Organ System Failure Research Articles

Siderophore-Functionalized Nanodrug for Treating Antibiotic-Resistant Bacteria.

The development of nanodrugs targeting multidrug-resistant bacteria, while sparing the beneficial constituents of the microbiome, has emerged as a promising approach to combat disease and curb the rise of antimicrobial resistance. In this investigation, we devised a siderophore-functionalized nanodrug based on a gold nanoparticle construct (AuNP-NSC; Gold nanoparticle_N-heterocyclic_Siderophore_Cyanine7), offering an innovative treatment modality against drug-resistant bacterial pathogens. As a proof of concept, the efficacy of this nanodrug delivery and antimicrobial therapy was evaluated against the notoriously resistant bacterium P. aeruginosa. N-Heterocyclic carbenes (NHCs) exhibit a strong affinity for transition metals, forming highly stable complexes resistant to ligand displacement. The entry of siderophore-conjugated nanodrugs into bacteria is facilitated through specific receptors on the outer membrane. In our study, AuNP-NSC was specifically targeted and imported into resistant Gram-negative P. aeruginosa via binding with ferric iron. Treatment with the developed nanodrug significantly inhibited the proliferation of antibiotic-resistant P. aeruginosa, reducing bacterial counts by more than 95% and mitigating drug resistance. Furthermore, AuNP-NSC markedly diminished P. aeruginosa-induced skin lesions and forestalled systemic organ failure triggered by secondary sepsis in mouse models. These findings underscore the potential of nanodrugs as specialized therapeutic agents for the management of antibiotic-resistant bacterial infections.

NEUROVASCULAR DYSREGULATION IN PREECLAMPSIA- PATHOPHYSIOLOGY AND CLINICAL IMPLICATIONS

After 20 weeks of pregnancy, proteinuria and new-onset hypertension are hallmarks of preeclampsia, a complex hypertensive pregnancy disease that frequently coexists with systemic organ failure. It continues to be a major cause of maternal and newborn morbidity and mortality, affecting 5–8% of pregnancies worldwide, especially in environments with low resources. Although it has historically been associated with placental malfunction, mounting data indicates a substantial neurovascular involvement, including disruption of the blood-brain barrier (BBB), neuroinflammation, and oxidative stress, which results in cerebral edema, ischemia, and bleeding. Headaches, seizures, visual abnormalities, and posterior reversible encephalopathy syndrome (PRES) are examples of neurological symptoms. The characteristics of preeclampsia, a complicated hypertensive pregnancy syndrome that often coexists with systemic organ failure, are proteinuria and new-onset hypertension after 20 weeks of pregnancy. It still accounts for 5–8% of pregnancies globally, particularly in low-resource settings, and is a leading cause of maternal and neonatal morbidity and mortality. Growing evidence suggests a significant neurovascular involvement, including disruption of the BBB, neuroinflammation, and oxidative stress, which leads to cerebral edema, ischemia, and bleeding, despite its historical association with placental dysfunction. Neurological symptoms include visual problems, headaches, seizures, and PRES. Long-term monitoring, supportive care, and neuroprotective techniques are crucial, especially for cardiovascular risks and postpartum problems. The burden of preeclampsia can be lessened by addressing health inequities and including preventive care. Its neurovascular and systemic interactions warrant more investigation in order to develop novel therapeutic strategies that will eventually enhance the results for mothers and newborns. KEYWORDS: Neurovascular dysregulation, preeclampsia, brain-blood barrier, Angiogenic dysregulation, Oxidative stress.

Conjugated bile acids alleviate acute pancreatitis through inhibition of TGR5 and NLRP3 mediated inflammation

IntroductionSevere acute pancreatitis (SAP) is a crucial gastrointestinal disease characterized by systemic inflammatory responses and persistent multiple organ failure. The role of bile acids (BAs) in diverse inflammatory diseases is increasingly recognized as crucial, but the underlying role of BA conjugation remains elusive.ObjectivesOur study aim to investigate the potential role of conjugated bile acids in SAP and reveal the molecular mechanisms underlying its regulatory effects. We hypothesized that taurochenodeoxycholic acid (TCDCA) and glycochenodeoxycholic acid (GCDCA) could protect SAP through inhibiting the activation of NLRP3 inflammasomes via the TGR5 pathway in macrophages.MethodsTo test our hypothesis, we used BA-CoA: amino acid N-acyltransferase knockout (Baat−/−) mice and established SAP mouse models using caerulein- and sodium taurocholate- induced. We utilized a range of methods, including pathology sections, qRT-PCR, immunofluorescence, Western blotting, and ELISA, to identify the mechanisms of regulation.ResultsBA-CoA: Amino acid N-acyltransferase knockout (Baat−/−) mice significantly exacerbated pancreatitis by increasing pancreatic and systemic inflammatory responses and pancreatic damage in SAP mouse models. Moreover, the serum TCDCA levels in Baat−/− mice were lower than those in wild-type (WT) mice with or without SAP, and GCDCA and TCDCA showed stronger anti-inflammatory effects than chenodeoxycholic acid (CDCA) in vitro. TCDCA treatment alleviated SAP in a Takeda G protein-coupled receptor 5 and NOD-like receptor family, pyrin domain containing 3—dependent manner in vivo. Reinforcing our conclusions from the mouse study, clinical SAP patients exhibited decreased serum content of conjugated BAs, especially GCDCA, which was inversely correlated with the severity of systemic inflammatory responses.ConclusionConjugated bile acids significantly inhibit NLRP3 inflammasome activation by activating TGR5 pathway, thereby alleviating pancreatic immunopathology. The results provide new insights into the variability of clinical outcomes and paves the way for developing more effective therapeutic interventions for AP.

Identification of cuproptosis-related genes in septic shock based on bioinformatic analysis.

Septic shock is a life-threatening condition characterized by a failure of organ systems and a high mortality rate. Cuproptosis is a new form of cell death that is triggered by copper overload. However, the relationship between cuproptosis-related genes and septic shock remains unclear. The GSE26440 dataset from the GEO database was used to screen differentially expressed genes (DEGs) between control and septic shock samples. Additionally, hub genes related to the progression of septic shock and cuproptosis were screened by Venn analysis. RT-qPCR was utilized to validate the expression of hub genes in peripheral blood lymphocytes from septic shock patients and healthy controls. Next, functional analysis and immune cells infiltration were performed. SLC31A1 and MTF1 levels were obviously elevated and LIAS and LIPT1 levels were downregulated in septic shock samples, compared to normal controls. The diagnostic values of the four genes were confirmed with receiver operating characteristic (ROC) curves. Additionally, SLC31A1 and MTF1 showed a positive correlation with natural killer cells and LIAS and LIPT1 exhibited a positive correlation with CD8+ T cells. Furthermore, compared to low-level groups, MAPK signaling was activated in the high-SLC31A1 level group, VEGF signaling was activated in the high-MTF1 level group and lipoic acid metabolism was activated in high-LIAS and high-LIPT1 level groups. This study demonstrates that SLC31A1, MTF1, LIAS, and LIPT1 are dysregulated in septic shock samples, and these genes exhibit potential diagnostic efficacy in septic shock, suggesting that these genes may be potential biomarkers for the diagnosis of septic shock.

Early identification of non-occlusive acute mesenteric ischemia

Acute mesenteric ischemia (AMI) is insidious in the early stage of the disease, and once ischemia reaches the late stage, irreversible intestinal necrosis and even multiple system organ failure occur, ultimately leading to death. Early diagnosis and intervention are the key to improving the outcome of AMI. Intensive care unit (ICU) patients mostly present with non-occlusive mesenteric ischemia (NOMI) due to hypoperfusion. This article reviews the high risk factors, clinical manifestations, biomarkers, and imaging examinations of AMI in order to provide ideas for clinicians in the early identification of this disease.

An initial exploratory clinical study and outcome assessment of gastrointestinal surgeries using advanced robotic-assisted techniques.

In addition to the Da Vinci surgical robot, domestic surgical robots are being developed rapidly. Chinese Toumai® laparoscopic surgical robot was approved for urological surgery in 2022.This study aims to systematically evaluate the safety and efficacy of the Toumai® robotic surgical system in performing complex gastrointestinal surgeries. This prospective, single-center, single-arm exploratory study was conducted at Gansu Provincial Hospital between June 2022 and October 2023, enrolling 12 patients undergoing gastrectomyand 9 patients undergoing colorectal resection. The primary endpoints are oncological outcomes and surgical success rates, while secondary endpoints encompassed intraoperative blood loss, operative duration, complication rates, system performance metrics, length of hospital stay, and postoperative pain levels. All patients successfully underwent robotic-assisted surgery with adequate oncological resection and favorable postoperative outcomes. There were no conversions to open or laparoscopic surgery, resulting in a 100% procedural success rate. The median docking time for radical gastrectomy was 17.50 (14.25, 21.50) minutes, with a median master-slave control time of 121.50 (105.50, 172.00) minutes, median intraoperative blood loss of 100.00 (50.00, 275.00) mL, and a median postoperative hospital stay of 9.00 (7.25, 10.75) days. For radical colorectal surgery, the median docking time was 22 (17.50, 30.50) minutes, the median master-slave control time was 68 (56.50, 119.00) minutes, with a median blood loss of 50 (50.00, 150.00) mL, and a median postoperative hospital stay of 7 (7.00, 10.00) days. No intraoperative organ injury, mortality, system failure, or severe postoperative complications were reported. These preliminary findings provide compelling evidence supporting the safety and efficacy of the Toumai® laparoscopic surgical robotic system in performing gastric and colorectal surgeries.

Etiologies and Outcomes Following Duodenal Perforation in Acute Peritonitis: A Systematic Review.

Duodenal perforation often presents as an acute onset of abdominal pain and potential complications such as systemic infection, multiple organ system failure, and even death. It can result from various causes, including peptic ulcer disease (PUD), trauma, malignancies, and infections. Prompt diagnosis and timely intervention are critical for better outcomes, though mortality can be high, particularly in delayed cases. This systematic review aims to synthesize available literature on the etiologies and outcomes associated with duodenal perforation presenting as acute peritonitis, offering a comprehensive overview for guiding effective management strategies. A systematic search was conducted across electronic databases including PubMed, CINAHL, andGoogle Scholar to identify relevant studies published up to August 2024. Inclusion criteria comprised observational studies, case reports, and case series on duodenal perforation in acute peritonitis. Review articles and non-English language studies were excluded. Two reviewers independently performed data extraction with the opinion of a third reviewer to resolve controversies. Information was gathered on study characteristics, patient demographics, etiology, treatment, and outcomes. A total of 18 studies with 536 participants were included, encompassing a diverse patient population. The primary etiologies identified were PUD, trauma, foreign body, and iatrogenic causes. Treatment approaches ranged from conservative management to surgical interventions, with outcomes varying based on the underlying cause and timeliness of treatment. Postoperative complications were significant, including wound infections, anastomotic leaks, and, in severe cases, multiorgan failure. Mortality was largely associated with delayed intervention. Despite advancements in surgical techniques, the condition still carries a significant risk of complications and mortality, underscoring the need for timely and effective medical care. Future research should focus on developing standardized guidelines to optimize the management of duodenal perforations and reduce associated morbidity and mortality.

On-demand imidazolidinyl urea-based tissue-like, self-healable, and antibacterial hydrogels for infectious wound care

Bacterial wound infections are a growing challenge in healthcare, posing severe risks like systemic infection, organ failure, and sepsis, with projections predicting over 10 million deaths annually by 2050. Antibacterial hydrogels, with adaptable extracellular matrix-like features, are emerging as promising solutions for treating infectious wounds. However, the antibacterial properties of most of these hydrogels are largely attributed to extrinsic agents, and their mechanisms of action remain poorly understood. Herein we introduce for the first time, modified imidazolidinyl urea (IU) as the polymeric backbone for developing tissue-like antibacterial hydrogels. As-designed hydrogels behave tissue-like mechanical features, outstanding antifreeze behavior, and rapid self-healing capabilities. Molecular dynamics (MD) simulation and density functional theory (DFT) calculation were employed to well-understand the extent of H-bonding and metal-ligand coordination to finetune hydrogels’ properties. In vitro studies suggest good biocompatibility of hydrogels against mouse fibroblasts & human skin, lung, and red blood cells, with potential wound healing capacity. Additionally, the hydrogels exhibit good 3D printability and remarkable antibacterial activity, attributed to concentration dependent ROS generation, oxidative stress induction, and subsequent disruption of bacterial membrane. On top of that, in vitro biofilm studies confirmed that developed hydrogels are effective in preventing biofilm formation. Therefore, these tissue-mimetic hydrogels present a promising and effective platform for accelerating wound healing while simultaneously controlling bacterial infections, offering hope for the future of wound care.

فرط فيرتين الدم كمتنبئ محتمل لشدة الإصابة بفيروس كورونا COVID-19 وارتفاع معدل الوفيات لدى عينة من مرضى مستشفى الحجر الصحي في مدينة أجدابيا / ليبيا

The COVID-19 pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has resulted in unprecedented global social and economic impacts. The disease is accompanied by a cytokine storm syndrome, which is an uncontrolled immune response characterized by the release of large quantities of inflammatory cytokines, including TNF-α, IL-6, IL-12, and IL-8, during the progression of the illness. This response leads to acute respiratory distress syndrome and systemic organ failure. Evidence suggests that serum levels of ferritin, D-dimer, and lactate dehydrogenase also increase during disease exacerbation, indicating a heightened risk of mortality. Serum ferritin serves as a marker of lymphocytic proliferation by phagocytosis, known as a complication of viral infections. Hyperferritinemia resulting from excessive inflammation due to viral infection is associated with an increased risk of admission to the intensive care unit and shows a close correlation with poor patient recovery and higher mortality rates. This study aimed to examine the association between serum ferritin levels and the severity of viral infection and mortality rate. The results indicated that older patients (>65 years) had elevated ferritin levels (876.857 ± 377.08) compared to younger patients (<65 years) (634.243 ± 282.140) (p < 0.05). Additionally, the results showed no significant difference between males and females in ferritin levels (p > 0.05). Furthermore, diabetic patients and those with hypertension exhibited higher ferritin levels (710.458 ± 283.62 and 637.810 ± 256.329, respectively) compared to patients without comorbidities (502.82 ± 160.72) (p > 0.05). KEYWORD: COVID-19,hyperferritinemia, potential predictor, mortality, severity.

Machine learning−derived multivariable predictors of postcardiotomy cardiogenic shock in high-risk cardiac surgery patients

ObjectiveTo develop a model for preoperatively predicting postcardiotomy cardiogenic shock (PCCS) in patients with poor left ventricular (LV) function undergoing cardiac surgery. MethodsFrom the Society of Thoracic Surgeons Adult Cardiac Database, 11,493 patients with LV ejection fraction ≤35% underwent isolated on-pump surgery from 2018 through 2019, of whom 3428 experienced PCCS. In total, 68 preoperative clinical variables were considered in machine-learning algorithms trained and optimized using scikit-learn software. ResultsCompared with patients with ideal recovery, those that did were younger (65 vs 67 years), more likely female, Black, with low LV ejection fraction (26.5 vs 28.9%), previous myocardial infarction, chronic lung disease, diabetes, reoperation, or advanced heart failure. Among those with PCCS versus ideal recovery, operative mortality was 27% (925/3428) versus 0.1% (5/8065). PCCS occurred more often after coronary artery bypass grafting with concomitant mitral valve repair or after longer perfusion and clamp times. Reliable preoperative PCCS predictors were more advanced cardiac, liver, and renal failure; frailty; and greater white cell count. Out of sample test set receiver operating curve achieved an area under the curve of 0.74 with acceptable calibration Hosmer-Lemeshow statistic χ2 = 1.33, P = .25. ConclusionsIn patients with severe LV dysfunction undergoing cardiac surgery, risk of PCCS is elevated by preoperative failure of other organ systems and complexity of the planned operation that prolongs myocardial ischemia and cardiopulmonary bypass. This risk calculator could serve as an important tool to preoperatively identify patients in need of advanced levels of support.

Unraveling the immune response of the spleen in sepsis using green-synthesized silver nanoparticles from pomegranate peel extracts.

Sepsis is a serious disease characterized by an inappropriate host response to infection, resulting in widespread inflammation and systemic organ failure. The aim of this research is to investigate the possibility of pomegranate peel-derived silver nanoparticles (PGNP) as a potential alternative therapy for sepsis. Characterization using transmission electron microscopy revealed 10-30 nm spherical nanoparticles. In a rat model of sepsis, PGNP treatment improved spleen health, histology, and immune response as compared with septic rats. In rats treated with PGNP during sepsis, significant alterations in oxidative stress markers (p < .01) were observed. These included elevated levels of glutathione (0.63 ± 0.08 mmol/mg protein), reduced concentrations of nitric oxide (8.7 ± 0.8 μ mol/mg protein) and malondialdehyde (2.2 ± 0.3 nmol/mg protein), as well as increased activity of superoxide dismutase (159 ± 33 U/mg protein). Following PGNP administration, gene expression analysis revealed a decrease in spleen IL-1β, IL-6, and TNF-α, highlighting its anti-inflammatory potential. Furthermore, PGNP effectively controlled apoptosis-related genes (Bax, Bcl-2, and Casp3), indicating its role in cellular survival pathways. This study sheds light on the immunological regulation of the spleen during sepsis using PGNP, demonstrating its potential as a new effective treatment approach. The study emphasizes the necessity of continuing to investigate and develop alternative medicines, particularly in light of antibiotic resistance and the global impact of sepsis. RESEARCH HIGHLIGHTS: The study explored the potential medicinal benefits of pomegranate peel-derived silver nanoparticles (PGNP) in the treatment of sepsis. PGNP suppressed pro-inflammatory cytokines and enhanced the immune response. The study recommends PGNP as a viable substitute treatment.

Comprehensive management of a child with X-linked lymphoproliferative disease undergoing stem cell transplantation: a case report

An uncommon immunodeficiency disease known as X-linked lymphoproliferative disease (XLP) has been associated with severe immunological dysfunction and a high susceptibility to Epstein-Barr virus (EBV) infections. This case report describes a four-year-old boy who had X-linked lymphoproliferative illness and died from multiple system organ failure (MSOF) after receiving treatment with a haploidentical hematopoietic stem cell transplant (halo-HSCT). While providing care in such circumstances, rational-based care, prompt identification, primary nursing care, health education, and emotional assistance for parents of individuals with X-linked lymphoproliferative diseases are vital.

Barriers and facilitators when seeking healthcare for septic children in Ghana: a single-centre qualitative study of patient caregivers and emergency department clinicians

Background/purposeSepsis is a leading cause of morbidity, mortality and healthcare utilisation for children worldwide, particularly in resource-limited regions. In Kumasi, Ghana, organ system failure and mortality in children who present...

Bacterial Infections in Acute-on-chronic Liver Failure: Epidemiology, Diagnosis, Pathogenesis, and Management.

Acute-on-chronic liver failure (ACLF) is a distinct condition characterized by the abrupt exacerbation of pre-existing chronic liver disease, often leading to multi-organ failures and significant short-term mortalities. Bacterial infection is one of the most frequent triggers for ACLF and a common complication following its onset. The impact of bacterial infections on the clinical course and outcome of ACLF underscores their critical role in the pathogenesis of systemic inflammation and organ failures. In addition, the evolving epidemiology and increasing prevalence of multidrug-resistant bacteria in cirrhosis and ACLF highlight the importance of appropriate empirical antibiotic use, as well as accurate and prompt microbiological diagnosis. This review provided an update on recent advances in the epidemiology, diagnosis, pathogenesis, and management of bacterial infections in ACLF.

An Interesting Case of Hemophagocytic Lymphohistiocytosis Secondary to Systemic Lupus Erythematosus

ABSTRACT Hemophagocytic lymphohistiocytosis (HLH) is a reactive condition marked by cytopenias and clinical features of systemic inflammation related to macrophage activation. It may be familial and may present early in life or sporadic and may affect people of any age. HLH secondary to systemic lupus erythematosus (SLE) is a rare clinical entity with an estimated prevalence of 0.9–4.6%. A 19-year-old man with no significant past medical history presented with complaints of high-grade fever with chills and bleeding manifestations, such as hematemesis, hemoptysis, epistaxis, and petechial rash in both upper limbs and lower limbs. Laboratory investigations showed significant pancytopenia and raised plasma levels of ferritin, triglycerides, and soluble interleukin (IL)-2. Ultrasonography of the abdomen showed mild hepatomegaly. A bone marrow biopsy showed evidence of mild hemophagocytosis. Antinuclear antibody (ANA) by indirect immunofluorescence assay (IFA) and double-strand deoxyribonucleic acid (dsDNA) came positive, and a diagnosis of HLH secondary to SLE was made. The patient was treated symptomatically with PCV and random donor platelet (RDP) transfusions and definitively with steroid therapy. HLH provokes potential life-threatening systemic toxicity and organ failure. Thus, prompt recognition when a patient presents with unexplained fever, cytopenias, and hepatosplenomegaly is required for timely treatment to prevent end-organ irreversible damage.

High Levels of Triggering Receptor Expressed in Myeloid Cells-Like Transcript-1 Positive, but Not Glycoprotein 1b+, Microparticles Are Associated With Poor Outcomes in Acute Respiratory Distress Syndrome.

To identify triggering receptor expressed in myeloid cells-like transcript-1 positive (TLT-1+) microparticles (MPs) and evaluate if their presence is associated with clinical outcomes and/or disease severity in acute respiratory distress syndrome (ARDS). Retrospective cohort study. ARDS Network clinical trials. A total of 564 patients were diagnosed with ARDS. None. Using flow cytometry, we demonstrated the presence of TLT-1+ platelet-derived microparticles (PMP) that bind fibrinogen in plasma samples from fresh donors. We retrospectively quantified TLT-1, glycoprotein (Gp) 1b, or αIIbβIIIa immunopositive microparticles in plasma samples from patients with ARDS enrolled in the ARMA, KARMA, and LARMA (Studies 01 and 03 lower versus higher tidal volume, ketoconazole treatment, and lisofylline treatment Clincial Trials) ARDS Network clinical trials and evaluated the relationship between these measures and clinical outcomes. No associations were found between Gp1b+ MPs and clinical outcomes for any of the cohorts. When stratified by quartile, associations were found for survival, ventilation-free breathing, and thrombocytopenia with αIIbβIIIa+ and TLT-1+ MPs (χ2p < 0.001). Notably, 63 of 64 patients in this study who failed to achieve unassisted breathing had TLT+ PMP in the 75th percentile. In all three cohorts, patients whose TLT+ MP counts were higher than the median had higher Acute Physiology and Chronic Health Evaluation III scores, were more likely to present with thrombocytopenia and were 3.7 times (p < 0.001) more likely to die than patients with lower TLT+ PMP after adjusting for other risk factors. Although both αIIbβIIIa+ and TLT+ microparticles (αIIbβIIIa, TLT-1) were associated with mortality, TLT-1+ MPs demonstrated stronger correlations with Acute Physiology and Chronic Health Evaluation III scores, unassisted breathing, and multiple system organ failure. These findings warrant further exploration of the mechanistic role of TLT-1+ PMP in ARDS or acute lung injury progression.

Acute Kidney Injury in ARDS: Insights into Physiology and Pathology

Abstract: Acute kidney injury is a common problem in the critically ill patient. It is often part of the multi system organ failure syndrome where other organs such as the lungs are involved. In the critically ill patient, primary pathology in one organ can affect other organs, and systemic illness can affect both at the same time. In this review article, we closely examine the definition and stages of dysfunction in lungs and kidneys and the relationship between the physiology and pathology of these two organs as they interact and affect each other in the critically ill patient. We also seek to understand the effects common intensive care units interventions have on both those organs, with a special emphasis on external life support devices such as mechanical ventilation, dialysis and extracorporeal membranous oxygenation.

Sitagliptin ameliorates L-arginine-induced acute pancreatitis via modulating inflammatory cytokines expression and combating oxidative stress.

Acute pancreatitis (AP) is an inflammatory condition that resolves spontaneously, but occasionally, develops into systemic inflammation, organ failure and mortality. Oxidative stress and activation of inflammatory pathways represent major players in AP pathogenesis. Current management of AP relies on attenuating injuries to the pancreas and putting the inflammatory process under control. In this study, we investigated the role of sitagliptin in modulating L-arginine-induced AP in rats. Swiss rats were subdivided into a healthy control group, AP group (a single dose of L-arginine 250mg/100g, intraperitoneal), and sitagliptin + L-arginine-treated group (10mg sitagliptin/kg body weight/day, orally). Sitagliptin treatment started 1hour after L-arginine injection and continued for 3days. Biochemical and histopathological investigations were performed on serum and tissue samples collected from test animals. L-arginine increased pancreatic meyloperoxidase and serum amylase- and lipase activities and serum levels of TNF-α, LT-α, IFN-γ, IL-1α/β, IL-6, IL-10, IL-12, and IL-15. AP animals showed elevated MDA and NO and decreased GSH and serum calcium levels. Histopathological changes were observed by H&E staining. Sitagliptin treatment significantly ameliorated these biochemical and histological changes diminishing the signs of AP. Sitagliptin treatment was effective in ameliorating L-arginine-induced AP which can be regarded to its anti-inflammatory and antioxidant effect.

#557 Seraph® 100 affinity blood cartridge as a potential adjunctive blood purification strategy for S. aureus-induced septic shock

Abstract Background and Aims S. aureus infections, particularly methicillin-resistant strains, can induce severe conditions, provoking an overwhelming immune response and contributing to systemic inflammation and organ failure. Effective antibiotic therapy and meticulous supportive care are crucial in the ICU to manage S. aureus-induced septic shock. In this context, blood purification strategies aim to target the microorganism and associated toxins, contributing to the systemic inflammatory cascade. The objective of this in-vitro study was to analyze the potential removal, through adsorption, by the Seraph100 Affinity Blood Cartridge (S100ABC) against S. aureus. Subsequently, the study assessed whether the adsorptive capabilities toward bacteria were maintained, and if so, whether the bacteria retained its bactericidal activity. Method The study employed an in vitro model of hemoadsorption to characterize the adsorption performed by the S100ABC on a circulating bacterial load inoculated in blood. A volume of 150 ml of blood served as a negative control (CTR-). The remaining 650 mL were enriched with a concentration of S. aureus bacteria equal to 1×106 and incubated for 4 h at 37°C. At 4 h, the blood was divided into 2 glass bowls and stirred at 37°C: 500 mL were circulated at a speed of 120 mL/min via a dedicated test platform (Galileo) with Seraph100, while another 150 mL was stirred and used as a positive control (CTR+). The experiment was performed twice. Samples were taken from circulating blood and the two controls for blood cultures and placement on CNA agar. Results This study demonstrated that the S100ABC reduces the circulating bacterial load (from 1x106 at T0 to 0.25x106 at T6 h), leading to the adsorption of bacteria onto the cartridge. Bacteria were found adhering to the beads contained in the cartridge. Conclusion Our preliminary data show that the S100ABC effectively reduces the circulating bacterial load. The S100ABC could be an adjunct sorbent for reducing S. aureus in human blood, supporting antibiotic therapy in patients with S. aureus-induced septic shock.

Acute Respiratory Failure in Autoimmune Rheumatic Diseases: A Review.

This review examines respiratory complications in autoimmune rheumatic diseases within intensive care units (ICUs). The respiratory system, primarily affected in diseases like rheumatoid arthritis, systemic lupus erythematosus, and scleroderma, often leads to respiratory failure. Common manifestations include alveolar hemorrhage, interstitial fibrosis, and acute respiratory distress syndrome. Early recognition and treatment of non-malignant conditions are crucial to prevent rapid disease progression, with ICU mortality rates ranging from 30% to 60%. Delayed immunosuppressive or antimicrobial therapy may result in organ system failure. Collaboration with rheumatic specialists is vital for accurate diagnosis and immediate intervention. Mortality rates for rheumatic diseases in the ICU surpass those of other conditions, underscoring the need for specialized care and proactive management. The review emphasizes comprehensive assessments, distinguishing disease-related complications from underlying issues, and the importance of vigilant monitoring to enhance patient outcomes.