Multiple Organ Failure Research Articles

Impact of arginine-vasopressin on regional perfusions in a porcine model of post-resuscitation syndrome

BackgroundPost-cardiac arrest (CA) shock is associated with multiple organ failure, including acute kidney injury, and is the leading cause of early death among patient successfully resuscitated from CA. Arginine-vasopressin (AVP) may be an interesting therapeutic alternative or complement to noradrenaline (NAD) to both control shock and preserve regional, especially renal, organ perfusions. Methods18 swine (24–39 kg) were submitted to 14 min of ventricular fibrillation and cardio-pulmonary resuscitation. After return of spontaneous circulation (ROSC), animals randomly received either AVP, NAD or AVP-NAD combination for maintaining a targeted mean arterial pressure of 70 ± 5 mmHg for 6 h. Haemodynamic and biological parameters, including kidney function biomarkers and diuresis, were monitored throughout the follow-up. ResultsTargeted mean arterial pressure was successfully obtained in the NAD (n = 6) and the AVP-NAD (n = 6) groups, but not in the AVP group (n = 6), where 4 animals died. As compared to NAD alone, renal blood flow (2.9 ± 1.15 vs 4.36 ± 0.64 mL//kg/min in NAD and AVP-NAD groups) and diuresis were higher in the AVP-NAD group. This was associated with a reduction of carotid blood flow and a more severe metabolic acidosis during the first 3 h of follow-up in the AVP-NAD group as compared to NAD group. ConclusionCombination of AVP and NAD improved renal perfusion and diuresis but reduced carotid blood flow as compared to NAD alone in a porcine model of post-resuscitation syndrome. AVP alone failed to manage shock and led to mortality.

Fulminant septic shock due to community-acquired pneumonia caused by Legionella pneumophila SG1 Olda OLDA ST1. Case report.

Legionellers’ desease accounts for 1-8% of cases of severe community-acquired pneumonia (CAP). Legionella spp. Is the causative organism that can result in respiratory failure, multi-organ dysfunction, sepsis, and death. Therefore, rapid diagnosis and efficient treatment are crucial. We report the clinical and microbiology study of a patient with community-acquired pneumonia caused by Legionella pneumophila, with fatal outcome. After death, the strain causing the infection was identified as Legionella pneumophila serogroup 1, Olda OLDA phenotype and sequence-type 1. This is the first reported case of septic shock and death associated with an isolate of these characteristics.

Amidst Cytokine Storm in Metabolic Diseases: Can 2-deoxy-D-glucose (2-DG) Cure COVID-19?

Abstract: The SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2)-related pandemic disease COVID-19, which began in China in 2019, became the leading cause of fatalities globally. The transmission rate of the virus is directly proportional to the so-called ‘dance dynamic’ energy of the spike protein as this phenomenon favours the ligand-receptor binding. The clinical spectrum of the COVID-19 disease, which includes (inflammation, cytokine storm, and multi-organ dysfunction), puts Corona Warriors active in various aspects of the disease, such as the efficient management of critically ill COVID-19 patients, in danger of losing their lives. Due to its effects on an ancient oxygen-independent glycolytic pathway, anti-inflammatory properties, and competitive interaction with viral proteins, 2-deoxy-D-glucose (2-DG), which is being developed in India at the Defence Research and Development Organization (DRDO), has emerged as a ground-breaking agent for COVID-19 treatment. After a virus gains entry into host cells, it is found that metabolic reprogramming takes place to meet the nutritional and energy requirements for virus reproduction. The recent approval of 2-DG for adjunctive emergency usage by the Drug Controller General of India (DCGI) may mark a turning point in the management of mild to moderate COVID-19 infection.

Cadherin-11 targeted cell-specific liposomes enabled skin fibrosis treatment by inducing apoptosis

Continuous and aberrant activation of myofibroblasts is the hallmark of pathological fibrosis (e.g., abnormal wound healing). The deposition of excessive extracellular matrix (ECM) components alters or increases the stiffness of tissue and primarily accounts for multiple organ dysfunctions. Among various proteins, Cadherin-11 (CDH11) has been reported to be overexpressed on myofibroblasts in fibrotic tissues. Anti-apoptotic proteins such as (B cell lymphoma-2) (BCL-2) are also upregulated on myofibroblasts. Therefore, we hypothesize that CDH11 could be a targeted domain for cell-specific drug delivery and targeted inhibition of BCL-2 to ameliorate the development of fibrosis in the skin. To prove our hypothesis, we have developed liposomes (LPS) conjugated with CDH11 neutralizing antibody (antiCDH11) to target cell surface CDH11 and loaded these LPS with a BCL-2 inhibitor, Navitoclax (NAVI), to induce apoptosis of CDH11 expressing fibroblasts. The developed LPS were evaluated for physicochemical characterization, stability, in vitro therapeutic efficacy using dermal fibroblasts, and in vivo therapeutic efficacy in bleomycin-induced skin fibrosis model in mice. The findings from in vitro and in vivo studies confirmed that selectivity of LPS was improved towards CDH11 expressing myofibroblasts, thereby improving therapeutic efficacy with no indication of adverse effects. Hence, this novel research work represents a versatile LPS strategy that exhibits promising potential for treating skin fibrosis.

Severe acute alcoholic pancreatitis complicated by distributive shock, abdominal compartment syndrome, and black pleural effusion

Severe acute pancreatitis (SAP) is a life-threatening medical emergency that can lead to multi-system organ failure and mortality. Here, we highlight a case of SAP complicated by a black pleural effusion (BPE), distributive shock, and acute abdominal compartment syndrome (ACS) requiring emergent decompressive laparotomy. BPE fluid analysis was consistent with previously reported exudative effusions from a pancreatic pseudocyst, though the computed tomography (CT) of abdomen and pelvis did not show definitive evidence of a pseudocyst. In addition, black fluid was also discovered during decompressive laparotomy for ACS. It is possible that the severely elevated intra-abdominal pressure contributed to a temporary translocation/transudation of this fluid from the abdominal cavity into the pleural space, as no re-accumulation of the BPE was observed on a follow-up CT after thoracostomy tube removal.

Clinical manifestations, diagnosis and long-term prognosis of adult autoimmune enteropathy: Experience from Peking Union Medical College Hospital

BACKGROUND Autoimmune enteropathy (AIE) is a rare disease whose diagnosis and long-term prognosis remain challenging, especially for adult AIE patients. AIM To improve overall understanding of this disease’s diagnosis and prognosis. METHODS We retrospectively analyzed the clinical, endoscopic and histopathological characteristics and prognoses of 16 adult AIE patients in our tertiary medical center between 2011 and 2023, whose diagnosis was based on the 2007 diagnostic criteria. RESULTS Diarrhea in AIE patients was characterized by secretory diarrhea. The common endoscopic manifestations were edema, villous blunting and mucosal hyperemia in the duodenum and ileum. Villous blunting (100%), deep crypt lymphocytic infiltration (67%), apoptotic bodies (50%), and mild intraepithelial lymphocytosis (69%) were observed in the duodenal biopsies. Moreover, there were other remarkable abnormalities, including reduced or absent goblet cells (duodenum 94%, ileum 62%), reduced or absent Paneth cells (duodenum 94%, ileum 69%) and neutrophil infiltration (duodenum 100%, ileum 69%). Our patients also fulfilled the 2018 diagnostic criteria but did not match the 2022 diagnostic criteria due to undetectable anti-enterocyte antibodies. All patients received glucocorticoid therapy as the initial medication, of which 14/16 patients achieved a clinical response in 5 (IQR: 3-20) days. Immunosuppressants were administered to 9 patients with indications of steroid dependence (6/9), steroid refractory status (2/9), or intensified maintenance medication (1/9). During the median of 20.5 months of follow-up, 2 patients died from multiple organ failure, and 1 was diagnosed with non-Hodgkin’s lymphoma. The cumulative relapse-free survival rates were 62.5%, 55.6% and 37.0% at 6 months, 12 months and 48 months, respectively. CONCLUSION Certain histopathological findings, including a decrease or disappearance of goblet and Paneth cells in intestinal biopsies, might be potential diagnostic criteria for adult AIE. The long-term prognosis is still unsatisfactory despite corticosteroid and immunosuppressant medications, which highlights the need for early diagnosis and novel medications.

Necrotizing Enterocolitis associated Acute Kidney Injury - transforming the paradigm.

Necrotizing enterocolitis (NEC) is one of the most common conditions requiring emergency surgery in the neonatal intensive care unit and is associated with a septic shock-like state contributing to multi-organ dysfunction. NEC affects 6-10% of very-low birth-weight infants and remains a leading cause of death. The occurrence of severe AKI following surgical NEC is a harbinger of multiple morbidities. This review presents current evidence about the clinical impact of NEC associated AKI on the clinical outcomes. Studies evaluating nephro-protective strategies to prevent AKI and its consequences are greatly needed to improve the post-operative recovery and clinical outcomes in neonates with NEC. Future observational studies and clinical trials in preterm-born infants with NEC prioritize measuring short-term (AKI) and longer term (chronic kidney disease) kidney outcomes. Impact: 1. Severe AKI (stage 2 and 3) occurs in 32.6% of neonates after NEC diagnosis and in 58.7% following surgical NEC diagnosis. 2. NEC associated AKI is associated with severe postoperative course, moderate to severe bronchopulmonary dysplasia, surgical complications, brain injury and longer hospital stay in preterm infants. 3. Severity of NEC associated AKI can be utilized by bedside providers for the prognostication of clinical outcomes in preterm infants.

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.

LYME AND DENGUE FEVER: FROM BANGLADESH TO ITALY

Abstract Background Dengue fever (Flavivirus) and Lyme disease (Borrelia burgdorferi) are rare tropical infectious diseases transmitted by hematophagous vectors (Aedes mosquitoes and ticks, respectively), and they are extremely uncommon in Italy. In European countries, both represent a public health concern as they manifest as imported diseases. Case Report A 54–year–old man from Bangladesh was admitted with symptoms of fever, dyspnea, and pericarditic chest pain. Laboratory and imaging examinations revealed severe acute respiratory failure secondary to left lower lobe pneumonia and pleuropericardial effusion. Broad–spectrum antibiotic therapy and anti–inflammatory treatment were initiated, suspecting para–pneumonic pleuropericarditis. During hospitalization, there was a gradual improvement with a reduction in inflammatory indices and resolution of lung consolidation. The patient was discharged after 14 days with anti–inflammatory therapy (ibuprofen and colchicine). Approximately 7 days later, the patient returned to the emergency department complaining of a recurrence of symptoms and fatigue. The EKG showed phases of 2:1 AV block, EAS and EPS, complete de novo left bundle branch block (LBBB), alternating with an escape atrial rhythm, not evident in previous EKG. During hospitalization, complete AV block emerged with prolonged asystolic phases, requiring urgent placement of a temporary pacemaker. Concurrently, blood tests revealed anemia and increased levels of inflammatory markers, troponin, creatinine, transaminases, cholestatic indices, LDH, and lipase, indicative of multiple organ failure (MOF). Acute pathologies or active bleeding were ruled out by total body CT with contrast. Blood cultures and serological tests were performed to exclude infections by Trichinella, Mycoplasma, Borrelia, Dengue, and other rare infectious diseases. Due to progressive deterioration, the patient was transferred to a tertiary care hospital. In the following days, laboratory results showed positive IgG and IgM for Dengue (without serological evidence of viral RNA) and positive IgG and IgM antibodies for Borrelia burgdorferi. Conclusion In Italy, the incidence of these diseases is low, and their coexistence in the same host is even rarer (if not anecdotal). However, coinfection cannot be excluded in patients from areas where these diseases are endemic, such as Bangladesh.

MYOCARDIAL AND PERICARDIAL DISEASES INCIDENCE IN COVID

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS–CoV–2), also referred to as COVID–19, was declared a pandemic by the World Health Organization in March 2020. The manifestations of COVID–19 are widely variable and range from asymptomatic infection to multi–organ failure and death. Like other viral illnesses, acute myocarditis and/or pericarditis has been reported to be associated with COVID–19 infection. The guidelines for the diagnosis of COVID–19 introduced the echocardiogram for diagnosis of carditis in these patients. Purpose In our study we investigated the incidences of myocarditis and/or pericarditis in a consecutive series of 1540 Athletes undergo to agonostic certification that performed echocardiogram, and subdivided the incidence of carditis depend on the period and the possible subtype of the covid (alpha, beta, gamma, delta, epsilon). Methods From March 2020 to October 2022 we enrolled in this epidemiological evaluation 1540 patients that was affected by COVID. Every patients was admitted to ambulatory of sport medicine of 2 Italian centres on the major islands to perform a return to play agonist certificate. Overall, 69% males and 31%. females were enrolled with a mean age of 24.3 years (12–67 years). None presented a risk factor of a cardiac disease. Results The incidence of Echocardiographic abnormality was 3,2% in our population The kind and the incidence of alteration was showed in table 1, and consist in dilated cardiomiopathy (0,4%), regional cinetic dysfunction (0,4%), pericardial effusion (1,9%), aspecific alterations (0,2%). Based on the period we evaluated the incidence of the echocardiographic alterations during the seasons and in corralation of variant of COVID . The results was showed in figure 1. Conclusions Based on our evalution the incidence of echocardiographic findings in COVID was 3,2% in all period, with a progressive reduction long the time, from alpha variant to epsilon variant.

Increasing Eligibility to Transplant Through the Selective Cytopheretic Device: A Review of Case Reports Across Multiple Clinical Conditions.

A stable, minimum physiological health status is required for patients to qualify for transplant or artificial organ support eligibility to ensure the recipient has enough reserve to survive the perioperative transplant period. Herein, we present a novel strategy to stabilize and improve patient clinical status through extracorporeal immunomodulation of systemic hyperinflammation with impact on multiple organ systems to increase eligibility and feasibility for transplant/device implantation. This involves treatment with the selective cytopheretic device (SCD), a cell-directed extracorporeal therapy shown to adhere and immunomodulate activated neutrophils and monocytes toward resolution of systemic inflammation. In this overview, we describe a case series of successful transition of pediatric and adult patients with multiorgan failure to successful transplant/device implantation procedures by treatment with the SCD in the following clinical situations: pediatric hemophagocytic lymphohistiocytosis, and adult hepatorenal and cardiorenal syndromes. Application of the SCD in these cases may represent a novel paradigm in increasing clinical eligibility of patients to successful transplant outcomes.

Clinical Presentation and Risk Factors of Acalculous Cholecystitis in Outpatients, a Literature Review and Retrospective Study

Abstract Background Acute acalculous cholecystitis in healthy patients is relatively understudied. It is usually described in patients within the intensive care unit, where it is associated with high mortality rates reaching 30%-50% in the literature. Aims To review patients who have developed AAC in outpatient or non-ICU settings, identify risk factors and clinical presentation, and compare these data with those in the literature. Methods We first performed a literature review. We then determined the inclusion criteria: acalculous cholecystitis confirmed by either an ultrasound, or CT scan, at pathology and intraoperatively. We excluded all patients hospitalized within the ICU or who developed AAC because of multiorgan failure or patients without histopathological evidence. We performed a 5-year search in our institution’s database with the terms “cholecystitis” and “acalculous cholecystitis. Results 23 patients were included in our study based on histopathology. The most frequent co-morbidities were cardiovascular and metabolic syndrome. The most common complaint was abdominal pain, ten patients (50%) presented to the emergency department with an increase of at least two of three biological markers (CRP, bilirubine and leucocytosis). We had no mortality reported at 30 days. Conclusion Epidemiologically, our population’s characteristics correspond to those of other studies, with most patients being male. The majority of patients were ASA III suggesting that this disease concerns more polymorbid patients despite a high percentage of healthy patients. Right upper quadrant pain, whether associated with leukocytosis or not, seems to be the main factor leading to further investigation. Abdominal US is considered the diagnostic technique of choice. However, most patients in our study underwent US and CT. We found that acalculous cholecystitis in outpatients, does not have the high mortality rate that was previously attributed to it, but is more frequent in polymorbid patients with cardiovascular risk factors.

Time to split: biomarker trajectories in pediatric acute respiratory distress syndrome hint at underlying disease.

Pediatric acute respiratory distress syndrome (ARDS) is severe, noncardiac hypoxemic respiratory failure that carries a substantial risk of death. Given the complexity of this clinically defined syndrome and the repeated failure of therapeutic trials, there has been an effort to identify subphenotypes of ARDS that may share targetable mechanisms of disease. In this issue of the JCI, Yehya and colleagues measured 19 plasma biomarkers in 279 children over the first seven days of ARDS. Increases in select tissue injury makers and inflammatory cytokines in peripheral blood were associated with multiple organ dysfunction syndrome and death, but not persistent ARDS. These findings argue that splitting patients by clinical and molecular phenotype may be more informative than lumping them under the umbrella diagnosis of ARDS. However, future studies are needed to determine whether these plasma factors represent targetable pathways in lung injury or are a consequence of systemic organ dysfunction.

Therapeutic plasma exchange in critically ill children: A single center experience.

Therapeutic plasma exchange (TPE) is used in a wide spectrum of diseases in critically ill pediatric patients. We aim to review the indications, complications, safety, and outcomes of critically ill children who received TPE. All of the TPE procedures performed in a pediatric intensive care unit providing tertiary care during 19 years (January 2013-January 2023) were evaluated retrospectively. A total of 154 patients underwent 486 TPE sessions. Median age was 6 years (2-12.5) and 35 children had a body weight of <10 kg (22.7%). Number of organ failure was 4 (2-6). Liver diseases were the most common indication for TPE (31.2%) followed by sepsis with multiorgan dysfunction syndrome (27.3%). Overall survival rate was 72.7%. The highest mortality was observed in hemophagocytic lymphohistiocytosis group. Non-survivors had significantly higher number of organ failure (p < 0.001), higher PRISM score (p < 0.001), and higher PELOD score on admission (p < 0.001). Adverse events were observed in 68 (13.9%) sessions. Hypotension (7.8%) and hypocalcemia (5.1%) were the most frequent adverse events. TPE is safe for critically ill pediatric patients with experienced staff. Survival rate may vary depending on the underlying disease. Survival decreases with the increase in the number of failed organs.

CD5L as a promising biological therapeutic for treating sepsis

Sepsis results from systemic, dysregulated inflammatory responses to infection, culminating in multiple organ failure. Here, we demonstrate the utility of CD5L for treating experimental sepsis caused by cecal ligation and puncture (CLP). We show that CD5L’s important features include its ability to enhance neutrophil recruitment and activation by increasing circulating levels of CXCL1, and to promote neutrophil phagocytosis. CD5L-deficient mice exhibit impaired neutrophil recruitment and compromised bacterial control, rendering them susceptible to attenuated CLP. CD5L-/- peritoneal cells from mice subjected to medium-grade CLP exhibit a heightened pro-inflammatory transcriptional profile, reflecting a loss of control of the immune response to the infection. Intravenous administration of recombinant CD5L (rCD5L) in immunocompetent C57BL/6 wild-type (WT) mice significantly ameliorates measures of disease in the setting of high-grade CLP-induced sepsis. Furthermore, rCD5L lowers endotoxin and damage-associated molecular pattern (DAMP) levels, and protects WT mice from LPS-induced endotoxic shock. These findings warrant the investigation of rCD5L as a possible treatment for sepsis in humans.

Algorithms for predicting COVID outcome using ready-to-use laboratorial and clinical data

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging crisis affecting the public health system. The clinical features of COVID-19 can range from an asymptomatic state to acute respiratory syndrome and multiple organ dysfunction. Although some hematological and biochemical parameters are altered during moderate and severe COVID-19, there is still a lack of tools to combine these parameters to predict the clinical outcome of a patient with COVID-19. Thus, this study aimed at employing hematological and biochemical parameters of patients diagnosed with COVID-19 in order to build machine learning algorithms for predicting COVID mortality or survival. Patients included in the study had a diagnosis of SARS-CoV-2 infection confirmed by RT-PCR and biochemical and hematological measurements were performed in three different time points upon hospital admission. Among the parameters evaluated, the ones that stand out the most are the important features of the T1 time point (urea, lymphocytes, glucose, basophils and age), which could be possible biomarkers for the severity of COVID-19 patients. This study shows that urea is the parameter that best classifies patient severity and rises over time, making it a crucial analyte to be used in machine learning algorithms to predict patient outcome. In this study optimal and medically interpretable machine learning algorithms for outcome prediction are presented for each time point. It was found that urea is the most paramount variable for outcome prediction over all three time points. However, the order of importance of other variables changes for each time point, demonstrating the importance of a dynamic approach for an effective patient’s outcome prediction. All in all, the use of machine learning algorithms can be a defining tool for laboratory monitoring and clinical outcome prediction, which may bring benefits to public health in future pandemics with newly emerging and reemerging SARS-CoV-2 variants of concern.

Expanding phenotype of MED13-associated syndrome presenting novel de novo missense variant in a patient with multiple congenital anomalies

BackgroundWhole exome sequencing allows rapid identification of causative single nucleotide variants and short insertions/deletions in children with congenital anomalies and/or intellectual disability, which aids in accurate diagnosis, prognosis, appropriate therapeutic interventions, and family counselling. Recently, de novo variants in the MED13 gene were described in patients with an intellectual developmental disorder that included global developmental delay, mild congenital heart anomalies, and hearing and vision problems in some patients.ResultsHere we describe an infant who carried a de novo p.Pro835Ser missense variant in the MED13 gene, according to whole exome trio sequencing. He presented with congenital heart anomalies, dysmorphic features, hydrocephalic changes, hypoplastic corpus callosum, bilateral optic nerve atrophy, optic chiasm atrophy, brain stem atrophy, and overall a more severe condition compared to previously described patients.ConclusionsTherefore, we propose to expand the MED13-associated phenotype to include severe complications that could end up with multiple organ failure and neonatal death.

Oroxylin A-induced Trained Immunity Promotes LC3-associated Phagocytosis in Macrophage in Protecting Mice Against Sepsis.

Sepsis is defined as a dysregulated host response to infection that leads to multiorgan failure. Innate immune memory, i.e., "trained immunity", can result in stronger immune responses and provide protection against various infections. Many biological agents, including β-glucan, can induce trained immunity, but these stimuli may cause uncontrolled inflammation. Oroxylin A (OA) is an active flavonoid compound that is derived from Scutellaria baicalensis.OA is an agonist for inducing trained immunity in vivo and in vitro, and β-glucan was used as a positive control. The protective effects of OA-induced trained immunity were evaluated in mouse models that were established by either lipopolysaccharide (LPS) administration or caecal ligation and puncture (CLP). The expression of inflammatory factors and signaling pathway components involved in trained immunity was evaluated in vitro using qRT‒PCR, western blotting (WB) and enzyme-linked immunosorbent assay (ELISA). Flow cytometry and confocal microscopy were used to examine reactive oxygen species (ROS) levels and phagocytosis in trained macrophages. A PCR array was used to screen genes that were differentially expressed in trained macrophages.Here, we revealed that OA alleviated sepsis via trained immunity. OA-treated macrophages displayed increased glycolysis and mTOR phosphorylation, and mTOR inhibitors suppressed OA-induced trained immunity by effectively reprogramming macrophages. The PCR array revealed key genes in the mTOR signaling pathway in OA-treated macrophages. Furthermore, OA targeted the Dectin-1-syk axis to promote LC3-associated phagocytosis (LAP) by trained macrophages, thereby enhancing the ability of these macrophages to protect against infection. This ability could be transferred to a new host via the adoptive transfer of peritoneal macrophages.This study is the first to provide new insights into the potential of OA-induced trained immunity to be used as a strategy to protect mice against sepsis by promoting LAP by macrophages.

Severe fever with thrombocytopenia syndrome with central nervous system symptom onset: a case report and literature review

BackgroundSevere fever with thrombocytopenia syndrome (SFTS) is a natural focal disease transmitted mainly by tick bites, and the causative agent is SFTS virus (SFTSV). SFTS can rapidly progress to severe disease, with multiple-organ failure (MOF) manifestations such as shock, respiratory failure, disseminated intravascular coagulation (DIC) and death, but cases of SFTS patients with central nervous system (CNS) symptoms onset and marked persistent involuntary shaking of the perioral area and limbs have rarely been reported.Case presentationA 69-year-old woman with fever and persistent involuntary shaking of the perioral area and limbs was diagnosed with SFTS with CNS symptom onset after metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) and peripheral blood identified SFTSV. The patient developed a cytokine storm and MOF during the course of the disease, and after aggressive antiviral, glucocorticoid, and gamma globulin treatments, her clinical symptoms improved, her laboratory indices returned to normal, and she had a good prognosis.ConclusionThis case gives us great insight that when patients with CNS symptoms similar to those of viral encephalitis combined with thrombocytopenia and leukopenia are encountered in the clinic, it is necessary to consider the possibility of SFTS involving the CNS. Testing for SFTSV nucleic acid in CSF and blood (mNGS or polymerase chain reaction (PCR)) should be carried out, especially in critically ill patients, and treatment should be given accordingly.

Urosepsis 30-day mortality, morbidity, and their risk factors: SERPENS study, a prospective, observational multi-center study

PurposeTo provide a descriptive report of mortality and morbidity in the first 30 days of diagnosis of urosepsis. Secondary aim is to identify risk factors of unfavourable outcomes.MethodsProspective observational multicentre cohort study conducted from September 2014 to November 2018 in European hospitals. Adult patients (≥ 18 years) diagnosed with acute urosepsis according to Sepsis-2 criteria with confirmed microbiological infection were included. Outcomes were classified in one of four health states: death, multiple organ failure, single organ failure, and recovery at day 30 from onset of urosepsis. Descriptive statistics and ordinal logistic regression analysis was performed.ResultsThree hundred and fifty four patients were recruited, and 30-day mortality rate was 2.8%, rising to 4.6% for severe sepsis. All patients who died had a SOFA score of ≥ 2 at diagnosis. Upon initial diagnosis, 79% (n = 281) of patients presented with OF. Within 30 days, an additional 5% developed OF, resulting in a total of 84% affected. Charlson score (OR 1.14 CI 1.01–1.28), patients with respiratory failure at baseline (OR 2.35, CI 1.32–4.21), ICU admission within the past 12 months (OR 2.05, CI 1.00–4.19), obstruction causative of urosepsis (OR 1.76, CI 1.02–3.05), urosepsis with multi-drug-resistant(MDR) pathogens (OR 2.01, CI 1.15–3.53), and SOFA baseline score ≥ 2 (OR 2.74, CI 1.49–5.07) are significantly associated with day 30 outcomes (OF and death).ConclusionsImpact of comorbidities and MDR pathogens on outcomes highlights the existence of a distinct group of patients who are prone to mortality and morbidity. These findings underscore the need for the development of pragmatic classifications to better assess the severity of UTIs and guide management strategies.Study registration: Clinicaltrials.gov registration number NCT02380170.