High Short-term Mortality Research Articles

Short-term mortality and associated factors among older hospitalized patients: A narrative retrospective analysis of end-of-life care in an acute geriatric unit

ObjectivesTo explore short-term mortality and its predictors among older patients hospitalized in a acute geriatric ward (AGW) in Northwestern Italy. DesignRetrospective observational single-center cohort study. Material and methodsPatients consecutively admitted for any reason between June 2021 and May 2022 were included in the analysis. Along with sociodemographic, clinical, and functional variables, prognosis estimation (Palliative Prognostic Index; PPI) at the time of admission was registered. Short-term all-cause mortality (in-hospital and within 3 months of discharge) was the primary outcome. ResultsAbout one-third of the total sample died in the short-term (32.4 %). Along with PPI score (OR 1.115, 95 %CI 1.034–1.202), short-term mortality was independently associated with functional dependency (OR 1.278, 95 %CI 1.170–1.395). ConclusionsThe high short-term mortality in our sample should call for the inclusion of palliative prognostic tools within the in-hospital comprehensive geriatric assessment to better recognize and appropriately manage older patients at the end of life.

G-CSF-In Patients With Severe Alcohol-Associated Hepatitis: A Real-World Experience.

Severe alcohol-associated hepatitis (SAH) is associated with high short-term mortality, and failure of response to corticosteroids is associated with a mortality of ~70%-80% within 6 months. Granulocyte colony-stimulating factor (G-CSF) has been studied in steroid non-responders; however, the data are limited. This is a multicentre retrospective cohort study. The study period was from January 2016 to November 2023. SAH was defined as alcohol-associated hepatitis (ICD-10-CM codes) with serum bilirubin ≥ 5.0 mg/dL and INR ≥ 1.5. Other aetiologies of acute hepatitis and biliary obstruction were excluded. The primary outcome was 90-day median overall survival in SAH patients treated with G-CSF compared with standard medical therapy (SMT) or corticosteroids. Propensity score (1:1) matching was performed to control confounding variables. Among 20 132 patients with SAH, 10800 (53.65%) were treated with corticosteroids and 224 (1.11%) G-CSF. The G-CSF group was younger (45.5 vs. 48.4) White (79.91% vs. 72.40%); however, there was no age or gender difference between G-CSF and corticosteroid groups. Whites and patients with more comorbidities received G-CSF more frequently than SMT or corticosteroids. After propensity score matching, 90-day overall survival was better in patients who received G-CSF (88.31% vs. 62.36%, p < 0.01) compared with SMT or corticosteroids (88.31% vs. 74.39%, p < 0.01). Patients on G-CSF had better 6-month transplant-free survival compared with SMT (83.53% vs. 55.36%, p < 0.001) or corticosteroids (82.89% vs. 60.21%, p < 0.001). Gastrointestinal bleeding was less common in G-CSF group compared with corticosteroids (5.02% vs. 10.50%, p < 0.001). A small minority of patients with severe alcohol-associated hepatitis receive G-CSF. G-CSF improves 90-day overall survival in patients with severe alcohol-associated hepatitis and is non-inferior to corticosteroids.

Managing multiorgan failure in Acute on chronic liver failure (ACLF).

Acute-on-chronic liver failure (ACLF) is defined as a clinical syndrome that develops in patients with chronic liver disease characterized by the presence of organ failure and high short-term mortality, although there is still no worldwide consensus on diagnostic criteria. Management of ACLF is mainly based on treatment of "precipitating factors" (the most common are infections, alcohol-associated hepatitis, hepatitis B flare, and bleeding) and support of organ failure, which often requires admission to the intensive care unit. Liver transplantation should be considered in patients with ACLF grade 2-3 as a potentially life-saving treatment. When transplant is not indicated, palliative care should be considered after 3-7 days of full organ support in patients with at least 4 organ failures or a CLIF-C ACLF score >70. This review summarizes the current knowledge on the management of organ failure in patients with ACLF, focusing on recent advances.

Association of liver dysfunction with outcomes after percutaneous coronary intervention – a systematic review and meta-analysis

BackgroundLiver dysfunction is a known risk factor in the cardiovascular field. It specifically increases perioperative risk in patients undergoing coronary bypass surgery. Since percutaneous coronary intervention (PCI) is the much less invasive procedure for the treatment of coronary artery disease, we aimed to assess the relationship of liver dysfunction with outcomes in patients undergoing PCI.MethodsThree libraries were searched (MEDLINE, Web of Science and The Cochrane Library). We performed a meta-analysis of all studies in patients who underwent PCI that provided information on the presence or absence of liver dysfunction. Primary outcome was short-term mortality. Secondary outcomes were major adverse cardio- and cerebrovascular events (MACCE), bleeding and acute kidney injury. Random-effects model was applied.ResultsFive studies were selected and the data from 10,710,317 patients were included in the final analysis. In comparison with the absence of liver dysfunction, patients with liver dysfunction were associated with higher short-term mortality (OR 2.97, 95%CI 1.23–7.18, p = 0.02), higher MACCE (OR 1.42, 95%CI 1.08–1.87, p = 0.01), and higher bleeding (OR 2.23, 95%CI 1.65-3.00, p < 0.01). There was no significant difference regarding acute kidney injury (OR 1.20, 95%CI 0.50–2.87, p = 0.69).ConclusionsThe analysis suggests that liver dysfunction in patients undergoing PCI is independently associated with higher risk of short-term mortality and increased occurrence of MACCE and bleeding. However, there appears to be no association to acute kidney injury.

Prognostic Survey of ECPELLA in Japanese Patients With Acute Myocardial Infarction and Cardiogenic Shock - Findings From the Japanese Registry for Percutaneous Ventricular Assist Device (J-PVAD).

The short-term mortality associated with veno-arterial extracorporeal membrane oxygenation combined with the Impella device (termed ECPELLA) for acute myocardial infarction complicated by cardiogenic shock (AMI-CS) remains unclear. The Japanese Registry for Percutaneous Ventricular Assist Devices (J-PVAD) includes data on all patients treated with an Impella in Japan. We extracted data for 922 AMI-CS patients who underwent ECPELLA support and conducted an exploratory analysis focusing on 30-day mortality. The median age of patients was 69 years, and 83.8% were male. The overall 30-day mortality was 46.1%. Factors associated with mortality included age >80 years, in-hospital cardiac arrest, systolic blood pressure <90 mmHg, serum creatinine >1.5 mg/dL, and serum lactate >4.0 mmol/L. In patients aged >80 years with any of these factors, mortality was significantly higher than in those without, ranging from 57.5% to 64.9%. The J-PVAD score assigns 1 point per predictor, with a C-statistic of 0.620 (95% confidence interval 0.586-0.654). The 30-day mortality was 20.0% for a J-PVAD score of 0, increasing to 70.0% for a score of 5. The J-PVAD data indicate high short-term mortality in AMI-CS patients treated with ECPELLA, particularly among older patients. Further studies are needed to validate this risk stratification in this patient subset.

‘ALERT’, a machine learning predictive model to identify six-month mortality in patients with advanced cancer: Perception of the utility and acceptability among patients.

189 Background: Machine learning (ML) models can predict mortality and guide end-of-life (EOL) care for patients with advanced solid cancers. Early advanced care planning (ACP) leads to more goal-concordant care, yet many patients, especially from minoritized groups, do not engage in serious illness conversations (SIC). Reasons for delay include inability of oncologists to identify patients at high short-term mortality risk, and uncertainties about prognosis. While ML may improve prognosis accuracy, research on its use and impact on racial biases affecting SIC is limited. This study aims to evaluate the acceptability of deploying a ML model to predict 6-month mortality among patients with advanced solid cancers. Methods: In order to inform the implementation of ‘ALERT,’ a predictive mortality model into a clinical alert system, we conducted one-on-one semi-structured interviews with patients with advanced solid cancer receiving care at a single institution (N=26). Interviews were recorded, transcribed verbatim, coded, and themes were reviewed by a team of interdisciplinary investigators. Results: Benefits and challenges to guide the future implementation of ALERT were identified. Patient-perceived benefits were: 1) EOL Planning: preparing family members (e.g., financial, emotional); 2) Emotional Freedom: knowledge would give freedom to live out life more carefree due to limited time left; 3) Medical Autonomy: the treatment could be worse than the actual disease, if at any point it was not helping, knowing allows individuals to make the decision to stop. Challenges identified were: 1) Loss of Control: “when you don’t know [the outcome], you just keep moving, you just keep pushing”- knowing can result in a loss of control patients may desire for their course of treatment 2) Emotional Impact: knowledge of mortality could lead to grief among patients and families leading to distress around acceptability; 3) Faith: mortality prediction can be seen “playing God,” many patients believed when their time comes, it will happen and a ML tool cannot accurately predict when that time will be. Conclusions: Patients expressed equal balance of acceptability and resistance of ALERT for themselves and their families. This resulted in the difference of preferences regarding whether or not the knowledge this tool could provide would be helpful. This could lead to clinicians taking a patient-centered approach where the delivery of results using ALERT can be based on patient preference. The findings underscore the complexity of implementing ALERT, balancing significant benefits with notable challenges. These insights will guide the refinement of ALERT, ensuring it supports patient care while ensuring ALERT’s benefits are maximized and challenges are overcome.

Metabolic Dysregulation and Metabolite Imbalances in Acute-on-chronic Liver Failure: Impact on Immune Status.

Liver failure encompasses a range of severe clinical syndromes resulting from the deterioration of liver function, triggered by factors both within and outside the liver. While the definition of acute-on-chronic liver failure (ACLF) may vary by region, it is universally recognized for its association with multiorgan failure, a robust inflammatory response, and high short-term mortality rates. Recent advances in metabolomics have provided insights into energy metabolism and metabolite alterations specific to ACLF. Additionally, immunometabolism is increasingly acknowledged as a pivotal mechanism in regulating immune cell functions. Therefore, understanding the energy metabolism pathways involved in ACLF and investigating how metabolite imbalances affect immune cell functionality are crucial for developing effective treatment strategies for ACLF. This review methodically examined the immune and metabolic states of ACLF patients and elucidated how alterations in metabolites impact immune functions, offering novel perspectives for immune regulation and therapeutic management of liver failure.

Lymphocyte to high density lipoprotein ratio can predict the short-term prognosis of hepatitis B virus-related acute-on-chronic liver failure patients

BackgroundAcute-on-chronic liver failure (ACLF) is a syndrome characterized by systemic inflammation, leading to high short-term mortality. The lymphocyte to high-density lipoprotein ratio (LHR) has been introduced as a novel marker of inflammation. However, its role as a prognostic inflammatory biomarker in the context of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) has received limited attention. MethodsWe retrospectively included 272 patients with HBV-ACLF who met the definition of APALC. Data on clinical features and laboratory tests were collected from medical records within 24 h. Logistic regression was used to identify risk factors for poor short-term prognosis, and LHR-based prediction (LHRB) models were constructed based on risk factors. Furthermore, the accuracy of the LHRB model was validated through rigorous testing. ResultsIn the survival and death groups, there were statistical differences in their CTP, MELD, MELD-Na, COSSH-ACLF II scores, and LHR. Multivariate logistic regression identified seven predictors significantly associated with 28-day mortality. Furthermore, statistically significant differences in short-term mortality and certain clinical laboratory tests for poor prognosis were observed between the high and low LHR groups. To assess the predictive performance of various models in terms of short-term mortality, the area under the receiver operating characteristic curve (AUROC) was calculated. The AUROC values for the CTP, MELD, MELD-Na, COSSH-ACLF II, and LHRB models were found to be 0.725, 0.788, 0.772, 0.871, and 0.877, respectively. The results in the validation group were similar to those in the training group, and the validation results suggested excellent performance of the LHRB model. ConclusionLHR levels have the potential to serve as indicators for the prognosis of HBV-ACLF. Additionally, the recently developed LHRB model offers an accessible risk assessment tool.

Design of RNA Polymerase Inhibitors as Therapeutics for Tuberculous Meningitis.

Tuberculosis is an infectious disease caused by Mycobacterium tuber-culosis. The current treatment protocols for pulmonary tuberculosis are quite effective, even though the treatment requires 3-6 months. The current treatment protocols for extrapulmonary tuberculosis are based on the same drugs that are used for pulmonary tuberculosis. However, the success rates are much lower for certain types of extrapulmonary tuberculosis, such as tubercu-lous meningitis. Tuberculous meningitis is one of the very few diseases attributable to bacteria that have a very high short-term mortality rate among diagnosed patients, even after treatment with antibiotics that are effective for pulmonary tuberculosis. For example, rifampicin is highly effective for the treatment of pulmonary tuberculosis, but its effectiveness for the treatment of tuberculous meningitis is much lower. The reason for the lower effectiveness of rifampicin against tuberculous meningitis is that it has low Blood-Brain Barrier (BBB) permeability, which results in lower concentrations of the drug at the required sites in the central nervous system. In this work, ligands having increased BBB permeability and pharmacokinetic and pharmacodynamic properties, either similar to or better than that of rifampicin, have been de-signed. The BBB permeability of the designed molecules was assessed by using pkCSM, a ma-chine-learning model. Pharmacokinetic properties, drug-likeness, and synthesizability were as-sessed by using SWISS-MODEL. The binding affinity of the designed drugs was assessed by using AutoDock Vina. A customized scoring function, StWN score, was used for a quantitative weighted assessment of all the properties of interest to rank the designed molecules. In this study, drug-like ligands have been designed that have been predicted to have high BBB permeability as well as high affinity for RNA polymerase  ofMycobacterium tuberculosis. The best ligands generated by the tools employed were selected as potential drugs to address the current need for better options for the treatment of tuberculous meningitis.

Age added to MELD or ACLF predicts survival in patients with alcohol-associated hepatitis declined for liver transplantation.

Severe alcohol-associated hepatitis (AH) that is nonresponsive to corticosteroids is associated with high mortality, particularly with concomitant acute-on-chronic liver failure (ACLF). Most patients will not be candidates for liver transplantation (LT) and their outcomes are largely unknown. Our aim was to determine the outcomes of these declined candidates and to derive practical prediction models for transplant-free survival applicable at the time of the waitlist decision. We analyzed a database of patients with severe AH who were hospitalized at a LT center from January 2012 to July 2021, using the National Death Index for those lacking follow-up. Clinical variables were analyzed based on the endpoints of mortality at 30, 60, 90, and 180 days. Logistic and Cox regression analyses were used for model derivation. Over 9.5 years, 206 patients with severe AH were declined for LT, mostly for unfavorable psychosocial profiles, with a mean MELD of 33 (±8), and 61% with ACLF. Over a median follow-up of 521 (17.5-1368) days, 58% (119/206) died at a median of 21 (9-124) days. Of 32 variables, only age added prognostic value to MELD and ACLF grade. CLIF-C ACLF score and 2 new models, MELD-Age and ACLF-Age, had similar predictability (AUROC: 0.73, 0.73, 0.72, respectively), outperforming Lille and Maddrey's (AUROC: 0.63, 0.62). In internal cross-validation, the average AUROC was 0.74. ACLF grade ≥2, MELD score >35, and age >45 years were useful cutoffs for predicting increased 90-day mortality from waitlist decision. Only two patients initially declined for LT for AH subsequently underwent LT (1%). Patients with severe AH declined for LT have high short-term mortality and rare rates of subsequent LT. Age added to MELD or ACLF grade enhances survival prediction at the time of waitlist decision in patients with severe AH declined for LT.

Low platelet to high-density lipoprotein ratio predicts poor short-term prognosis in hepatitis B-related acute-on-chronic liver failure

BackgroundAcute-on-chronic liver failure (ACLF) is characterized by a systemic inflammatory response, predominantly associated with hepatitis B virus in the Asia-Pacific region, with a high short-term mortality rate. The platelet to high-density lipoprotein ratio (PHR) has been used to predict the prognosis of patients with various inflammatory diseases. We aim to is to use the PHR to predict the short-term prognosis of patients with HBV-ACLF.MethodIn this study, we retrospectively analyzed clinical data from 270 HBV-ACLF patients. Using logistic regression, we identified independent risk factors for short-term mortality and developed a prognostic model. This model was then validated, compared, and its clinical utility assessed via decision curve analysis (DCA).ResultsAmong the 270 HBV-ACLF patients, 98 patients died within 28 days. The deceased group exhibited a higher proportion of severe hepatic encephalopathy and ascites. Additionally, there was a statistically significant difference (P = 0.046) in the novel inflammation scoring system, PHR, between the two groups. Following stringent variable selection, PHR was identified as a predictive factor for short-term mortality in HBV-ACLF patients using logistic regression analysis (OR: 0.835 (0.756–0.999), P = 0.009), and it exhibited a synergistic effect with certain traditional scores. The prognostic model constructed based on PHR demonstrated a superior ability to predict short-term mortality compared to traditional scores such as Child-Turcotte-Pugh (AUC: 0.889). Evaluation using calibration curves and decision curve analysis (DCA) suggested its practical utility.ConclusionPHR can predict short-term mortality in patients, with a low PHR upon admission being associated with an increased risk of death.

Early living donor liver transplantation for alcohol-associated hepatitis: Status in the era of increasing demand, unmet needs, and future considerations.

Hazardous alcohol consumption is the leading cause of liver disease worldwide. Alcohol-associated hepatitis (AH) is an acute and serious presentation of alcohol-associated liver disease (ALD) that is associated with high short-term mortality. Medical management remains limited to corticosteroid therapy and intensive nutrition but improves survival in less than 50% of individuals. Liver transplantation (LT) is increasingly recognized as a treatment option for many patients with AH and may lead to greater survival benefit than medical management alone. The rate of wait-listings and LTs for AH has doubled in recent years, especially in the US. Several studies from the West have reported early LT for AH to be successful, where deceased donor LT is the norm. The challenges of LT in living donor centers, particularly for those with AH, are unique and have previously not been discussed in depth. In this review, we aim to discuss the challenges unique to LDLT with respect to candidate and donor selection, ethical considerations, disparities in LDLT, post-LT alcohol relapse, and measures to prevent them while also addressing the definitions and outcomes of early-living donor liver LT (eLDLT) for AH.

Clinical and epidemiologic characteristics of hospitalized oncological patients with hypercalcemia: alongitudinal, multicenter study.

There are few studies that have analyzed the characteristics of hypercalcemia in hospitalized oncological patients. Our objectives were to describe the clinical characteristics of hospitalized patients with paraneoplastic hypercalcemia and to identify prognostic variables for mortality. This was an observational, longitudinal, retrospective, and bicentric study. It included adult patients admitted to two hospitals in Málaga, Spain (2014-2018). The minimum follow-up period was 2years or until death. Atotal of 154 patients were included; the majority (71.4%) were admitted to the internal medicine department. The median follow-up was 3.5weeks (interquartile range [IQR] 1.1-11.5). The mean (standard deviation) age was 67.6 (12.3) years, with apredominance of males (58.4%). The median (IQR) serum calcium at admission was 13.2 (11.8-14.6) mg/dl. The most common neoplasms were pulmonary (27.3%), hematologic (23.4%), urological (13%), and breast (12.3%). Furthermore, 56.5% of cases had aknown history of neoplasia at the time of diagnosis. The parathyroid hormone (PTH) level was determined in 24%; of these, 10.8% had elevated levels. In all, 95.5% of patients died during follow-up. The median survival was 3.4weeks (95% confidence interval 2.6-4.3). Factors associated with higher mortality were age, serum calcium at admission, previous history of neoplasia, etiology other than multiple myeloma, and noncorrection of hypercalcemia. In hospitalized patients, paraneoplastic hypercalcemia was associated with high short-term mortality. Several factors associated with aworse prognosis were identified in these patients.

Venous thromboembolism in adrenocortical carcinoma: a retrospective analysis.

Venous thromboembolism (VTE) is a leading cause of death in patients with cancer. Limited data exist about VTE in patients with adrenocortical carcinoma (ACC). The primary objective of this study was to identify the prevalence of VTE in a cohort of patients with ACC. Secondary objectives were to determine the impact of VTE events on overall survival (OS) and to describe the characteristics of VTE in patients with ACC. We retrospectively reviewed data from 289 patients with ACC cared for at a major referral center from February 2010 to June 2022. VTE prevalence was 18.7% (54 events). Thirty patients (55.6%) had pulmonary embolism (PE); 12 patients (22.2%) had deep vein thrombosis (DVT); and 12 patients (22.2%) had both PE and DVT. VTE occurred after ACC diagnosis in 50 patients (92.6%) including 44 patients (88%) with stage 3 or 4 ACC. VTEs were CTCAE grade ≤2 in 32 cases (59.3%), grade 3 in 17 (31.5%), and grade 4 in 2 (3.7%). Thirteen patients (24%) died within 6 months after VTE diagnosis, although there was no statistically significant association between VTE and overall survival. Despite the potential to underestimate the prevalence of VTEs, we found a high frequency of VTE events in patients with ACC. A majority of VTEs occurred in the context of advanced ACC and we observed high short-term mortality. Further studies are needed to validate our findings and investigate mechanisms associated with VTE in ACC.

Endograft Thrombosis as an Indication for Open Conversion after Endovascular Aneurysm Repair in a Multicenter Experience over 25 Years

To describe the outcomes of aortic endograft thrombosis (AET) as an indication for open conversion (OC) after endovascular aortic aneurysm repair (EVAR) in a multicenter experience. This study retrospectively analyzed cases of OC for AET following EVAR across 12 Italian Vascular Surgery centers from 1997 to September 2022. The end points were as follows: 30-day mortality and major postoperative complications. Follow-up data included survival and aortic-related complications. Sixteen patients (mean age: 68.6±8.5years) were included. The median elapsed time between EVAR and OC was 26.46months (interquartile range: 13.8-45.9). Proximal aortic cross-clamping site was supraceliac in 8 out of 16 (50%) patients, and complete removal of the stentgraft was achieved in 75% of cases (12/16 patients). Reconstructions were aorto-bi-iliac grafts in 8 cases (50%), 7 aortobifemoral bypass grafts (43.8%), and 1 aortoaortic tube graft (6.3%). All patients were symptomatic at presentation (68.7% unilateral acute limb ischemia, 25% bilateral acute limb ischemia, 1 patient had chronic severe claudication). Thirty-day mortality was 12.5% (2/16 patients). The overall morbidity rate was 43.8% (7 of 16 patients). No specific risk factors for early mortality were found. The overall estimated survival rate was 80.4% at 1year, 62.5% at 2years, and 41.7% at 3years. OC for AET is typically reserved for complex cases that are not amenable to endovascular solutions. The frequent need for suprarenal clamping and complete endograft removal seems to be associated with high short-term mortality.

Human umbilical cord mesenchymal stem cell transplantation for the treatment of acute-on-chronic liver failure: protocol for a multicentre random double-blind placebo-controlled trial

IntroductionAcute-on-chronic liver failure (ACLF) is a prevalent and life-threatening liver disease with high short-term mortality. Although recent clinical trials on the use of mesenchymal stem cells (MSCs) for ACLF treatment...

A nutrition-based radiomics–clinical model to predict the prognosis of patients with acute-on-chronic liver failure

BackgroundAcute-on-chronic liver failure (ACLF) lead to high short-term mortality. Effective identification of patients with poor prognoses and early intervention are crucial. Meanwhile, the nutritional status of patients is vital in the prognosis of chronic liver diseases. Hence, the study applies artificial intelligence to extract nutrition-based radiomics features in ACLF patients and construct a radiomics-clinical model to predict the 90-day prognosis. Patients and methods163 ACLF patients were recruited from our hospital. The patients were randomly assigned to the training cohort (n = 99) and the test cohort (n = 64). The skeletal muscle, subcutaneous fat and visceral fat radiomics features were extracted. The blood markers were collected. The LASSO regression model was applied to select radiomics features and form the best feature subset. Finally, the linear discriminant classifier was used for endpoint prediction. ResultsIn both the training and test cohorts, 30.3 % and 29.7 % of patients, respectively, experienced disease progression. In the training cohort, this progression included 23.2 % experiencing death and 7.1 % undergoing liver transplantation. Similarly, in the test cohort, 20.3 % experienced death, while 9.4 % underwent liver transplantation. LASSO regression screened 15 features for constructing a radiomics-clinical model, 6 of 15 features were texture features of skeletal muscles. The area under the curve (AUC) of this model in the test cohort was 0.873 (95 % CI 0.773–0.972). To use Delong test compared the AUC of the radiomics-clinical model with sub-models (radiomics model and clinical model) and traditional classical models (MELD and MELD-Na). The results showed that the radiomics-clinical model was superior to any of the above models (p < 0.05). ConclusionThe nutrition-based radiomics-clinical machine learning model can effectively predict the 90-day adverse prognosis of ACLF patients.

Distinct immunometabolic signatures in circulating immune cells define disease outcome in acute-on-chronic liver failure.

Acute-on-chronic liver failure (ACLF) is a complication of cirrhosis characterized by multiple organ failure and high short-term mortality. The pathophysiology of ACLF involves elevated systemic inflammation leading to organ failure, along with immune dysfunction that heightens susceptibility to bacterial infections. However, it is unclear how these aspects are associated with recovery and non-recovery in ACLF. Here we mapped the single-cell transcriptome of circulating immune cells from ACLF-, acute decompensated (AD) cirrhosis patients and healthy individuals. We further interrogate how these findings as well as immunometabolic- and functional profiles associate with ACLF recovery (ACLF-R) or non-recovery (ACLF-NR). Our analysis unveiled two distinct states of classical monocytes (cMon). Hereto, ACLF-R cMons were characterized by transcripts associated with immune- and stress tolerance, including anti-inflammatory genes such as RETN and LGALS1. Additional metabolomic- and functional validation experiments implicated an elevated oxidative phosphorylation metabolic program as well as an impaired ACLF-R cMon functionality. Interestingly, we observed a common stress-induced tolerant state, oxidative phosphorylation program and blunted activation among lymphoid populations in ACLF-R patients. Conversely, ACLF-NR cMon featured elevated expression of inflammatory- and stress response genes such as VIM, LGALS2, and TREM1 along with blunted metabolic activity and increased functionality. This study identifies distinct immuno-metabolic cellular states that contribute to disease outcome in ACLF patients. Our findings provide valuable insights into the pathogenesis of ACLF, shedding light on factors driving either recovery or non-recovery phenotypes which may be harnessed as potential therapeutic targets in the future.

Cancer-associated ischemic stroke: current knowledge and future directions

Because cancer is a strong prothrombotic, there is an increased risk of thromboembolism, which includes ischemic stroke, especially in the first six to twelve months following a cancer diagnosis. The risk of ischemic stroke differs according to the location and stage of cancer. Given that the risk increases prior to a cancer diagnosis, stroke may be the initial sign of occult cancer. Although data on the risk, treatment, and outcomes of cancer-associated stroke are more limited than those on cancer-associated venous thromboembolism, the condition is still recognized as a thrombotic complication of cancer. Up to 10% of ischemic stroke patients also have a concurrent cancer diagnosis, and these patients seem to have higher short-term mortality and morbidity rates. With more people expected to survive longer after cancer treatment and an increasing number of cancer survivors, the burden of stroke among cancer patients is predicted to rise. This narrative review aims to provide an overview of the pathophysiologic mechanisms, treatment options, and epidemiology of ischemic stroke, including cancer screening for those who have cryptogenic (unexplained) stroke.

Sex disparities in mid-term outcomes of ST-segment elevation myocardial infarction across age

Abstract Funding Acknowledgements None. Background Women with ST-segment elevation myocardial infarction (STEMI) have been reported to have higher short-term mortality than men, especially in younger patients. However, data on long-term outcomes did not corroborate this association. Purpose We aimed to evaluate if sex was an independent predictor of major adverse cardio-cerebrovascular events (MACCE) at 1-year follow-up. A sub-analysis across different age subgroups was performed. Methods We retrospectively studied consecutive STEMI patients treated by primary percutaneous coronary intervention (PCI) from January 2008 to December 2017. Cox proportional hazard models were used to identify predictors of MACCE at 1-year follow-up (death, cerebrovascular accident, new myocardial infarction in any vessel, or target lesion revascularization). Patients were divided into four age groups, according to quartiles, for subgroup analysis (≤50, 51-60, 61-70, &amp;gt;71 years). Results Of the 1131 patients included in the study, 291 (25.7%) were women. Women were older [68.2 (±14.2) vs 60.6 (±12.2) years, p&amp;lt;0.001], more often non-smokers (21.5% vs 60.2%, p&amp;lt;0.001), and had a higher prevalence of diabetes (34,8% vs 20.9%, p&amp;lt;0.001) and hypertension (71.6% vs 50.2%, p&amp;lt;0.001). They also had lower haemoglobin [12.8 (±1.6) vs 14.5 (±1.7) g/dl, p&amp;lt;0.001] and lower creatinine clearance at admission [73.8 (±35.3) vs 92.6 (±35.2) ml/min, p&amp;lt;0.001], as well as longer door-to-balloon times [90 (60-166) vs 75(50-120) min, p=0.005]. However, total ischemic time was not significantly different between groups [250(175-480) vs 224(150-440) min, p=0.054]. Overall, women had a higher occurrence of MACCE (22.1% vs 15.4%; log-rank P = 0.008, Figure 1). On multivariate analysis, sex was not found to be an independent predictor of MACCE (HR 1.12; 95% CI, 0.77–1.65; P = 0.547). The risk of unfavourable outcomes was mainly driven by other comorbidities (namely, age, presence of peripheral arterial disease, lower haemoglobin concentration, lower systolic blood pressure on admission, a higher peak CK activity, and the utilization of a femoral approach). When MACCE was stratified by age, sex was not an independent predictor of MACCE in any age group (Figure 2). Conclusion Women with STEMI submitted to PCI had a higher rate of MACCE at 1-year follow-up compared with men, however, sex was not an independent predictor of these events on multivariate analysis, regardless of the age subgroups considered.