18S rDNA PCR and sequencing. Clinicians should consider babesiosis as a differential diagnosis in patients with unexplained hemolysis. [ABSTRACT FROM AUTHOR]

West Nile virus (WNV) is the most common cause of human arboviral disease in the contiguous United States, where only lineage 1 (L1) WNV had been found. In 2023, an immunocompetent patient was hospitalized in Nebraska with West Nile neuroinvasive disease and multisystem organ failure. Testing at the Centers for Disease Control and Prevention indicated an unusually high viral load and acute antibody response. Upon sequencing of serum and cerebrospinal fluid, we detected lineage 3 (L3) and L1 WNV genomes. L3 WNV had previously only been found in Central Europe in mosquitoes. The identification of L3 WNV in the United States and the observed clinical and laboratory features raise questions about the potential effect of L3 WNV on the transmission dynamics and pathogenicity of WNV infections. Determining the distribution and prevalence of L3 WNV in the United States and any public health and clinical implications is critical. [ABSTRACT FROM AUTHOR]

A 68-year-old male presented with a one-month history of progressive proptosis and vision loss in the left eye. Examination of the left eye showed visual acuity of NLP, marked relative proptosis of 10 mm, and complete external ophthalmoplegia. CT orbits showed an extensive left orbital lesion with proptosis. Urgent orbital biopsy was undertaken. Intraoperatively, the patient developed new atrial flutter and fever. Bloodwork revealed metabolic derangements suggestive of tumor lysis syndrome. Systemic evaluation revealed a large tumor burden involving the retroperitoneal space. Histopathology of the orbital specimen showed non-germinal center diffuse large B-cell lymphoma. The patient passed away 3 days postoperatively due to rapidly progressive multisystem organ failure. Our case demonstrates an unusually aggressive presentation of DLBCL in which orbital mass was the first presentation of spontaneous tumor lysis syndrome owing to large systemic tumor burden. [ABSTRACT FROM AUTHOR]

Multi-organ transplantation involves the transplant of two or more organs from a single donor into a single recipient; in most cases, one of these organs is a kidney. Multi-organ transplantation is uncommon in pediatric transplantation but can be life-saving or significantly life-improving for children with rare diseases, including primary heart, liver, pancreas, or intestinal failure with secondary kidney failure, metabolic disorders, and genetic conditions causing multi-organ dysfunction. This manuscript reviews the current state of pediatric multi-organ transplantation that includes a kidney, with a focus on indications, evaluation, and key differences in management compared to kidney-alone transplantation. Guidelines and consensus statements for pediatric multi-organ transplantation are nonexistent; this review condenses reported statistics and peer-reviewed expert opinion while highlighting areas in need of further research. [ABSTRACT FROM AUTHOR]

Paediatric acute liver failure (PALF) is often characterised by its rapidity of onset and potential for significant morbidity and even mortality. Patients often develop multiorgan dysfunction/failure, including severe acute kidney injury (AKI). Whilst the management of PALF focuses on complications of hepatic dysfunction, the associated kidney impairment can significantly affect patient outcomes. Severe AKI requiring continuous kidney replacement therapy (CKRT) is a common complication of both PALF and liver transplantation. In both scenarios, the need for CKRT is a poor prognostic indicator. In adults, AKI has been shown to complicate ALF in 25–50% of cases. In PALF, the incidence of AKI is often higher compared to other critically ill paediatric ICU populations, with reports of up to 40% in some observational studies. Furthermore, those presenting with AKI regularly have a more severe grade of PALF at presentation. Observational studies in the paediatric population corroborate this, though data are not as robust—mainly reflecting single-centre cohorts. Perioperative benefits of CKRT include helping to clear water-soluble toxins such as ammonia, balancing electrolytes, preventing fluid overload, and managing raised intracranial pressure. As liver transplantation often takes 6–10 h, it is proposed that these benefits could be extended to the intraoperative period, avoiding any hiatus. Intraoperative CKRT (IoCKRT) has been shown to be practicable, safe and may help sicker recipients tolerate the operation with outcomes analogous with less ill patients not requiring IoCKRT. Here, we provide a comprehensive guide describing the rationale, practicalities, and current evidence base surrounding IoCKRT during transplantation in the paediatric population. [ABSTRACT FROM AUTHOR]

\nIntroduction: Septic shock, a severe manifestation of infection-induced systemic immune response, poses a critical threat resulting in life-threatening multi-organ failure. Early diagnosis and intervention are imperative due to the potential for irreversible organ damage. However, specific and sensitive detection tools for the diagnosis of septic shock are still lacking. Methods: Gene expression files of early septic shock were obtained from the Gene Expression Omnibus (GEO) database. CIBERSORT analysis was used to evaluate immune cell infiltration. Genes related to immunity and disease progression were identified using weighted gene co-expression network analysis (WGCNA), followed by enrichment analysis. CytoHubba was then employed to identify hub genes, and their relationships with immune cells were explored through correlation analysis. Blood samples from healthy controls and patients with early septic shock were collected to validate the expression of hub genes, and an external dataset was used to validate their diagnostic efficacy. Results: Twelve immune cells showed significant infiltration differences in early septic shock compared to control, such as neutrophils, M0 macrophages, and natural killer cells. The identified immune and disease-related genes were mainly enriched in immune, cell signaling, and metabolism pathways. In addition, six hub genes were identified (PECAM1, F11R, ITGAL, ICAM3, HK3, and MCEMP1), all significantly associated with M0 macrophages and exhibiting an area under curve of over 0.7. These genes exhibited abnormal expression in patients with early septic shock. External datasets and real-time qPCR validation supported the robustness of these findings. Conclusion: Six immune-related hub genes may be potential biomarkers for early septic shock. Septic shock is a dangerous condition that happens when an infection spreads through the body and triggers a strong immune response, leading to the failure of multiple organs. Recognizing and treating septic shock quickly is crucial to prevent lasting damage to the body’s organs. However, doctors currently do not have highly effective tools to diagnose septic shock early. In this study, we looked at genetic information from patients with early septic shock. We used a large public database to find patterns in gene activity that could help identify the condition. By analyzing the genes, we could tell which types of immune cells were involved. We discovered that certain immune cells, like neutrophils, M0 macrophages (a kind of white blood cell that helps fight infections), and natural killer cells, were more active in patients with septic shock. We also found genes that are active during immune responses and disease progression. These genes were mostly involved in the body’s defense system, cell communication, and energy use. Among these genes, six stood out as being closely connected to M0 macrophages. These six genes could potentially serve as early warning signs for doctors to detect septic shock, as they were good at distinguishing between patients with and without the condition. In summary, the study identified six genes that might be useful for spotting septic shock early on. These findings could lead to better diagnostic tools, helping doctors to treat patients before their condition becomes critical. [ABSTRACT FROM AUTHOR]

Hemophagocytic lymphohistiocytosis (HLH) is a rare but often fatal condition characterized by a hyperinflammatory immune response leading to multiorgan failure. It is predominantly observed in the pediatric population and can be classified as familial or acquired HLH. The latter is more common in adults, often associated with malignancy, infection, or autoimmune diseases. Among acquired HLH cases, hematologic neoplasms account for the majority, with only a few isolated reports documenting solid neoplasms as the cause. Herein, we present a case of adult HLH associated with colorectal adenocarcinoma, which, to the best of our knowledge, is only the second reported case of HLH associated with this type of cancer. [ABSTRACT FROM AUTHOR]

Despite the increasing efficacy of chemotherapy, permanently unresectable colorectal liver metastases are associated with poor long-term survival. We aimed to assess whether liver transplantation plus chemotherapy could improve overall survival. TransMet was a multicentre, open-label, prospective, randomised controlled trial done in 20 tertiary centres in Europe. Patients aged 18−65 years, with Eastern Cooperative Oncology Group performance score 0−1, permanently unresectable colorectal liver metastases from resected BRAF -non-mutated colorectal cancer responsive to systemic chemotherapy (≥3 months, ≤3 lines), and no extrahepatic disease, were eligible for enrolment. Patients were randomised (1:1) to liver transplantation plus chemotherapy or chemotherapy alone, using block randomisation. The liver transplantation plus chemotherapy group underwent liver transplantation for 2 months or less after the last chemotherapy cycle. At randomisation, the liver transplantation plus chemotherapy group received a median of 21·0 chemotherapy cycles (IQR 18·0−29·0) versus 17·0 cycles (12·0−24·0) in the chemotherapy alone group, in up to three lines of chemotherapy. During first-line chemotherapy, 64 (68%) of 94 patients had received doublet chemotherapy and 30 (32%) of 94 patients had received triplet regimens; 76 (80%) of 94 patients had targeted therapy. Transplanted patients received tailored immunosuppression (methylprednisolone 10 mg/kg intravenously on day 0; tacrolimus 0·1 mg/kg via gastric tube on day 0, 6−10 ng/mL days 1–14; mycophenolate mofetil 10 mg/kg intravenously day 0 to <2 months and switch to everolimus 5−8 ng/mL), and postoperative chemotherapy, and the chemotherapy group had continued chemotherapy. The primary endpoint was 5-year overall survival analysed in the intention to treat and per-protocol population. Safety events were assessed in the as-treated population. The study is registered with ClinicalTrials.gov (NCT02597348), and accrual is complete. Between Feb 18, 2016, and July 5, 2021, 94 patients were randomly assigned and included in the intention-to-treat population, with 47 in the liver transplantation plus chemotherapy group and 47 in the chemotherapy alone group. 11 patients in the liver transplantation plus chemotherapy group and nine patients in the chemotherapy alone group did not receive the assigned treatment; 36 patients and 38 patients in each group, respectively, were included in the per-protocol analysis. Patients had a median age of 54·0 years (IQR 47·0−59·0), and 55 (59%) of 94 patients were male and 39 (41%) were female. Median follow-up was 59·3 months (IQR 42·4−60·2). In the intention-to-treat population, 5-year overall survival was 56·6% (95% CI 43·2−74·1) for liver transplantation plus chemotherapy and 12·6% (5·2–30·1) for chemotherapy alone (HR 0·37 [95% CI 0·21−0·65]; p=0·0003) and 73·3% (95% CI 59·6–90·0) and 9·3% (3·2–26·8), respectively, for the per-protocol population. Serious adverse events occurred in 32 (80%) of 40 patients who underwent liver transplantation (from either group), and 69 serious adverse events were observed in 45 (83%) of 54 patients treated with chemotherapy alone. Three patients in the liver transplantation plus chemotherapy group were retransplanted, one of whom died postoperatively of multi-organ failure. In selected patients with permanently unresectable colorectal liver metastases, liver transplantation plus chemotherapy with organ allocation priority significantly improved survival versus chemotherapy alone. These results support the validation of liver transplantation as a new standard option for patients with permanently unresectable liver-only metastases. French National Cancer Institute and Assistance Publique–Hôpitaux de Paris. [ABSTRACT FROM AUTHOR]

Sepsis is a dysregulated immune response to an infection that leads to organ dysfunction. Sepsis-associated organ dysfunction involves multiple inflammatory mechanisms and complex metabolic reprogramming of cellular function. These mechanisms cooperate through multiple organs and systems according to a complex set of long-distance communications mediated by cellular pathways, solutes, and neurohormonal actions. In sepsis, the concept of organ crosstalk involves the dysregulation of one system, which triggers compensatory mechanisms in other systems that can induce further damage. Despite the abundance of studies published on ​​organ crosstalk in the last decade, there is a need to formulate a more comprehensive framework involving all organs to create a more detailed picture of sepsis. In this paper, we review the literature published on organ crosstalk in the last 10 years and explore how these relationships affect the progression of organ failure in patients with septic shock. We explored these relationships in terms of the heart–kidney–lung, gut-microbiome–liver–brain, and adipose tissue–muscle–bone crosstalk in sepsis patients. A deep connection exists among these organs based on crosstalk. We also review how multiple therapeutic interventions administered in intensive care units, such as mechanical ventilation, antibiotics, anesthesia, nutrition, and proton pump inhibitors, affect these systems and must be carefully considered when managing septic patients. The progression to multiple organ dysfunction syndrome in sepsis patients is still one of the most frequent causes of death in critically ill patients. A better understanding and monitoring of the mechanics of organ crosstalk will enable the anticipation of organ damage and the development of individualized therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Serotonin syndrome and Parkinson's disease (PD) are two diseases whose symptoms partially overlap; this poses challenges in distinguishing them in clinical practice. Early manifestations such as tremor, akathisia, diaphoresis, hypertonia and hyperreflexia are common in mild-to-moderate serotonin syndrome and can also occur in PD. Without prompt recognition and treatment, serotonin syndrome can rapidly progress, potentially leading to severe complications such as multiple organ failure within hours. Given their disparate treatment strategies, accurate clinical distinction is crucial for effective treatment. This case study explores a patient with serotonin syndrome triggered by escitalopram in the context of PD psychosis (PDP), providing insights into diagnosis and treatment planning. Case presentation: A 75-year-old Asian woman with a one-year history of PD, a two-month history of PDP, and a six-year history of depression presented with symptoms including hyperreflexia, tremor, hypertonia, impaired level of consciousness, and inappropriate behavior following a recent one-month adjustment in medication. Initially suspected of being drug-induced parkinsonism or worsening PD, therapeutic drug monitoring revealed warning levels of escitalopram. Subsequent diagnoses confirmed serotonin syndrome. This syndrome may result from increased cortical serotonin activity at the serotonin2A receptor due to dopamine and serotonin imbalances in PDP, compounded by increased dopamine-mediated serotonin release. Additionally, being an intermediate metabolizer of cytochrome P450 enzyme 2C19, the patient experienced excessive escitalopram accumulation, exacerbating her condition. Conclusions: This case underscores the critical need to differentiate between symptoms of serotonin syndrome and PD, particularly in manifestations like tremor and hypertonia. Careful consideration of receptor profiles in patients with PDP is essential when selecting antidepressants to mitigate the risk of serotonin syndrome. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions The SynCardia® temporary total artificial heart (TAH) serves as a mechanical circulatory support device for patients suffering from irreversible biventricular failure.This retrospective study analyzed 196 consecutive patients who underwent TAH implantation at our center from 2001 to 2021. We assessed survival rates and all‐cause mortality during TAH support, including survival post‐heart transplantation.The median age of patients was 55 years, with 88% being male. The primary diagnoses included cardiomyopathy (43.9%), acute myocardial infarction (26.5%), and postcardiotomy heart failure (15.5%). At implantation, 87.2% of patients were classified as INTERMACS Profile 1. The median duration of support was 96 days (IQR: 23–227). Survival rates at 1, 6, and 12 months were 72%, 41%, and 34%, respectively. Postoperative rethoracotomy was necessary in 44.4% of patients; 39.3% experienced neurological events and 24.6% developed gastrointestinal bleeding. Overall, 64.8% of patients died while on support, primarily due to multiple organ failure (55.9%). Factors such as older age, higher bilirubin levels, postcardiotomy and specific underlying diagnoses were independent predictors of mortality during TAH support. On a positive note, 35.2% of patients underwent successful heart transplants, with 1‐, 5‐, and 10‐year posttransplant survival rates of 65%, 58%, and 51%, respectively.While high mortality rates persist among patients with biventricular failure, the SynCardia® TAH offers a viable interim solution for critically ill patients, particularly those who can be successfully bridged to heart transplantation. [ABSTRACT FROM AUTHOR]

Background: Recent studies suggest that low-molecular-weight heparin (LMWH) may play a role in mitigating the severity of acute pancreatitis (AP). This systematic review and meta-analysis aims to synthesise existing evidence on the effectiveness and safety of LMWH in the treatment of moderately-severe and severe AP. Methods: This systematic review and meta-analysis was conducted in accordance with the 2020 update of the PRISMA guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. The systematic search was conducted in MEDLINE, the Cochrane Central Register of Controlled Trials, Scopus, and EMBASE, covering studies published up to February 2024. Randomised controlled trials (RCTs) and observational studies (n-RCTs) that reported the differences in the outcomes of AP for patients receiving LMWH in addition to the standard treatment (Intervention), compared to patients managed by standard treatment without LMWH (Control) were eligible. A random-effects model was used to calculate the pooled relative risk (RR) and mean differences (MD) with the corresponding 95% CI. Results: Thirteen studies were included in the meta-analysis, all published between 2004 and 2022. Eight studies were RCTs, and five were n-RCTs. Data from 13,709 patients (6.971 Interventions and 6.738 Controls) were analysed. The comparison of Intervention and Control groups showed the superiority of LMWH to standard treatments in terms of overall mortality (RR = 0.44, 95% CI = 0.31; 0.64, P < 0.0001, I2 = 51%), acute necrotic collections (RR = 0.24, 95% CI = 0.09; 0.62, P = 0.003, I2 = 0%), and organ failure (RR = 0.67, 95% CI = 0.48; 0.93, P = 0.02, I2 = 78%). The Intervention group showed superior outcomes compared with the Control group for gastrointestinal bleeding (RR = 0.64, 95% CI = 0.44; 0.94, P = 0.02, I2 = 0%), length of hospital stay (MD= − 6.08, 95% CI = − 10.08; − 2.07, P = 0.003, I2 = 98%), need for operative interventions (RR = 0.50, 95% CI = 0.29; 0.87, P = 0.01, I2 = 61%), and vascular thrombosis (RR = 0.43, 95% CI = 0.31; 0.61, P < 0.00001, I2 = 0%). Conclusions: Moderate to high-quality evidence suggests that early intervention with LMWH could improve the prognosis of non-mild AP in terms of mortality, organ failure, and decreased incidence of vascular thrombosis. In light of our findings, integrating LMWH into the treatment regimen for moderate-severe to severe AP is advocated. [ABSTRACT FROM AUTHOR]

Introduction: Classic heat stroke is a severe trauma which can lead to multi-organ dysfunctions and is associated with a high mortality. Case presentation: In this case report we present a 73-year-old patient with a classic heat stroke. His initial core body temperature was over 42 °C and he had a GCS of 3. Due to severe burn injuries the patient was transferred to a specialized burn center. The patient developed different organ failures and showed a prolonged course on the intensive care unit. Although the patient demonstrated different impaired organ systems, he recovered completely after receiving painstaking supportive therapy. Conclusions: This is a rare case of a patient who fully recovered after a heat stroke with a temperature over 42 °C and severe sequelae. [ABSTRACT FROM AUTHOR]

Introduction: The proportion of very elderly patients in the intensive care unit (ICU) is expected to rise. Furthermore, patients are likely more prone to suffer a cardiac arrest (CA) event within the ICU. The occurrence of intensive care unit cardiac arrest (ICU-CA) is associated with high mortality. To date, the incidence of ICU-CA and its clinical impact on outcome in the very old (≥ 90 years) patients treated is unknown. Methods: Retrospective analysis of all consecutive critically ill patients ≥ 90 years admitted to the ICU of a tertiary care university hospital in Hamburg (Germany). All patients suffering ICU-CA were included and CA characteristics and functional outcome was assessed. Clinical course and outcome were assessed and compared between the subgroups of patients with and without ICU-CA. Results: 1,108 critically ill patients aged ≥ 90 years were admitted during the study period. The median age was 92.3 (91.0–94.2) years and 67% (n = 747) were female. 2% (n = 25) of this cohort suffered ICU-CA after a median duration 0.5 (0.2–3.2) days of ICU admission. The presumed cause of ICU-CA was cardiac in 64% (n = 16). The median resuscitation time was 10 (2–15) minutes and the initial rhythm was shockable in 20% (n = 5). Return of spontaneous circulation (ROSC) could be achieved in 68% (n = 17). The cause of ICU admission was primarily medical in the total cohort (ICU-CA: 48% vs. No ICU-CA: 34%, p = 0.13), surgical - planned (ICU-CA: 32% vs. No ICU-CA: 37%, p = 0.61) and surgical - unplanned/emergency (ICU-CA: 43% vs. No ICU-CA: 28%, p = 0.34). The median Charlson Comorbidity Index (CCI) was 2 (1–3) points for patients with ICU-CA and 1 (0–2) for patients without ICU-CA (p = 0.54). Patients with ICU-CA had a higher disease severity according to SAPS II (ICU-CA: 54 vs. No ICU-CA: 36 points, p < 0.001). Patients with ICU-CA had a higher rate of mechanically ventilation (ICU-CA: 64% vs. No ICU-CA: 34%, p < 0.01) and required vasopressor therapy more often (ICU-CA: 88% vs. No ICU-CA: 41%, p < 0.001). The ICU and in-hospital mortality was 88% (n = 22) and 100% (n = 25) in patients with ICU-CA compared to 17% (n = 179) and 28% (n = 306) in patients without ICU-CA. The mortality rate for patients with ICU-CA was observed to be 88% (n = 22) in the ICU and 100% (n = 25) in-hospital. In contrast, patients without ICU-CA had an in-ICU mortality rate of 17% (n = 179) and an in-hospital mortality rate of 28% (n = 306) (both p < 0.001). Conclusion: The occurrence of ICU-CA in very elderly patients is rare but associated with high mortality. Providing CPR in this cohort did not lead to long-term survival at our centre. Very elderly patients admitted to the ICU likely benefit from supportive care only and should probably not be resuscitated due to poor chance of survival and ethical considerations. Providing personalized assurances that care will remain appropriate and in accordance with the patient's and family's wishes can optimise compassionate care while avoiding futile life-sustaining interventions. [ABSTRACT FROM AUTHOR]

Rationale: Intensive care unit-acquired weakness (ICUAW) is common in critically ill patients, characterized by muscle weakness and physical function loss. Determining risk factors for ICUAW poses challenges due to variations in assessment methods and limited generalizability of results from specific populations, the existing literature on these risk factors lacks a clear and comprehensive synthesis. Objective: This overview aimed to synthesize risk factors for ICUAW, categorizing its modifiable and nonmodifiable factors. Methods: An overview of systematic reviews was conducted. Six relevant databases were searched for systematic reviews. Two pairs of reviewers selected reviews following predefined criteria, where bias was evaluated. Results were qualitatively summarized and an overlap analysis was performed for meta-analyses. Results: Eighteen systematic reviews were included, comprising 24 risk factors for ICUAW. Meta-analyses were performed for 15 factors, while remaining reviews provided qualitative syntheses. Twelve reviews had low risk of bias, 4 reviews were unclear, and 2 reviews exhibited high risk of bias. The extent of overlap ranged from 0 to 23% for the corrected covered area index. Nonmodifiable factors, including advanced age, female gender, and multiple organ failure, were consistently associated with ICUAW. Modifiable factors, including neuromuscular blocking agents, hyperglycemia, and corticosteroids, yielded conflicting results. Aminoglycosides, renal replacement therapy, and norepinephrine were associated with ICUAW but with high heterogeneity. Conclusions: Multiple risk factors associated with ICUAW were identified, warranting consideration in prevention and treatment strategies. Some risk factors have produced conflicting results, and several remain underexplored, emphasizing the ongoing need for personalized studies encompassing all potential contributors to ICUAW development. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to evaluate whether integrated traditional Chinese medicine (TCM) and Western medicine (WM) is more effective than WM for acute pancreatitis (AP). Methods: Patients with AP were enrolled and divided into the TCM and WM (TCM&WM) and WM groups according to the therapeutic protocol in real clinical settings. We applied 1:3 propensity score matching, which was to adjust confounding factors. The primary outcome was mortality, whereas the secondary outcomes were organ failure, organ supportive therapies, local complications, hospitalization cost, and length of hospital stay. Sensitivity and subgroup analyses were also performed. Results: Of 5442 patients with AP, 4691 and 751 were included in the TCM&WM and WM groups, respectively. After PSM, patient baseline characteristics were well balanced. Compared with the WM group (n = 734), the TCM&WM group (n = 2096) had lower overall mortality rate (1.7% vs. 3.4%; risk ratio, 0.482; 95% confidence interval, 0.286–0.810; p = 0.005). The TCM&WM group was associated with lower risk of persistent renal failure, multiple organ failure, and infection, lower utilization of organ supportive therapies, shortened lengths of hospital and intensive care unit stay, and lower hospital costs. Sensitivity analyses showed similar results. Subgroup analysis favored TCM&WM treatment for patients aged < 60 years, with hypertriglyceridic etiology, and with admission interval between 24 and 48 h. Conclusion: TCM&WM treatment can achieve lower risks of mortality and organ failure and better economic effectiveness in patients with AP than WM treatment. This study provides a promising alternative of TCM&WM treatment for AP in the real‐world setting. [ABSTRACT FROM AUTHOR]

Introduction: ExtraCorporeal Membrane Oxygenation (ECMO) in pediatric patients with COVID-19 has a survival rate similar to adults. Occasionally, patients may need to be cannulated by an ECMO team in a referring hospital and transported to an ECMO center. The ECMO transport of a COVID-19 patient has additional risks than normal pediatric ECMO transport for the possible COVID-19 transmissibility to the ECMO team and the reduction of the ECMO team performance due to the need of wearing full personal protective equipment. Since pediatric data on ECMO transport of COVID-19 patients are lacking, we explored the outcomes of the pediatric COVID-19 ECMO transports collected in the EuroECMO COVID_Neo/Ped Survey. Methods: We reported five European consecutive ECMO transports of COVID-19 pediatric patients collected in the EuroECMO COVID_Neo/Ped Survey including 52 European neonatal and/or pediatric ECMO centers and endorsed by the EuroELSO from March 2020 till September 2021. Results: The ECMO transports were performed for two indications, pediatric ARDS and myocarditis associated to the multisystem inflammatory syndrome related to COVID-19. Cannulation strategies differed among patients according to the age of the patients, transport distance varied between 8 and 390 km with a total transport duration between 5 to 15 h. In all five cases, the ECMO transports were successfully performed without major adverse events. One patient reported a harlequin syndrome and another patient a cannula displacement both without major clinical consequences. Hospital survival was 60% with one patient reporting neurological sequelae. No ECMO team member developed COVID-19 symptoms after the transport. Conclusion: Five transports of pediatric patients with COVID-19 supported with ECMO were reported in the EuroECMO COVID_Neo/Ped Survey. All transports were performed by an experienced multidisciplinary ECMO team and were feasible and safe for both the patient and the ECMO team. Further experiences are needed to better characterize these transports and draw insightful conclusions. [ABSTRACT FROM AUTHOR]

MicroRNAs (miR) are a group of small, non-coding RNAs of 17–25 nucleotides that regulate gene expression at the post-transcriptional level. Dysregulation of miRNA expression or function may contribute to abnormal gene expression and signaling pathways, leading to disease pathology. Lagovirus europaeus (L. europaeus) causes severe disease in rabbits called rabbit hemorrhagic disease (RHD). The symptoms of liver, lung, kidney, and spleen degeneration observed during RHD are similar to those of acute liver failure (ALF) and multi-organ failure (MOF) in humans. In this study, we assessed the expression of miRs and their target genes involved in the innate immune and inflammatory response. Also, we assessed their potential impact on pathways in L. europaeus infection—two genotypes (GI.1 and GI.2)—in the liver, lungs, kidneys, and spleen. The expression of miRs and target genes was determined using quantitative real-time PCR (qPCR). We assessed the expression of miR-155 (MyD88, TAB2, p65, NLRP3), miR-146a (IRAK1, TRAF6), miR-223 (TLR4, IKKα, NLRP3), and miR-125b (MyD88). We also examined biomarkers of inflammation: IL-1β, IL-6, TNF-α, and IL-18 in four tissues at the mRNA level. Our study shows that the main regulators of the innate immune and inflammatory response in L. europaeus/GI.1 and GI.2 infection, as well as RHD, are miR-155, miR-223, and miR-146a. During infection with L. europaeus/RHD, miR-155 has both pro- and anti-inflammatory effects in the liver and anti-inflammatory effects in the kidneys and spleen; miR-146a has anti-inflammatory effects in the liver, lungs and kidneys; miR-223 has anti-inflammatory effects in all tissues; however, miR-125b has anti-inflammatory effects only in the liver. In each case, such an effect may be a determinant of the pathogenesis of RHD. Our research shows that miRs may regulate three innate immune and inflammatory response pathways in L. europaeus infection. However, the result of this regulation may be influenced by the tissue microenvironment. Our research shows that infection of rabbits with L. europaeus/GI.1 and GI.2 genotypes causes an overexpression of two critical acute phase cytokines: IL-6 in all examined tissues and TNF-α (in the liver, lungs, and spleen). IL-1β was highly expressed only in the lungs after L. europaeus infection. These facts indicate a strong and rapid involvement of the local innate immune and inflammatory response in L. europaeus infection—two genotypes (GI.1 and GI.2)—and in the pathogenesis of RHD. Profile of biomarkers of inflammation in rabbits infected with L. europaeus/GI.1 and GI.2 genotypes are similar regarding the nature of changes but are different for individual tissues. Therefore, we propose three inflammation profiles for L. europaeus infection for both GI.1 and GI.2 genotypes (pulmonary, renal, liver, and spleen). [ABSTRACT FROM AUTHOR]

Cytokine release syndrome (CRS) occurs frequently after haplo-identical allogeneic stem cell transplantation (alloSCT) with post-transplant cyclophosphamide (PTCy), increasing nonrelapse mortality (NRM) and decreasing survival. Data on CRS in HLA-matched alloSCT are limited and effects of specific HLA-mismatches on CRS development unknown. We hypothesized that in HLA-matched alloSCT increasing degrees of HLA-mismatching influence CRS incidence, NRM and survival. Retrospective analysis of 126 HLA-matched PTCy-alloSCT patients showed that higher degrees of HLA-mismatching significantly increased CRS incidence (26%, 75% and 90% CRS with 12/12, 10/10 and 9/10 matched donors, respectively). Maximum temperature during CRS increased with higher HLA-mismatch. Specific associations between HLA-mismatches and CRS could be determined. Grade 2 CRS and CRS-induced grade 3 fever were associated with significantly increased NRM (p < 0.001 and p = 0.003, respectively) and inferior survival (p < 0.001 and p = 0.005, respectively). NRM was mainly caused by disease conditions that may be considered CRS-induced inflammatory responses (encephalopathy, cryptogenic organizing pneumonia and multi-organ failure). [ABSTRACT FROM AUTHOR]

Background Phaeochromocytoma multisystem crisis (PMC) is characterized by labile blood pressures (extremes of hypo- and/or hypertension) and multiorgan failure as a result of catecholamine excess. Initial stabilization requires pharmacological and/or mechanical circulatory support, followed by the institution of antihypertensives to correct the underlying pathophysiology. Case summary A previously well 40-year-old male developed a sudden onset of breathlessness. On presentation, he was in shock with multiorgan failure. He required intubation, mechanical ventilation, dual inotropic support, and renal replacement therapy. Bedside echocardiogram showed a severely impaired left ventricular ejection fraction (LVEF) of 25%. Coronary angiography revealed normal coronary arteries. In view of raised inflammatory markers and transaminitis, a computed tomography abdomen/pelvis was performed. An incidental left adrenal mass was found. Further work-ups revealed raised plasma metanephrine and normetanephrine, 24-h urine epinephrine, and norepinephrine. A cardiac magnetic resonance (CMR) showed myocardial inflammation and reverse Takotsubo pattern of regional wall motion abnormality (RWMA). The diagnosis of cardiogenic shock and stress cardiomyopathy secondary to PMC was made. He was subsequently initiated on α- and β-blockers and goal-directed medical therapy for heart failure. A 68Ga-DOTATATE scan showed avid tracer uptake of the left phaeochromocytoma. An interval CMR 3 weeks from presentation showed near normalization of the LVEF and RWMA. He underwent a successful laparoscopic left adrenalectomy and was antihypertensive-free since. Discussion The clinical suspicion for PMC as the cause of cardiogenic shock requires astute clinical judgement, while the management requires an understanding of the underlying pathophysiology that calls for multidisciplinary inputs. [ABSTRACT FROM AUTHOR]

Background Recent studies have analyzed the qSOFA (quick sequential organ failure assessment) score as a prognostic indicator in many diseases, particularly sepsis. However, the effect of qSOFA score on prognosis and mortality in critical care patients has not been sufficiently analyzed. There is not enough data, especially regarding its use as critical care mortality and prognosis scoring. In this study, we aimed to analyze the effect of qSOFA score on mortality and prognosis in critical care unit (CCU) patients. Methods This study was conducted retrospectively using the chart review method. The APACHE II (Acute Physiology and Chronic Health Evaluation II) and SOFA (Sequential Organ Failure Assessment) scores of patients admitted to our CCU were compared with the qSOFA score. In addition, the need for intubation and mechanical ventilation, short- and long term mortality rates, the relationship between blood gas lactate values and qSOFA score were analyzed. Results A total of 1816 patients were included in the study. During critical care follow-up, 374 (20.6%) of our patients died, and at the end of 6 months, 796 (43.8%) of our patients died. A statistically significant association was found between in-hospital mortality and qSOFA, SOFA scores and lactate levels (P = 0.001, P = 0.001, P = 0.01 respectively). A statistically significant association was found between 6-month mortality and SOFA score only. (P = 0.001) The SOFA score appeared to be the most successful predictor of mortality. The cut-off for mortality using the ROC curve was = 7 [sensitivity 78.1%; specificity 85.9%; AUC 0.91; 95% confidence interval (CI), 0.89 to 0.92; P = 0.001]. qSOFA scoring also performed well. The cut-off value for mortality using the ROC curve was = 2 (sensitivity 42.5%; specificity 93.9%; AUC 0.83;95% CI, 0.80-0.85; P = 0.001). Conclusion We believe that the qSOFA score can be used as a marker for in-hospital mortality and prognosis in critical care patients. Especially in cases where the qSOFA score is = 2, it provides valuable information regarding mortality and prognosis. [ABSTRACT FROM AUTHOR]